1

Philippine National Formulary

8th Edition

Published by

Department of Health
Manila, Philippines

2019
 DISCLAIMER
The list of medicines and the prescribing information contained in this edition of
the Formulary were collated as meticulously as possible through the collaborative efforts of
the Formulary Executive Council (FEC), pharmacists, medical specialists, and specialty
societies applying the standard clinical practice current at the time of the undertaking. Thus,
the medicines and the accompanying prescribing information in this edition are the most
recent only insofar as the dates of the actual collaboration are concerned. There is no
guarantee, therefore, that after the final drafting for this edition, the new medicines or new
information that may subsequently become available will be included.

While diligent effort has been made to ensure the accuracy of each entry, it is
essential to bear in mind that the information presented here is a synopsis of key points in
the official product labeling, and that the complete labeling contains additional precautionary
information that may be of significance in specific cases. Thus, the editors do not warrant
that the information contained herein is in every aspect accurate.

Since a manual of this volume cannot be as exhaustive, the editors have included
only the information which they consider to be essential, and the most relevant and useful
for rapid reference by the physicians. It is the hope of the editors that this Formulary is
perceived as a readily accessible, easily understandable, up-to-date source of independent
medicine information. Nevertheless, this Formulary should be supplemented, where
necessary, by more recent and comprehensive materials and publications.

Moreover, the recommendations incorporated into this Formulary are intended to

serve only as guides that will supplement and not replace the best clinical judgment of the
prescribing clinicians. Readers are enjoined to confirm the information contained herein with
other sources, particularly with regard to new or the latest updates.

ISBN 978-621-95540-3-9

All rights reserved 2019

The Formulary Executive Council

Pharmaceutical Division, Health Regulation Team

Published by:
Department of Health
San Lazaro Compound, Rizal Ave., Sta. Cruz, Manila, Philippines, 1003

Any part or the whole book may be reproduced or transmitted without any alteration, in any form
or by any means, with permission from DOH provided it is not sold commercially.
THE PHILIPPINE NATIONAL FORMULARY
8th Edition
2019

DEPARTMENT OF HEALTH

FRANCISCO T. DUQUE III, MD, MSc

Secretary of Health

ROLANDO ENRIQUE D. DOMINGO, MD, DPBO

Undersecretary of Health
Health Regulation Team

ANNA MELISSA S. GUERRERO, MD, MPH (HTA)

Chief
Pharmaceutical Division

FORMULARY EXECUTIVE COUNCIL

Froilan A. Bagabaldo, RPh, Ll.B.
Cleotilde H. How, MD, FPSECP, FPPS
Cecilia A. Jimeno, MD, FPCP, FPSEDM
Cecilia C. Maramba-Lazarte, MD, MScID, MScCT, FPPS, FPIDSP,
FPSECP
Paul Matthew Pasco, MD, FPNA
Imelda G. Peña, RPh, MS, DrPH
John Q. Wong, MD, MSc
THE PHILIPPINE NATIONAL FORMULARY
8th Edition
2019

EDITORIAL TEAM
Yolanda R. Robles, RPh, MPharm, PhD
Shiela Mae J. Nacabu-an, RPh, MHPEd
Christine Aileen C. Benosa, RPh, MPH
Ian Theodore G. Cabaluna, RPh, MD GDip (Epi)
Editors

Jeanne Genevive A. Pillejera, RPh

Associate Editor

Joshua Elijah M. Chavez, RPh

Ena Elizabeth L. Naoe, RPh
Kristel Keith N. Nieva, RPh
Frances Lois U. Ngo
Jarvin Enosh T. Tan, RPh
Rose Charisse L. Traballo, RPh
Ryan Joseph C. Tuzon
Mikaella B. Santos
Martha O. de la Paz
Arizaldo E. Castro, MSc
Leo Miguel S. Vergeire
Technical Writers

Irene V. Florentino-Fariñas, RPh, MD, MNSA

Joyce Anne D. Ceria-Pereña, RPh, MPM
Johanna B. Mallari, RPh
Kate D. Dunlao, RPh
April Rose B. Macandog, RPh
Members of the Editorial Team

John Michael L. Roque

Technical Assistant
 CONTRIBUTORS

DOH Disease Prevention and Control Bureau

DOH Family Health Office

National Antiobiotic Guidelines Committee

National Center for Mental Health

Rodney Ribleza Boncajes, MD

National Kidney and Transplant Institute

Jean Anne B. Toral, MD, MSc
Lynn B. Bonifacio, MD
Chrystal Catli Burog, MD
Teresita Dumagay, MD
Roxan Perez, MD

National Poison Management and Control Center

Pediatric Infectious Disease Society of the Philippines

Philippine Academy of Ophthalmology

Philippine Academy of Pediatric Pulmonologists

Philippine Children’s Medical Center

Marilou A. Abrera, MD
Cecilia Cruz, MD

Philippine College of Chest Physicians

Philippine College of Geriatric Medicine

Philippine College of Radiology

Philippine Dermatological Society

Philippine Heart Association

Philippine Heart Center

Maria Teresa B. Abola, MD
Eden A. Gabriel, MD
 Philippine Neurological Association

Philippine Obstetrical and Gynecological Society

Philippine Orthopaedic Association

Philippine Psychiatric Association

Philippine Rheumatology Association

Philippine Society of Allergy, Asthma and Immunology, Inc.

Philippine Society of Anesthesiologists, Inc.

Angel M. Gomez, MD

Philippine Society of Endocrinology, Diabetes and Metabolism

Philippine Society of Gastroenterology

Philippine Society of Hematology and Blood Transfusion

Philippine Society of Medical Oncology

Mary Claire V. Soliman, MD, FPCP, FPSMO
Marcelo Severino B. Imasa, MD, FPCP

Philippine Society for Microbiology and Infectious Diseases

Philippine Society of Nephrology

Philippine Society of Newborn Medicine

Philippine Society of Otolaryngology, Head and Neck Surgery

Philippine Society of Parenteral and Enteral Nutrition

Philippine Society of Pediatric Metabolism and Endocrinology

Philippine Society of Pediatric Oncology

Philippine Urological Association

Stroke Society of the Philippines

 Department of Health - Office of the Secretary

Message

The revitalization of the Fourmula One Plus for Health as the framework of the
healthcare reform agenda of the national government is anchored on the values of
equitable and inclusive health system, transparent and accountable provision of
quality health services, and efficient use of resources.

The 8th edition of the Philippine National Formulary (PNF) is a tool to exercise
these values while contributing to the achievement of the objectives of financial
protection and better health outcomes.

Its previous editions have been the basis of tailored procurement of medicines in
public health facilities while providing efficient use of limited resources. It is also the
basis of the Philippine Health Insurance Corporation (PhilHealth) in reimbursing
claims to end-users for medicines use.

With its new format and content, the PNF 8th edition can now maximize the PNF’s
contribution to the rational use of medicines. Its abridged content is intended to
provide concise evidence-based drug information which is vital in medical practice.

The latest PNF is a useful tool to ensure rational prescribing, dispensing, and
administration of medicines. I would like to encourage our health professionals to fully
utilize it in their medicines procurement as well as in their day-to-day clinical decision-
making.

Let us continue to work for our shared vision of all for health towards health for all!

Mabuhay!

FRANCISCO T. DUQUE III, MD, MSc

Secretary of Health
 Department of Health – Health Regulation Team

Message

Greetings!

The Philippine National Formulary (PNF) plays a vital role in promoting the rational
use of medicines in the country. As mandated by Republic Act 9502, otherwise known
as the “Universally Accessible Cheaper and Quality Medicines Act of 2008,” and in
accordance with Republic Act 9184, also known as “Government Procurement
Reform Act,” the PNF serves as the basis of procurement of medicines in all
government agencies, including government units.

PNF requires continuous revisions and updating to ensure its relevance. It is part
of the important role of the Department of Health (DOH) in regulating health products
and services and providing technical assistance to health providers and stakeholders.
While the FDA ensures that only quality medicines are available in the market, the
PNF helps assure that only safe, effective, and affordable medicines are procured by
public health facilities.

The 8th edition of the PNF includes critical revisions that would facilitate the work
of physicians, nurses, pharmacists, and other healthcare professionals. Thus, in
behalf of the DOH, particularly the Health Regulation Team, I would like to commend
the movers behind the PNF in promoting rational prescribing, dispensing, and use of
medicines. Their valuable efforts in revising the National Formulary enable the country
to ACHIEVE better health outcomes.

Congratulations!

ROLANDO ENRIQUE D. DOMINGO, MD, DPBO

Undersecretary of Health
Health Regulation Team
 ACKNOWLEDGMENTS

This Formulary is adapted from the World Health Organization (WHO) Model
Formulary (2008) with the publisher’s permission. We acknowledge, with sincere
thanks, the work of the WHO in producing the Model Formulary so that countries and
organizations can compile and produce their own national formularies.

For their invaluable contribution to the current edition of the Philippine National
Formulary (PNF), sincere gratitude is also due to the following:

Members of the Formulary Executive Council (FEC) who thoroughly reviewed the
list of essential medicines and the Formulary monographs: Atty. Froilan Bagabaldo,
Dr. Cleotilde H. How, Dr. Cecilia A. Jimeno, Dr. Hilton Y. Lam, Dr, Cecilia C. Maramba-
Lazarte, Dr, Paul Matthew Pasco, Dr. Imelda G. Peña, and Dr. John Q. Wong;

Hospitals who participated in the pilot run of the formulary: Philippine Children’s
Medical Center, Philippine Heart Center, Lung Center of the Philippines, National
Kidney and Transplant Institute, Luis Hora Memorial Regional Hospital, Bicol Medical
Center, and San Lazaro Hospital; and

All the experts from the national health programs (NHA), specialty hospitals, and
professional medical societies who participated in the review of the content of the
Formulary and provided valuable and indispensable comments and corrections.
 TABLE OF CONTENTS
GENERAL GUIDE ON THE USE OF THIS FORMULARY ......................................................................................... i
MEDICINE MONOGRAPH KEY ............................................................................................................................ ii
FDA PREGNANCY RISK CATEGORIES .................................................................................................................. iii
SYMBOLS AND ABBREVIATIONS ........................................................................................................................ iv
GENERAL GUIDE TO PRESCRIBING
A. RATIONAL APPROACH TO THERAPEUTICS ............................................................................................. v
B. VARIATION IN DOSE RESPONSE
1. PHYSIOLOGICAL AND PHARMACOKINETIC VARIABLES ................................................................. vii
2. MEDICINE DISTRIBUTION ................................................................................................................ ix
3. MEDICINE METABOLISM AND EXCRETION ................................................................................... ix
4. PHARMACODYNAMIC VARIABLES ................................................................................................... ix
5. DISEASE VARIABLES ........................................................................................................................ ix
6. ENVIRONMENTAL VARIABLES ......................................................................................................... x
C. ADHERENCE TO (COMPLIANCE WITH) MEDICINE TREATMENT .............................................................. x
1. PATIENT-RELATED REASONS .......................................................................................................... x
2. DISEASE-RELATED REASONS ......................................................................................................... xi
3. DOCTOR-RELATED REASONS .......................................................................................................... xi
4. THE DOCTOR-PATIENT INTERACTION ............................................................................................. xi
5. PRESCRIPTION-RELATED REASONS .............................................................................................. xi
6. PHARMACIST-RELATED REASONS ................................................................................................. xi
7. RECOMMENDATIONS TO THE PRESCRIBERS ............................................................................... xi
D. ADVERSE EFFECTS
1. ADVERSE DRUG REACTIONS (ADR) ................................................................................................ xii
2. MAJOR FACTORS PREDISPOSING TO ADVERSE EFFECTS ............................................................ xii
E. PRESCRIPTION WRITING
1. PRESCRIPTION FORM ....................................................................................................................... xiii
2. INCORRECT PRESCRIPTIONS .......................................................................................................... xiv
3. NARCOTICS AND CONTROLLED SUBSTANCES .............................................................................. xiv
F. PATIENT COUNSELING ............................................................................................................................... xv
1. WHAT TO COUNSEL ......................................................................................................................... xv
2. WHO AND WHEN TO COUNSEL ....................................................................................................... xv
3. COUNSELING: PROCESS STEPS ..................................................................................................... xvi
ANTIMICROBIAL RESISTANCE ............................................................................................................................. xvii

MEDICINE AND THERAPEUTIC INFORMATION

A – ALIMENTARY TRACT AND METABOLISM 1
DRUGS FOR ACID RELATED DISORDERS ................................................................................................... 1
DRUGS FOR FUNCTIONAL GASTROINTESTINAL DISORDERS .................................................................. 8
ANTIEMETICS AND ANTINAUSEANTS ......................................................................................................... 11
BILE AND LIVER THERAPY .......................................................................................................................... 13
DRUGS FOR CONSTIPATION ....................................................................................................................... 14
ANTIDIARRHEALS, INTESTINAL ANTIINFLAMMATORY/ANTIINFECTIVE AGENTS .................................... 17
DRUGS USED IN DIABETES ........................................................................................................................ 22
VITAMINS ..................................................................................................................................................... 26
MINERAL SUPPLEMENTS ........................................................................................................................... 33
OTHER ALIMENTARY TRACT AND METABOLISM PRODUCTS ................................................................... 41
B – BLOOD AND BLOOD FORMING ORGANS 43
ANTITHROMBOTIC AGENTS ........................................................................................................................ 43
ANTIHEMORRHAGICS ................................................................................................................................. 57
ANTIANEMIC PREPARATIONS ..................................................................................................................... 61
BLOOD SUBSTITUTES AND PERFUSION SOLUTIONS ............................................................................... 66
C – CARDIOVASCULAR SYSTEM 94
CARDIAC THERAPY ...................................................................................................................................... 94
AGENTS ACTING ON ARTERIOLAR SMOOTH MUSCLE............................................................................... 112
AGENTS ACTING ON THE RENIN-ANGIOTENSIN SYSTEM......................................................................... 115
BETA-BLOCKING AGENTS............................................................................................................................ 124
CALCIUM CHANNEL BLOCKERS ................................................................................................................. 129
CENTRALLY ACTING ANTIADRENERGIC AGENTS....................................................................................... 139
DIURETICS.................................................................................................................................................... 140
 LIPID MODIFYING AGENTS ......................................................................................................................... 148
D – DERMATOLOGICALS 152
ANTIFUNGALS FOR DERMATOLOGICAL USE ............................................................................................. 152
EMOLLIENTS AND PROTECTIVES ............................................................................................................... 156
ANTIPRURITICS, INCLUDING ANTIHISTAMINES, ANESTHETICS, ETC. ...................................................... 156
ANTIPSORIATICS ......................................................................................................................................... 156
ANTIBIOTICS AND CHEMOTHERAPEUTICS FOR DERMATOLOGICAL USE ............................................... 158
CORTICOSTEROIDS, DERMATOLOGICAL PREPARATIONS ........................................................................ 160
ANTISEPTICS AND DISINFECTANTS ........................................................................................................... 162
ANTI-ACNE PREPARATIONS ........................................................................................................................ 165
G – GENITO URINARY SYSTEM AND SEX HORMONES 167
ANTIINFECTIVES AND ANTISEPTICS, EXCLUDING COMBINATIONS WITH CORTICOSTEROIDS ...... ……. 167
OTHER GYNECOLOGICALS ........................................................................................................................ 167
SEX HORMONES AND MODULATORS OF THE GENITAL SYSTEM ............................................................. 170
UROLOGICALS ............................................................................................................................................. 184
H – SYSTEMIC HORMONAL PREPARATIONS, EXCLUDING SEX HORMONES AND INSULINS 187
PITUTARY AND HYPOTHALAMIC HORMONES AND ANALOGUES .............................................................. 187
CORTICOSTEROIDS FOR SYSTEMIC USE ................................................................................................... 189
THYROID THERAPY ...................................................................................................................................... 197
J – ANTIINFECTIVES FOR SYSTEMIC USE 202
ANTIBACTERIALS FOR SYSTEMIC USE ....................................................................................................... 202
ANTIFUNGALS FOR SYSTEMIC USE ............................................................................................................ 250
ANTIMYCOBACTERIALS .............................................................................................................................. 255
ANTIVIRALS FOR SYSTEMIC USE ................................................................................................................ 266
IMMUNE SERA AND IMMUNOGLOBULINS ............................................................................................... 280
VACCINES .................................................................................................................................................... 287
L – ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS 312
ANTINEOPLASTIC AGENTS ........................................................................................................................ 312
ENDOCRINE THERAPY ................................................................................................................................ 366
IMMUNOSTIMULANTS ................................................................................................................................ 374
IMMUNOSUPPRESSANTS ........................................................................................................................... 381
M – MUSCULO-SKELETAL SYSTEM 397
ANTIINFLAMMATORY AND ANTIRHEUMATIC PRODUCTS ......................................................................... 397
MUSCLE RELAXANTS .................................................................................................................................. 406
ANTIGOUT PREPARATIONS ......................................................................................................................... 415
DRUGS FOR TREATMENT OF BONE DISEASE ............................................................................................ 417
OTHER DRUGS FOR DISORDERS OF THE MUSCULO-SKELETAL SYSTEM............................................... 420
N – NERVOUS SYSTEM 424
ANESTHETICS .............................................................................................................................................. 424
ANALGESICS ................................................................................................................................................ 438
ANTIEPILEPTICS .......................................................................................................................................... 465
ANTI-PARKINSON DRUGS ........................................................................................................................... 481
PSYCHOLEPTICS ......................................................................................................................................... 487
PSYCHOANALEPTICS .................................................................................................................................. 519
OTHER NERVOUS SYSTEM DRUGS ............................................................................................................ 529
P – ANTIPARASITIC PRODUCTS, INSECTICIDES, AND REPELLENTS 540
ANTIPROTOZOALS ....................................................................................................................................... 540
ANTHELMINTICS ......................................................................................................................................... 548
ECTOPARASITICIDES, INCLUDING SCABICIDES, INSECTICIDES, AND REPELLENTS .............................. 551
R – RESPIRATORY SYSTEM 553
NASAL PREPARATIONS ............................................................................................................................... 553
THROAT PREPARATIONS ............................................................................................................................ 554
DRUGS FOR OBSTRUCTIVE AIRWAY DISEASES ......................................................................................... 555
COUGH AND COLD PREPARATIONS ........................................................................................................... 571
ANTIHISTAMINES FOR SYSTEMIC USE ...................................................................................................... 572
OTHER RESPIRATORY SYSTEM PRODUCTS ............................................................................................. 575
S – SENSORY ORGANS 579
OPHTHALMOLOGICALS .............................................................................................................................. 579
OTOLOGICALS ............................................................................................................................................. 601
EAR, NOSE, AND THROAT PREPARATIONS ................................................................................................ 603
V – VARIOUS 605
ALL OTHER THERAPEUTIC PRODUCTS ...................................................................................................... 605
DIAGNOSTIC AGENTS ................................................................................................................................ 631
 GENERAL NUTRIENTS ................................................................................................................................. 633
CONTRAST MEDIA ....................................................................................................................................... 640
DIAGNOSTIC RADIOPHARMACEUTICALS ................................................................................................... 650
THERAPEUTIC RADIOPHARMACEUTICALS ................................................................................................. 651
X – HERBAL PREPARATIONS 653

APPENDICES
SUMMARY STATISTICS .............................................................................................................................. A1
LIST OF DRUG MOLECULES ADDED TO THE PNF 8TH EDITION................................................................ A2
LIST OF DRUG MOLECULES DELETED FROM THE PNF 7th EDITION....................................................... A4
LIST OF ESSENTIAL MEDICINES INCLUDED IN THE PNF BUT NOT REGISTERED WITH THE FDA .......... A6
LIST OF DANGEROUS DRUG PREPARATIONS INCLUDED IN THE PNF.................................................... A9
LIST OF CONTROLLED CHEMICALS INCLUDED IN THE PNF.................................................................... A10
LIST OF ESSENTIAL MEDICINES WITH NARROW THERAPEUTIC RANGE................................................. A11
LIST OF RESTRICTED ANTIMICROBIALS ................................................................................................... A12
LIST OF MEDICINAL PLANT PRODUCTS REGISTERED WITH THE FDA AND INCLUDED IN THE PNF A13
DEFINITION OF DOSAGE FORMS .............................................................................................................. A14
FDA ADVERSE DRUG REACTION (ADR) REPORTING FORM ...................................................................... A17

DIRECTORY ........................................................................................................................................................... A20

REFERENCES ........................................................................................................................................................ A22
ISSUANCES ........................................................................................................................................................... A26
INDEX .................................................................................................................................................................... A93
GENERAL
GUIDANCE
 GENERAL GUIDANCE
ON THE USE OF THIS FORMULARY

The Philippine National Formulary 8th Edition allows healthcare practitioners – physicians,
dentists, pharmacists, nurses, and other allied healthcare professionals – to find important
medicine information to guide them in the rational use of medicines.

In this new edition of the PNF, the essential medicines list and monographs have been
integrated into a single manual. The medicines are arranged using the Anatomical Therapeutic
Chemical (ATC) Classification System. Medicines with more than one therapeutic indication
appear in more than one category. Each monograph consists of:

• Generic Name
• Dosage Form/Strength
• Indications
• Contraindications
• Dosage (weight and/or age-specific dosage recommendations)
• Dose Adjustments (for patients with renal or hepatic disease; or the elderly patients)
• Precautions/Warnings
• Adverse Drug Reactions
• Drug Interactions
• Administration Guide
• Pregnancy Category
• ATC Code

The therapeutic information in this Formulary have been adapted from various current and
comprehensive references (refer to Appendix M. This edition also followed and adapted previously
approved format and contents of the Philippine National Formulary Manual for Primary Healthcare.

i
 MEDICINE MONOGRAPH KEY
The medicine monograph key summarizes and describes the types of information contained
in this edition that the physicians and dentists can utilize in prescribing medicines for their
patients. This key also shows the format of how the prescribing information is arranged.

GENERIC NAME

DOSAGE FORM/STRENGTH

INDICATION/S: This section only includes Philippine FDA-approved indications. In addition, the
indications listed for the Anti-Infective Agents are restricted to those included in the most current
local clinical practice guidelines that were made available to the editors and/or the latest
published recommendations of the Philippine Antimicrobial Resistance Surveillance Program
(ARSP).

CONTRAINDICATION/S: This section details disease states where and patient populations for
whom the medicine should not be used.

DOSE: This section lists dosages of the medicines for adult, child and elderly patients, if
specified, as indicated in the official FDA-approved labeling and/or other main references.

DOSE ADJUSTMENT/S: This section gives dosage adjustment recommendations for the elderly,
or for patients with renal or hepatic impairment.

PRECAUTIONS: This section details (1) harmful conditions related to the use of the medicine
(e.g., exacerbations, increased risk of adverse effects), and (2) disease states or patient
populations where caution is advised. This may also include precautions for breastfeeding
mothers and nursing infants. Black Box Warnings are included.

ADVERSE DRUG REACTIONS: This section denotes side effects and adverse drug reactions
(ADRs) listed in the official FDA-approved labeling. Only Common ADRs are listed in this
Formulary. A complete listing of ADRs can be viewed on the online copy of the formulary.

DRUG INTERACTION/S: This section includes the effects and implications of the concomitant
administration of different medicines, or their use together with food.

ADMINISTRATION: This section lists recommendations on the proper intake or administration of

the medicines.

PREGNANCY CATEGORY: This section is based on the US FDA Pregnancy Risk Categories.

ATC CODE: This section is based on the WHO ATC/DDD Index 2016. (WHO Collaborating Centre
for Drug Statistics Methodology).

ii
 US FDA PREGNANCY RISK CATEGORIES
The FDA-assigned pregnancy categories as used in the Drug Formulary are as follows:

Category Interpretation

A CONTROLLED STUDIES SHOW NO RISK.

Adequate and well-controlled studies in pregnant women have failed to

demonstrate a risk to the fetus in the first trimester of pregnancy (and there
is no evidence of risk in later trimesters).

B NO EVIDENCE OF RISK IN HUMANS.

Animal reproduction studies have failed to demonstrate a risk to the fetus and
there are no adequate and well-controlled studies in pregnant women.

C RISK CANNOT BE RULED OUT.

Animal reproduction studies have shown an adverse effect on the fetus and
there are no adequate and well-controlled studies in humans, but potential
benefits may warrant use of the drug in pregnant women despite potential
risks.

D POTENTIAL EVIDENCE OF RISK.

There is positive evidence of human fetal risk based on adverse reaction

data from investigational or marketing experience or studies in humans, but
potential benefits may warrant use of the drug in pregnant women despite
potential risks.

X CONTRAINDICATED IN PREGNANCY.

Studies in animals or humans have demonstrated fetal abnormalities

and/or there is positive evidence of human fetal risk based on adverse
reaction data from investigational or marketing experience, and the risks
involved in the use of the drug in pregnant women clearly outweigh potential
benefits.

iii
 SYMBOLS AND ABBREVIATIONS
ACE - Angiotensin-converting (IM) - Intramuscular
enzyme Inj. - Injection
ADR - Adverse drug reaction INR - International Normalized
AIDS - Acquired Ratio
Immunodeficiency IU - International Unit(s)
Syndrome (IV) - Intravenous
a.m. - Morning; before noon L - Liter
Amp - Ampule LA - Long-Acting
AV - Atrioventricular lin. - Liniment
BCG - Bacille Calmette-Guérin lot. - Lotion
BP - Blood pressure MAOI - Monoamine Oxidase
BSA - Body surface area Inhibitor
cap., caps - Capsule(s) MDI - Metered Dose Inhaler
CNS - Central Nervous System MDR-TB - Multidrug-resistant
comp. - Compound tuberculosis
cr., crm. - Cream mEq - Milliequivalent
CR - Controlled-release Mg - Milligram
CSF - Cerebrospinal fluid mL - Milliliter
D5NS - Glucose (dextrose) 5% in Mmol - Millimole
normal saline (0.9%) MR - Modified release
D5W - Glucose (dextrose) 5% [includes CR, ER, SR, LA]
solution nebul. - Spray
DOTS - Directly observed NSAID - Non-steroidal Anti-
treatment, short-course Inflammatory Drugs
DMARD - Disease modifying agents p.m. - Afternoon / Evening
in rheumatoid disorders RE - Retinol Equivalent
DPI - Dry powder inhaler Resp. Soln. - Respiratory Solution
EC - Enteric-coated Rx - Prescription
ECG - Electrocardiogram (SC) - Subcutaneous
emuls. - Emulsion (SL) - Sublingual; under the
EPS - Extrapyramidal syndrome tongue
ER - Extended Release sig. - Signa / write on label
FC - Film-coated Soln. - Solution
G - Gram spp. - Species
GFR - Glomerular Filtration Rate SR - Sustained Release
GI - Gastrointestinal SSRI - Selective Serotonin
gtt(s) - Drop(s) Reuptake Inhibitor
h, hr. - Hour supp. - Suppository
HAI - Hospital-Acquired susp. - Suspension
Infections syr. - Syrup
HIV - Human tab., tabs. - Tablet(s)
Immunodeficiency Virus TB - Tuberculosis
HRT - Hormone Replacement top. - Topical
Therapy XDR-TB - Extensively Drug-resistant
(ID) - Intradermal Tuberculosis

iv
 GENERAL GUIDE TO PRESCRIBING

A RATIONAL APPROACH TO THERAPEUTICS

Rational use of medicines (RUM) is the fundamental concept where patients receive
medicines, when these are needed, that are appropriate for the clinical needs, in doses
that meet the individual requirements, for an adequate period of time, at the lowest
possible cost, and administered correctly by the right person.

The problem of irrational use of medicines concerns the following:

a. This is one of the most critical causes of unsuccessful treatment outcomes, health
hazards that include antimicrobial resistance (AMR), wastage of resources, and
increased health costs.
b. Worldwide, 50% of medicines are prescribed, dispensed or sold inappropriately;
moreover, half of the patient population fails to take them correctly.
c. In the Philippines, many irrational practices are prevalent such as rationing (often
termed as “diby-diby”), prescribing of inappropriate alternative medicines, “shotgun”
therapy, misuse and overuse of antibiotics, dispensing of antibiotics without a
prescription, self-medication, buying medicines piecemeal (“tingi”), and failure to
complete treatment.
d. The problems that underlie the irrational practices are far-reaching and include
inadequate supplies of medicines that are in turn due to the sheer number of patients
coming for consultation, the lack of funds or poor support from the government
officials, poverty, inherent limitations of the National Formulary, anomalous
transactions, geographical isolation and poor health literacy of patients and even
some health care providers.

The solutions for many of the causes of irrational practices are often beyond the
control of the physicians. However, the physicians, as stewards of the people’s health,
must lead by example the efforts to adhere faithfully to the principles of RUM. The
basic tenets of RUM include:
a. Prescribing medicines only when these are necessary;
b. Prescribing appropriately; and,
c. Considering the benefits of administering medicines in relation to the risks
involved.

The key points of the systematic processes that will assist in determining the proper
treatment are:
a. Defining the patient’s problem;
b. Specifying the therapeutic objective; and,
c. Selecting the therapeutic strategy.

The selected strategy for achieving a health outcome should be agreed upon
with the patient. The total costs for all therapeutic options should be considered.
Strategies can either be non-pharmacologic and/or pharmacologic.
1) Non-pharmacologic Treatment
This implies that patients do not always need medicine for the treatment
of their conditions. This includes changes in lifestyle or diet, use of
physiotherapy or exercise, provision of adequate psychological support,
and other non-pharmacologic treatments. This is of equal importance as
prescription medicines; instructions for such treatments must be written,
explained, and monitored in the same way.

v
 2) Pharmacologic Treatment
a) Selecting the correct group of medicines:
There are two fundamental principles for rational therapeutics:
i. Knowledge about the pathophysiology involved in the clinical
situation of each patient
ii. Pharmacodynamics of the chosen group of medicines

b) Verifying the suitability of the chosen pharmaceutical treatment:

i. Is the active substance chosen suitable for the patient?
ii. Is the dosage form suitable for the patient?
iii. Is the standard dosage schedule suitable for the patient?
iv. Is the standard duration of treatment suitable for the patient?

c) Prescription Writing:
i. This serves as the link between the prescriber, the pharmacist (or
dispenser), and the patient.
ii. This is vital to the successful management of presenting
medical conditions (see detailed Prescription Writing below).
iii. In the Philippines, only validly registered medical doctors and
dentists (as well as veterinarians) are allowed to prescribe.

d) Giving information, instructions, and warnings:

This is essential in ensuring patient adherence.

e) Monitoring treatment:
i. The evaluation of the follow-up and the outcome of treatment
allows for possible termination of treatment (if the patient’s
problem is solved), or its reformulation when necessary.
ii. This step gives rise to important information about the effects
of medicines, contributing to the pool of knowledge on
pharmacovigilance; that in turn is needed to promote the
rational use of medicines.

B VARIATION IN DOSE-RESPONSE
Correct dose regimen is necessary for the success in medicine treatment. The use of
standard doses in the marketing literature suggests that standard responses are the rule,
but in reality there is considerable variation in medicine response. The reasons for the
variation include: adherence (see Adherence with Medicine Treatment), medicine
formulation, body weight and age, composition, variation in medicine absorption,
distribution, metabolism, and excretion, variation in pharmacodynamics, disease variables,
and genetic and environmental variables.

MEDICINE FORMULATION
a. Poorly formulated medicines may fail to disintegrate or to dissolve.
b. Enteric-coated medicines may pass through the GI tract intact. Changes in
absorption can produce sudden changes in medicine concentrations of
medicines with a narrow therapeutic-to-toxic ratio.
For such medicines, quality control surveillance should be carried out.

BODY WEIGHT AND AGE

Although the concept of varying the dose with the body weight or age of children
has long been a tradition, adult doses have been assumed to be the same irrespective
of size or shape. However, adult weights vary 2- to 3-folds. Furthermore, a patient with
vi
 a large fat mass can store large excesses of highly lipid-soluble medicines compared
with a lean patient of the same weight.

Age can also be important. Adolescents may metabolize some medicines relatively
more rapidly than adults, while the elderly may have reduced renal function and
eliminate some medicines more slowly.

DOSE CALCULATION IN CHILDREN

Many children’s doses are standardized by weight (and therefore require multiplying
by the body-weight in kilograms to determine the child’s dose). Occasionally, the
doses have been standardized by body surface area (BSA) in m2.

To calculate a child’s medication based on BSA, use the formula:

child′ s BSA
× adult dose = child′ s dose
1.73
with the BSA computed as follows:
W × H
A = �
3600
where:
A – patient’s BSA (m2)
W – patient’s weight in kg
H – patient’s height in cm
3600 – conversion / correction factor (kg/m2)

If the weight is expressed in pounds (lbs) and the height in inches (in):

W × H
A = �
3131

o Young children may require a higher dose for each kilogram than adults because
of their faster metabolic rates.
o Calculation by body weight in an overweight child may result in higher than
necessary doses being administered. In such cases, doses should be calculated
using an ideal weight, related to height and age.
o Nomograms can also be used to calculate body surface values based on a
child’s height and weight.
o Where the dose for children is not readily available, prescribers should seek
specialist advice before prescribing for a child.

PHYSIOLOGICAL AND PHARMACOKINETIC VARIABLES

a. Pharmacokinetics
This area of study deals with changes of concentration in the drug product, or in a drug
and its metabolites, in the body, after it has been administered. This includes the time
course of drug absorption, distribution, metabolism, and elimination.
A basic understanding of the factors which control drug concentration at the site of
action (e.g., bioavailability, area under the curve, and half-life) is important for the
optimal use of drugs.
1) Bioavailability
This refers to the amount of medicine from an administered dosage form which
enters the systemic circulation, and the rate at which it appears in the bloodstream.
Changes in a drug’s bioavailability may be thought of in terms of changes in

vii
 exposure to the drug which, if substantial, can relate to safety and efficacy
concerns.

2) Bioequivalence
This indicates that a drug in two or more similar dosage forms reaches the
general circulation at the same relative rate and the same relative extent (i.e.,
that the plasma level profiles of the drug obtained using the two dosage forms
are the same).
This is an important consideration in several key situations involving lot-to-lot
consistency, innovator to generic product therapeutic equivalence, and
situations where a marketed product undergoes changes in certain aspects
(formulation, manufacturing process, and dosage strength).

3) Half-life
This indicates the time required to reduce the amount of medicine in the body
or the plasma concentration by 50%.
This is a clinically useful pharmacokinetic parameter because this indicates
when the next dose of a medicine needs to be administered, and thus helpful
in determining an optimal dosing regimen.

b. Medicine absorption rates may vary widely among individuals and in the same individual
at different times and in different physiological states.
Medicines taken after a meal are delivered to the small intestine more slowly than in
the fasting state, leading to much lower medicine concentrations. In pregnancy, gastric
emptying is also delayed, while some medicines may increase or decrease gastric
emptying, and affect absorption of other medicines.

MEDICINE DISTRIBUTION
a. Fat-soluble medicines (vitamins A, D, E, and K) are stored in adipose tissues.
b. Water-soluble medicines are distributed chiefly in the extracellular space.
c. Acidic medicines bind strongly to plasma albumin.
d. Basic medicines go to muscle cells.
e. Hence, variations in plasma albumin concentration, fat content, or muscle mass may
all contribute to dose variation.

MEDICINE METABOLISM AND EXCRETION

a. Medicine metabolism is affected by genetic, environmental, and disease-state
factors.
b. Medicine acetylation shows genetic polymorphism, where individuals fall clearly into either
fast or slow acetylator types. This means that some patients can metabolize medicines
more rapidly (fast acetylators) than the others (slow acetylators).
c. Medicine oxidation, however, is polygenic.
Although a small proportion of the population can be classified as very slow
oxidizers of some medicines, there is a normal distribution of medicine-
metabolizing capacity for most medicines and most subjects.
d. Many medicines are eliminated by the kidneys without being metabolized.
e. Renal disease or toxicity of some medicines on the kidney can slow excretion of some
medicines.
f. Hepatic disease or toxicity of some medicines on the liver can slow excretion of some
medicines.

viii
PHARMACODYNAMIC VARIABLES
Significant variations in receptor response to some medicines (especially CNS
responses, such as pain and sedation) are attributed to genetic factors, tolerance,
medicine interactions, and medicine dependence.

DISEASE VARIABLES
a. Both liver and kidney diseases can have major effects on metabolism and elimination,
respectively (resulting in increasing toxicity), but also through effects on plasma
albumin (resulting in increasing free medicine and thus toxicity).
b. Heart failure can also affect metabolism of medicines with rapid hepatic clearance
(e.g., lidocaine).
c. Respiratory disease and hypothyroidism can impair oxidation of drugs.

ENVIRONMENTAL VARIABLES
a. Many medicines and environmental toxins can induce the hepatic microsomal
enzyme oxidizing system or cytochrome P450 oxygenases, leading to more rapid
metabolism and elimination, and thus less effective treatment.
b. Environmental pollutants, anesthetic medicines, and other compounds, such as
pesticides, can also induce metabolism.
c. Diet and nutritional status also affect pharmacokinetics:
1) In malnourished infantile and elderly populations, medicine oxidation rates are
decreased.
2) High protein diets, charcoal-cooked foods, and certain other foods act as
metabolizing enzyme inducers.
3) Chronic alcohol use induces oxidation of some medicines; but in the presence
of high circulating alcohol concentrations, medicine metabolism may be
inhibited.

C ADHERENCE TO (COMPLIANCE WITH) MEDICINE TREATMENT

One of the most important reasons for treatment failure is poor adherence to
(compliance with) the treatment plan.

Reasons for non-compliance may be related to: (1) the patient, (2) the disease, (3) the
doctor, (4) the prescription, (5) the pharmacist, or (6) the health system.
o For instance, patients' perceptions of the risk and severity of adverse drug
reactions may differ from those of the healthcare provider and may affect
adherence.
o Poor prescribing or a dispensing error may also create a problem, which patients
may have neither the insight nor the courage to question. Even with good
prescribing though, failure to adhere to treatment is common.

Valid reasons for poor adherence include the ff.: the medicine may be poorly tolerated,
may cause obvious adverse effects, or may be prescribed in a toxic dose. Failure to adhere
with such a prescription has been described as “intelligent non-compliance”.

Low-cost strategies for improving adherence increase effectiveness of health

interventions and reduce costs. Such strategies must be tailored to the individual patient.
Healthcare providers should be familiar with techniques for improving adherence and they
should employ systems to assess adherence and to determine what influences it.

ix
 1. PATIENT-RELATED REASONS
a. Women tend to be more adherent than men.
b. Younger patients and the very elderly tend to be less adherent.
c. People living alone are less adherent than those living with partners or spouses.
d. Specific education interventions have been reported and shown to improve
adherence and compliance.
e. Some patient disadvantages include illiteracy, poor eyesight, or cultural
attitudes, which includes preference for traditional or alternative medicines, and
distrust of modern medicines.
f. Economic factors affect patient adherence, compliance and maintenance.

2. DISEASE-RELATED REASONS
Conditions with a known worse prognosis (e.g., cancer) or painful conditions (e.g.,
rheumatoid arthritis) elicit better adherence than asymptomatic “perceived as
benign” conditions such as hypertension.

3. DOCTOR-RELATED REASONS
a. Failure to inspire confidence in the treatment offered
b. Little or no explanation provided
c. Too many medicines prescribed
d. Errors in prescribing
e. Overall attitude to the patient

4. THE DOCTOR-PATIENT INTERACTION

a. Quality of the doctor–patient interaction is crucial to adherence and compliance.
b. “Satisfaction with the interview” is one of the best predictors of good adherence.
c. If they are in doubt or dissatisfied, they may turn to alternative options, including
complementary medicine.

5. PRESCRIPTION-RELATED REASONS
a. Illegible or inaccurate prescriptions may discourage patients to adhere to
medications.
b. Lost prescriptions may delay patients to start or continue medications.
c. Prescriptions not refilled as intended or instructed for a chronic disease may
reduce maintenance.
d. Too complex prescriptions (greater number of different medicines, poorer
adherence).
e. Multiple doses decrease adherence and compliance especially if more than two
doses per day are given.
f. Adverse effects, like drowsiness, impotence, or nausea, reduce adherence.

6. PHARMACIST-RELATED REASONS
a. Manner and professionalism
b. Pharmacist information and counseling can serve as a valuable reinforcement,
as long as they agree with the physician’s advice.

7. RECOMMENDATIONS TO THE PRESCRIBERS

a. Review the prescription to make sure it is correct.
b. Spend time explaining the health problem and the reason for the medicine.
c. Establish good rapport with the patient.
d. Explore problems, such as difficulty with reading the label or getting the
prescription filled.
x
 e. Encourage patients to bring their medication to the clinic so that tablet counts
can be done to monitor compliance.
f. Encourage patients to learn the names of their medicines, and review their
regimen with them. Write notes for them.
g. Keep treatment regimens simple.
h. Communicate with other healthcare professionals to develop a team approach
and to collaborate on helping and advising the patient.
i. Involve the partner or another family member.
j. Listen to the patient.

D ADVERSE EFFECTS AND INTERACTIONS

1. ADVERSE DRUG REACTIONS (ADR)
Any response to a medicine which is noxious, unintended and occurs at doses
normally used for prophylaxis, diagnosis, or therapy. These reactions are different
from accidental OR deliberate excessive dosage or medicine maladministration.

2. MAJOR FACTORS PREDISPOSING TO ADVERSE EFFECTS

a. EXTREMES OF AGE
1) The very old and the very young populations are more susceptible to ADRs.
Examples of which are: hypnotics, antihypertensives, Non-Steroidal Anti-
inflammatory Drugs (NSAIDs), psychotropics, diuretics, and digoxin.
2) All children, particularly neonates, differ from adults in their response to
medicines.
Some medicines are likely to cause problems in
o Neonates, but are generally tolerated in children
o Children of all ages, who are at increased risk of ADRs for
other medicines

b. INTERCURRENT ILLNESSES/COMORBIDITIES
This occurs when a patient suffers from another disease aside from the
current condition being treated (kidney, liver or heart disease). The genetic
make-up of the individual patient plays a role.

c. MEDICINE INTERACTIONS
These may occur among medicines which compete for the same receptor, or
which act on the same physiological system.
1) These may occur indirectly when a medicine-induced disease, or a change
in fluid/electrolyte balance, alters the response to another medicine.
2) These may occur when one medicine alters the absorption, distribution, or
elimination of another medicine, such that the amount which reaches the
site of action is either increased or decreased.

Drug–drug interactions are some of the most common causes of adverse effects. When
two medicines are administered to a patient, they may either act independently of each
other, or interact with each other. Interaction may increase or decrease the effects of the
medicines concerned and may cause unexpected toxicity. As newer and more potent
medicines become available, the frequency of serious drug interactions is likely to increase.

NOTE: Interactions which modify the effects of a medicine may involve non-prescription
medicines, non-medicinal chemical agents, and social drugs such as alcohol,
marijuana and tobacco, and traditional remedies, as well as certain types of food.
The physiological changes in individual patients, caused by such factors as age and
sex, also influence the predisposition to ADRs resulting from drug interactions.

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 d. INCOMPATIBILITIES BETWEEN MEDICINES AND IV FLUIDS
Medicines should not be added to blood, amino acid solutions, or fat emulsions.
o Certain medicines, when combined with intravenous fluids, may be
inactivated by pH changes, precipitation, or chemical reaction.

e. ADVERSE EFFECTS CAUSED BY TRADITIONAL MEDICINES

Patients who have been, or are taking, traditional herbal remedies may
develop ADRs. In these types of preparation, it is not always easy to identify the
responsible constituents. Refer to the medicine and toxicology information
service if available or to suitable literature.

f. EFFECT OF FOOD ON MEDICINE ABSORPTION

Food delays gastric emptying and reduces the rate of absorption of many
medicines; however, the total amount of medicine absorbed may or may not be
reduced. On the other hand, some medicines are taken with food, either to
increase absorption or to decrease the irritant effect on the stomach.

E PRESCRIPTION WRITING
1. PRESCRIPTION FORM
Administrative Order No. 62 (series of 1989) on the rules and regulations to
implement prescribing requirements under the Generics Act defines a prescription as
a written order and instruction of a validly-registered physician, dentist or veterinarian
for the use of a specific medicine (or medical device) for a specific patient.

The most important requirement for a prescription is that it should be clear. It

should be legible and indicate precisely what should be given. The language used may
be in English, Filipino, or the local dialect.

In accordance with R.A. 5921, or the Pharmacy Act as amended, all prescriptions
should contain the following information:
o The patient’s name, age and sex;
o The prescriber’s name, office address, professional registration number, and
professional tax receipt number; and,
o Date of the prescription

In addition, Section 3 of the Generics Act lists the following specific guidelines to
prescribing:
o Generic names shall be used in all prescriptions. For drugs with a single active
ingredient, the generic name of that active ingredient shall be used in
prescribing. For drugs with two or more active ingredients, the generic name as
determined by the Philippine FDA shall be used.
o The generic name must be written in full, but the salt or chemical form may be
abbreviated. The symbol Rx means prescription which originated in medieval
manuscripts as an abbreviation of the Latin verb recipe. The imperative form is
recipere which means “to take” or “take thus.”)
o The generic name must be clearly written immediately after the Rx symbol or on
the order chart.
o The pharmaceutical form (e.g., “tablet”, “oral solution”, “eye ointment”) should
also be stated.
o The strength of the medicine should be stated in standard units using
abbreviations which are consistent with the Système International (SI) [Refer to
Appendices for abbreviations and symbols].

xii
 o Avoid decimals whenever possible. If this is unavoidable, a zero should be
written before the decimal point.

2. INCORRECT PRESCRIPTIONS
Three types of incorrect prescriptions may be identified:
a. Erroneous prescription:
o Where the brand name precedes the generic name
o Where the generic name is the one in parenthesis
o Where the brand name is not in parenthesis

b. Violative prescription:
o Where the generic name is not written
o Where the generic name is not legible, and a brand name which is
legible is written
o Where the brand name is indicated and instructions added (such as
the phrase “no substitution”) which tend to obstruct, hinder or
prevent proper dispensing

c. Impossible prescription:
o When only the generic name is written, but it is not legible
o When the generic name does not correspond to the brand name
o When both the generic and brand names are not legible
o When the drug product prescribed is not registered with the
Philippine Food and Drug Administration

If an erroneous prescription is received, the prescription may be filled but it should

be kept and reported to the nearest Department of Health (DOH) office for appropriate
action. In contrary, violative and impossible prescriptions are not to be filled and
should also be kept and reported to the nearest DOH office.

3. NARCOTICS AND CONTROLLED SUBSTANCES

The prescribing of a medicinal product which is liable to abuse requires special
attention and may be subjected to specific statutory requirements. Practitioners may
need to be authorized to prescribe controlled substances. In such cases, it might be
necessary to indicate details of the authority on the prescription.

In particular, the strength, directions, and the quantity of the controlled substance
to be dispensed should be stated clearly, with all quantities written in words, as well
as in figures to prevent alteration. Other details, such as patient particulars and date,
should also be filled in carefully to avoid alteration.

F PATIENT COUNSELING
One-to-one, dynamic interaction between a health care practitioner and a patient and/or
caregiver, which should include an assessment if the information was received as
intended, and that the patient understands how to use the information to improve the
probability of positive therapeutic outcomes.

1. WHAT TO COUNSEL
Routinely, effectively and appropriately educate patients on the following: (1) when
dispensing prescription and non-prescription drugs, (2) when counseling on discharge
medications, and (3) when providing recommendations about management of
specific drug-related problems:
a. The medication’s name (generic), indication and when appropriate to use;

xiii
 b. The medication’s expected onset of action and what to do if the action
does not occur;
c. The medication’s route, dosage form, dosage and administration schedule
(including duration of therapy);
d. Directions for use including education about drug devices;
e. Proper storage requirements;
f. Common or important drug-drug or drug-food interactions;
g. Potential common and severe adverse effects, and actions to prevent or
minimize their occurrence;
h. What the patient should do to monitor his/her therapeutic response or
when side effects develop;
i. What actions the patient should take if the intended therapeutic response
is not obtained or if side effects develop; and,
j. Proper disposal of contaminated, discontinued or unused medications.

2. WHO AND WHEN TO COUNSEL

a. Patients who should always be counseled together with their families and
caregivers:
o Confused patients;
o Patients who are sight- or hearing-impaired;
o Patients with poor literacy;
o Patients whose profiles show change in medications or
dosing;
o New patients, or those receiving a medication for the first time; and,
o Patients who have medications with significant side effects, specific
storage requirements, and complicated directions.
b. Patients who should be counseled at certain intervals:
o Asthmatic patients;
o Diabetic patients;
o Patients taking four (4) or more prescribed medications;
o Patients who are mentally ill;
o Epileptic patients; and,
o Patients with skin complaints.

3. COUNSELING: PROCESS STEPS

Steps in patient education and counseling process will vary according to the health
system’s policies and procedures, environment, and practice setting. Generally, the
following steps are appropriate for patients receiving new medications or returning
for refills:

a. Establish caring relationship with the patient as appropriate to the practice

setting, and stage in the patient’s health care management. Show interest
in the patient verbally and non-verbally
o Explain the purpose and expected length of sessions.
o Obtain the patient’s agreement to participate.
b. Assess the patient’s knowledge about his or her health problems,
medications, physical and mental capability to use the medications
appropriately, and attitude towards the health problems and medications.
o Ask why the patient is being prescribed with the medication
(if known), or the medication’s use, expected benefits and
action.
o Provide information orally, and use demonstrations or visual
aids to fill the patient’s gaps in knowledge and
understanding.

xiv
 o Open the medication containers and show patient what the
medication looks like, or demonstrate use. Explain how to
take the medication.
o Discuss when to take and how long to take the medication.
o Plan what to do if a dose is missed.
o Determine any special precautions to heed and follow.
Explain how to store the medication.
o Demonstrate if the prescription can be refilled, and if so,
determine when it is done.
o Give specific details on how the patient will know if the
medication is working.
c. Verify patient’s knowledge and understanding of medication use.
o Ask the patient to describe (or show) how the medication
should be used, and its effects.
o Ask the patient if they have any questions.

xv
 ANTIMICROBIAL RESISTANCE
A. DEFINITION OF ANTIMICROBIAL RESISTANCE
1. Antimicrobial Resistance (AMR) refers to the resistance of a micro-organism
(including bacteria, viruses and some parasites) to an antimicrobial agent to which it
was previously sensitive. Resistant organisms withstand attack by antibacterials,
antivirals, or antimalarials. Thus, standard treatments become ineffective, allowing
infections to persist and spread.
2. AMR which is a consequence of the use or misuse of antimicrobials develops when
the organism mutates or acquires a resistance gene.

B. CAUSES OF ANTIMICROBIAL RESISTANCE

1. Although the ultimate causes of AMR are microbial, clinical, and programmatic in
nature, it is essentially a man-made occurrence.
2. The proliferation of drug-resistant strains is associated with various management,
healthcare provider, and patient-related issues. Table 1 enumerates several of the
causes leading to drug resistance.
3. The general categories of the causes, i.e., therapeutic protocols, drug characteristics,
and drug selling and purchasing practices, provide opportunities where potential
strategies to combat AMR arise.

Table 1. Causes of inadequate treatment which may contribute to emergence of drug

resistance
Drugs:
Healthcare providers: Patients:
Inadequate
Inadequate regimens Inadequate drug intake
supply/quantity
- Inappropriate guidelines - Poor quality - Poor adherence (or poor
- Noncompliance with - Unavailability of certain directly observed
guidelines drugs (stock-outs or therapy)
- Absence of guidelines delivery disruptions) - Lack of information
- Poor training - Poor storage conditions - Lack of money (no
- No treatment monitoring - Wrong dose or treatment available free
- Poorly organized or combinations of charge
funded control - Lack of transportation
programs - Adverse effects
- Social barriers
- Malabsorption
- Substance dependency
disorders
Source: Final Report, Country Situation Analysis on Antimicrobial Resistance, Philippines,
2012.

C. ANTIMICROBIAL RESISTANCE: A GROWING GLOBAL CONCERN

1. The WHO cites the following alarming reasons: AMR is already a global concern, AMR kills,
AMR challenges control of infectious disease, AMR threatens a return to the pre-antibiotic
era, AMR increases the costs of health care, AMR jeopardizes healthcare gains to society,
and AMR compromises health security, and damages trade and economy.

2. Furthermore, the following facts collated by WHO1 indisputably demonstrate the

potential and real dangers that AMR causes and has caused:
a. About 440,000 new cases of multi-drug resistant TB (MDR-TB which is defined
as resistance to Rifampicin and Isoniazid) emerge annually, causing at least

xvi
 150,000 deaths. Therapy of MDR-TB requires 18-24 months of treatment with
expensive second-line drugs, like capreomycin and kanamycin.
b. Extensively drug-resistant TB (XDR-TB defined as MDR plus resistance to any
member of the quinolone family and at least to any second-line anti-TB
injectable, such as kanamycin, capreomycin or amikacin) is a global threat with
a case-fatality rate of 50%. XDR-TB is a big problem because there are very few
options for treatment, which probably accounts for the high mortality rate among
them.
c. Resistance to earlier generation antimalarial medicines such as chloroquine
and sulfadoxine-pyrimethamine is widespread in most malaria-endemic
countries. Falciparum malaria parasites resistant to artemisinins are emerging
in Southeast Asia; infection showed delayed clearance after the start of
treatment (indicating resistance).
d. Ciprofloxacin is the only antibiotic currently recommended by WHO for the
management of bloody diarrhea due to Shigella, now that wide-spread
resistance has developed to any previously effective antibiotics. But rapidly
increasing prevalence of resistance to Ciprofloxacin in Shigellosis is reducing
the options for safe and efficacious treatment especially for children. New
antibiotics suitable for oral use are badly needed.
e. AMR has become a serious problem for treatment of gonorrhea (caused by
Neisseria gonorrhoea), involving even “last-line” oral cephalosporins, and this is
increasing in prevalence worldwide. In multidrug-resistant N. gonorrhoea,
resistance is found against tetracyclines, macrolides (including azithromycin),
sulfonamide and trimethoprim combinations and more recently, to quinolones.
Untreatable gonococcal infections will result in higher rates of illness and death
thus reversing the gains made in the control of the sexually transmitted
infections.
f. ESBLs (extended-spectrum beta-lactamases) are resistant to third-generation
cephalosporins (ceftazidime, cefotaxime and cefpodoxime) as well as
monobactams (aztreonam); common in the Enterobacteriaceae, particularly
E.coli and K. pneumoniae.
g. New resistance mechanisms, such as the beta-lactamase NDM-1 (New Delhi metalo-
beta-lactamase 1), have emerged among several gram-negative bacilli. This is
considered as a new superbug that has resistance to broad spectrum antibiotics that
are often the last defense against multi-resistant bacterial strains.
h. A high percentage of hospital acquired infections is caused by highly resistant
bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) and
vancomycin resistant enterococci.
i. Resistance is an emerging concern for treatment of HIV infection, following the
rapid expansion in access to anti-retroviral medicines in recent years.

D. STATUS OF ANTIMICROBIAL RESISTANCE IN THE PHILIPPINES

1. The need to approach the problem of AMR in the Philippines with a sense of urgency
is clearly elucidated by several evidence of the dangers it poses.
a. The most dreaded recognized AMR gene, the NDM-1, was identified in the
Escherichia coli isolated from the urine of a 33 year old female in 2011. The
gene can render even the most powerful antibiotics ineffective.
b. Many of the causative bacterial pathogens that cause infections included in the Top
Ten causes of morbidity in the Philippines have already become resistant to multiple
antibiotics. At the forefront is TB, with MDR-TB and even XDR-TB already present in
the Philippines which ranked 6th among 27 identified countries with MDR-TB. In 2006,
the occurrence of MDR-TB was 4% among new cases and a high 27% among
previously treated patients.

xvii
 2. The DOH established in 1988 the Antimicrobial Resistance Surveillance Program (ARSP) to
determine the current status and developing trends of antimicrobial resistance of selected
bacteria to specific antimicrobials. The ARSP, which now has 24 sentinel sites hospital
bacteriology laboratories in 16 regions of the Philippines and 2 gonococcal surveillance
sites, submits and publishes annual summary reports focusing on aerobic bacterial
pathogens of public health importance causing common infectious diseases.

All readers are enjoined to refer to the yearly published ARSP surveillance data
provided by RITM for updated information and proper guidance.

3. The ARSP found alarming rates of resistance among various bacterial pathogens. 1,2
a. The ESBL enzyme, which can render pathogens resistant to many antibiotics,
has been identified in Escherichia coli and Klebsiella spp.
b. Multi-drug resistant Pseudomonas aeruginosa and Acinetobacter spp. which
account for 43% of all hospital-acquired pneumonia have been identified.
c. The percent resistance, in all ARSP sites from January-December of 2013 of
Streptococcus pneumonia (which causes acute respiratory tract infections) to
penicillin was 5% compared to 0 in 2010. Resistance to cotrimoxazole was 20%
in 2013.²
d. The percent resistance of non-typhoidal Salmonella from January-December,
2013, to ampicillin and cotrimoxazole were 56% and 34%, respectively. ²
e. There is a steady increase in the resistance rates of Staphylococcus aureus and
consequently higher prevalence of MRSA which is also an important cause of hospital
acquired infections.
f. In the period 2012-2013, there were very high resistance rates of Neisseria
gonorrhoea to ciprofloxacin (74%), penicillin (80%), and tetracycline (55%). ²

4. These alarming increasing trends of AMR in the country are clearly demonstrated in
Table 2 which summarized the results of a comparison of the antimicrobial resistance
of selected organisms in 1993 and 2011.

Please refer to the Antimicrobial Resistance Surveillance Program (ARSP) Summary Report
for antimicrobial resistance patterns of specific organisms.

E. RECOMMENDATIONS OF THE PHILIPPINE ANTIMICROBIAL RESISTANCE

SURVEILLANCE PROGRAM
Below are the recommendations of the ARSP regarding antibiotic treatment for aerobic
bacterial pathogens of public health importance based on the reported antimicrobial
resistance surveillance data for 2013 (Carlos, C, 2013):

1. Respiratory Bacterial Pathogens:

a. Infections secondary to Streptococcus pneumoniae can still be covered with
penicillin or one of the anti-pneumococcal macrolides, although there is a need
to closely monitor the changing trends of resistance among pneumococci.
Improved local data on serotype distribution will allow for better surveillance
information especially needed for vaccination recommendations.
b. Due to high resistance rate of Haemophilus influenzae to ampicillin, this
antibiotic is no longer recommended for empiric therapy for infections
secondary to the pathogen.
c. Recommended empiric treatment for suspected H. influenzae infections may
consist of beta-lactam-beta-lactamase inhibitor combinations, extended
spectrum oral cephalosporins and the newer macrolides.
xviii
 2. Bacterial Enteric Pathogens:
a. For suspected uncomplicated enteric fever, empiric treatment can still consist
of either chloramphenicol or cotrimoxazole or amoxicillin/ampicillin. There are
increasing reports of nalidixic acid resistance and ciprofloxacin non-
susceptibility which may result to clinical treatment failures when treating
enteric fever using fluoroquinolones. Microbiological data is recommended for
pathogen directed therapy.
b. In Salmonella gastroenteritis, increasing rates of ciprofloxacin resistance should
remind clinicians to use antibiotics judiciously as this is usually a self-limiting
disease.
c. Due to the emerging resistance of Shigellae to the quinolones and limited data
available, more vigilant surveillance of the resistance pattern of this organism
should be pursued by encouraging clinicians to send specimens for culture.
d. For cholera, tetracycline, chloramphenicol and cotrimoxazole remain to be good
treatment options.

3. Sexually-Transmitted Bacterial Pathogens:

a. Limited data is available on N. gonorrhoeae in recent years, but based on
reported isolates, ceftriaxone remains as empiric antibiotic of choice for
gonococcal infections. More vigilant surveillance of the resistance patterns of
this organism must be pursued by encouraging clinicians to send specimens for
culture.

4. Gram-positive Cocci:
a. In view of the continuous high rates of methicillin/oxacillin resistance among
staphylococci, there may be an indication to shift empiric treatment of
suspected staphylococcal infections from oxacillin to alternative agents such as
cotrimoxazole, doxycycline, clindamycin, linezolid or vancomycin.

5. Gram-negative Bacilli:
a. Hospitals should base their treatment recommendations for the Enterobacteriaceae
on their institution’s prevailing resistance patterns as these have been found to be
variable from hospital to hospital. The high percentage of possible ESBL-producing
isolates complicates treatment of serious infections caused by these organisms and
may lead to the increased use of carbapenems that may favor the spread of the
carbapenem-resistant Enterobacteriaceae.
b. Increasing resistance among the bacterial organisms Pseudomonas aeruginosa
and Acinetobacter baumannii continue to be a concern as both carry intrinsic
resistance to a number of antimicrobial classes and acquisition of additional
resistance severely limits the available treatment options.
c. Prudent antimicrobial use, monitoring of resistance patterns and antimicrobial
use, and improved standards of infection control are essential in addressing the
clinical and public health concerns.

All readers are enjoined to refer to the yearly published ARSP surveillance data
provided by RITM for updated information and proper guidance.

F. DRIVING FORCES BEHIND ANTIMICROBIAL RESISTANCE

1. The inappropriate and irrational use of medicines provides favorable
conditions for resistant microorganisms to emerge and spread. WHO enumerates the
following as the underlying factors that drive AMR:
a. Inadequate national commitment to a comprehensive, coordinated response,
ill-defined accountability, and insufficient engagement of communities;
xix
 b. Weak or absent surveillance and monitoring systems;
c. Inadequate systems to ensure quality and uninterrupted supply of medicines;
d. Inappropriate and irrational use of medicines, in both clinical practice and
animal husbandry, and aquaculture;
e. Poor infection prevention and control practices; and,
f. Depleted arsenals of diagnostics, medicines, and vaccines as well as
insufficient research and development of new products.

G. THE RESPONSE OF THE NATIONAL GOVERNMENT TO THE RISING

ANTIMICROBIAL RESISTANCE
1. Creating an Inter-Agency Committee on AMR (ICAMR).
2. Developing a National Plan that will include, but not limited to, the following
strategies:
a. Establishing short and long term programs to address the different aspects of
response to AMR;
b. Strengthening the surveillance system and laboratory detection capacity of AMR
in both humans and animals;
c. Ensuring accessibility, affordability, availability and quality of antimicrobial drugs
for humans and its appropriate use in food producing animals including banning
the use of antibiotics as growth promoters;
d. Developing relevant and utilizable essential medicines list for human and
veterinary use;
e. Monitoring the rational use of antimicrobials in humans, animal husbandry and
aquaculture;
f. Advocating the rational use of antimicrobials to consumers and community
through media and the academe;
g. Training and educating on, and promotion of infection prevention and control
measures in health care facilities and the community;
h. Conducting researches to develop new antimicrobials and innovative technology
to improve diagnosis and treatment;
i. Monitoring and evaluating compliance with existing policies and on the proper
execution of the AMR control plan;
j. Engaging all relevant stakeholders such as government agencies, healthcare
providers, non-government institutions, professional organizations, drug
industry, veterinary and aquaculture groups, consumer groups, researchers and
civil societies; and,
k. Ensuring that activities are well financed for sustainability.

H. ACTION PLANS, WHICH THE PRIMARY PHYSICIANS AND DENTISTS CAN

ADOPT TO HELP COMBAT ANTIMICROBIAL RESISTANCE
1. Assuring the judicious use of antimicrobial agents through faithful adherence to the
principles of rational use of medicines and utilizing antimicrobial agents only for the
appropriate indications as recommended by the Antimicrobial Resistance
Surveillance Program (ARSP) or the task force for Clinical Practice Guidelines and
included in the Philippine National Formulary. The choice of antibiotics must strictly
conform to the best standard treatment guidelines or clinical practice guidelines (e.g.,
National Antibiotic Guidelines), and guided by the latest findings and
recommendations of the ARSP;
2. Keeping abreast of the latest information on AMR through reviews of the latest
antibiotic susceptibility data published by the ARSP, literature search, attendance in
seminars, and participation in continuing medical education programs;
3. Devoting sufficient time to educate the patients and their families and caregivers about the
appropriate use of antibiotics and the reasons behind the need for strict adherence to the

xx
 prescribed dosage schedule and completion of full course of treatment as well as to
educate them on the prevention of AMR;
4. Careful monitoring of the patients’ compliance and their response to the antimicrobial
agents;
5. Submitting specimen for culture when indicated (e.g., for suspected gonococcal
infections);
6. Complying with the rules on prescribing, and other regulations in the Pharmacy Law;
7. Developing better communication with pharmacists and other dispensers;
8. Educating other healthcare providers (nurses, midwives, barangay health workers)
about the RUM and prevention of AMR; and,
9. Educating the community continually on the need for and proper ways of maintaining
good personal hygiene and sanitation, avoidance of vices or unhealthy habits,
sanitation, and prevention of infections, including maintaining cleanliness of their
surroundings.

xxi
MEDICINE AND
THERAPEUTIC
INFORMATION
ALIMENTARY TRACT AND METABOLISM

Less Common: Chalky taste, fecal discoloration,

ALIMENTARY TRACT AND METABOLISM hypophosphatemia, nausea, vomiting.
Rare: Anemia, encephalopathy, fecal impaction,

A
hypermagnesemia, hypophosphatemia, intestinal
obstruction, osteomalacia, proximal myopathy.

DRUGS FOR ACID-RELATED Drug Interactions:

DISORDERS Monitor closely with:
Increases excretion due to urine alkalinization:
Acetylsalicylic Acid
ANTACIDS
Reduces absorption of the following drugs:
ALUMINUM HYDROXIDE + Azithromycin, Chloroquine, Digoxin, Enalapril, Isoniazid,
OTC Rifampicin
MAGNESIUM HYDROXIDE
Oral: 200 mg aluminum hydroxide + 100 mg magnesium Avoid concomitant use with:
hydroxide tablet Reduces therapeutic effect of the following drugs
225 mg aluminum hydroxide + 200 mg magnesium Bisphosphonates e.g., Alendronate, Iron, Ketoconazole,
hydroxide per 5 mL suspension, 60 mL and 120 mL Quinolones e.g., Nalidixic acid, Rosuvastatin,
Tetracyclines, e.g., Doxycycline. [Separate dosing by at
An antacid that combines aluminum hydroxide and least 2 hours before, or 4–6 hours after the antacid]:
magnesium hydroxide to reduce effect on bowel
movement and to relieve epigastric pain from peptic Administration: Shake well before use.
ulcer through acid neutralization.
Best given 1–3 hours after the last meal to neutralize and
Indication: Symptomatic relief of symptoms related to buffer the acid produced.
hyperacidity from heartburn, hiatal hernia, upset
stomach, peptic ulcer, peptic esophagitis, or gastritis. NOTE: Antacids should preferably not be taken at the same
time as other oral drugs since they may impair
Contraindications: Severe renal impairment; absorption (interactions may be avoided by having an
hypophosphatemia; undiagnosed GI and rectal bleeding; interval of at least 2 hours between taking an antacid
porphyria; appendicitis. and the other drug).

Dose: Pregnancy Category: B

Hyperacidity, by mouth, ADULT, 10-20 mL 4 times daily
(maximum 80 mL daily). ATC Code: A02AD01

Dose Adjustment:
Renal Impairment: OTC SODIUM BICARBONATE
Use with caution due to risk of accumulation and toxicity.
For mild-to-moderate renal impairment, dose reduction is
warranted. Oral: 325 mg and 650 mg tablet
For severe impairment, avoid use and refer patient to a
specialist. A short-acting, potent systemic antacid that rapidly
neutralizes gastric acid to form sodium chloride, carbon
Precautions: dioxide, and water. After absorption of sodium
bicarbonate, plasma alkali reserve is increased, and
WARNING: Aluminum and magnesium salts may be excess sodium and bicarbonate ions are excreted in
hazardous in patients with renal insufficiency. If urine, rendering urine less acid.
intensive antacid therapy is to be used, only non-
systemic (non-absorbable) antacids should be Indications: Symptomatic relief of hyperacidity (belching,
considered because of the potential danger of heartburn, indigestion, gas pains), gastritis, and peptic
alkalosis with systemic therapy. ulcer; urine alkalinizer.

Acute porphyria; prolonged antacid therapy may result in Contraindications: Diuretics known to produce
hypophosphatemia (i.e., decreased phosphate hypochloremic alkalosis; edema; hypertension;
absorption in the GI tract); dehydration; fluid restriction; hypocalcemia; hypochloremia; hypernatremia; impaired
constipation; diarrhea; hepatic impairment; renal renal function; metabolic alkalosis; respiratory alkalosis
impairment; GI disorders associated with decreased or acidosis; any situation where administration of sodium
bowel motility or obstruction; some products may contain could be clinically detrimental.
phenylalanine.
Elderly (may be predisposed to diarrhea or constipation); Dose:
children. Antacid, by mouth, ADULT, 2–8 tablets every 4 hours
(maximum, 48 tablets in 24 hours); ADULT ≥60 years, 2–
Adverse Drug Reactions: 4 tablets every 4 hours (maximum, 24 tablets in 24
Common: Constipation, diarrhea, GI irritation. hours.

1
 ALIMENTARY TRACT AND METABOLISM

Urine alkalinizer, by mouth, ADULT, initially 3.94 g, then FOR PEPTIC ULCER AND GASTRO-ESOPHAGEAL
0.97–1.95 g every 4 hours; CHILD, 84–840 mg/kg daily, REFLUX DISEASE (GERD)
in divided doses.
A

H2-RECEPTOR ANTAGONISTS
Dose Adjustment:
Geriatric, Renal and Hepatic Impairment:
Dose adjustment may be required. Rx (Inj.)
OTC (Oral)
FAMOTIDINE
Precautions:
Oral: 20 mg tablet
WARNING: Ask attending physician before use if on a Inj.: 10 mg/mL, 2 mL ampule / vial (IM, IV)
sodium restricted diet.
A competitive inhibitor of histamine H2­receptor, inhibiting
Do not use maximum dose for more than 2 weeks. both daytime and nocturnal basal gastric acid secretion,
as well as food-stimulated and pentagastrin-stimulated
gastric acid secretion.
Cardiac, liver, or renal disease;
Fluid or solute overload;
Indications: Relief and prevention of heartburn; treatment
Postoperative patients with cardiovascular or renal
and maintenance of active duodenal ulcers, pathological
insufficiency (e.g., sodium or water retention and edema
hypersecretory conditions (e.g., Zollinger-Ellison
which may result in serious pulmonary edema);
Syndrome or multiple endocrine adenomas),
Arrested patients with preexisting metabolic acidosis,
Gastroesophageal Reflux Disease (GERD) and active
hyperkalemia, or tricyclic or barbiturate overdose;
benign gastric ulcer.
Elderly;
Pregnancy (restrict intake in hypertension and toxemia).
Contraindications: Cirrhosis of the liver; impaired renal or
hepatic function; lactation; other H2 antagonists.
Adverse Drug Reactions:
Common: Belching, gastric distention, flatulence, metabolic
Dose:
alkalosis, electrolyte imbalance, (sodium overload,
Duodenal ulcer, acute therapy, by mouth, ADULT, 40 mg
hypocalcemia, hypokalemia, milk-alkali syndrome,
daily at bedtime (or 20 mg twice daily) for 4-8 weeks.
dehydration), reduction in CSF pressure, intracranial
Duodenal ulcer, maintenance therapy, by mouth, ADULT, 20
hemorrhage, severe tissue damage following
mg daily at bedtime.
extravasation of IV solution, renal calculi or crystals,
Gastric ulcer, acute therapy, by mouth, ADULT, 40 mg daily
impaired kidney function
at bedtime.
Peptic ulcer, by mouth, CHILD 1-16 years, 0.5 mg/kg daily
Drug Interactions:
at bedtime or divided twice daily (maximum dose, 40 mg
Monitor closely with:
daily) (doses of up to 1 mg/kg daily have been used in
Decreases the absorption of Ketoconazole
clinical studies); by IV injection, CHILD 1-16 years, 0.25
mg/kg every 12 hours (maximum dose, 40 mg daily)
Decreases therapeutic effect of the following drugs:
(doses of up to 0.5 mg/kg have been used in clinical
Chlorpropamide, Lithium Carbonate, Salicylates,
studies).
Tetracyclines
GERD, by mouth, ADULT, 20 mg twice daily for 6 weeks;
CHILD 1-16 years, 1 mg/kg daily divided twice daily
Increases therapeutic effect of the following drugs:
(maximum dose, 40 mg twice daily) (doses of up to 2
Appetite Suppressants (e.g., Amphetamines), Flecainide,
mg/kg/day have been used in clinical studies); CHILD 3-
Mecamylamine, Quinidine, Sympathomimetics (e.g.,
12 months, 0.5 mg/kg twice daily; CHILD <3 months, 0.5
Ephedrine, Dopamine)
mg/kg once daily.
Esophagitis and accompanying symptoms due to GERD, by
NOTE: Sodium bicarbonate raises intra-gastric pH, which
mouth, ADULT, 20 mg or 40 mg twice daily for up to 12
may affect the absorption of certain drugs.
weeks.
Hypersecretory conditions, by mouth, ADULT, initially, 20 mg
Administration: Should be taken on an empty stomach.
every 6 hours, may increase in increments up to 160 mg
Tablets may be swallowed whole or dissolved in water
every 6 hours.
prior to use.
Patients unable to take oral medication, by IV injection,
ADULT, 20 mg every 12 hours.
Do NOT add oral preparation to calcium-containing
solutions.
Dose Adjustment:
Renal Impairment:
Pregnancy Category: C
For creatinine clearance <50, reduce dose by half or
increase dosing interval to 36–48 hours.
ATC Code: A02AH
Precautions:
Increases risk of community-acquired pneumonia with
prolonged use; prolonged treatment (≥2 years) may lead
to vitamin B12 malabsorption and subsequent vitamin
B12 deficiency; gastric malignancy.

2
ALIMENTARY TRACT AND METABOLISM

Elderly >50 years. gastric ulcer, GERD, pathological hypersecretory

Lactation (excreted into breast milk). conditions (e.g., Zollinger-Ellison syndrome, systemic
mastocytosis)

A
Adverse Drug Reactions:
Common: Headache, dizziness, constipation, diarrhea, Contraindications: Cirrhosis of the liver; impaired renal or
nausea and vomiting, anxiety, confusion. hepatic function; acute porphyria
Less Common: Acne, pruritus, urticaria, dry skin, fever,
hypertension, flushing, musculoskeletal pain, arthralgia, Dose:
tinnitus Duodenal ulcer, acute therapy, by mouth, ADULT, 150 mg
twice daily, or 300 mg once daily after the evening meal
Drug Interactions: or at bedtime; INFANT, CHILD, and ADOLESCENT ≤16
Monitor closely with: years, 4-8 mg/kg daily divided twice daily (maximum,
Decreases absorption of the following drugs: 300 mg daily).
Cefpodoxime, Cefuroxime, Iron salts Duodenal ulcers, maintenance therapy, by mouth, ADULT,
150 mg once daily at bedtime; INFANT, CHILD, and
Decreases serum concentration of the following drugs: ADOLESCENT ≤16 years, 4–8 mg/kg daily divided twice
Indinavir, Multivitamins / Minerals with ADEK, daily; 2–4 mg/kg once daily (maximum, 150 mg daily);
Folate, Iron by IM injection, ADULT, 50 mg every 6–8 hours;
by IV intermittent bolus or IV infusion, ADULT, 50 mg
Increases the absorption of: Methylphenidate every 6–8 hours (if increased doses are necessary utilize
more frequent administration up to a maximum of 400
Increases serum concentration of Famotidine: mg daily);
Bupropion by IV injection, INFANT, CHILD, and ADOLESCENT ≤16
years, 2–4 mg/kg daily divided every 6–8 hours
(maximum dose, 50 mg/dose);
Avoid concomitant use with: by continuous IV infusion, ADULT, 6.25 mg/hour.
Decreases absorption of Famotidine: Benign gastric ulcer, acute therapy, by mouth, ADULT, 150
Antacid mg twice daily; INFANT, CHILD, and ADOLESCENT ≤16
years, 4-8 mg/kg daily divided twice daily (maximum,
Decreases absorption of Diazepam 300 mg daily).
Benign gastric ulcer, maintenance therapy, by mouth,
Decreases serum concentration of the following drugs: ADULT, 150 mg once daily at bedtime; INFANT, CHILD,
Atazanavir, Cefditoren, Itraconazole and ADOLESCENT ≤16 years, 2-4 mg/kg once daily
Ketoconazole (systemic) (maximum, 150 mg daily).
Erosive esophagitis, acute therapy, by mouth, ADULT, 150
Increases serum concentration of Risedronate mg 4 times daily, INFANT, CHILD, and ADOLESCENT ≤16
years, 5-10 mg/kg daily divided twice daily (maximum,
Administration: 300 mg daily).
For oral administration, may be taken with or without Erosive esophagitis, maintenance therapy, by mouth,
food ADULT, 150 mg twice daily.
Gastroesophageal reflux disease (GERD), by mouth, ADULT,
For IV injection or IV push, inject over at least 2 minutes. 150 mg twice daily; INFANT, CHILD, and ADOLESCENT
If administered by IV infusion, administer over 15–30 ≤16 years, 5-10 mg/kg daily divided twice daily
minutes. (maximum, 300 mg daily).
Heartburn, prevention, by mouth, CHILD ≥12 years, 75-150
Pregnancy Category: B mg 30-60 minutes before eating food or drinking
beverages that cause heartburn (maximum, 2 doses
ATC Code: A02BA03 daily), not to be used for more than 14 days.
Pathological hypersecretory conditions (e.g. Zollinger Ellison
Syndrome), by mouth, ADULT, 150 mg twice daily, adjust
dose or frequency as clinically indicated (doses of up to
Rx RANITIDINE 6 g daily have been used in patients with severe
disease);
Oral: 150 mg and 300 mg tablet (as hydrochloride) by IM injection, ADULT, 50 mg every 6–8 hours;
75 mg/5 mL syrup (as hydrochloride), 60 mL and 150 by continuous IV infusion, ADULT, 6.25 mg/hour, initially,
mL 1 mg/kg per hour (measure gastric acid output at 4
Inj.: 25 mg/mL, 2 mL ampule / vial (IM, IV, IV infusion) (as hours, if >10 mEq or if patient is symptomatic, increase
hydrochloride) dose in increments of 0.5 mg/kg per hour) (doses of up
to 2.5 mg/kg per hour (220 mg/hour) have been used
A competitive inhibitor of histamine H2­receptor, inhibiting by IV intermittent bolus or infusion); 50 mg every 6–8
both daytime and nocturnal basal gastric acid secretion, hours (if increased doses are necessary utilize more
as well as food- and pentagastrin-stimulated gastric acid frequent administration up to a maximum of 400 mg
secretion. Ranitidine is also a weak cytochrome P-450 daily).
enzyme inhibitor. Patients not able to take oral medication, by IM injection,
Indications: Relief and prevention of heartburn. ADULT, 50 mg every 6–8 hours;
Management of duodenal ulcer, erosive esophagitis,

3
 ALIMENTARY TRACT AND METABOLISM

by IV intermittent bolus or infusion, ADULT, 50 mg every Decreases therapeutic effect of Diazepam

6–8 hours; 50 mg every 6–8 hours (if increased doses
are necessary utilize more frequent administration up to Administration:
For IM administration, no dilution is required.
A

a maximum of 400 mg daily);

by continuous IV infusion, ADULT, 6.25 mg/hour; by IV
injection, INFANT, CHILD, and ADOLESCENT <16 years, For IV administration, solution must be diluted. May be
2–4 mg/kg daily divided every 6–8 hours (maximum administered by intermittent bolus, intermittent IV
dose, 50 mg/dose). infusion, or continuous IV infusion.

Dose Adjustment: Pregnancy Category: B

Renal Impairment:
For patients with creatinine clearance <50 mL/minute, ATC Code: A02BA02
adjust dose cautiously. Adjust dosing schedule to not
coincide with the end of hemodialysis.
PROTON PUMP INHIBITORS
Precautions:
WARNING: NOT to be used if there is trouble or pain Rx LANSOPRAZOLE
when swallowing food, vomiting with blood, or bloody
or black stools.
Oral: 15 mg and 30 mg capsule
NOT to be used in combination with other acid 15 mg and 30 mg MR tablet
reducers. Avoid the use of 150 mg tablet for patients
with kidney disease. A substituted benzimidazole, which acts as a proton pump
inhibitor (PPI), by blocking the final step of acid
Relief of symptoms does not preclude the presence production. It acts by inhibiting the H+/K+–ATPase
of a gastric malignancy. system at the parietal cells of the stomach, suppressing
both basal and stimulated gastric acid secretion.
Rare cases of reversible confusion have been associated
with use, usually among elderly or severely ill patients, or Indications: Management of acid-related dyspepsia, erosive
in patients with renal or hepatic impairment. esophagitis, Gastroesophageal Reflux Disease (GERD),
Prolonged treatment (≥2 years) may lead to vitamin B12 peptic ulcer, Helicobacter pylori infection, NSAID-
malabsorption and subsequent vitamin B12 deficiency. associated ulcer, Zollinger-Ellison syndrome.
Decreased renal or hepatic function (use with caution).
Elderly (use with caution) Contraindication: Known severe hypersensitivity to
Pregnancy; lactation (excreted into breast milk; use with lansoprazole or any ingredient in the formulation
caution).
Dose:
Adverse Drug Reactions: Acid-related dyspepsia, by mouth, ADULT, 15–30 mg once
Common: Headache, abdominal pain, constipation, daily in the morning for 2–4 weeks.
diarrhea, nausea, and vomiting. GERD, acute therapy, by mouth, ADULT, 15–30 mg once
Less Common: Asystole, atrioventricular block, bradycardia daily in the morning for 4–8 weeks.
(with rapid IV administration), premature ventricular GERD, maintenance therapy, by mouth, ADULT,
beats, tachycardia, vasculitis. maintenance therapy, 15–30 mg once daily (adjust
dosing according to response); CHILD 12–17 years, 15
Drug Interactions: mg once daily for up to 8 weeks; CHILD 1–11 years (≤30
Monitor closely with: kg), 15 mg once daily in the morning for up to 12 weeks;
Decreases absorption of the following drugs: CHILD >30 kg, 30 mg once daily in the morning for up to
Cephalosporins, Iron salts [except ferric carboxymaltose, 12 weeks (may increase doses up to 30 mg twice daily if
ferric citrate, ferric gluconate, ferric pyrophosphate patient is still symptomatic after 2 or more weeks of
citrate, iron dextran complex, iron sucrose] treatment).
Erosive esophagitis, acute therapy, by mouth, ADULT, 30 mg
Enhances therapeutic effect of: Procainamide once in the morning for up to 8 weeks; by IV injection,
ADULT, 30 mg over 30 minutes for up to 7 days; CHILD
Reduces therapeutic effect of: 12–17 years, 30 mg once daily for up to 8 weeks; CHILD
Warfarin (decreased prothrombin time) 1–11 years (≤30 kg), 15 mg once daily in the morning for
up to 12 weeks; CHILD >30 kg, 30 mg once daily in the
Avoid concomitant use with: morning for up to 12 weeks (may increase doses up to
Decreases absorption of the following drugs: 30 mg twice daily if patient is still symptomatic after 2 or
Cyanocobalamin / Vitamin B12 more weeks of treatment).
Erosive esophagitis, maintenance therapy, by mouth,
Decreases serum concentration of Azoles, e.g., ADULT, 15 mg once daily.
Ketoconazole Peptic ulcer, acute therapy, by mouth, ADULT, 15 mg once
daily.
Decreases therapeutic effect of Ranitidine: Peptic ulcer, maintenance therapy, by mouth, ADULT, 30 mg
Cigarette smoking once daily in the morning for up to 4 weeks (for duodenal
ulcer) or up to 8 weeks (for gastric ulcer).

4
ALIMENTARY TRACT AND METABOLISM

Helicobacter pylori infection, by mouth, ADULT, 1-week For patients with swallowing difficulties, the contents of
triple therapy, 30 mg twice daily (administered with the capsules (enteric-coated granules) can be sprinkled
clarithromycin and amoxicillin or metronidazole; see on a small amount of soft food (such as yogurt or apple

A
under Chapter 1: Alimentary Tract and Metabolism – sauce) or mixed with a little fruit juice and swallowed.
Drugs for eradication of H. pylori).
NSAID-associated ulceration, treatment, by mouth, ADULT, For dosage by nasogastric tube, the contents of a
30 mg once daily in the morning for 4 to 8 weeks. capsule may be mixed with 40 mL of apple juice and
NSAID-associated ulceration, prophylaxis, by mouth, ADULT, flushed with additional apple juice.
15–30 mg once daily in the morning.
Zollinger-Ellison syndrome, by mouth, ADULT, initially 60 mg Pregnancy Category: B
once daily in the morning to be adjusted as required
(daily doses >120 mg should be given in 2 divided ATC Code: A02BC03
doses).

Dose Adjustment:
Hepatic Impairment: Rx OMEPRAZOLE
Adjust the dose in patients with severe hepatic impairment
(maximum dose, 30 mg daily). Oral: 20 mg and 40 mg capsule
Inj.: 40 mg powder, vial + 10 mL solvent, ampule/vial (IV)
Precautions:
Gastric malignancy should be ruled out; A benzimidazole, which acts as a proton pump inhibitor
Hepatic impairment; (PPI), by blocking the final step of acid production. It acts
Lactation (not known if excreted in breastmilk; potential for by inhibiting the H+/K+–ATPase system at the parietal
serious adverse reactions in the nursing infant). cells of the stomach, suppressing both basal, and
stimulated gastric acid secretion.
Adverse Drug Reactions:
Common: Abdominal pain, constipation, diarrhea, Indications: Management of duodenal ulcer, gastric ulcer,
flatulence, headache, nausea, vomiting. and NSAID-associated gastric and duodenal ulcers and
Less Common: Decreased absorption of vitamin B12, erosions, symptomatic GERD, reflux esophagitis, acid-
dizziness, drowsiness, dry mouth, fatigue, insomnia, related dyspepsia; H. pylori eradication in peptic ulcer
malaise, paresthesia, pruritus, rash, somnolence, disease prophylaxis of acid aspiration before surgery, or
urticarial, vertigo, atopic gastritis, Clostridium difficile- aspiration of gastric contents during general anesthesia.
associated diarrhea (CDAD), anaphylaxis (potentially
fatal), Stevens-Johnson syndrome (potentially fatal), Dose:
toxic epidermal necrolysis (potentially fatal). Duodenal ulcer, by mouth, ADULT, 20–40 mg daily for at
Rare: Alopecia, arthralgia, blurred vision, confusion, least 4 weeks; CHILD >20 kg, 20 mg daily; CHILD 10–20
dermatitis, gynecomastia, hemolytic anemia, kg, 10 mg daily; CHILD 5–10 kg, 5 mg daily.
hypersensitivity reactions, hypomagnesemia, hepatitis, Gastric ulcer, by mouth, ADULT, 20–40 mg daily for 4–8
interstitial nephritis, jaundice, leukopenia, microscopic weeks; CHILD >20 kg, 20 mg daily; CHILD 10–20 kg, 10
colitis, myalgia, myopathy pancreatitis, peripheral mg daily; CHILD 5–10 kg, 5 mg daily.
edema, raised liver enzymes, skin reactions, taste Erosive esophagitis, by mouth, ADULT, 20–40 mg for at
disturbance, thrombocytopenia. least 4 weeks; maintenance, 20 mg daily for up to one
year; CHILD >20 kg, 20 mg daily; CHILD 10–20 kg, 10
Drug Interactions: mg daily; CHILD 5–10 kg, 5 mg daily.
Monitor closely with: Helicobacter pylori infection, by mouth, ADULT, 40 mg every
Decreases bioavailability of Azoles, e.g., Itraconazole, 12 hours for 10 days, WITH amoxicillin at 1 g every 12
Ketoconazole hours, AND clarithromycin at 500 mg every 12 hours for
10–14 days; CHILD >20 kg, 20 mg daily; CHILD 10–20
Increases risk of adverse or toxic effects of the following kg, 10 mg daily; CHILD 5–10 kg, 5 mg daily.
drugs: Hypersecretory conditions (e.g., Zollinger-Ellison Syndrome),
Digoxin (hypomagnesemia), Diuretics by mouth, ADULT, 60 mg daily (initial) up to 360 mg daily
(hypomagnesemia) divided every 8 hours; if dose >80 mg, divide it;
by IV injection, ADULT, initially 60 mg once daily, higher
Reduces bioavailability of Lansoprazole doses may be required; administer doses >60 mg in 2
Antacids, Sucralfate divided doses.
Alternative to oral therapy, by IV injection, ADULT, 40 mg
Avoid concomitant use with: once daily at a rate no greater than 4 mL/minute; shift to
Decreases serum concentration and therapeutic effects of oral omeprazole as soon as feasible.
the following drugs (possibly fatal):
Atazanavir, Ripivirine Dose Adjustment:
Hepatic Impairment:
Administration: To be taken on an empty stomach, For mild-to-moderate hepatic impairment, dose reduction is
preferably before meals. Swallow whole. Do NOT crush or warranted; for severe impairment, the patient should be
chew. referred to a specialist.

5
 ALIMENTARY TRACT AND METABOLISM

Precautions: Contraindication: Lactation

GI infection; Gastric malignancy; Fractures;
Hypomagnesemia; Hepatic impairment; Surgery; Dose:
A

Lactation. GERD, acute therapy, by mouth, ADULT, 20 mg daily for 4–

8 weeks; CHILD ≥12 years, 20 mg once daily in the
Adverse Drug Reactions: morning for up to 8 weeks.
Common: Abdominal pain, constipation, diarrhea, GERD, maintenance therapy, by mouth, ADULT, 10 or 20 mg
flatulence, headache, nausea, vomiting. once daily in the morning.
Less Common: Decreased absorption of vitamin B12, Helicobacter pylori eradication, by mouth, ADULT, 1–week
dizziness, drowsiness, dry mouth, fatigue, insomnia, triple therapy, 20 mg twice daily (combined with
malaise, paresthesia, pruritus, rash, somnolence, clarithromycin 500 mg twice daily and amoxicillin 1 g
urticarial, vertigo. twice daily or combined with clarithromycin 250 mg
Rare: Alopecia, arthralgia, blurred vision, confusion, twice daily and metronidazole 400 mg twice daily).
dermatitis, gynecomastia, hemolytic anemia, hepatitis, Zollinger-Ellison Syndrome, by mouth, ADULT, initially, 60
hypersensitivity reactions, hypomagnesemia, interstitial mg once daily in the morning, adjusted to maximum dose
nephritis, jaundice, leukopenia, microscopic colitis, of 120 mg daily, if needed; daily doses >100 mg should
myalgia, myopathy pancreatitis, peripheral edema, be given in 2 divided doses.
raised liver enzymes, skin reactions, taste disturbance, Peptic ulcer, by mouth, ADULT, initially, 20 mg once daily in
thrombocytopenia. the morning for 4–8 weeks (duodenal ulcer) or for 6–12
weeks (gastric ulcer).
Drug Interactions: Erosive esophagitis, acute therapy, by mouth, ADULT,
Monitor closely with: initially, 20 mg daily for 4–8 weeks; may continue for
Enhances therapeutic effect of the following drugs: another 8 weeks if healing is incomplete.
Anticoagulants, e.g., Warfarin, Anti-epileptic agents e.g. Erosive esophagitis, maintenance therapy, by mouth,
Phenytoin, Digoxin ADULT, initially, 10 or 20 mg daily once in the morning.

Reduces therapeutic effect of the following drugs: Dose Adjustment:

Azoles, e.g., Ketoconazole, Clopidogrel (antiplatelet Geriatric:
activity), Iron salts, Mycophenolate Consider dose adjustment.

Administration: Precautions:
For IV administration, administer by slow IV injection (not Symptomatic response to therapy does not preclude the
less than 2.5 minutes) at a rate of no greater than 4 presence of gastric malignancy.
mL/minute. Do NOT administer as an IV infusion. Elderly (greater sensitivity is possible).
Lactation (not known if excreted in breast milk; potential for
For oral administration, take 30 minutes before meals, serious adverse reactions in the nursing infant).
preferably at breakfast if to be taken once a day.
Adverse Drug Reactions:
For patients with swallowing difficulties, capsules can be Common: Headache, GI upset, diarrhea, insomnia,
opened, and the contents swallowed or suspended in a nervousness, rash, itching, dry mouth, dizziness,
slightly acidic fluid, e.g., fruit juice or in non-carbonated peripheral edema, hepatic enzyme increase, hepatitis,
water. Drink the suspension within 30 minutes. hepatic encephalopathy, myalgia, arthralgia.
Alternatively, the contents of the capsule can be sucked Less Common: Rectal hemorrhage, melena, anorexia,
and swallowed. Do NOT chew or crush the contents of cholelithiasis, mouth ulceration, convulsions, myocardial
the capsule. infarction.
Rare: agranulocytosis, hemolytic anemia, leukopenia,
Pregnancy Category: C pancytopenia, thrombocytopenia, sudden death, coma,
jaundice, rhabdomyolysis, disorientation, delirium,
ATC Code: A02BC01 anaphylaxis (potentially fatal), angioedema, bullous,
severe dermatologic reactions (e.g., toxic epidermal
necrolysis, potentially fatal), Stevens-Johnson syndrome
(potentially fatal), erythema multiforme, interstitial
Rx RABEPRAZOLE pneumonia, interstitial nephritis.

Oral: 10 mg and 20 mg tablet Drug Interactions:

Monitor closely with:
A substituted benzimidazole, gastric proton-pump inhibitor Decreases bioavailability of Rabeprazole:
that suppresses gastric secretion by inhibiting gastric Sucralfate
H+/K+ ATPase at the parietal cells.
Decreases bioavailability of the following drugs:
Indications: Management of active duodenal ulcer, active Azoles, e.g., Itraconazole, Ketoconazole, Clopidogrel
benign gastric ulcer, anastomotic ulcer, symptomatic
erosive or Gastroesophageal Reflux Disease (GERD); Enhances therapeutic effect of Warfarin (prothrombin time
pathological hypersecretory conditions (e.g. Zollinger and INR)
Ellison Syndrome; eradication of Helicobacter pylori
peptic ulcer disease.

6
ALIMENTARY TRACT AND METABOLISM

Increases risk of adverse or toxic effects of the following Cimetidine, Digoxin, Ketoconazole, Phenytoin
drugs: Ranitidine, Tetracyclines, Theophylline
Digoxin (hypomagnesemia), Diuretics

A
(hypomagnesemia) Increases risk of adverse and toxic effects of Citrate-
containing preparations
Avoid concomitant use with:
Decreases serum concentration and therapeutic effects of Avoid concomitant use with:
the following drugs (possibly fatal): Reduces therapeutic effect of Sucralfate:
Atazanavir, Ripivirine Antacids (take at least 30 minutes apart)

Administration: May be taken with or without food. Administration: To be taken 1 hour before meals or 2 hours
after meals
Pregnancy Category: C
NOTE: Dosing Intervals. Ensure a dosing interval of at least
ATC Code: A02BC04 2 hours between sucralfate and other non-antacid
medications, an interval of at least 30 minutes between
sucralfate and antacids, and an interval of at least 1 hour
DRUGS FOR THE MANAGEMENT OF ACID PEPTIC between sucralfate and enteral feeding.
DISEASE
Pregnancy Category: B

Rx SUCRALFATE ATC Code: A02BX02

Oral: 1 g tablet
DRUGS FOR ERADICATION OF Helicobacter pylori
An anionic sulfated disaccharide, that acts as an inhibitor of
pepsin. It also acts as an antiulcer agent by binding to Helicobacter pylori treatment should be preceded by H.
the surface of ulcers, forming a protective barrier. pylori diagnostic testing. Eradication treatment includes
the standard triple regimen reflected on Table A.
Indications: Management of duodenal ulcer, gastric ulcer Antibiotics should NOT be used singly (i.e., should use 2-
and chronic gastritis. 3 antibiotic combination) because of risk of emergence
of drug resistance.
Contraindication: Patients undergoing dialysis

Dose: Table A. Standard triple H. pylori eradication regimen

Chronic gastritis, acute therapy, by mouth, ADULT, 1 g 4 Regimen Dosage Duration
times daily for 4–8 weeks for up to 12 weeks, if needed. If not allergic to Penicillin
Chronic gastritis, maintenance therapy, by mouth, ADULT, 1
g twice daily to prevent the recurrence of duodenal ulcers Omeprazole Standard dose
10–14
(maximum, 8 g daily); CHILD 12–18 years, 1 g 4–6 times Clarithromycin 500 mg twice a day
days
daily; CHILD 2–12 years, 500 mg 4–6 times daily; CHILD Amoxicillin 1 g twice a day
1 month to 2 years, 250 mg 4–6 times daily. If Allergic to Penicillin
GI hemorrhage from stress ulceration, prophylaxis, by
mouth, ADULT, 1 g 6 times daily (maximum, 8 g daily); Omeprazole Standard dose
10–14
CHILD 12–18 years, 1 g 4–6 times daily; CHILD 2–12 Metronidazole 500 mg thrice a day
days
years, 500 mg 4–6 times daily; CHILD 1 month to 2 Clarithromycin 500 mg twice a day
years, 250 mg 4–6 times daily.

Precautions:
Chronic renal failure (e.g., systemic aluminum toxicity). AMOXICILLIN
Children; neonates.
Lactation (not known if excreted in breastmilk).
See Amoxicillin under Chapter 7 Antiinfectives under Beta-
Lactam Antibacterials, Penicillins
Adverse Drug Reactions:
Common: Constipation, diarrhea, nausea, vomiting,
dizziness, dry mouth, flatulence, GI disturbances, rash,
pruritus, headache, vertigo, back pain, drowsiness. CLARITHROMYCIN
Less Common: Insomnia, hypersensitivity reactions (e.g.,
pruritus, edema, urticaria, respiratory difficulty, rhinitis,
laryngospasm, facial swelling). See Clarithromycin under Chapter 7 Antiinfectives under
Rare: Urticaria (hives), angioedema, respiratory difficulty, Macrolides, Lincosamides and Streptogramins
rhinitis, bezoars.
METRONIDAZOLE
Drug Interactions:
Monitor closely with:
Decreases absorption of the following drugs:

7
 ALIMENTARY TRACT AND METABOLISM

See Metronidazole under Chapter 7 Anti-infectives under Precautions:

Other Antibacterials GI disorders; pyrexia and in warm environments; Down
syndrome; prostatic enlargement; cardiac disorders;
A

hypoxia; constipation; delirium; tachycardia; or fever

from any cause.
DRUGS FOR FUNCTIONAL Elderly; children.
GASTROINTESTINAL DISORDERS Lactation (may cause anti-muscarinic effects in infants).

ANTICHOLINERGICS NOTE: Since atropine has a short duration, late unopposed

bradycardia may result. Close monitoring is necessary.

Rx ATROPINE Adverse Drug Reactions:

Common: Blurred vision, constipation, cycloplegia, delirium,
dryness of mouth, nose and skin, difficulty in micturition
Oral: 600 micrograms (as sulfate) (equivalent to 500
and swallowing, fever, flushing, mydriasis, palpitations,
micrograms atropine) tablet
photophobia, thirst, transient bradycardia followed by
Inj.: 500 micrograms/mL, 600 micrograms/mL, and 1
tachycardia, urinary retention.
mg/mL (as sulfate), 1 mL ampule (IM, IV, SC)
Less Common: Agitation, arrhythmias, ataxia, confusion (in
elderly), disorientation, excitement, headache, heat
A naturally occurring tertiary amine anti-muscarinic alkaloid
prostration, hyperpyrexia, hypertension, paralytic ileus,
from Atropa belladonna that competitively blocks
psychosis, rapid respiration, rash, restlessness,
acetylcholine action in central and peripheral muscarinic
vomiting.
autonomic receptors.
Drug Interactions:
Indications: Pre-operative medication to reduce salivary,
Monitor closely with:
bronchial, and nasal secretions; treatment of functional
Decreases oral absorption of Atropine:
disturbances of GI motility such as irritable bowel
Antacids
syndrome.
Increases risk of adverse or toxic effects of the following
NOTE: Has limited efficacy as an anti-muscarinic and should
drugs:
be used only if other measures (e.g., diet, sedation,
Alcohol (CNS depression), Chlorpromazine (anti-
counseling, amelioration of environmental factors) have
muscarinic)
been of little or no benefit.
Increases bioavailability of Beta Blockers, e.g., Metoprolol
Contraindications: Angle-closure glaucoma; severe
inflammatory GI disease or GI obstruction; prostatic
Avoid concomitant use with:
hypertrophy; prostatism and urinary obstruction;
Decreases serum concentration of the following drugs,
myasthenia gravis; thyrotoxicosis; organochlorine
decreasing their therapeutic effects:
poisoning; pyloric stenosis; poisoning caused by CNS
Haloperidol (schizophrenic symptoms may worsen)
adrenergic stimulants, phenothiazines, tricyclic
antidepressants; and, other anticholinergics.
Enhances therapeutic effect of Atropine:
Drugs with anticholinergic effects, e.g., Amantadine,
Dose:
Belladonna Alkaloids, Ipratropium
Diverticular disease, irritable bowel syndrome, non-ulcer
dyspepsia, by mouth, ADULT, 0.6–1.2 mg as a single
Enhances therapeutic effect of the following drugs:
dose at bedtime.
Digoxin, Norepinephrine (pressor effect; blocks its reflex
Premedication in balanced anesthesia, by IM or SC
bradycardia)
injection, ADULT, 300–600 micrograms 30–60 minutes
before anesthesia; CHILD >20 kg, 300 to 600
Increases risk of adverse or toxic effects of Atropine:
micrograms 30–60 minutes before anesthesia; CHILD
Drugs with anticholinergic effects, e.g., Amantadine,
12–16 kg, 300 micrograms 30–60 minutes before
Belladonna Alkaloids, Ipratropium (central
anesthesia; CHILD 7–9 kg, 200 micrograms 30–60
anticholinergic delirium)
minutes before anesthesia; CHILD 3 kg, 100 micrograms
30 to 60 minutes before anesthesia;
Increases risk of adverse or toxic effect of the following
by IV injection, ADULT, 300–600 micrograms
drugs:
immediately before induction of anesthesia.
Digoxin, Phenylephrine eye drops (severe
hypertension)
Dose Adjustment:
Renal Impairment:
Increases serum concentration of Digoxin
For mild-to-moderate renal impairment, dose reduction, or
less frequent doses, after initial atropinization is
Reduces therapeutic effect of Atropine:
warranted (since atropine may be eliminated more
Anticholinesterases, e.g., Neostigmine, Pyridostigmine
slowly).
(antagonizes anticholinergic effect of Atropine)
For severe impairment, the patient should be referred to a
specialist.
Reduces therapeutic effect of Metoclopramide
(antagonism)

8
ALIMENTARY TRACT AND METABOLISM

Administration: SKILLED TASKS. May cause drowsiness or blurred vision. Avoid

For oral administration, may be taken with or without performing tasks, which require mental alertness, e.g., operating
food. machinery or driving.

A
For IV administration, administer undiluted by rapid IV Adverse Drug Reactions:
injection. Common: Dizziness, xerostomia, nausea, blurred vision,
somnolence, nervousness, weakness.
Pregnancy Category: C
Drug Interactions:
ATC Code: A03BA01 Monitor closely with:
Increases risk of adverse or toxic effects of Dicycloverine:
Anticholinergic Agents e.g., Atropine

Rx DICYCLOVERINE (DICYCLOMINE) Increases risk of adverse or toxic effects of Opioid

Analgesics (constipation; urinary retention)

Oral: 10 mg tablet (as hydrochloride) Avoid concomitant use with:

10 mg/5 mL syrup (as hydrochloride), 60 mL Enhances therapeutic effect of Dicycloverine:
Ipratropium, Oral Inhalation (anticholinergic effect)
An anti-muscarinic agent used primarily as anti-spasmodic.
It has a much less marked anti-muscarinic action than Administration: May be taken before or after meals
atropine and may also have some direct action on
smooth muscle. Pregnancy Category: B

Indications: Treatment of patients with functional bowel or ATC Code: A03AA07

irritable bowel syndrome; adjunct in GI disorders
characterized as functional disturbances of
gastrointestinal motility.
Rx HYOSCINE (HYOSCYAMINE)
Contraindications: Obstructive diseases of the GI tract;
severe ulcerative colitis; reflux esophagitis; unstable Oral: 10 mg tablet (as N-butyl bromide)
cardiovascular status in acute hemorrhage; obstructive 5 mg/5 mL syrup (as N-butyl bromide), 60 mL
uropathy; glaucoma; myasthenia gravis; breastfeeding; Inj.: 20 mg/mL (as N-butyl bromide), 1 mL ampule (IM, IV,
infants <6 months of age; hypersensitivity to SC)
dicycloverine or any component of the formulation.
A poorly-absorbed, quaternary amine, anticholinergic agent
Dose: that is used to relax smooth muscles, and reduce GI
Gastrointestinal motility disorders or irritable bowel, by motility and spasm.
mouth, ADULT, 20 mg 4 times daily for 7 days; after 1
week, may increase to 40 mg 4 times daily; CHILD 2–12 Indication: Smooth muscle spasm of the genito-urinary or GI
years, 10 mg per dose 3–4 times daily; INFANT 6–24 tract (e.g., renal and biliary spasm).
months, 5 mg per dose 3–4 times daily.
Contraindications: Glaucoma; megacolon; myasthenia
NOTE: In adults, if doses <80 mg daily does not achieve gravis; stenotic lesions of the GI tract; paralytic ileus;
desired results or if adverse effects occur, discontinue acute hemorrhage; tachycardia; angina or heart failure;
therapy. Safety data are not available for doses >80 mg obstructive prostatic hypertrophy; IM administration in
daily for duration >2 weeks. patients with anticoagulant therapy; hypersensitivity to
hyoscine or any component of the formulation.
Dose Adjustment:
Geriatric: Dose:
Use with caution. Lower doses may be warranted. Acute therapy of smooth muscle spasm, by mouth, ADULT,
10–20 mg daily; prolonged therapy, by mouth, ADULT,
Renal and Hepatic Impairment: 10 mg 3–5 times daily (maximum, 60 mg daily);
Dose adjustment in this population has not been studied. by IM, IV, or SC injection, 10–20 mg (maximum, 100 mg
Use with caution. daily); CHILD >6 years, 10 mg 3 times daily.
Precautions: NOTE: Doses can be repeated after 30 minutes if needed
WARNING: Do NOT administer to children <6 months. (may need to be repeated more frequently in endoscopy).

Diarrhea; Dose Adjustment:

Hot weather and/or exercise (heat exhaustion may occur); Renal Impairment:
Psychosis and delirium; For mild-to-moderate renal impairment, dose reduction is
Elderly (avoid long-term use); warranted.
Infants (serious respiratory reactions, central nervous For severe impairment, refer patient to a specialist.
system symptoms, and deaths have been reported). For patients with renal failure, use of this drug is not
recommended.

9
 ALIMENTARY TRACT AND METABOLISM

Precautions: Indications: Symptomatic relief of abdominal pain and

CNS effects; Idiosyncratic reactions (e.g., acute toxic cramps, bowel disturbances and intestinal discomfort
psychosis, agitation, confusion, delusions, associated with irritable bowel syndrome; GI spasm
A

hallucinations, paranoid behavior, and rambling secondary to organic diseases.

speech);
Visual disturbances; Contraindication: Paralytic ileus
Withdrawal (e.g., dizziness, headache, nausea, and
vomiting, following abrupt discontinuation); Dose:
Dementia; Irritable bowel syndrome, by mouth, ADULT, 135 mg 3 times
Fever, high ambient temperature; daily before meals (or 100 mg 4 times daily), may
Cardiovascular disease; GI obstruction or atony; gradually reduce after several weeks of symptomatic
Genitourinary disease and obstruction; relief.
Glaucoma; Gastrointestinal smooth muscle spasm, symptomatic relief,
Hiatal hernia; by mouth, ADULT and CHILD >10 years, 135 mg 3 times
Hyperthyroidism; daily (or 100 mg 4 times daily), may gradually reduce
Psychosis; after several weeks when desired effect has been
Seizure disorders; obtained; CHILD 8-10 years, 100 mg 3 times daily; CHILD
Ulcerative colitis; 4–8 years, 50 mg 3 times daily; CHILD 3–4 years, 25 mg
Renal and hepatic impairment; 3 times daily.
Anaphylaxis;
Elderly (avoid use); Precautions:
Children (increased risk of adverse effects). Cardiac disorders, e.g., heart block; renal and hepatic
impairment.
SKILLED TASKS. May cause drowsiness or blurred vision. Avoid Lactation (no data available, use with caution).
performing tasks, which require mental alertness, e.g., operating
machinery or driving.
Adverse Drug Reactions:
Adverse Drug Reactions: Common: Urticaria, angioedema, face edema, exanthema,
Less Common: Diarrhea, dry mouth, nose, throat, or skin, anaphylactic reactions.
dyshidrosis, headache, increased eye pressure, itching, Less Common: Gastrointestinal disturbances, dizziness,
mydriasis, nausea, skin reactions (e.g., urticaria, headache, insomnia, anorexia, decreased heart rate.
pruritus, erythema, rash), tachycardia, vomiting.
Drug Interactions: No information found
Drug Interactions:
Monitor closely with: Administration: To be taken 20 minutes before meals.
Enhances therapeutic effect of Alcohol (CNS depressant) Swallow whole with at least 100 mL of water. Do NOT
chew or crush.
Increases risk of adverse or toxic effects of the following
drugs: Pregnancy Category: Not available
Topiramate (hyperthermia; decreased sweating),
Zonisamide (hyperthermia; decreased sweating) ATC Code: A03AA04

Avoid concomitant use with:

Enhances therapeutic and toxic effects of Anticholinergic PROPULSIVES
Drugs, e.g., Atropine

Reduces therapeutic of Anticholinesterases, e.g.,

Rx DOMPERIDONE
Neostigmine
Oral: 10 mg tablet
Administration: Swallow tablets whole with full glass of 1 mg/mL suspension, 60 mL
water.
A peripheral dopamine-receptor blocker that facilitates
Pregnancy Category: C gastric emptying by increasing esophageal peristalsis,
enhancing gastroduodenal coordination and lower
ATC Code: A03BA03 esophageal sphincter pressure, as well as gastric motility
and peristalsis.

Indication: Gastrointestinal motility disorders e.g., diabetic

Rx MEBEVERINE gastroparesis and gastritis.

Oral: 100 mg tablet (as hydrochloride) Contraindications: Prolactin-releasing pituitary tumor

(prolactinoma); known existing prolongation of cardiac
An antispasmodic with direct effects on smooth muscles of conduction intervals, particularly QT; significant
the gastrointestinal (GI) tract without altering normal gut electrolyte disturbances; underlying cardiac disease
motility. (e.g., heart failure); moderate or severe hepatic
impairment; patients with GI hemorrhage, mechanical
obstruction, or perforation; concomitant use with potent

10
ALIMENTARY TRACT AND METABOLISM

CYP3A4 inhibitors, macrolides (e.g., erythromycin), Ivabradine, Mifepristone, QTc-prolonging Agents

protease inhibitors, or nefazodone; concomitant use with
QT-prolonging drugs. Increase serum concentration Domperidone:

A
Conivaptan, CYP3A4 Inhibitors, Fusidic Acid
Dose:
Gastrointestinal motility disorders, by mouth, ADULT, 10 mg Administration: To be taken 15–30 minutes before meals.
3 times daily (maximum, 30 mg daily), (use the lowest It should be taken on an empty stomach.
effective dose for the shortest duration necessary);
ADOLESCENT <35 kg, CHILD <12 years, and INFANT, Pregnancy Category: C
0.25 mg/kg up to 3 times daily (maximum, 0.75 mg/kg
daily or 30 mg daily). ATC Code: A03FA03
Gastroparesis, by mouth, ADULT, initially 10 mg 3 times
daily.

Dose Adjustment: ANTIEMETICS AND ANTINAUSEANTS

Geriatric:
In patients >60 years, there is an increased risk of serious
ventricular arrhythmia or sudden cardiac death. Use with SEROTONIN (5HT3) ANTAGONISTS
caution
Renal Impairment:
In severe renal impairment, reduce dose or dosing
Rx ONDANSETRON
frequency with prolonged treatment.
Oral: 8 mg tablet (as hydrochloride dihydrate)
Hepatic Impairment: Inj.: 2 mg/mL (as hydrochloride), 2 mL and 4 mL ampule
In mild hepatic impairment, use with caution (undergoes (IM, IV)
hepatic metabolism).
In moderate to severe hepatic impairment, use is A selective type 3 serotonin (5-HT3) receptor inhibitor that
contraindicated. acts as an antiemetic by blocking the effect of serotonin
on the vagal afferent nerves.
Precautions:
Indications: Treatment of nausea and vomiting induced by
WARNING: Prolongs QT interval and poses a risk of cytotoxic chemotherapy and radiotherapy; prevention
torsades de pointes. Consult with physician prior to and treatment of postoperative nausea and vomiting.
concomitant use of a vasoconstrictor. Use
epinephrine, mepivacaine, and levonordefrin with Contraindication: Concomitant use of apomorphine;
caution.
Dose:
Cardiac conduction disorders or cardiac disease; Moderate Prevention of nausea and vomiting associated with
or severe hepatic impairment; chemotherapy, by mouth, ADULT, 8 mg twice daily; by IV
Prolactinoma; injection, ADULT, 0.15 mg/kg per dose (maximum, 16
In patients >60 years, there is an increased risk of serious mg/dose) administered over 15 minutes for 3 doses,
ventricular arrhythmia or sudden cardiac death. beginning 30 minutes prior to chemotherapy, followed by
subsequent doses 4–8 hours after the first dose;
Adverse Drug Reactions: ADOLESCENT, CHILD, and INFANT ≥6 months, 0.15
Common: Headache, migraine, xerostomia mg/kg per dose (maximum, 16 mg/dose) over 15
Less Common: Abdominal cramps, appetite changes, minutes for 3 doses, beginning 30 minutes prior to
conjunctivitis, constipation, diarrhea, dizziness, drug chemotherapy, followed by subsequent doses
intolerance, dysuria, edema, extrapyramidal symptoms administered 4–8 hours after the first dose.
(EPS). Prevention of nausea and vomiting associated with highly
Rare: Galactorrhea, gynecomastia, heartburn, hot flashes, emetogenic chemotherapy, by mouth, ADULT, 24 mg 30
insomnia, irritability, lethargy, leg cramps, mastalgia, minutes prior to the start of single-day chemotherapy.
menstrual irregularities, nausea, nervousness, Prevention of nausea and vomiting associated with
palpitation, increased prolactin, pruritus, rash, moderately emetogenic chemotherapy, by mouth,
regurgitation, stomatitis, sudden death, thirst, torsade ADULT, 8 mg 30 minutes prior to the beginning of
de pointes, urinary frequency, urticaria, weakness. chemotherapy, repeat dose 8 hours after initial dose,
then 8 mg every 12 hours for 1 to 2 days after completion
Drug Interactions: of chemotherapy; CHILD 4–11 years, 4 mg 30 minutes
Monitor closely with: prior to chemotherapy, repeat 4 and 8 hours after the
Decreases therapeutic effects of both Domperidone and first dose, then 4 mg every 8 hours for 1–2 days after
MAO Inhibitors e.g., Selegeline completion of chemotherapy.
Prevention of radiation therapy-induced nausea and
Increases risk of adverse or toxic effects of Domperidone: vomiting, total body irradiation, by mouth, ADULT, 8 mg
MAO Inhibitors e.g., Selegeline 1–2 hours before each fraction of radiotherapy.
Prevention of radiation therapy-induced nausea and
Avoid concomitant use with: vomiting, single high-dose fraction radiotherapy to
Enhances QTc-prolonging effect of the following drugs: abdomen, by mouth, ADULT, 8 mg 1–2 hours before

11
 ALIMENTARY TRACT AND METABOLISM

irradiation, then 8 m every 8 hours after first dose for 1– Reduces therapeutic effect of the following drugs:
2 days after completion of radiotherapy. Tapentadol (analgesic effect), Tramadol (analgesic
Prevention of radiation therapy-induced nausea and effect)
A

vomiting, daily fractionated radiotherapy to abdomen, by

mouth, ADULT, 8 mg 1–2 hours before irradiation, then Avoid concomitant use with:
8 mg every 8 hours after first dose for each day of Decreases serum concentration of Ondansetron:
radiotherapy. CYP3A4 Inducers, Dabrafenib, Mitotane
Prevention of postoperative nausea and vomiting, by IM or
IV injection, ADULT, 4 mg as a single dose (over 2–5 Increases risk of adverse or toxic effects of the following
minutes if by IV), administered approximately 30 minutes drugs:
before the end of anesthesia or as treatment if vomiting Apomorphine (hypotensive effect), Ivabradine,
occurs after surgery, repeat doses are generally Mifepristone, QTc-prolonging agents (QTc-prolonging
ineffective; effect)
by IV injection, CHILD >40 kg, 4 mg as a single dose over
2–5 minutes; CHILD ≤40 kg, 0.1 mg/kg as a single dose Increases serum concentration of the following drugs:
over 2–5 minutes. Tizanidine [if concomitant use cannot be avoided, initiate
tizanidine at 2 mg and increase in 2–4 mg increments
NOTE: Single IV doses >16 mg is not recommended due to based on patient response]
the potential for QT prolongation.
Administration:
Dose Adjustment: For oral administration, administer 30 minutes prior to
Hepatic Impairment: chemotherapy, 1–2 hours before radiotherapy, or 1 hour
For severe hepatic impairment, maximum daily dose for oral prior to induction of anesthesia.
and parenteral administration is 8 mg.
For IM injection, administer undiluted.
Precautions:
QT prolongation (e.g., torsade de pointes); ileus or gastric For IVPB, infuse diluted solution over 15–30 minutes.
distention.
For IV push, single doses may be administered by IV
Adverse Drug Reactions: injection as undiluted solution over 2–5 minutes.
Common: Headache, fatigue, malaise, constipation,
drowsiness, sedation, dizziness, agitation, anxiety, For IV infusion, dilute in 50 mL D5W or NS.
paresthesia, sensation of cold, pruritus, skin rash,
diarrhea, urinary retention, elevated ALT and AST, Pregnancy Category: B
injection site reaction, hypoxia, fever.
Less Common: Abdominal pain, accommodation ATC Code: A04AA01
disturbance, anaphylaxis, angina pectoris, angioedema,
atrial fibrillation, anaphylactoid reaction, bradycardia,
bronchospasm, cardiac arrhythmia, cardiorespiratory
arrest, bullous skin disease, chest pain, chills, Rx METOCLOPRAMIDE
depression of ST segment on ECG, dyspnea, dystonic
reaction, ECG changes, extrapyramidal reaction, Oral: 10 mg tablet (as hydrochloride)
hypersensitivity reaction, hypokalemia, hepatic failure, 5 mg/5 mL syrup (as base and as hydrochloride), 60
hypotension, ischemic heart disease, laryngeal edema, mL
laryngospasm, mucosal tissue reaction, myocardial Inj.: 5 mg/mL (as base and as hydrochloride), 2 mL
infarction, neuroleptic malignant syndrome, oculogyric ampule (IM, IV)
crisis, palpitations, positive lymphocyte transformation
test, prolonged Q­T interval on ECG, second-degree A dopamine (D2) antagonist that blocks receptors in the
atrioventricular block, serotonin syndrome, shock, chemoreceptor trigger zone of the medulla, resulting in
Stevens-Johnson syndrome, stridor, supraventricular potent anti-nausea and antiemetic action; also blocks
tachycardia, syncope, tachycardia, tonic-clonic seizures, receptors in the GI tract, stimulating gastric emptying
torsade de pointes, toxic epidermal necrolysis, transient and small intestinal transit.
blindness (≤48 hours), transient blurred vision (following
infusion), urticaria, vascular occlusive events, ventricular Indications: Management of nausea and vomiting in GI
premature contractions, ventricular tachycardia, disorders, in migraine, and in chemotherapy and
weakness, xerostomia. radiotherapy; disorders of decreased gastrointestinal
motility such as gastroparesis or ileus; Gastroesophageal
Drug Interactions: Reflux Disease (GERD).
Monitor closely with:
Enhances therapeutic effect of the following drugs: NOTE: In children and adolescents <20 years, use is
QTc-prolonging agents, Serotonin Modulators restricted to treatment of severe intractable vomiting of
(serotonergic effect) known etiology, as an aid to GI intubation, management
of radiotherapy and chemotherapy-induced nausea and
Increases risk of adverse or toxic effects of Serotonin vomiting, and as premedication.
Modulators

12
ALIMENTARY TRACT AND METABOLISM

Contraindications: Pheochromocytoma; GI obstruction; 3 to Avoid concomitant use with:

4 days after GI surgery; perforation or hemorrhage; Increases risk of adverse or toxic effects of the following
convulsive disorders. drugs:

A
Dose: Extrapyramidal reactions-causing drugs, e.g.,
Nausea and vomiting, GERD, gastroparesis, by mouth, IM Chlorpromazine, Fluphenazine, Haloperidol
injection, or slow IV injection (over 1–2 minutes), ADULT,
10 mg 3 times daily; YOUNG ADULT 15–19 years (under Reduces therapeutic effect of Metoclopramide
60 kg), 5 mg 3 times daily; CHILD 9–14 years (30 kg and Opioid-containing Medications
over), 5 mg 3 times daily; CHILD 5–9 years (20 to 29 kg),
2.5 mg 3 times daily; CHILD 3–5 years (15–19 kg), 2 mg Administration: Administer by IV injection over 1–2 minutes
2–3 times daily; CHILD 1–3 years (10–14 kg), 1 mg 2–3 to lessen transient agitation and restlessness.
times daily; INFANT <1 year (or up to 10 kg), 1 mg twice
daily; (usual maximum 500 micrograms/kg daily, Pregnancy Category: B
particularly for children and young adults).
ATC Code: A03FA01
NOTE: High-dose use in cytotoxic chemotherapy is reserved for
patients at a high risk of emesis or when other therapies are
ineffective.
BILE AND LIVER THERAPY
Dose Adjustment:
Renal Impairment:
For mild-to-moderate renal impairment, dose reduction is BILE ACID PREPARATIONS
warranted.
For severe impairment, refer patient to a specialist.
URSODEOXYCHOLIC ACID
Rx
Precautions: (URSODIOL)
WARNING: Can cause tardive dyskinesia (TD). Avoid Oral: 250 mg capsule/tablet
treatment >12 weeks unless therapeutic benefit is 500 mg tablet
thought to outweigh the risk of developing TD.
A naturally occurring bile acid that decreases the cholesterol
May mask underlying disorders, such as cerebral irritation; content of bile and bile stones by reducing the secretion
Avoid for 3–4 days after GI surgery. of cholesterol from the liver and the fractional
for short-term use only, i.e., <12 weeks (increased risk of reabsorption of cholesterol by the intestines. It is used as
tardive dyskinesia with cumulative dose and length of a gallstone dissolution agent for its cholelitholytic or
treatment). anticholestatic action.
Edematous conditions; Parkinson’s disease; Depression;
epilepsy; hypertension; porphyria; severe renal Indications: Management of Primary biliary cirrhosis;
impairment. prevention and dissolution of gallstones.
Elderly (more sensitive to adverse effects); young adults and
children (increased risk of EPS). Contraindications: Calcified cholesterol stones, radiopaque
Breastfeeding (present in milk; adverse effects may develop stones, or radiolucent bile pigment stones; unremitting
in infants). acute cholecystitis, cholangitis, biliary obstruction,
gallstone pancreatitis, or biliary-gastrointestinal fistula;
SKILLED TASKS. May cause drowsiness or blurred vision. Avoid allergy to bile acids; hypersensitivity to ursodeoxycholic
performing tasks, which require mental alertness, e.g., operating acid or any component of the formulation.
machinery or driving.
Dose:
Adverse Drug Reactions: Primary biliary cirrhosis, by mouth, ADULT, 13–15 mg/kg
Common: Akathisia, dizziness, drowsiness, fatigue, daily in 2–4 divided doses.
headache, somnolence. Gallstone dissolution, by mouth, ADULT, 8–10 mg/kg daily
Less Common: Bronchospasm, constipation, depression, in 2–3 divided doses for 6–12 months.
diarrhea, edema, EPS, hyperprolactinemia leading to Gallstone prevention, by mouth, ADULT, 300 mg twice daily.
galactorrhea, hypertension, hypotension, pruritus, rash,
restlessness, urticaria. Precautions:
Biliary obstruction; non-visualizing gallbladder.
Drug Interactions:
Monitor closely with: Adverse Drug Reactions:
Decreases absorption of Digoxin Common: Headache, dizziness, diarrhea, constipation,
Enhances therapeutic effect of the following drugs: dyspepsia nausea, back pain, upper respiratory tract
Alcohol (CNS depressant effects) infection, alopecia, skin rash, hyperglycemia, vomiting,
Analgesics, e.g., aspirin, paracetamol (analgesic peptic ulcer, urinary tract infection, leukopenia,
effect) thrombocytopenia, cholecystitis, hypersensitivity
reaction, viral infection, arthritis, musculoskeletal pain,
Increases absorption of Alcohol (accelerated gastric pharyngitis, bronchitis, cough, flu-like symptoms.
emptying) Less Common: biliary colic, esophagitis, facial edema, fever,
hepatobiliary disease, jaundice, laryngeal edema,

13
 ALIMENTARY TRACT AND METABOLISM

malaise, metallic taste, myalgia, peripheral edema, by rectum, ADULT, 10 mg in the morning; CHILD ≤10
pruritus, urticaria, weakness. years, 5 mg in the morning.
A

Drug Interactions:
Monitor closely with: Precautions:
Reduces therapeutic effect of Ursodeoxycholic Acid: Intestinal obstruction or acute abdominal conditions such
Estrogen Derivatives e.g. estriol, Fibric Acid Derivatives as appendicitis; inflammatory bowel disease; severe
e.g. clofibrate dehydration; anal fissures, proctitis, ulcerated
hemorrhoids (avoid use of suppositories).
Avoid concomitant use with:
Decreases absorption of Nitrendipine Adverse Drug Reactions:
Common: Abdominal discomfort, diarrhea, electrolyte
Decreases serum concentration of Ursodeoxycholic Acid: disturbance, nausea, vertigo, vomiting, hematochezia.
Aluminum Hydroxide [administer Ursodeoxycholic Acid 2 Less Common: Irritation, proctitis (rectal)
hours before or 6 hours after Aluminum-containing Rare: Hypersensitivity reactions
Antacid products], Bile Acid Sequestrants [administer
Ursodeoxycholic Acid at least 5 hours after Bile Acid Drug Interactions: No information found
Sequestrants]
Administration: To be taken on an empty stomach.
Administration: To be taken with food.
For tablets, administer the evening before if a morning
Pregnancy Category: B bowel movement is desired. MR tablets must be
swallowed whole and not crushed or chewed. Do NOT
ATC Code: A05AA02 take within 1 hour of antacids or milk.

For suppositories, administer at the time a bowel

movement is desired.
DRUGS FOR CONSTIPATION
Pregnancy Category: C
LAXATIVES ATC Code: A06AB02

OTC BISACODYL
OTC CASTOR OIL
Oral: 5 mg tablet
5 mg MR tablet Oral: USP grade
Rectal: 5 mg suppository (for children)
10 mg suppository (for adults) A fixed oil obtained from the seeds of Ricinus communis
that is used as a stimulant laxative. It is hydrolyzed to
A diphenylmethane stimulant laxative that acts by ricinoleic acid in the small intestine, which reduces net
stimulating peristalsis by directly irritating the smooth absorption of fluid and electrolytes and stimulates
muscle of the large intestine. It also alters water and peristalsis.
electrolyte secretion, producing net interstitial fluid
accumulation and laxation. Indication: Temporary relief of occasional constipation;
bowel evacuation.
Indications: Bowel evacuation before investigational
procedures or surgery; management of constipation. Contraindications: Abdominal pain, nausea, vomiting
Contraindications: Acute abdominal conditions (e.g. Dose:
appendicitis, intestinal inflammatory bowel disease); Bowel evacuation / constipation, by mouth, ADULT, 15 to 60
intestinal obstruction; ileus; severe dehydration; severe mL as a single dose; CHILD 2–11 years, 5 to 15 mL as a
abdominal pain associated w/ nausea and vomiting; single dose.
anal fissures or ulcerative colitis w/ mucosal damage
(rectal). Precautions:
Dose:
Bowel evacuation, by mouth, ADULT, initially 10–20 mg the WARNING: Do NOT use for >1 week or when
night before the procedure followed by 10 mg rectal abdominal pain, nausea, vomiting, or rectal
suppository the next morning (or 10 mg on each of the 2 bleeding are present unless directed by health care
nights before the procedure); CHILD 4–10 years, 5 mg provider.
the night before the procedure and 5 mg rectal
suppository the following morning. Elderly (e.g., severe fluid and electrolyte loss, which may
Constipation, by mouth, ADULT, 5–10 mg at night, up to 20 affect mental function);
mg may be given as necessary; CHILD 4 to 10 years, 5 Pregnancy (associated with induction of labor).
mg at night;

14
ALIMENTARY TRACT AND METABOLISM

Adverse Drug Reactions:

Dizziness, electrolyte disturbance, abdominal cramps, Rx LACTULOSE
diarrhea, nausea, pelvic congestion

A
Oral: 3.3 g/5 mL (3.35 g/5 mL) syrup, 120 mL
Drug Interactions: No known significant interactions
A synthetic lactose derivative that can act as an ammonia
Administration: Should be administered on an empty (NH3) detoxicant. It is degraded by bacteria in the gut
stomach, with juice or carbonated beverages. resulting in an acidic pH, which inhibits NH3 diffusion into
the blood, while enhancing the diffusion of NH3 from the
Do NOT administer at bedtime because of rapid onset of blood into the gut. It also produces an osmotic effect in
action. the colon with resultant distention, promoting peristalsis
and reducing blood ammonia concentration to reduce
Shake emulsions well before use. May be mixed with the degree of portal systemic encephalopathy.
120–240 mL of water, milk, fruit juice, or soft drink
before administration. Indications: Prevention and treatment of hepatic
encephalopathy, management of constipation
Pregnancy Category: Not available
Contraindication: Patients requiring low galactose diet
ATC Code: A06AB05
Dose:
Constipation, by mouth, ADULT, 10–20 g (15–30 mL) daily,
may be increased to 40 g (60 mL) daily if necessary.
OTC GLYCEROL (GLYCERIN) Portal Systemic Encephalopathy (PSE), prevention, by
mouth, ADULT, 20–30 g (30–45 mL) 3–4 times daily
Oral: USP grade (liquid) (adjust dose every 1–2 days to produce 2 to 3 soft stools
Rectal: 2 g suppository daily); CHILD, 26.7–60 g daily (40–90 mL daily) in
divided doses (adjust dosage to produce 2–3 stools
An osmotic dehydrating agent that possesses hygroscopic daily); INFANT, 1.7–6.7 g daily (2.5–10 mL daily) in
and lubricating properties. It increases osmotic pressure, divided doses (adjust dosage to produce 2–3 stools
drawing water into the colon and stimulating evacuation. daily).
Acute PSE, treatment, by mouth, ADULT, 20–30 g (30–45
Indication: Management of constipation mL) every 1 hour to induce rapid laxation, reduce to 20–
30 g (30–45 mL) 3–4 times daily after laxation is
Contraindications: No information found achieved (titrate to produce 2–3 soft stools/day).
Overt Hepatic Encephalopathy (OHE), treatment, by mouth,
Dose: ADULT, 20–30 g 16.7 g (25 mL) every 1 to 2 hours until
Constipation, by rectum, ADULT, 2.250 g suppository, as at least 2 soft or loose bowel movements are produced
needed; CHILD, 1.375 g suppository, as needed. daily (titrate to maintain 2–3 bowel movements daily).

Precautions: Precautions:
May cause rectal discomfort or a burning sensation; Electrolyte imbalance (monitor periodically for electrolyte
Hypovolemia, cardiac failure, or renal disease (e.g., imbalance when used >6 months or in patients
circulatory overload, pulmonary edema, and heart predisposed to electrolyte abnormalities);
failure) Hepatic disease.
Dehydration; Diabetes (contains galactose and lactose; use with caution).
Diabetes mellitus. Elderly (may predispose electrolyte imbalance; more likely
to show CNS signs of dehydration and electrolyte loss;
Adverse Drug Reactions: Local irritation (e.g., rectal sorbitol is equally effective as a laxative and less
discomfort, burning sensation), cramping pain, expensive, however, sorbitol cannot be substituted in the
tenesmus. treatment of hepatic encephalopathy); infants; may
develop hyponatremia and dehydration).
Drug Interactions: No information found
Adverse Drug Reactions:
Administration: Insert suppository high in the rectum and Common and Less Common: Dehydration, hypernatremia,
retain for approximately 15 minutes. Suppository does hypokalemia, abdominal discomfort, abdominal
not need to melt to produce response. distention, belching, cramping, diarrhea, flatulence,
nausea, vomiting.
Pregnancy Category: Not available Rare: Lactic acidosis

ATC Code: A06AX01 Drug Interactions:

Monitor closely with:
Reduces the therapeutic effect of Lactulose:
Glutamine (ammonia-lowering effects)

Administration: May mix with fruit juice, water, or milk. When

administered via a gastric tube, dilute to prevent

15
 ALIMENTARY TRACT AND METABOLISM

induction of vomiting and the possibility of aspiration

pneumonia. Drug Interactions:
Monitor closely with:
A

Pregnancy Category: B Increases risk of adverse or toxic effects of the following

drugs:
ATC Code: A06AD11 Calcium-containing Antacids (ectopic calcification),
Calcium Supplements (ectopic calcification)

MONOBASIC / DIBASIC Avoid concomitant use with:

OTC Increases absorption of Phosphates:
SODIUM PHOSPHATE Vitamin D (decreases laxative effect)
Oral: 48 g/18 g per 100 mL solution, 45 mL bottle Increases risk of adverse or toxic effects of the following
drugs:
A saline laxative that promotes bowel movements by Diuretics, Drugs that affect serum electrolytes
increasing water retention in the intestines. (hyperphosphatemia, hypocalcemia, hypernatremia),
(Vitamin D (hyperphosphatemia)
Indication: Management of constipation
Reduced therapeutic effects of Phosphates:
NOTE: NOT for bowel cleansing. Aluminum Salts, Calcium Salts, Magnesium Salts
Contraindications: Previous kidney problem, congestive Administration: Recommended doses are to be diluted in 1
heart failure, impaired renal functions, decreased full glass (8 fl. oz.) of cool water, followed with at least 1
intervascular volume, dehydration, uncorrected additional full glass (8 fl. oz.) of cool water.
electrolyte abnormalities, children under 5 years.
NOTE: Drink plenty of water after use to prevent dehydration
Dose: associated with significant loss of liquid when using this
Constipation, by mouth, ADULT, 15 mL (1 tablespoon) product.
(maximum dose, 30–45 mL or 2–3 tablespoons); CHILD
10–11 years, 15 mL (1 tablespoon) (maximum dose, 15 Pregnancy Category: Not available
mL or 1 tablespoon); CHILD 5–9 years, 7.5 mL (½
tablespoon) (maximum dose, 7.5 mL or ½ tablespoon). ATC Code: A06AD17
NOTE: Not to be administered in children under 5 years.
1 tablespoon = 3 teaspoons
(CALCIUM SENNOSIDES) STANDARD
Dose Adjustment: OTC SENNA
Renal Impairment: CONCENTRATE
Do not administer in severe renal impairment.
Oral: 187 mg and 374 mg tablet
Precautions: 8.77 mg and 17.54 mg (calculated as sennoside B)
WARNING: Taking more than the recommended dose tablet (as Calcium sennosides, equivalent to
in 24 hours can be harmful. Standardized Senna Concentrate)

An anthraquinone glycoside preparation consisting of the

Low serum calcium concentrations; dried leaflet of Cassia acutifolia or Cassia angustifolia,
Infected phosphate renal calculi; with sennosides A and B as active cathartic principles.
Hyperkalemia;
Congestive heart failure; Indications: Short-term treatment of constipation;
Hypertension; evacuation of colon for bowel or rectal examinations.
Edema;
GI obstruction; Contraindications: Intestinal obstruction, acute intestinal
Inflammatory bowel disease; inflammation (e.g., Crohn Disease), colitis ulcerosa,
Conditions where there is likely to be increased colonic appendicitis, abdominal pain of unknown origin.
absorption;
Debilitated patients; Dose:
Patients with pre­existing electrolyte disturbances. Bowel evacuation, by mouth, ADULT, 130 mg between 2–4
Elderly. in the afternoon of the day prior to the procedure.
Adverse Drug Reactions: Constipation, by mouth, ADULT, 15 mg once daily
Common and Less Common: Nausea, vomiting, diarrhea, (maximum, 70–100 mg daily taken in 2 divided doses);
abdominal pain hyperkalemia, hypernatremia, CHILD 6–12 years, initially 7.5–8.6 mg once daily
dehydration, hypokalemia, hyperphosphatemia and (maximum, 50 mg daily taken in 2 divided doses); CHILD
hypocalcemia (resulting in tetany and death), 2–6 years, initially 3.75 mg once daily (maximum, 15 mg
generalized tonic-clonic seizures and/or loss of daily taken in 2 divided doses).
consciousness.
Rare: Acute renal failure, nephrocalcinosis.

16
ALIMENTARY TRACT AND METABOLISM

Precautions:
WARNING: Taking more than the recommended dose
WARNING: NOT recommended for use in patients in 24 hours can be harmful.
experiencing stomach pain, nausea, vomiting, or

A
sudden change in bowel movements which lasts >2 Adverse Drug Reactions: Local irritation, hyperkalemia,
weeks. hypernatremia, dehydration, hypokalemia,
hyperphosphatemia and hypocalcemia (resulting in
NOT recommended for use in children <2 years. tetany and death), rectal gangrene (elderly).

Administration: Administer additional liquid during therapy

Prolonged use (has been associated with finger clubbing,
to ensure adequate hydration.
hypokalemia, tetany, hypertrophic osteoarthropathy,
See under Alimentary Tract and Metabolism – Drugs for
hypogammaglobulinemia, intermittent urinary excretion
Constipation, Laxatives for more information.
of aspartyl glucosamine, reversible cachexia, hepatitis,
or hepatic failure);
Pregnancy Category: Not available
Nausea or vomiting;
Undiagnosed abdominal pain;
ATC Code: A06AG01
Intestinal obstruction;
Inflammatory bowel disease;
Elderly (increased risk for dehydration due to predisposition
to constipation and decreased thirst reflex). ANTIDIARRHEALS,
INTESTINAL ANTIINFLAMMATORY/
Adverse Drug Reactions: ANTIINFECTIVE AGENTS
Common: Abdominal discomfort (e.g., colic, cramps),
diarrhea with excessive loss of water and electrolytes,
yellowish-brown discoloration of the urine at acid pH and INTESTINAL ANTIINFECTIVES
red at alkaline pH
Less Common: Reversible melanosis coli ANTIBIOTICS
Rare: Atonic non-functioning colon

Drug Interactions: No known significant interactions Rx RIFAXIMIN

Administration: Once daily doses should be taken at
Oral: 200 mg tablet
bedtime.
Rifaximin inhibits bacterial RNA synthesis by binding to
Pregnancy Category: Not available bacterial DNA-dependent RNA polymerase. It lowers
incidence of hepatic encephalopathy due to its broad-
ATC Code: A06AB06 spectrum activity against ammonia-producing enteric
bacteria.

ENEMAS Indication: Prevention and treatment of hepatic

encephalopathy.
MONOBASIC / DIBASIC
OTC Contraindications: Hypersensitivity to rifaximin, other
SODIUM PHOSPHATE rifamycin antibiotics, or any component of the
formulation.
Rectal: 19 g/7 g solution per 66 mL and 133 mL bottle
Dose:
A saline laxative that promotes bowel movements by Hepatic encephalopathy, by mouth, ADULT, 400 mg every 8
increasing water retention in the intestines. hours for 5-10 days.
Indications: Management of constipation Dose Adjustment:
Renal and Hepatic impairment:
NOTE: Not for bowel cleansing.
No dosage adjustment necessary; use with caution.
Contraindications: Previous kidney problem, congestive
Precautions:
heart failure, impaired renal functions, decreased
Hypersensitivity (e.g., exfoliative dermatitis, rash, urticarial,
intervascular volume, dehydration, uncorrected
flushing, angioneurotic edema, pruritus, and
electrolyte abnormalities, children under 2 years.
anaphylaxis);
Superinfection (Prolonged use may result in fungal or
Dose:
bacterial superinfection, i.e. C. difficile-associated
Constipation, by rectum, CHILD 5–11 years, one 66 mL
diarrhea (CDAD) and pseudomembranous colitis, CDAD
bottle; CHILD 2–5 years, one–half 66 mL bottle.
has been observed >2 months post-antibiotic
treatment);
NOTE: Not to be administered in children under 2 years.
Hepatic impairment (Monitor patients with severe hepatic
impairment for increased systemic exposure).

17
 ALIMENTARY TRACT AND METABOLISM

Dose Adjustment:
Adverse Drug Reactions: Renal Impairment:
Common: Peripheral edema, dizziness, fatigue, ascites, and Select doses with care.
A

nausea.
Less Common: Headache, depression, pruritus, skin rash, Precautions:
abdominal pain, pseudomembranous colitis, anemia, Renal impairment; severe dehydration should be treated
muscle spasm, arthralgia, nasopharyngitis, dyspnea, with IV electrolyte solutions.
epistaxis, and fever.
Rare: Anaphylaxis, angioedema, Clostridium difficile- Adverse Drug Reactions:
associated diarrhea, exfoliative dermatitis, flushing, Rare: Hypernatremia, vomiting
hypersensitivity reaction, and urticarial.
Drug Interactions: No information found
Drug Interactions:
Avoid concomitant use with: Administration: May be taken with or without food.
BCG, intravesical (live), Cholera vaccine (Do not administer Reconstitute with clean potable water. Discard unused
cholera vaccine to patients who have received oral or reconstituted solution after 24 hours.
parenteral antibiotics within 14 days prior to
vaccination.) Pregnancy Category: C

Administration: May be taken with or without food. ATC Code: A07CA

Pregnancy Category: C
ANTIPROPULSIVES
ATC Code: A07AA11

OTC LOPERAMIDE
ORAL REHYDRATION SALT FORMULATIONS
Oral: 2 mg capsule (as hydrochloride)
ORAL REHYDRATION SALTS
OTC A synthetic pethidine derivative that inhibits gut motility and
(ORS 75-REPLACEMENT)
may also reduce gastrointestinal secretions. It acts
Oral: Composition: (Reduced osmolarity ORS per liter of directly on circular and longitudinal muscles through the
water, as recommended by WHO) opioid receptor to inhibit peristalsis and prolong transit
time.
Composition g/L mmol/L
Indications: Inhibition of gut motility for the reduction of
Sodium 2.6 75
gastrointestinal secretion; symptomatic control of acute
Chloride
and chronic non-specific diarrhea; adjunct to fluid
Trisodium 2.9 10 electrolytes replacement in the management of acute
citrate dihydrate and chronic non-specific diarrhea; management of
Potassium 1.5 20 colostomies or ileostomies.
chloride
Glucose, 13.5 75 Contraindications: Hypersensitivity to loperamide or any
anydrous component of the formulation; abdominal pain without
Total weight 20.5 diarrhea; children <2 years.

Dose:
An oral rehydration salt formulation containing reduced
Acute diarrhea, by mouth, ADULT, initially 4 mg, followed by
osmolar concentration of sodium and glucose that is
2 mg after each loose stool (maximum, 16 mg daily,
widely used in treating children with acute non-cholera
usual dose is 6-8 mg); CHILD 8–12 years (>30 kg), 2 mg
diarrhea, and in adults and children with cholera.
3 times daily; CHILD 6–8 years (20–30 kg), 2 mg twice
daily; CHILD 2–5 years (13–20 kg), 1 mg 3 times daily.
Indications: Replacement of fluid and electrolyte losses in
Chronic diarrhea, by mouth, ADULT, initially 4 mg, followed
mild to moderate dehydration due to acute diarrhea or
by 2 mg after each loose stool (maximum, 16 mg daily),
vomiting; replacement of continuing loss from vomiting
maintenance dose must be slowly titrated downward to
or diarrhea.
minimum required to control symptoms (typically 4–8 mg
daily, in divided doses), if no improvement is seen after
Contraindications: Severe dehydration; severe and
treatment with 16 mg for at least 10 days, further use is
sustained vomiting; diarrhea; glucose malabsorption; to
unlikely to be of benefit.
patients with difficulty in drinking.
Traveler’s diarrhea, by mouth, ADULT, initially 4 mg after
first loose stool, followed by 2 mg after each subsequent
Dose:
stool (maximum, 8 mg daily); CHILD 9–11 years, 2 mg
Fluid and electrolyte loss in acute diarrhea, by mouth,
after first loose stool, followed by 1 mg after each
ADULT, 200–400 mL solution after every loose motion;
subsequent stool (maximum dose, 6 mg daily); CHILD 6–
INFANT and CHILD, refer to WHO IMCI.
8 years, 2 mg after first loose stool, followed by 1 mg
after each subsequent stool (maximum dose, 4 mg daily)

18
ALIMENTARY TRACT AND METABOLISM

Ulcerative colitis, acute treatment, by mouth, ADULT,

NOTE: NOT recommended for infants and children <2 years. Asacol 400 mg
Initially 2.4 g daily in divided
tablet
Precautions: doses

A
Ipocol tablet
WARNING: If diarrhea lasts longer than 2 days, Mezavant Initially 2.4–4.8 g once daily
symptoms worsen, or abdominal swelling or Initially up to 4 g daily in 2–3
bulging develops, discontinue use and consult Pentasa tablet
divided doses
healthcare provider.
Initially up to 4 g daily in 2–4
Pentasa granules
Ileus and constipation; abdominal distension; divided doses
Acute inflammatory bowel disease; Initially 1.5–3 g daily in 3
Antibiotic-associated colitis; Salofalk tablet
divided doses
Dysentery;
Hepatic impairment;
Ulcerative colitis, maintenance, by mouth, ADULT,
Children;
Asacol 400 mg
Pregnancy. 1.2–2.4 g once daily or in
tablet
divided doses
Ipocol tablet
Adverse Drug Reactions:
Common: Dizziness, constipation, abdominal cramping, Asacol 800 mg Up to 2.4 g daily in divided
nausea. tablet doses
Less Common: Abdominal distention, abdominal pain, Mezavant 2.4 g once daily
allergic reactions, anaphylactic shock, anaphylactoid
reactions, angioedema, drowsiness, dyspepsia, fatigue, Initially 2 g once daily, then
Pentasa tablet
flatulence, hypersensitivity, paralytic ileus, megacolon, adjusted individually
pruritus rash, toxic megacolon, urinary retention, Pentasa granule 2 g once daily
urticarial, vomiting, xerostomia.
Rare: Bullous eruption, erythema multiforme, Stevens- Salofalk granules 1.5 g daily in 3 divided doses
Johnson Syndrome, toxic epidermal necrolysis.
Ulcerative colitis, acute exacerbations, by mouth, ADULT,
Drug Interactions:
Monitor closely with: MILD: 2.4 g daily in divided doses
Asacol 800
Enhances therapeutic effects Loperamide: mg tablet
Ramosetron (constipation effects) MODERATE: 4.8 g daily in divided
doses
Administration: May be taken with or without food.
Ulcerative colitis, by mouth, CHILD ≥6 years, <40 kg,
Pregnancy Category: C ACUTE MAINTENANCE
ATTACK OF REMISSION
ATC Code: A07DA03
Initially 30–
INTESTINAL ANTI-INFLAMMATORY AGENTS 50 mg/kg
Ipocol tablet daily in Initially 15–30
Salofalk divided mg/kg daily in
OTC MESALAZINE tablet doses, then divided doses,
Salofalk adjusted then adjusted
granules individually individually
Oral: 500 mg enteric coated tablet (maximum,
500 mg enteric MR tablet 75 mg/kg)
Rectal: 250 mg suppository

A 5-aminosalicylic acid derivative that modulates local Ulcerative proctitis, by rectum, ADULT,
chemical mediators of the inflammatory response, ACUTE MAINTENANCE
especially leukotrienes. ATTACK OF REMISSION
Initially 15–30
Indications: Ulcerative colitis, ulcerative proctitis 0.75–1.5 g mg/kg daily in
Asacol supp. daily in divided doses,
Contraindications: GFR < 20ml/min; hypersensitivity to divided doses then adjusted
mesalazine, aminosalicylates, salicylates, or any individually
component of the formulation (including suppository
Pentasa 1 g daily for –-
vehicle of vegetable fatty acid esters). 1 g daily
supp. 4 weeks
Dose: Salofalk 0.5–1 g 2–3
NOTE: Dose is dependent on product used. supp. times daily

19
 ALIMENTARY TRACT AND METABOLISM

Dose Adjustment: Pregnancy Category: B / C (product specific)

Renal Impairment:
Dose adjustment may be necessary because mesalazine is ATC Code: A07EC02
A

renally eliminated. Use with caution.

If GFR <20 mL/min, use is contraindicated.
HORMONAL DRUGS USED FOR ESOPHAGEAL
Hepatic Impairment: VARICES
Use with caution.
HYPOTHALAMIC HORMONES
Precautions:
Elderly (may have difficulty administering and retaining
rectal suppositories). Rx OCTREOTIDE
Adverse Drug Reactions:
Common: Headache, abdominal pain, eructation, nausea, Inj.: 100 micrograms/mL and 500 micrograms/mL (as
exacerbation of ulcerative colitis, nasopharyngitis, acetate), 1 mL ampule (IV infusion) wort
pharyngitis, chest pain, peripheral edema, vasodilation,
hypertension, dizziness, chills, fatigue, vertigo, anxiety, Octreotide is a synthetic polypeptide related to
migraine, nervousness, paresthesia, insomnia, malaise, somatostatin, a. growth hormone inhibiting factor.
skin rash, diaphoresis, pruritus, alopecia, acne vulgaris,
weight loss, diarrhea, dyspepsia, flatulence, Indication: For hemostasis for esophageal varices
constipation, vomiting, intolerance syndrome, abnormal
stools, gastroenteritis, gastrointestinal hemorrhage, Dose:
rectal hemorrhage, tenesmus, bloody diarrhea, For esophageal varices bleeding, by IV injection, ADULT, IV
pancreatitis, rectal pain, sclerosing cholangitis, bolus of 25–100 micrograms (usual bolus dose, 50
abdominal distention, anorectal pain (on insertion of micrograms) followed by continuous IV infusion of 25–
enema tip), hemorrhoids, polyuria, decreased hematocrit 50 micrograms per hour for 2–5 days; may repeat bolus
and hemoglobin, abnormal hepatic function tests, in first hour if hemorrhage is not controlled. [NOTE:
infection, back pain, hypertonia, arthralgia, myalgia, Withdraw yearly for a 4-week interval (8 for depot
weakness, arthritis, musculoskeletal pain, visual injection) in patients who have received irradiation.
disturbance, conjunctivitis, tinnitus, otalgia, hematuria, Resume if levels increase and signs or symptoms recur].
decreased creatinine clearance, sinusitis, rhinitis, cough, For vasoactive intestinal peptide tumors (VIPomas), by IV
flu-like symptoms, dyspnea, bronchitis. injection, ADULT, 200–300 micrograms daily in 2–4
divided doses for the first 2 weeks; titrate dose based on
Drug Interactions: response or tolerance (range, 150–750 micrograms
Monitor closely with: daily; doses >450 micrograms daily are rarely required).
Decreases metabolism of Thiopurine Analogues e.g.,
azathioprine Dose Adjustment:
Geriatric:
Decreases serum concentration of Cardiac Glycosides e.g., Dose adjustment may be required. Begin dosing at the lower
Digoxin end of dosing range. Elimination half-life is increased by
46% and clearance is decreased by 26%.
Increases risk of adverse or toxic effects of Mesalazine:
NSAIDs (nephrotoxic effect) Renal Impairment:
If dialysis-dependent, no specific dose adjustments
Increases risk of adverse or toxic effects of Heparin (risk for indicated. However, dose adjustment may be needed
bleeding / bruising) since clearance is reduced by ~50%.

Avoid concomitant use with: Precautions:

Increases risk of adverse or toxic effects of Varicella virus- Cholelithiasis; Glucose regulation; Hypothyroidism;
containing Vaccines (potential development of Reye’s Pancreatitis; Cardiovascular disease; Excessive fluid
Syndrome) loss.
Prophylactic cholecystectomy is recommended in patients
Reduces therapeutic effect of Mesalazine with gastrointestinal or pancreatic neuroendocrine
Antacids (separate administration and/or lower antacid tumors undergoing abdominal surgery if octreotide
doses to prevent interaction) treatment is planned
H2-Antagonists, Proton Pump Inhibitors Patients on TPN (periodically monitor for elevations in zinc
levels).
Administration:
For tablets, swallow whole. Do NOT break, chew, or TEST INTERACTION. Chronic treatment has been associated
crush. Do NOT administer with antacids. with abnormal Schillings test.

For suppositories, remove foil wrapper prior to Adverse Drug Reactions:

administration. Avoid excessive handling. Retain for at Common: Sinus bradycardia, fatigue, headache, malaise,
least 1–3 hours to achieve maximum benefit. dizziness, pruritus, hyperglycemia, fever, abdominal
pain, loose stools, nausea, diarrhea, flatulence,

20
ALIMENTARY TRACT AND METABOLISM

cholelithiasis, biliary sludge, constipation, vomiting, Hypoglycemic Properties (hypoglycemic effect), MAO
biliary duct dilatation, injection site pain, back pain, Inhibitors (hypoglycemic effect), Other Hypoglycemia-
arthropathy, myalgia, upper respiratory tract infection, associated Agents (hypoglycemic effect), Pegvisomant

A
dyspnea, antibodies to octreotide, flu symptoms (hypoglycemic effect), Quinolone Antibiotics
Less Common: Hypertension, conduction abnormalities, (hypoglycemic effect), Ruxolitinib (bradycardic effect),
arrhythmia, palpitation, peripheral edema, pain, anxiety, Salicylates (hypoglycemic effect), Selective Serotonin
confusion, hypoesthesia, insomnia, rash, alopecia, Reuptake Inhibitors e.g. fluoxetine (hypoglycemic effect),
dyspepsia, steatorrhea, tenesmus, anorexia, cramping, Tofacitinib (bradycardic effect)
arthralgia, myalgia, paresthesia, anemia, weakness,
earache, renal calculus, cough, pharyngitis, rhinitis, Increases risk of adverse or toxic effects of the following
sinusitis, allergy, diaphoresis, angina, cardiac failure, drugs:
edema, flushing, hematoma, phlebitis, abnormal gait, Lacosamide (AV-blocking effect), Moderate Risk QTc-
amnesia, depression, dysphonia, hallucinations, Prolonging Agents (QTc-prolonging effect), Pegvisomant
nervousness, neuralgia, somnolence, vertigo, acne, (significant elevations of liver enzymes)
rigors, bruising, cellulitis, hypoglycaemia, hypokalemia,
gout, cachexia, breast pain, impotence, colitis, Reduces therapeutic effect of Octreotide:
diverticulitis, dysphagia, gastritis, gastroenteritis, Quinolone Antibiotics e.g. Levofloxacin
gingivitis, glossitis, melena, stomatitis, taste perversion,
xerostomia, incontinence, urinary tract infection, Reduces therapeutic effect of Antidiabetic Agents
injection site hematoma, fat malabsorption,
hyperkinesia, hypertonia, joint pain, neuropathy, tremor, Avoid concomitant use with:
blurred vision, visual disturbance, tinnitus, renal Decreases serum concentration of Cyclosporine (Systemic)
abscess, bronchitis, epistaxis, bacterial infection,
moniliasis Increases risk of adverse or toxic effects of the following
Rare: Amenorrhea, anaphylactic shock, anaphylactoid drugs:
reactions, aneurysm, aphasia, appendicitis, arthritis, Ceritinib (bradycardic effect), Highest-Risk QTc-
ascending cholangitis, ascites, atrial fibrillation, basal Prolonging Agent (QTc-prolonging effect), Mifepristone
cell carcinoma, Bell's palsy, biliary obstruction, breast (QTc-prolonging effect)
carcinoma, cardiac arrest, cerebral vascular disorder,
CHF, cholecystitis, cholestatic hepatitis, CK increased, Administration: Administer IV injections between meals to
creatinine increased, deafness, diabetes insipidus, decrease GI effects. May alter absorption of dietary fats.
diabetes mellitus, facial edema, fatty liver, galactorrhea,
GI bleeding, GI hemorrhage, GI ulcer, glaucoma, Pregnancy Category: B
gynecomastia, gallbladder polyp, hematuria,
hemiparesis, hemorrhoids, hearing impairment, ATC Code: H01CB02
hepatitis, hyperesthesia, hypertensive reaction,
hypoadrenalism, hypoxia (children), intestinal
obstruction, intracranial hemorrhage, intraocular
pressure increased, iron deficiency, ischemia, jaundice, Rx SOMATOSTATIN
joint effusion, increased LFTs, decreased libido,
malignant hyperpyrexia, MI, necrotizing enterocolitis Inj.: 250 micrograms and 3 mg ampule / vial (IV, IV
(neonates), migraine, nephrolithiasis, neuritis, infusion)
oligomenorrhea, pancreatitis, orthostatic hypotension,
pancytopenia, paranoia, paresis, petechiae, pituitary A cyclic tetradecapeptide that inhibits the release of human
apoplexy, pleural effusion, pneumonia, pneumothorax, growth hormone
polymenorrhea, pulmonary embolism, pulmonary
hypertension, pulmonary nodule, QT prolongation, Indication: Hemostatic medicines for esophageal varices
Raynaud’s syndrome, rectal bleeding, renal failure, renal
insufficiency, retinal vein thrombosis, scotoma, seizures, Contraindications: Pregnancy or breastfeeding (consult
status asthmaticus, suicide attempt, syncope, specific product labeling)
tachycardia, thrombocytopenia, thrombophlebitis,
thrombosis, urticaria, vaginitis, visual field defect, Dose:
vitamin B12 deficiency, weight loss, wheal or erythema For esophageal varices bleeding, by IV bolus, ADULT, initially
250 micrograms over at least 1 minute, followed by
Drug Interactions: maintenance dose as continuous IV infusion at 250
Monitor closely with: micrograms/hour for 2–5 days, may repeat initial bolus
Decreases metabolism of Codeine [impairs formation of two in first hour if hemorrhage is not controlled.
major metabolites, morphine and norcodeine]
Dose Adjustment:
Enhances therapeutic effect of the following drugs: Renal Impairment:
Antidiabetic Agents, Bradycardia-causing Agents, For CrCl ≤30 mL/minute, administer 50% of the usual dose.
Ivabradine (bradycardic effect)
Precautions:
Increases risk of adverse or toxic effects of Octreotide: Glucose regulation; Insulin-dependent diabetes; Oliguria;
Androgens [except Danazol] (hypoglycemic effect), Cardiovascular disease (monitor vital functions closely,
Bretylium (bradycardic effect; AV blockade), Herbs with especially following initial bolus injection).

21
 ALIMENTARY TRACT AND METABOLISM

Adverse Drug Reactions: AV block, bradycardia,

hypertension, hypotension, hyperglycemia, DRUGS USED IN DIABETES
hypoglycemia, vertigo, flushing (rapid administration),
A

abdominal discomfort, diarrhea, nausea, vomiting

(infusion greater than 50 micrograms/minute), INSULIN
bronchospasm, allergic reaction, severe water retention,
hyponatremia GENERAL INFORMATION

Drug Interactions: Insulin is a polypeptide hormone of complex structure

Monitor closely with: produced by the pancreas that plays a key role in the
Decreases metabolism of the following drugs: metabolism of carbohydrate, fat, and protein. All insulins
Codeine [impairs formation of 2 major codeine are developed by recombinant DNA technology but the
metabolites, morphine and norcodeine] amino acid sequence of human and analogue insulins
differ. These explain the differences in pharmacokinetics
Increases risk of adverse or toxic effects of Somatostatin, between human and analogue insulins.
specifically, those associated with its hypoglycemic Mode of Action: Increase or restore ability to metabolize
effect: glucose by enhancing cellular glucose uptake; inhibit
Androgens [except Danazol], Antidiabetic Agents, Herbs endogenous glucose output and lipolysis.
with Hypoglycemic Properties, MAO Inhibitors, Other
Hypoglycemia-associated Agents, Pegvisomant, Types of Insulin: The various formulations of insulin are
Quinolone Antibiotics Levofloxacin, Salicylates, Selective classified according to their duration of action after
Serotonin Reuptake Inhibitors subcutaneous injection, as: short-acting and rapid-acting
insulins, intermediate-acting insulins, and long-acting
Increases serum concentration of the following drugs: insulins and ultra- long acting insulins. The intermediate-
Bromocriptine (delays Bromocriptine absorption and acting and long-acting insulins are given for the basal
time to maximum plasma concentrations) requirements, while the short-acting and rapid-actin
insulins are given before meals to control post-prandial
Reduces therapeutic effect of the following drugs: hyperglycemia.
Antidiabetic Agents, Pegvisomant (significant elevations
of liver enzymes) Indications:
Management of type 1 diabetes mellitus; type 2 diabetes
Avoid concomitant use with: mellitus inadequately controlled with diet, exercise, and
Decreases metabolism of Cyclosporine (Systemic) oral antidiabetic medications, and where oral therapy
cannot be used (e.g., during surgery, or in pregnant
Increases risk of adverse or toxic effects of Barbiturates e.g. women with Type 2 DM when diet alone fails to control
Phenobarbital (sedative effects) the diabetes), children with diabetes; diabetic
emergencies (e.g. diabetic ketoacidosis and
Administration: Administer IV bolus slowly over at least 1 hyperosmolar hyperglycemic states).
minute, followed immediately by continuous infusion. If
infusion is interrupted for more than 3–5 minutes, re- Contraindications: Hypoglycemia
administer initial bolus dose to maintain continuous
treatment. Dose:
Dose of insulin and regimen depend on the individual
NOTE: Avoid abrupt discontinuation of therapy; decrease treatment endpoints and are adjusted according to
infusion gradually for 24 hours before discontinuing. (capillary) blood glucose monitoring.
Dose of human insulin is always expressed in units. Do NOT
Pregnancy Category: B abbreviate the word “unit.” One unit of human insulin,
which is contained in 0.03846 mg of the first
ATC Code: H01CB01 International Standard (1986) is equivalent to the
amount of insulin required to reduce the concentration
of blood glucose to 45 mg/dL in a fasting rabbit.

NOTE: Diabetes self-management education (DSME) is

essential to maximize the effectiveness of therapy.

Dose Adjustment:
Renal Impairment:
In mild-to-moderate impairment, reduce dose.
In severe impairment, refer to a specialist.
CrCl 10–50 Administer at 75% of normal dose
mL/minute and monitor glucose closely

CrCl <10 Administer at 25% to 50% of normal

mL/minute dose and monitor glucose closely

22
ALIMENTARY TRACT AND METABOLISM

Hepatic Impairment: Nifedipine (impairs glucose tolerance),

Insulin requirements may be decreased in patients with Thiazolidinediones (increases risk of edema and heart
hepatic impairment. failure)

A
Precautions: Reduces therapeutic effect of Insulin:
Acute illness or conditions, e.g., trauma, Drugs increasing blood glucose concentration, e.g.,
Myocardial Infarction; Glucocorticoids, Antipsychotics, Calcineurin Inhibitors,
Infections; High-dose Thiazide Diuretics
Stroke;
Coma; Avoid concomitant use with:
Infections; Reduces therapeutic effect of Insulin:
Diabetic ketoacidosis Contraceptives, Oral, e.g., Levonorgestrel,
Surgery; Medroxyprogesterone (Corticosteroids, e.g.,
Renal impairment; Dexamethasone, Hydrocortisone, Prednisolone;
Exercise; Diuretics, e.g., Furosemide, Hydrochlorothiazide)
Pregnancy
SKILLED TASKS. Driving may be hazardous when Administration: Administered via injection because it is
hypoglycemic since awareness is impaired. Check blood easily inactivated by the body enzymes.
glucose concentration before driving, and at intervals of The SC route is ideal in most situations, usually injected
approximately 2 hours when on long journeys. in the upper arms, thighs, buttocks, or abdomen. The
rate of absorption from different sites may vary
MONITORING: The facility should have monitoring at the depending on local blood flow (absorption in the arm is
point of care. Blood glucose concentration varies faster than in the buttock or thigh).
throughout the day. Diabetes patients should aim to
maintain their blood glucose concentration between 4– Do NOT administer mixtures of insulin formulations
9 mmol/L for most of the time [ideally, 80-130 mg/dL intravenously.
(4–7 mmol/L before meals and <180 mg/dL (<9
mmol/L) after meals]. Prevent blood glucose
concentration from falling below 72mg/dL (4 mmol/L) REGULAR INSULIN
because of the risk of hypoglycemia. Glycated Rx
hemoglobin concentration (HbA1c) should be <7% (53 (RECOMBINANT DNA, HUMAN)
mmol/L).
Inj.: 100 IU/mL, 3 mL pre-filled syringe (SC, IV/IM)
100 IU/mL, 5 mL and 10 mL vial (SC, IV/IM)
STABILITY and STORAGE: Insulin preparations should be
stored in a refrigerator at 2–8oC, protected from light and
A short-acting, regular crystalline zinc insulin, which is
not allowed to freeze. Patients should be advised not to
prepared as a sterile, clear aqueous solution. It contains
expose their vials or cartridges to excessive heat or
a polypeptide hormone structurally identical to the
sunlight.
human insulin synthesized through rDNA technology for
Adverse Drug Reactions: treatment of diabetes.
Common: Hypoglycemia Regular or soluble insulin is the most appropriate form of
Less Common: Edema, lipodystrophy (either as lipoatrophy insulin for use in diabetic emergencies and during
or lipohypertrophy) at the site of injection, weight gain. surgery, and in these cases, are typically given in an
Rare: Localized reactions (e.g., redness, swelling, itching), intravenous infusion (insulin drip). When injected IV, it
generalized hypersensitivity reactions (including rash has a very short half-life of only about 5 minutes and its
over the whole body, shortness of breath, wheezing, effect disappears within 30 minutes.
hypotension, tachycardia, sweating, or very rarely,
anaphylactic reactions). Indications: Management of diabetes mellitus; diabetic
ketoacidosis.
Drug Interactions:
Monitor closely with: Dose:
Enhances therapeutic effect of Insulin: Diabetes mellitus, by SC, IM, IV injection or IV infusion (IV
ACE Inhibitors, e.g., Enalapril, Beta Blockers, e.g., route is reserved for urgent treatment, e.g., DKA and for
Atenolol, Propranolol (hypoglycemic effect), Alcohol fine control in serious illness and peri-operatively),
(inhibits hepatic glucose output; decreases blood according to requirements. [see under Insulin and
glucose concentratin) Analogues].

Increases risk of adverse effects of Insulin: Administration: Shake the suspension gently before
Alcohol (hypoglycemia; masks warning symptoms), Beta withdrawing a dose. Do NOT use if solution is viscous or
Blockers, e.g., Atenolol, Propranolol (masks warning cloudy. Use only if clear and colorless. Follow
signs of hypoglycemia), Drugs increasing blood glucose manufacturer’s instructions.
concentration, e.g., Glucocorticoids, Antipsychotics,
Calcineurin Inhibitors, High-dose Thiazide Diuretics See General Information on Insulin and Analogues listed
(alters diabetes control of insulin) above for further information.

Pregnancy Category: B

23
 ALIMENTARY TRACT AND METABOLISM

ATC Code: A10AB01

NOT suitable for the emergency treatment of
diabetic ketoacidosis.
A

ISOPHANE HUMAN INSULIN / Administration: For SC injection only. Administer 30–45

Rx NPH HUMAN INSULIN minutes before meals. Shake the suspension gently
(RECOMBINANT DNA) before withdrawing a dose. Follow manufacturer’s
instructions.
Inj.: 100 IU/mL, 3 mL pre-filled syringe (SC)
100 IU/mL, 5 mL and 10 mL vial (SC) Inspect visually prior to use. It should not contain
particulate matter and should appear uniformly cloudy
Neutral Protamine Hagedorn (NPH Insulin) or isophane after mixing. Do NOT use if particulate matter is seen. Do
insulin is a crystalline suspension of human insulin with NOT mix with other insulins or diluents.
protamine and zinc providing an intermediate-acting
insulin with a slower onset of action (within about 2 See General Information on Insulin and Analogues listed
hours), with peak activity at about 10-12 hours and a above for further information.
longer duration of activity (up to about 24 hours) than
that of regular insulin. It is of particular value for the Pregnancy Category: B
initiation of twice-daily insulin regimens. NPH insulin is
often combined with regular insulin to achieve a more ATC Code: A10AB30; A10AC30
rapid onset of action compared to NPH insulin alone.

Indication: Management of diabetes mellitus BLOOD GLUCOSE LOWERING DRUGS, EXCLUDING

INSULINS
Administration: For SC injection only. Shake the suspension
gently before withdrawing a dose. Follow manufacturer’s
instructions.
BIGUANIDES

WARNING: NEVER administer intravenously. Rx METFORMIN

NOT suitable for the emergency treatment of diabetic
ketoacidosis. Oral: 500 mg tablet / film-coated tablet (as hydrochloride)
850 mg tablet (as hydrochloride)
See General Information on Insulin and Analogues listed
above for further information. A biguanide that exerts its effects by inhibiting hepatic
gluconeogenesis and increasing peripheral glucose
Pregnancy Category: B utilization and is useful in overweight and obese patients
since it does not increase weight or provoke
ATC Code: A10AC01 hypoglycemia when used.

Indication: Management of type 2 diabetes mellitus

BIPHASIC ISOPHANE HUMAN Contraindications: Ketoacidosis; severe infection or trauma;
dehydration; alcohol misuse; moderate to severe heart
Rx INSULIN 70/30 failure; risk of tissue hypoxia caused by sepsis,
(RECOMBINANT DNA) respiratory failure, recent MI, or hepatic impairment.
Inj.: 70% isophane suspension + 30% soluble insulin in: Dose:
100 IU/mL, 5 mL and 10 mL vial (SC) Diabetes mellitus, by mouth, ADULT and CHILD >10 years,
100 IU/mL, 3 mL disposable syringe (SC) initially 500 mg with breakfast for at least 1 week, then
100 IU/mL, 3 mL glass cartridge (SC) 500 mg with breakfast and evening meal for at least 1
week, then 500 mg with breakfast, lunch, and evening
A fixed ratio premix recombinant human insulin formulation meal, or 850 mg every 12 hours with or after food (usual
containing a short-acting insulin and an intermediate- maximum, 2.5 g daily in divided doses).
acting insulin (70% isophane insulin and 30% soluble
insulin). Human insulin is produced by recombinant DNA Dose Adjustment:
technology utilizing a non-pathogenic laboratory strain of Geriatric:
Escherichia coli. It is a suspension of crystals produced Use with caution. Reduce dose or discontinue, if necessary.
from combining human insulin and protamine sulfate
under appropriate conditions for crystal formation and Renal and Hepatic Impairment:
mixing with human insulin injection. For mild-to-moderate impairment, dose reduction is
warranted.
Indication: Management of diabetes mellitus For severe impairment, refer patient to a specialist.

WARNING: NEVER administer intramuscularly or

intravenously.

24
ALIMENTARY TRACT AND METABOLISM

Precautions: SULFONYLUREAS
WARNING: May cause lactic acidosis rarely but with
potentially severe consequences. Rx GLICLAZIDE

A
Use of iodine-containing X-ray contrast media (do not restart Oral: 80 mg tablet (immediate-release)
metformin until renal function returns to normal); 30 mg and 60 mg MR tablet
Use of general anesthesia (suspend metformin on the
morning of surgery and restart when renal function A second-generation sulfonylurea, which acts by increasing
returns to normal); the pancreatic insulin secretion. Elevated insulin levels
Monitor renal function before treatment and once or twice are only seen with acute exposure to the drug.
annually;
Substitute insulin during severe infection, trauma, or Indication: Management of type 2 diabetes mellitus
surgery;
Severe renal and hepatic impairment; Contraindications: Type 1 diabetes mellitus (insulin-
Moderate-to-severe heart failure; dependent, IDDM); diabetic ketoacidosis; diabetic
Surgery (stop metformin before surgery; monitor plasma precoma and coma; severe renal or hepatic impairment;
glucose concentration; restart when patient is no longer stress conditions (e.g., serious infection, trauma,
fasting and renal function has recovered); surgery); porphyria; pregnancy; breastfeeding;
Pregnancy (avoid use during all trimesters; may be given for sulfonamide “sulfa” allergy (risk of cross-reaction);
pregnant women previously diagnosed with PCOS as
prescribed by the physician); Dose:
Lactation (monitor infant). NOTE: There is no fixed-dosage regimen for the
management of diabetes mellitus with gliclazide.
Adverse Drug Reactions: Individualize doses based on frequent blood glucose
Common: Abdominal pain, anorexia, asthenia, diarrhea, monitoring during dose titration and throughout
disturbance in taste, dyspepsia, headache, indigestion, maintenance.
flatulence, metallic taste, nausea, upper respiratory tract
infection, vitamin B12 malabsorption, vomiting Type 2 diabetes, by mouth, ADULT,
Less Common: Erythema, pruritus, rash, urticaria as modified-release tablet, initially 30 mg once daily,
Rare: Acute hepatitis, lactic acidosis titrate in 30 mg increments every 2 weeks based on
blood glucose levels (maximum, 120 mg once daily);
Drug Interactions: as immediate-release tablet, initially 80 mg twice daily,
Monitor closely with: titrate based on blood glucose levels, usual dosage
Enhances therapeutic effect of Metformin: range, 80-320 mg daily (maximum, 320 mg daily);
Alcohol (decreases blood glucose concentration); dosage of ≥160 mg should be divided into 2 equal parts
Enalapril (hypoglycemic effect) for twice-daily administration.

Increases risk of adverse or toxic effects of Metformin: Dose Adjustment:

Alcohol (hypoglycemia; masks warning symptoms); Beta Renal Impairment:
Blockers e.g. Propranolol (masks warning signs of In severe renal impairment, avoid use.
hypoglycemia; increases risk of lactic acidosis), Drugs
increasing blood glucose concentration, e.g., Precautions:
Glucocorticoids, Antipsychotics, Calcineurin Inhibitors, Acute illness, including MI, coma, trauma, or infection;
High-dose Thiazide Diuretics (alters diabetes control of Hypoglycemia;
insulin) G6PD deficiency;
Nifedipine (impairs glucose tolerance); Renal impairment;
Thiazolidinediones (increases risk of edema and heart Severe hepatic disease;
failure) Stress-related states e.g. surgery.
Elderly;
Reduces therapeutic effect of Metformin: Pregnancy;
Drugs increasing blood glucose concentration, e.g., Lactation (monitor infants).
Glucocorticoids, Antipsychotics, Calcineurin Inhibitors,
High-dose Thiazide Diuretics Adverse Drug Reactions:
Common: Dizziness, hypoglycemia, weight gain
Avoid concomitant use with: Less Common: Abdominal pain, angina pectoris, arthralgia,
Reduces therapeutic effect of Metformin: arthrosis, back pain, bronchitis, constipation, cough,
Contraceptives (Oral); Furosemide Hydrocortisone diarrhea, dyspepsia, headache, hypertension, metallic
taste, nausea, rash, rhinitis, upper respiratory infection,
Administration: Take with meals to reduce stomach upset. urinary tract infection, viral infection, vomiting
Rare: Allergic reactions, blood disorders, erythema
Pregnancy Category: B multiforme, exfoliative dermatitis, fever, hepatic failure,
hepatitis, jaundice, malaise, photosensitivity, Stevens-
ATC Code: A10BA02 Johnson syndrome

25
 ALIMENTARY TRACT AND METABOLISM

Drug Interactions:
Monitor closely with:
Enhances adverse effect of the following drugs: VITAMINS
A

Alcohol (flushing reaction; decreases blood glucose

concentration), Beta Blockers [except Levobunolol,
MULTIVITAMINS, PLAIN
Metipranolol] (may mask symptoms of hypoglycemia),
Carbocisteine (may enhance adverse effects of alcohol
present in liquid formulations), Porfimer, Verteporfin OTC MULTIVITAMINS
(photosensitizing effect)

Enhances hypoglycemic effect of Gliclazide: Oral:

Alcohol (masks warning symptoms, Alpha-Lipoic Acid; For infants, drops, per 1 mL contains:
Androgens [except Danazol]; Antidiabetic Agents; Beta Vitamin A 325–380 micrograms RE
Blockers [except Levobunolol, Metipranolol]; Cyclic Vitamin B1 0.2–0.4 mg
Antidepressants; Fibric Acid Derivatives Vitamin B2 0.3–0.4 mg
Hypoglycemia-associated Agents; MAO Inhibitors; Vitamin B6 0.3–0.6 mg
Miconazole; Pegvisomant Vitamin B12 0.3–0.4 micrograms
Quinolone Antibiotics; Salicylates; SSRIs; Sulfonamide Vitamin C 30 mg
Derivatives; Vitamin K Antagonists, e.g., Warfarin Vitamin D 200 – 400 IU (5 - 10 micrograms)
Enhances therapeutic effect Vitamin K Antagonists, e.g., Vitamin E 3–4 mg
Warfarin (anticoagulant effect) Folic Acid 20–65 micrograms
Niacin 1–5 mg
Increases risk of adverse or toxic effects of Gliclazide:
Dexketoprofen For children, syrup, per 5 mL contains:
Reduces therapeutic effect of Gliclazide: Vitamin A 350–400 micrograms RE
Corticosteroids, systemic, Hyperglycemia-associated Vitamin B1 0.5–1.0 mg
Agents, Loop Diuretics (hypoglycemic effect), Quinolone Vitamin B2 0.7–0.9 mg
Antibiotics (loss of blood sugar control may occur), Vitamin B6 0.9–1.6 mg
Thiazide Diuretics Vitamin B12 0.9–3.0 micrograms
Vitamin C 35–55 mg
Avoid concomitant use with: Vitamin D 200 – 400 IU (5 - 10 micrograms)
Decreases serum concentration of Gliclazide: Vitamin E 5–7 mg
CYP2C9 Inducers, Dabrafenib, Rifampin Folic Acid 40–300 micrograms
Niacin 5–18 mg
Enhances hypoglycemic effect of Gliclazide:
DPP-IV Inhibitors, Glucagon-like Peptide-1 Agonists / For adults, tablet or capsule, each tablet / capsule contains:
GLP­1 Agonists, Sodium Glucose Cotransporter Inhibitors Vitamin A 600–700 micrograms RE
/ SGLT2 Inhibitors (consider dose reduction of (2000 – 2500 IU)
gliclazide), Thiazolidinedione Vitamin B1 1.3–1.7 mg
Vitamin B2 0.7–1.3 mg
Increases risk of adverse or toxic effects of Gliclazide: Vitamin B6 1.6–2 mg
CYP2C9 Inhibitors, Fluconazole, (hypoglycemia) Vitamin B12 2–6 micrograms
Vitamin C 60–80 mg
Increases risk of adverse or toxic effects of Mecamylamine Vitamin D 400 IU (10 micrograms)
Vitamin E 6–10 mg (15 – 30 IU)
Increases serum concentration of Gliclazide: Folic Acid 400 micrograms
CYP2C9 Inhibitors, Fluconazole, Mifepristone (monitor Niacin 13–23 mg
closely for adverse effects, during and in the 2 weeks
following mifepristone treatment) A dietary supplement containing essential multivitamins
and minerals that are needed for good health, growth,
Reduces therapeutic effect of Gliclazide: and development.
Dabrafenib, Rifampin
Indications: Dietary supplementation, management of
Administration: vitamin deficiencies
Take immediate-release tablets before meals.
Contraindications: Known hypersensitivity to any
Take MR tablets with food to minimize the risk of component of the preparations
hypoglycemia.
Dose:
Pregnancy Category: C Prevention or treatment of vitamin deficiencies, by mouth,
ADULT, 1 tablet or capsule daily.
ATC Code: A10BB09
Precautions:
Avoid taking similar vitamin products.

26
ALIMENTARY TRACT AND METABOLISM

NOTE: Not all products can be used in children of all age manifesting as hypocalcemia, by mouth, ADULT,
groups. Consult specific product labeling prior to use. Do ADOLESCENT, and CHILD ≥6 years, initially 0.25
NOT exceed recommended doses. micrograms once daily in the morning; may be increased

A
at 2– to 4–week intervals; maintenance, 0.5-2
Drug Interactions: micrograms once daily; CHILD 1-5 years, 0.25-0.75
Decreases serum concentration of certain components of micrograms daily; NEONATE and INFANT, 0.25
Multivitamins: micrograms daily.
Food, e.g., eggs, milk (inhibits absorption of iron) Vitamin D-dependent rickets, by mouth, ADULT,
ADOLESCENT, and CHILD, 1 microgram once daily.
Administration: May be taken with or without food. Postmenopausal osteoporosis, by mouth,
POSTMENOPAUSAL FEMALES, 0.25 micrograms twice
May be taken with meals for better absorption or if GI daily; modify dose according to serum calcium
discomfort occurs. concentration.
Osteoporosis, by mouth, CHILD, 1-2 micrograms/kg daily
Pregnancy Category: Not available given in 4-6 divided doses.

ATC Code: A11BA Precautions:

WARNING: Administration of more than the daily
requirement can cause hypercalcemia,
VITAMIN A AND D hypercalciuria, and hyperphosphatemia.

Rx CALCITRIOL Renal impairment;

Hepatic and biliary disease;
Excessive doses;
Oral: 0.25 micrograms capsule Immobilized patients.
Also known as 1,25­dihydroxy-cholecalciferol, it is the active Adverse Drug Reactions:
form of vitamin D3 (cholecalciferol). Calcitriol is Common: Hypervitaminosis D, hypercalcemia, fatigue,
structurally similar to calcifediol and plays an important weakness, headache, nausea, vomiting, abdominal pain,
role in maintaining calcium balance and in the regulation constipation, diarrhea, vertigo, tinnitus, ataxia, myalgia,
of parathyroid hormone (PTH). It is the preferred form for arthralgia, irritability, hypercalciuria,
the management of hypocalcemia in dialysis-dependent hyperphosphatemia, metallic taste.
renal failure patients.
Drug Interactions:
Indications: Management of Hypocalcemia due to Monitor closely with:
secondary hyperparathyroidism, and resultant metabolic Decreases intestinal absorption of Calcitriol:
bone disease; hypocalcemia associated with vitamin D Cholestyramine, Colestipol, Mineral Oil, Orlistat
deficiency; postsurgical hypoparathyroidism; vitamin D-
dependent rickets; postmenopausal osteoporosis and Increases risk of adverse or toxic effects of the following
osteoporosis drugs:
Calcium-containing Antacids (hypercalcemia); Cardiac
Contraindications: Accidental exposure; arteriosclerosis; Glycosides, e.g., Digoxin (hypercalcemia; cardiac
breastfeeding; cardiac disease; dehydration; geriatric; arrhythmias)
hypercalcemia; hyperphosphatemia; hypervitaminosis D;
occlusive dressing; ocular exposure; pregnancy; renal Reduces therapeutic effect of Calcitriol:
failure; sarcoidosis; sunlight (UV) exposure Anticonvulsants, e.g., Phenobarbital, Primidone,
Phenytoin, Fosphenytoin
Dose:
NOTE: Serum calcium, phosphorus, alkaline phosphatase, Avoid concomitant use with:
and creatinine concentrations should be determined Increases risk of adverse or toxic effects of Calcitriol:
initially, monthly for 6 months, then periodically. Serum Phosphorus Salts
PTH should be monitored initially and every 3–4 months.
Increases risk of adverse or toxic effects of the following
Hypocalcemia, secondary hyperparathyroidism, and drugs:
resultant metabolic bone disease (renal osteodystrophy) Aluminum-containing Antacids (aluminum retention and
in patients with chronic kidney disease, by mouth, toxicity); Vitamin D Analogues (additive effects and
ADULT, initially 0.25 micrograms daily; may increase toxicity)
dose to 0.5 micrograms daily if necessary; titrate doses
as necessary to obtain target range; ADOLESCENT and Administration: May be administered without regard to
CHILD 1-2 years, initially 0.25 micrograms daily. meals. Protect from light.
Management of hypocalcemia associated with vitamin D
deficiency, by mouth, ADOLESCENT, CHILD, and INFANT, NOTE: Patients must receive an adequate amount of
0.05 micrograms/kg daily (maximum, 0.5 micrograms calcium while taking Calcitriol. Advise patients to have a
daily) until calcium levels normalize. dietary intake of calcium of at least 600 mg daily.
Postsurgical hypoparathyroidism, idiopathic
hypoparathyroidism, and pseudohypoparathyroidism

27
 ALIMENTARY TRACT AND METABOLISM

Calcitriol is readily absorbed from the intestine. Precautions:

Absorption can be delayed in patients with hepatic,
biliary, or GI disease. WARNING: Severe congenital malformations may occur
in infants of mothers consuming large amounts of
A

Pregnancy Category: C oral retinoids for acne treatment.

ATC Code: A11CC04 Patients on prolonged daily administration over 25,000 IU

should be under close supervision;
Chronic intake of vitamin A at levels 10–20 times the RDA
can lead to hypervitaminosis A;
Rx RETINOL (VITAMIN A) Pregnancy (excessive doses during the first trimester may
be teratogenic);
Oral: 10,000 IU, 25,000 IU, and 50,000 IU soft gel capsule Breastfeeding (there is theoretical risk of toxicity in infants
(as palmitate) of mothers taking large doses).
100,000 IU and 200,000 IU soft gel capsule with
nipple (as palmitate) [only for DOH program] NOTE: Dietary reference intakes (DRIs): Tolerable upper
intake level (UL) for adults is 3,000 micrograms daily of
A fat-soluble vitamin and dietary supplement that is preformed vitamin A, based on teratogenicity as the
required by the eyes for the transduction of light into critical adverse effect for women of childbearing age and
neural signs necessary for vision. liver pathology for all other adults.

Indications: For the prevention and treatment of vitamin A Adverse Drug Reactions:
deficiency states (e.g., xerophthalmia and night Less Common: Diplopia, headache, nausea, symmetric
blindness); prevention of complications of measles. papilledema, vomiting
Rare: Birth defects (e.g., tense and bulging fontanelle in
Contraindications: Hypervitaminosis A; known infants), dry hair, enlarged liver, increased intracranial
hypersensitivity to vitamin A, or any component of the pressure
formulation; dosages exceeding the Recommended
Energy and Nutrient Intake (RENI); women who are, or Drug Interactions:
may become, pregnant. Monitor closely with:
Increases therapeutic effect of Warfarin (anticoagulant
Dose: effect)
Prevention of vitamin A deficiency (universal or targeted
distribution programs), by mouth, ADULT, 200,000 IU Avoid concomitant use with:
every 6 months; ADULT (pregnant woman), maximum of Decreases absorption of Retinol:
10,000 IU daily or maximum 25,000 IU weekly; ADULT Bile Acid–binding Resins, e.g., Cholestyramine,
(woman of childbearing age), 200,000 IU at delivery or Colestipol
within 8 weeks of delivery; CHILD >1 year (preschool),
200,000 IU every 4–6 months; INFANT 6–12 months, Increases risk of adverse or toxic effects of the following
100,000 IU every 4–6 months, preferably at measles drugs:
vaccination; INFANT <6 months, 50,000 IU. [NOTE: Retinoid Drugs, e.g., Acitretin, All-trans-retinoic Acid,
Administer an additional dose the next day in Isotretinoin (hypervitaminosis A); Tetracyclines (benign
hospitalized children with measles infection.] intracranial hypertension)
Treatment of xerophthalmia, by mouth, ADULT (except
woman of childbearing age) and CHILD >1 year, 200,000 Administration: This vitamin is absorbed along with fat in the
IU on diagnosis, repeated the next day and again after 2 diet. Take it with food.
weeks; ADULT (woman of childbearing age with severe
signs of xerophthalmia), as for other adults; ADULT Pregnancy Category: A; X if dose is greater than RENI
(woman of childbearing age with less severe symptoms,
e.g., night blindness), either 5,000 to 10,000 IU daily for ATC Code: A11CA01
at least 4 weeks or up to 25,000 IU weekly; INFANT 6–
12 months, 100,000 IU immediately on diagnosis,
repeated the next day and again after 2 weeks; INFANT
under 6 months, 50,000 IU on dis, repeat the next day
and again after 2 weeks. [NOTE: Oral vitamin A
preparations are preferred for the prevention and
treatment of vitamin A deficiency.]

Dose Adjustment:
Pregnant women susceptible to vitamin A deficiency during
the third trimester:
Should be given low dose vitamin A supplements on a daily
or weekly basis.

28
ALIMENTARY TRACT AND METABOLISM

VITAMIN B1, PLAIN AND IN COMBINATION WITH Hepatic impairment; Lactation (not known if excreted in
VITAMIN B6 AND B12 breastmilk).

A
Adverse Drug Reactions:
(Oral) OTC Common: Sneezing, pruritus (generalized), warmth,
(Inj.) Rx
THIAMINE (VITAMIN B1)
urticaria, weakness, diaphoresis, nausea, restlessness,
tightness of throat, angioedema, cyanosis, pulmonary
Oral: 100 mg and 300 mg tablet (as hydrochloride) edema, GI bleeding, injection site reaction
Inj.: 100 mg/mL, 1 mL ampule / vial (IV) Rare: Hypersensitivity reactions
100 mg/mL, 10 mL vial (as hydrochloride) (IM, IV)
Drug Interactions:
A water-soluble vitamin found in yeast, cereal grains, Avoid concomitant use with:
legumes, peas, nuts, pork, and beef. It is used to prevent Decreases serum concentration of Thiamine:
peripheral neuritis associated with pellagra (Vitamin B3 Ethyl Alcohol, Chronic Consumption (results in deficiency
deficiency) and pregnancy. It combines with adenosine of several nutrients)
triphosphate (ATP) to form thiamine pyrophosphate, an
essential coenzyme in carbohydrate metabolism. Administration:
For oral administration, may be taken without regards to
Indications: Management of beriberi (Vitamin B1 deficiency, meals.
maple syrup urine disease (MSUD) and Wernicke /
Korsakoff syndrome; nutritional supplementation. Parenteral administration is reserved for patients for
which oral thiamine is not feasible.
Contraindications: Breast-feeding; encephalopathy;
pregnancy Inspect visually for particulate matter and discoloration
prior to administration.
Dose:
Nutritional supplementation, by mouth, ADULT and For slow IV push, no dilution is necessary.
ADOLESCENT (pregnant or lactating female), 1.4 mg
daily; ADULT and ADOLESCENT (male), 1.2 mg daily; For continuous IV infusion, dilute thiamine in a
ADULT (female), 1.1 mg daily; ADOLESCENT (females), 1 compatible infusion solution. Administer at a rate
mg daily; CHILD 9–13 years, 0.9 mg daily; CHILD 4-8 prescribed by the physician.
years, 0.6 mg daily; CHILD 1–3 years, 0.5 mg daily;
INFANT 7–12 months, 0.3 mg daily; INFANT 0–6 months, Pregnancy Category: A
0.2 mg daily.
Prevention of thiamine deficiency in patients receiving total ATC Code: A11DA01
parenteral nutrition (TPN), by IV injection, ADULT, 3 mg
daily admixed with TPN.
Beriberi, by mouth, ADULT, 5–30 mg once daily or in 3
(Oral) OTC
divided doses for 1 month; CHILD and INFANT, 10–50
(Inj.) Rx
VITAMIN B1 B6 B12
mg once daily for 2 weeks, then 5-10 mg once daily for 1
month;
by IV or IM injection, ADULT, initially 5–30 mg once daily Oral: 100 mg B1 + 5 mg B6 + 50 micrograms B12 per tablet
or in 3 divided doses, then convert to oral route once / capsule
patient is taking PO (total treatment duration, 1 month); 10 mg B1 + 5 mg B6 + 5 micrograms B12 per 0.6 mL
CHILD and INFANT, 10–25 mg daily for 2 weeks, then 5– drops, 15 mL
Inj.: 100 mg B1 + 100 mg B6 + 1 mg B12 per 3 mL, ampule
10 mg once daily for 1 month. [NOTE: If beriberi occurs
in a breast-fed infant, both lactating mother and infant (IV)
should receive treatment.] 100 mg B1 + 100 mg B6 + 1 mg B12 per mL, 10 mL
Wernicke/Korsakoff Syndrome, by IV or IM injection, ADULT, vial (IV)
initially 100 mg, followed by 50–100 mg daily until
normal dietary intake is established (clinical practice A dietary supplement, which contains vitamins B1, B6, and
guidelines recommend 200–500 mg 3 times daily for 5– B12 for nerve cell metabolism, and for vitamin B-complex
7 days or until there is no further improvement in deficiencies.
symptoms).
Metabolic disorders including necrotizing Indications: Prevention and treatment of vitamin B complex
encephalomyelopathy, maple syrup urine disease deficiencies; adjunct in the management of
(MSUD), and lactic acidosis associated with pyruvate neuromuscular pain responsive to vitamin B1, B6, and
carboxylase deficiency, by mouth, ADULT, 10–20 mg B12, including neuralgia, neuritis and neuropathies.
daily as a single dose, up to 4 g daily in divided doses.
Contraindications: Leber’s disease or tobacco amblyopia;
Precautions: known hypersensitivity to any component of the
formulation.
WARNING: Serious hypersensitivity or anaphylactic
reactions can occur, especially after repeated Dose:
administration. Prevention and treatment of vitamin B complex deficiency,
by mouth, ADULT, 1–2 tablets or capsules daily; by slow
IV injection, ADULT, 0.25–2 mL.

29
 ALIMENTARY TRACT AND METABOLISM

Precautions: once daily; CHILD 1–3 years, 15 mg once daily; INFANT,

Vitamin B12 >10 micrograms daily may produce 40–50 mg once daily.
hematological response in folic acid deficiency. Scurvy, by mouth, ADULT, 100–250 mg 1–2 times daily;
A

Neurotoxicity (long-term administration of large doses >2 g CHILD, 100–300 mg daily in divided doses; INFANT, 50–
daily) 100 mg daily in divided doses.
Malabsorption; Anemia; Neuropathy; Undiagnosed vitamin Adjunct to deferoxamine therapy in the treatment of chronic,
B12 deficiency. iron toxicity, by mouth, ADULT, 100–200 mg once daily
initiated 1–2 hours after deferoxamine infusion is
Adverse Drug Reactions: started.
Less Common: Headache, peripheral neuropathy (high Chronic recurrent furunculosis in patients with neutrophil
doses) dysfunction, by mouth, ADULT, 1,000 mg daily for 4–6
Rare: Hypersensitivity reactions weeks [NOTE: Studies show that ascorbic acid does not
alter the course of furunculosis in patients without
Drug Interactions: neutrophil dysfunction].
Avoid concomitant use with:
Decreases therapeutic effect of Levodopa Dose Adjustment:
Renal Impairment:
Administration: Removed by hemodialysis. Adjust dosing accordingly.
For oral administration, may be taken with or without For patients receiving intermittent hemodialysis, doses
food. May be taken with meals to reduce GI discomfort. greater than 200 mg daily are not recommended.

High concentration IV solutions may be diluted using Precautions:

parenteral infusion solutions Heart failure (do not administer concurrently with
deferoxamine without approval of their health care
Pregnancy Category: A; C (doses greater than RENI) professional);
Hyperoxaluria;
ATC Code: A11DB Renal impairment;
Lactation

ASCORBIC ACID (VITAMIN C) Adverse Drug Reactions:

Common: Renal tubular obstruction (oxalate, urate, or
cystine renal stones), lower back pain (costovertebral),
OTC ASCORBIC ACID (VITAMIN C) hyperoxaluria, flushing, headache, nausea, vomiting,
abdominal cramps, diarrhea, flatulence, heartburn,
dental caries (chewable tablets), fatigue, insomnia,
Oral: 100 mg and 500 mg tablet
sleepiness
100 mg/mL drops, 15 mL and 30 mL
Less Common: Hemolytic anemia
100 mg/5 mL syrup, 60 mL and 120 mL
Rare: Sickle-cell crisis
Inj.: 250 mg/mL, 2 mL ampul (IV)
Drug Interactions:
A water-soluble vitamin that acts as a free radical, an
NOTE: Decreases urine pH, which may cause an increase in
antioxidant scavenger, and plays a major role in
the excretion of alkaline drugs and an increase in renal
oxidation-reduction reactions. Ascorbic acid is a cofactor
tubular reabsorption of acidic compounds.
for enzymes involved in the biosynthesis of collagen,
carnitine, and neurotransmitters.
Monitor closely with:
Decreases therapeutic effect of the following drugs:
Indications: Nutritional supplementation; management of
Mexiletine;
iron toxicity, scurvy and furunculosis
Propranolol [take ascorbic acid at least 1 hour prior to
propranolol] (bradycardic effect)
Contraindications: Anemia, breastfeeding, diabetes
mellitus, G6PD deficiency, hemochromatosis,
Increase absorption of the following drugs:
nephrolithiasis, pregnancy, sideroblastic anemia,
Iron Salts, Polysaccharide-Iron Complex
sodium restriction, sulfite hypersensitivity, tartrazine dye
hypersensitivity, thalassemia
Avoid concomitant use with:
Decreases therapeutic effect of the following drugs:
Dose:
Disulfiram; Warfarin (anticoagulation effects)
Nutritional supplementation, by mouth, ADULT (male), 90
mg once daily, or 100 mg once or twice daily; ADULT
Increases risk of adverse or toxic effects of the following
(female), 75 mg once daily, or 100 mg once or twice
drugs:
daily; ADULT and ADOLESCENT (pregnant female), 80-85
Deferoxamine (e.g., impairment of cardiac function,
mg once daily; ADULT and ADOLESCENT (lactating
causing cardiac decompensation)
female), 115–120 mg once daily; ADULT (male
smokers), 125 mg once daily; ADULT (female smokers),
Administration: May be taken without regard to meals.
110 mg once daily; ADOLESCENT (male), 75 mg once
Administer with a full glass of water.
daily; ADOLESCENT (female), 65 mg once daily; CHILD 9–
13 years, 45 mg once daily; CHILD 4–8 years, 25 mg
Pregnancy Category: C

30
ALIMENTARY TRACT AND METABOLISM

ATC Code: A11GA01 Adverse Drug Reactions: Flushing, malaise, erythema,

pruritus, rash, bronchospasm, allergic reaction

A
OTHER PLAIN VITAMIN PREPARATIONS Drug Interactions:
Avoid concomitant use with:
Reduces therapeutic effect of Raltitrexed
Rx FOLIC ACID
Administration: May be administered by deep IM injection.
Oral: 400 micrograms, 800 micrograms, 1 mg and For IV injection or infusion, administer ≤5 mg dose
5 mg tablet / capsule undiluted over ≥1 minute or dilute ≤5 mg in 50 mL of NS
2.5 mg/mL pediatric drops or D5W and infuse over 30 minutes. May be added to IV
5 mg/5 mL syrup maintenance solutions and given as an infusion.
Also known as Vitamin B9, it is reduced in the body to Pregnancy Category: A
tetrahydrofolate, which is a coenzyme for various
metabolic processes, including the synthesis of purine ATC Code: Not available
and pyrimidine nucleotides, and hence in the synthesis
of DNA. It is also involved in some amino acid
conversions, and in the formation and utilization of
formate. Folic acid is also used in women of child­bearing Rx MECOBALAMIN
potential and pregnant women to protect against neural
tube defects in their offspring.
Oral: 500 micrograms tablet
Indications: Treatment of megaloblastic and macrocytic Inj.: 500 micrograms/mL, 1 mL ampule (IM, IV)
anemias due to folate deficiency; used for diarrhea in
pediatric patients Vitamin B12, a water-soluble vitamin, occurs in the body
mainly as methylcobalamin (mecobalamin), and as
adenosylcobalamin (cobamamide) and
Contraindication: Hypersensitivity to folic acid or any
hydroxocobalamin. Mecobalamin and cobamamide act
component of the formulation
as coenzymes in nucleic acid synthesis. Mecobalamin is
Dose: also closely involved with folic acid in several important
Anemia, by mouth, IV, IM, or SC injection, ADULT, 0.4 mg metabolic pathways.
daily; PREGNANT AND LACTATING WOMEN, 0.8 mg daily;
CHILD <4 years, up to 0.3 mg daily; INFANT, 0.1 mg daily. Indications: Symptomatic treatment of peripheral
Adequate intake (expressed as folate equivalents), by neuropathy associated with vitamin B12 deficiency (e.g.,
mouth, INFANT 7–12 months, 80 micrograms daily; numbness, pain, paralysis), including diabetic
INFANT 1–6 months, 65 micrograms daily. neuropathy and polyneuropathy and megaloblastic
Recommended daily allowance, RDA (expressed as dietary anemia associated with vitamin B12 deficiency.
folate equivalents), by mouth, ADULT, 400 micrograms
daily; PREGNANT WOMEN, 600 micrograms daily; Dose:
LACTATING WOMEN, 500 micrograms daily; CHILD 9–13 Peripheral neuropathy, by mouth, ADULT, 500 micrograms
years, 300 micrograms daily; CHILD 4–8 years, 200 3 times daily;
micrograms daily; CHILD 1–3 years, 150 micrograms by IV or IM injection, ADULT, 500 micrograms 3 times
weekly.
daily.
Megaloblastic anemia, by IV or IM injection, ADULT, initially
Dose Adjustment: 500 micrograms 3 times weekly; (maintenance dose
Geriatric: given after approximately 2 months of treatment, 500
Vitamin B12 deficiency must be ruled out before initiating micrograms every 1–3 months).
folate therapy due to frequency of combined nutritional
deficiencies. RDA requirements, 400 micrograms daily Precautions:
(minimum, 0.4 mg). Anaphylactoid reactions;
CNS effects;
Precautions: Hypokalemia;
Anemia (not appropriate for monotherapy with pernicious, Thrombocytosis;
aplastic, or normocytic anemias when anemia is present Pregnancy and lactation (vitamin B12 requirements may be
with vitamin B12 deficiency); pernicious anemia (doses increased).
>0.1 mg daily may obscure pernicious anemia with
continuing irreversible nerve damage progression); Adverse Drug Reactions:
Depressed hematopoiesis, alcoholism, and deficiencies of Common: Decreased blood pressure, diaphoresis,
other vitamins. induration at injection site, pain at injection site,
Elderly; dyspnea.
Neonates;
Lactation (excreted in breastmilk; increased folate Drug Interactions:
requirement).
Monitor closely with:
Decreases therapeutic effect of Mecobalamin:
Chloramphenicol

31
 ALIMENTARY TRACT AND METABOLISM

Administration: Administer immediately after removing from Adverse Drug Reactions:

package to limit direct exposure to light. Common: Erythema, flushing, nausea, pain, tenderness,
tiredness, vomiting, warmth sensation
For IM administration, avoid multiple injections at the Less Common: Allergic reactions (including anaphylaxis),
A

same site. Do NOT inject near highly innervated regions. bradycardia, bronchospasm, dizziness, dyspnea,
hypotension, rebound bleeding
NOTE: Do NOT use for more than 1 month without clear Rare: Anaphylactoid reactions, hemolytic anemia,
signs of clinical improvement. Avoid long term use in hyperbilirubinemia, kernicterus
patients regularly exposed to mercury or mercury
compounds. Drug Interactions:
Monitor closely with:
Pregnancy Category: C Decreases therapeutic effect of Phytomenadione:
Anticonvulsants, e.g., Phenobarbital, Phenytoin, Anti-
ATC Code: Not available tuberculosis Drugs, e.g., Isoniazid, Rifampicin (may
cause vitamin K deficiency bleeding on the first day of
life in newborns)
PHYTOMENADIONE
Rx Avoid concomitant use with:
(PHYTONADIONE, VITAMIN K1)
Decreases therapeutic effect of the following drugs:
Anticoagulants, e.g., Warfarin (increases synthesis of
Oral: 2 mg/0.2 mL pediatric ampule (as mixed micelle)
blood clotting factors)
Inj.: 2 mg/0.2 mL pediatric ampule (as mixed micelle) (IM,
IV)
Administration: IV administration should be slow, over 30
10 mg/mL, 1 mL ampule (as mixed micelle) (IM, IV,
seconds. Rapid infusion can cause dyspnea, chest pain,
SC)
and back pain.
10 mg/mL, 1 mL ampule (as aqueous colloidal
solution with benzyl alcohol) (IM, IV, SC)
Pregnancy Category: C; X in 3rd trimester or near term
A fat-soluble vitamin that is an essential cofactor in the
ATC Code: Not available
synthesis of blood coagulation factors: prothrombin (II),
proconvertin (VII), plasma thromboplastin component
(IX), Stuart factor (X), and proteins C and S.
OTC PYRIDOXINE (VITAMIN B6)
Indications: Management of anticoagulant-induced
prothrombin deficiency caused by indanedione or
coumarin derivatives such as warfarin; treatment and Oral: 100 mg tablet (as hydrochloride)
prophylaxis against hemorrhagic disease of the newborn.
A naturally occurring, water-soluble vitamin. It is converted
Contraindications: Known hypersensitivity to in erythrocytes to its active moiety, pyridoxal phosphate,
phytomenadione or any component of the formulation; which acts as coenzymes in metabolic processes,
avoid IM if bleeding; pregnancy (3rd trimester); it is not including metabolism of fat, protein, and carbohydrate.
effective in hereditary hypoprothrombinemia caused by
liver disease. Indications: Nutritional supplementation; Management of
cystathionuria, management of homocystinuria,
Dose: hyperoxaluria, neuritis, pregnancy-inducednausea and
Prophylaxis of hemorrhagic disease of the newborn, by IM vomiting, premenstrual syndrome (PMS), pyridoxine-
injection, NEONATE, 0.5-1 mg as single dose; dependent seizures, sideroblastic anemia, vitamin B6
by mouth, NEONATE, 2 mg followed by a second dose deficiency and xanthurenic aciduria.
after 4-7 days and for breastfed babies a third dose after
1 month. Contraindications: Breastfeeding, pregnancy, premature
Treatment of hemorrhagic disease of the newborn, by slow neonates, renal impairment.
IV or IM injection, NEONATE, 1 mg (with further doses if
necessary, at 8-hour intervals). Dose:
Nutritional supplementation, by mouth, ADULT and
Dose Adjustment: ADOLESCENT (pregnant female), 1.9 mg daily; ADULT
Geriatric: and ADOLESCENT (lactating female), 2 mg daily; ADULT
Dose should be at the lower end of the recommended (male ≥51 years), 1.5 mg daily; ADULT (female ≥51
range. years), 1.7 mg once daily; ADULT, 1.3 mg daily;
ADOLESCENT (male), 1.3 mg daily (RDA); ADOLESCENT
Hepatic Impairment: (female), 1.2 mg daily (RDA); CHILD 9-13 years, 1 mg
For mild-to-moderate impairment, use with caution. daily (RDA); CHILD 4-8 years, 0.6 mg daily (RDA); CHILD
For severe impairment, refer patient to a specialist. 1-3 years, 0.5 mg daily (RDA); INFANT >6 months, 0.3 mg
Precautions: daily (weight-based dosing is approximately 0.033
Hepatic impairment; Elderly. mg/kg daily); INFANT ≤6 months and NEONATE, 0.1 mg
NOTE: Fat-soluble Vitamin. Patients with fat malabsorption, daily (weight-based dosing is approximately 0.014
especially in biliary obstruction or hepatic disease may mg/kg daily); PREMATURE NEONATE, 150 TO 210
become Vitamin K deficient. micrograms/kg daily.

32
ALIMENTARY TRACT AND METABOLISM

Vitamin B6 deficiency including neuritis (not drug-induced),

by mouth, ADULT (without neuritis), 2.5-10 mg daily; may MINERAL SUPPLEMENTS
be adjusted to 2-5 mg daily once deficiency has been

A
corrected; ADULT (with neuritis), 100-200 mg daily for 3
CALCIUM
weeks, then 25-100 mg daily thereafter; CHILD (without
neuritis), 5-25 mg daily for 3 weeks, then 1.5-2.5 mg
daily (may be supplemented in a multivitamin product); GENERAL INFORMATION
CHILD (with neuritis), 10-50 mg daily for 3 weeks, then
1-2 mg daily (may be supplemented in a multivitamin An essential cation for the maintenance of the nervous,
product. muscular, and skeletal systems, as well as for cell
Sideroblastic anemia, by mouth, ADULT, 200-600 mg daily; membrane and capillary permeability. It is the primary
following an adequate response, 30-50 g daily may be component of skeletal tissue, providing structural
used. integrity and support for individual growth.
Selected metabolic disorders, including primary
cystathioniuria, primary homocystinuria, or xanthurenic Indications: Cardiac arrest; cardiopulmonary resuscitation;
aciduria, by mouth, ADULT, 100 to 500 mg daily or more, exchange transfusion-induced hypocalcemia
adjusted to clinical response; CHILD, 200-1000 mg daily, prophylaxis; hyperkalemia; hypermagnesemia;
adjusted to clinical response. hyperphosphatemia; hypocalcemia; nutritional
Primary hyperoxaluria, in combination with oral supplementation; osteoporosis prophylaxis.
orthophosphate therapy, by mouth, ADULT and CHILD,
initially 1.8-7 mg/kg daily with a final dose of 1-7 mg/kg Contraindications: Breastfeeding; cardiac arrhythmias;
daily. dehydration; digitalis toxicity; extravasation;
Premenstrual syndrome (PMS), by mouth, ADULT, 80-500 hypercalcemia; hypercalciuria; necrotizing enterocolitis;
mg daily. hyperphosphatemia; hypoparathyroidism; pregnancy;
Pregnancy-induced nausea / vomiting, by mouth, ADULT, sarcoidosis; ventricular fibrillation; diarrhea; vitamin D
10-25 mg 3 times daily; ADOLESCENT, 25-100 mg daily; toxicity.
CHILD, 1-2 mg daily.
Pyridoxine-dependent seizures, maintenance, by mouth, Dose Adjustment:
CHILD, INFANT, and NEONATE, initially 5 mg/kg once or Renal Impairment:
divided twice daily; titrate as needed to suppress In end-stage renal disease, administer with meals (e.g., 10–
seizures. 15 minutes before or during).

Precautions: Adverse Drug Reactions:

Seizures (associated with high-dose administration). Common: Mild to severe local irritation, chalky taste,
flushing, tingling sensation, hypotension (dizziness,
Adverse Drug Reactions: syncope), sinus bradycardia, cardiac arrhythmias,
Common: Nausea, vomiting, headache, paresthesia, cardiac arrest, diarrhea, gastric irritation.
hyperesthesia, somnolence, low serum folic acid levels, Less Common: Milk-alkali syndrome, muscle cramps
peripheral neuropathy.
Less Common: Neuronopathy syndrome, unstable gait, Drug Interactions:
perioral numbness, “stocking-globe” sensory loss, Monitor closely with:
seizures, metabolic acidosis. Decreases absorption of Calcium:
Corticosteroids
Drug Interactions:
Monitor closely with: Decreases absorption of the following drugs:
Decreases therapeutic effect of Pyridoxine: Dibasic Sodium Phosphate, Anhydrous, Monobasic
Cycloserine (secondary niacin deficiency) Sodium Phosphate, Monohydrate, Phenytoin (forms non-
absorbable complexes), Phosphorus Salts, Strontium-89
Decreases therapeutic effect of Levodopa Chloride

Avoid concomitant use with: Decreases therapeutic effect of Magnesium Salts

Not to be administered concomitantly without consent of (neutralized by Calcium)
healthcare provider:
Altretamine, Cisplatin Increases risk of adverse or toxic effects of the following
drugs:
Administration: Administer whole. Do not crush, break, or Calcitriol (hypercalcemia), Vitamin D Analogs (Vitamin D-
chew. induced hypercalcemia)

Pregnancy Category: A Avoid concomitant use with:

Decreases absorption of Bisphosphonates e.g. Alendronate
ATC Code: A11HA02 (administer at least 2 hours apart)

Decreases bioavailability of the following drugs:

Fluoroquinolones e.g., Levofloxacin, Quinolones
[administer at least 2 hours before or 6 hours after
Calcium Salts], Tetracyclines [administer at least 1 hour

33
 ALIMENTARY TRACT AND METABOLISM

before Calcium Salts], Thyroid Hormones [administer at Dose Adjustment:

least 4 hours before or after Calcium Salts] (forms non- Renal Impairment:
absorbable complexes) In CrCl <30 mL/min, use with caution.
A

Decreases therapeutic effect of Calcium: Precautions:

Vitamin A Renal impairment;
Hypoparathyroid disease;
Decreases therapeutic effect of the following drugs: Hypercalcemia-associated diseases;
Calcitonin, Nondepolarizing Neuromuscular Blockers, Achlorhydria;
Sucralfate [stagger doses], Thyroid Hormones History of kidney stones.
(hypothyroidism)
Adverse Drug Reactions:
Increases risk of adverse effects of Calcium: Common: Gastric hypersecretion, acid rebound, flatulence,
Vitamin A (bone loss) gastric distention, constipation, eructation
Less Common: Hypercalcemia, nephrolithiasis, milk-alkali
Increases risk of adverse effects of the following drugs: syndrome, renal failure
Cardiac Glycosides e.g., digoxin (arrhythmias), Rare: Hypophosphatemia
Ceftriaxone (fatal reactions involving ceftriaxone-
calcium precipitates in the lungs and kidneys), Sodium Drug Interactions:
Bicarbonate, Thiazide Diuretics (milk-alkali syndrome), Monitor closely with:
Decreases absorption of Calcium:
Pregnancy Category: C Corticosteroids, systemic

Increases risk of adverse effects of the following drugs:

Calcipotriene, Calcitriol (hypercalcemia), Mefloquine,
OTC CALCIUM CARBONATE Thiazide Diuretics (hypercalcemia), Vitamin D Analogues
(Vitamin D-induced hypercalcemia)
Oral: tablet or chewable tablet (equivalent to 500 mg and
600 mg elemental calcium) Avoid concomitant use with:
Decreases absorption of the following drugs:
An inorganic Calcium salt useful in the treatment of Bisacodyl [administer at least 1 hour apart]
hyperphosphatemia secondary to chronic renal failure. Bisphosphonates e.g., Alendronate [administer at least 2
hours apart]
Indications: Management of hyperphosphatemia,
hypocalcemia, and premenstrual syndrome (PMS); Decreases absorption of the following drugs:
nutritional supplementation; prevention of osteoporosis. Cefuroxime, oral [administer at least 1 hour before or 2
hours after Calcium Carbonate]
Contraindications: Breastfeeding; constipation; Delavirdine [administer at least 1 hour apart]
dehydration; GI bleeding; GI obstruction; hypercalcemia; Ethotoin [administer Calcium Carbonate at least 1 hour
hyperparathyroidism; ileus; hypercalciuria; necrotizing before or 6 hours after Ethotoin]
enterocolitis; neoplastic disease; nephrolithiasis; peptic Itraconazole [administer at least 2 hours after
ulcer disease; pregnancy; renal disease; sarcoidosis. Itraconazole]
Ketoconazole, Oral [administer at least 2 hours after
Dose: Ketoconazole]
Oral hypocalcemia, by mouth, ADULT, 5–10 g daily Phenytoin, oral [administer Calcium Carbonate at least 1
(equivalent to 2–4 g elemental calcium), given in 3–4 hour before or 6 hours after Phenytoin]
divided doses; CHILD, 112.5–162.5 mg/kg daily Rifampin [administer at least 1 hour apart]
(equivalent to 45–65 mg/kg), given in 4 divided doses;
NEONATE, 125–375 mg/kg daily (equivalent to 50–150 Decreases bioavailability of the following drugs:
mg/kg), given in 4–6 divided doses (maximum dose, 1 g Fluoroquinolones e.g., Levofloxacin [administer at least
daily). 2 hours before or 6 hours after Calcium Salts],
Nutritional supplementation and prevention of Quinolones [administer at least 2 hours before or 6 hours
osteoporosis, by mouth, ADULT ≥51 years, 2,500–3,750 after Calcium Salts], Tetracyclines [administer at least 1
mg daily (equivalent to 1,000 to 1,500 mg elemental hour before Calcium Salts], Thyroid Hormones
calcium); ADULT 19–50 years, 2,500 mg daily [administer at least 4 hours before or after Calcium
(equivalent to 1,000 mg elemental calcium); Salts] (forms non-absorbable complexes)
ADOLESCENT and CHILD 9–18 years, 3,250 mg daily
(equivalent to 1,300 mg elemental calcium); CHILD 4–8 Decreases serum concentration of the following drugs:
years, 2,000 mg daily (equivalent to 800 mg elemental Ezetimibe and Rosuvastatin [administer at least 1 hour
calcium); CHILD 1–3 years, 1,250 mg daily (equivalent before or 2 hours after Calcium Carbonate]
to 500 mg elemental calcium); INFANT 6–12 months, Gefitinib [administer at least 6 hours apart]
equivalent to 270 mg elemental calcium, based on total
intake; INFANT <6 months and NEONATE, equivalent to Decreases therapeutic effect of Calcium:
210 mg elemental calcium, based on total intake. Vitamin A

34
ALIMENTARY TRACT AND METABOLISM

Decreases therapeutic effect of the following drugs: CNS depression due to hypermagnesemia, by slow IV
Calcitonin, Cefuroxime (decrease antibiotic efficacy), infusion, ADULT, 500–2,000 mg at a rate not exceeding
Methenamine, Sucralfate [stagger doses], Thyroid 200 mg/minute (2 mL/minute of a 10% solution).

A
Hormones (leads to hypothyroidism) Nutritional supplementation to prevent hypocalcemia in
patients receiving total parenteral nutrition (TPN), by IV
Decreases urinary excretion of Quinidine injection, ADULT, 10–15 mEq daily admixed with TPN.
Exchange transfusion-induced hypocalcemia, prophylaxis,
Increases risk of adverse effects of Calcium: by IV injection, NEONATE, 97 mg after each 100 mL of
Vitamin A (bone loss) citrated blood exchanged.

Increases risk of adverse effects of the following drugs: Precautions:

Cysteamine [administer at least 1 hour apart] (increased Impaired renal function; cardiac disease; hypercalcemia-
WBC cystine concentration) associated diseases, e.g., sarcoidosis.
Sodium Bicarbonate (milk-alkali syndrome) Lactation (excreted in breastmilk; use with caution).

Not to be use concomitantly with Calcium Carbonate: Administration: Administer by slow IV injection as a 10%
Ammonium Chloride solution slowly through a small needle into a large vein
to avoid too rapid increase in serum calcium and
Administration: Administer with meals to improve extravasation of calcium solution into the surrounding
absorption. Follow each dose with appropriate fluid tissue that may lead to tissue necrosis. Following IV
intake. injection, the patient should remain recumbent for a
short time.
Separate administration with other medicines to prevent
interactions. Visually inspect parenteral products for particulate
matter and discoloration prior to administration.
Pregnancy Category: C
Close monitoring of serum calcium concentrations is
ATC Code: A12AA04 essential during IV administration of calcium.

Oral administration of calcium supplements or calcium-

rich foods should replace IV calcium therapy as soon as
Rx CALCIUM GLUCONATE (IV) possible.

Inj.: 10% solution, 10 mL ampule (IV) NOTE: Do NOT administer by IM or SC route.

10% solution, 20 mL and 25 mL bottle (IV)
Closely monitor serum calcium concentrations during IV
An organic Calcium salt used to prevent or treat negative administration of calcium.
calcium balance. It also helps facilitate nerve and muscle
performance as well as normal cardiac function. Oral administration of calcium supplements or calcium-
rich foods should replace IV calcium therapy as soon as
Indications: Hypocalcemia; hyperkalemia; possible.
hypermagnesemia; nutritional supplementation.
See General Information on Calcium listed above for other
Dose: information.
Hypocalcemia, by IV infusion, ADULT, 2-3 g slowly at a rate
not exceeding 5 mL/minute, repeat every 6 hours, as ATC Code: A12AA03
needed (maximum dose, 15 g daily); alternatively, 15
mg/kg elemental calcium over 4–6 hours if symptoms
recur after initial IV calcium replacement; CHILD and
INFANT, 200 to 500 mg/kg daily as continuous IV
OTC CALCIUM LACTATE
infusion or in 4 divided doses at a rate not exceeding 5
mL/minute; may be repeated after 6 hours or followed Oral: tablet (equivalent to 500 mg elemental calcium)
by 500 mg/kg daily as continuous IV infusion or in 3–4
divided doses; NEONATE, 200–800 mg/kg daily as An organic Calcium salt used to prevent or treat negative
continuous IV infusion or in 3–4 divided doses, followed calcium balance. It also helps to prevent or reduce the
by 500 mg/kg daily as continuous IV infusion or in 3–4 rate of bone loss, moderate nerve and muscle
divided doses. performance and allow normal cardiac function.
Hyperkalemia, hypermagnesemia, and ionized
hypocalcemia, including life-threatening cardiac Indications: Management of hypocalcemia; nutritional
arrhythmias, or during cardiopulmonary resuscitation supplementation
(CPR) associated with suspected or documented
hypermagnesemia, hyperkalemia, or ionized Dose:
hypocalcemia, by IV injection, ADULT, 500–800 mg of Hypocalcemia, by mouth, ADULT, 15.4–30 g daily divided
10% solution (maximum dose, 3 g); CHILD and INFANT, every 8 hours; CHILD, 345–500 mg/kg daily in divided
60–100 mg/kg (maximum dose, 3 g). doses every 6–8 hours (maximum dose, 9 g daily);

35
 ALIMENTARY TRACT AND METABOLISM

INFANT, 400–500 mg/kg daily in divided doses every 4– Dose Adjustment:

6 hours. NOTE: Check Recommended Energy and Nutrient Intakes (RENI) per
Nutritional supplementation, by mouth, ADULT, 1000 mg day for Calcium and Vitamin D for dose of different population
groups.
A

daily; ADOLESCENT and CHILD ≥9 years, 1300 mg daily;

CHILD 4–8 years, 800 mg daily; CHILD 1–3 years, 500 Precautions:
mg daily; INFANT 6–12 months, 270 mg daily; INFANT <6 Should not be used in osteoporosis due to prolonged
months and NEONATE, 210 mg daily. immobilization, renal stones, or severe hypercalciuria;
Mild to moderate renal failure or mild hypercalciuria
Precautions: (supervise carefully, including periodic checks of plasma
WARNING: Avoid IV administration of calcium in calcium levels and urinary calcium excretion);
patients on cardiac glycosides e.g. Digoxin, History of renal stones;
digitoxin Patients receiving treatment for cardiovascular diseases;
Rare hereditary problems of glucose-galactose
malabsorption or fructose intolerance;
Renal impairment; Achlorhydria;
Sarcoidosis; Hypercalcemia and hypercalciuria.
History of nephrolithiasis
Hypoparathyroidism; NOTE: Allowances should be made for calcium and vitamin
History of kidney stones (use with caution). D supplements from other sources.

Administration: Administer 1–1.5 hours after meals or with Adverse Drug Reactions:
a demulcent (e.g., milk). Follow each dose with Less Common: Hypercalcemia, hypercalciuria
appropriate fluid intake. Separate administration with Rare: Abdominal pain, acid rebound, anorexia, arrhythmia,
other medicines to prevent interactions. bone or muscle pain, constipation or diarrhea,
headache, hypophosphatemia, flatulence, loss of
See General Information on Calcium listed above for other appetite, metallic taste, milk-alkali syndrome, nausea,
information. pruritus, rash, urticaria, vomiting, xerostomia

ATC Code: A12AA05 Drug Interactions:

Monitor closely with:
Decreases absorption of Calcium:
CALCIUM CARBONATE + Corticosteroids
OTC CHOLECALCIFEROL
(VITAMIN D3) Decreases absorption of Quinolone Antibiotics, e.g.,
Ciprofloxacin
Oral: equivalent to 500 mg elemental calcium + 400 IU
Increases risk of adverse effects of the following drugs:
vitamin D3
Digoxin (hypercalcemia), Thiazide Diuretics
equivalent to 600 mg elemental calcium + 400 IU
(hypercalcemia; milk-alkali syndrome with high doses)
vitamin D3

A two-component dietary supplement of calcium and fat-

Avoid concomitant use with:
Decreases absorption of the following drugs:
soluble vitamin D, which serves to increase the calcium
Iron Salts, Levothyroxine, Tetracyclines, Zinc Salts
pool available for GI absorption and assimilation into
bones.
Decreases serum concentration of Bisphosphonate e.g.,
Alendronate
Indications: Adjunct inosteoporosis; therapeutic
supplementation (e.g., lactose intolerance or with milk
Decreases therapeutic effect of Calcium Channel Blockers
allergy; established vitamin D dependent osteomalacia;
e.g., Amlodipine
post-menopausal women; chronic kidney disease with or
without renal replacement therapy);
FOOD INTERACTION. Foods that are rich in oxalic acid (e.g.,
hyperphosphatemia.
spinach) and phytic acid (e.g., whole cereals) may reduce
calcium absorption due to formation of insoluble calcium
Contraindications: hypercalcemia; hyperparathyroidism;
salts. Do NOT take calcium products within 2 hours of
renal calculi; hypophosphatemia; vitamin D toxicity;
eating such foods.
abnormal sensitivity to the effects of vitamin D;
malabsorption syndrome; renal failure or severe renal
impairment; known hypersensitivity to the preparation or Administration: Administer, preferably with food, 2 hours
any of the excipients (e.g. soya oil). before or after other medications.
Dose:
Calcium deficiency, by mouth, ADULT, supplementary intake Maintain adequate fluid intake. Administration is
to achieve a total elemental calcium dosage of 1 g in 2 followed by increased serum gastric acid secretion,
divided doses for male and premenopausal female within 2 hours.
patients; 1.2–1.5 g in 3 divided doses for post-
menopausal women; not recommended for children <12 Pregnancy Category: C
years.

36
ALIMENTARY TRACT AND METABOLISM

ATC Code: A12AX

Rx POTASSIUM CITRATE

A
POTASSIUM Oral: 10 mEq tablet

A major cation of the intracellular fluid that plays an active

Rx POTASSIUM CHLORIDE role in the conduction of nerve impulses in the heart,
brain, and skeletal muscle.
Oral: 600 mg tablet
750 mg durules (equivalent to approximately 10 mEq Indications: Management of renal lithiasis, hypocitraturia,
potassium) chronic formers of calcium oxalate, phosphate calculi,
1 mmol/mL syrup, 30 mL and 60 mL uric acid lithiasis and renal tubular acidosis with calcium
Inj.: 2 mEq/mL, 2 mL and 5 mL ampul (IV infusion) nephrolithiasis.
2 mEq/mL, 10 mL and 20 mL vial (IV infusion)
Contraindications: Renal insufficiency; persistent alkaline
A major cation of the intracellular fluid that plays an active urinary infections; urinary tract obstruction;
role in the conduction of nerve impulses in the heart, hyperpotassemia; adrenal insufficiency; respiratory or
brain, and skeletal muscle. metabolic alkalosis; active peptic ulcer; intestinal
obstruction; patients on anticholinergic therapy; slow
Indication: Treatment and prevention of hypokalemia gastric emptying.

Contraindications: Hyperchloremia; severe renal or adrenal Dose:

insufficiency Severe hypocitraturia, by mouth, ADULT, initially 60 mEq
daily in 3 divided doses.
Dose: Mild hypocitraturia, by mouth, ADULT, initially 30 mEq daily
Hypokalemia, prophylaxis, by mouth, ADULT, 20 mEq daily. in 3 divided doses.
Hypokalemia, treatment, by mouth, ADULT, 40-100 mEq
daily; give in divided doses if >20 mEq daily. Precautions:
Altered potassium excretion mechanism; Renal
Precautions: insufficiency.
WARNING: Monitor urine output, plasma potassium, Adverse Drug Reaction:
and other electrolyte concentrations. Discontinue if Common: Slight GI disturbances
severe nausea, vomiting, or abdominal distress
develops. Drug Interactions:
Avoid concomitant use with:
Renal impairment (e.g., accumulation of potassium); Increases risk of adverse or toxic effects of the following
adrenocortical insufficiency; cardiac disease; acute drugs:
dehydration; extensive tissue destruction. Potassium-sparing Diuretics e.g., Spironolactone
(hyperkalemia)
Adverse Drug Reactions: GI ulceration, hyperkalemia,
nausea, vomiting, diarrhea, abdominal cramps Administration: To be taken 30 minutes after meals. Do NOT
chew, crush, or dilute tablets.
Drug Interactions:
Monitor closely with: Determine urinary citrate and pH approximately 24 hours
Increases risk of adverse or toxic effects of Antimuscarinics after the first dose and adjust dose accordingly. Do NOT
(GI adverse effects) exceed 100 mEq daily.

Avoid concomitant use with: Pregnancy Category: A

Increases risk of adverse or toxic effects of the following
drugs: ATC Code: A12BA02
ACE Inhibitors, Potassium-containing Drugs, Potassium-
sparing Diuretics e.g. Spironolactone (hyperkalemia),

Administration: Should be taken with food.

Pregnancy Category: C

ATC Code: A12BA01

37
 ALIMENTARY TRACT AND METABOLISM

ZINC (elemental zinc) daily for 10-14 days; INFANT <6 months,
10 mg (elemental zinc) daily for 10-14 days.
GENERAL INFORMATION
A

See General Information on Zinc listed above for other

An essential, mineral supplement in the diet, which is used information.
as an adjunct to oral rehydration in the treatment of
acute and persistent diarrhea. Pregnancy Category: C

Indication: Adjunct to oral rehydration therapy in acute and ATC Code: A12CB02
persistent diarrhea

Contraindication: Severe renal impairment OTC ZINC SULFATE

Precaution:
Acute renal failure (may accumulate). Oral: 88 mg dispersible tablet (equivalent to 20 mg zinc)
solution (equivalent to 10 mg elemental zinc/mL)
Adverse Drug Reactions: drops (as monohydrate), 15 mL
Common: Diarrhea, dry mouth, dyspepsia, GI upset, mouth solution (equivalent to 20 mg elemental zinc/5 mL)
irritation, nausea, regurgitation and vomiting (in syrup (as monohydrate), 60 mL
children), unpleasant taste
Less Common: Gastritis, headache, irritability, lethargy, Zinc sulfate is widely distributed in the body but is
copper deficiency (with prolonged use) concentrated in the muscle, bone, skin, and prostatic
fluids.
Drug Interactions:
Avoid concomitant use with: Indication: Adjunct to oral rehydration therapy in acute and
Decreases absorption of Zinc: persistent diarrhea
Calcium Salts [separate doses by 2–3 hours],
Ethambutol, Ferrous Salts, Food, e.g., milk, phytates Dose:
present in cereals, rice, corn, or legumes Oral rehydration therapy in acute and persistent diarrhea
(adjunct), by mouth, CHILD 6 months to 5 years, 20 mg
Decreases absorption of the following drugs: (elemental zinc) daily for 10-14 days; INFANT <6 months,
Bisphosphonates e.g., Alendronate; Ferrous Salts e.g., 10 mg (elemental zinc) daily for 10-14 days.
Ferrous sulfate; Quinolones, e.g., Ofloxacin, Ciprofloxacin
[separate doses by at least 2 hours]; Tetracyclines See General Information on Zinc listed above for other
[separate administration by at least 2 hours] information.

Decreases therapeutic effect of the following drugs: Pregnancy Category: C

Tetracyclines (anti-infective activity)
ATC Code: A12CB01
Administration: Tablets may be dispersed in breastmilk, oral
rehydration solution, or water on a small spoon. Older
children may chew the tablets or swallow them with OTHER MINERAL PRODUCTS
water.

Pregnancy Category: C OTC FERROUS SALT

Oral: tablet (equivalent to 60 mg elemental iron)

OTC ZINC GLUCONATE solution (equivalent to 15 mg elemental iron/0.6 mL)
drops, 15 mL and 30 mL
solution (equivalent to 30 mg elemental iron/5 mL)
Oral: tablet (equivalent to 30 mg elemental zinc) (as syrup, 60 mL
trihydrate)
chewable tablet (equivalent to 10 mg elemental zinc) NOTE: The elemental iron content of a ferrous salt depends on
70 mg/5 mL syrup (equivalent to 10 mg elemental the type of preparation as follows:
zinc), 60 mL and 120 mL Ferrous fumarate 33%
Ferrous gluconate 12%
Zinc gluconate is commonly used to treat and to prevent Ferrous lactate 19%
zinc deficiency, as well as for other purposes. Ferrous sulfate, hydrated 20%
Ferrous sulfate, desiccated 32%
Indication: Adjunct to oral rehydration therapy in acute and
persistent diarrhea An essential trace element required for the formation of
hemoglobin and for the efficient oxygen transport in the
Dose: blood.
Oral rehydration therapy in acute and persistent diarrhea
(adjunct), by mouth, CHILD 6 months to 5 years, 20 mg

38
ALIMENTARY TRACT AND METABOLISM

Indications: Treatment of iron-deficiency anemia and Decreases therapeutic effect of the following drugs:
supplement and prophylaxis in people on hemodialysis Bisphosphonates e.g., Alendronate, Quinolones, e.g.,
receiving erythropoietin. Ciprofloxacin, Tetracyclines (anti-infective activity)

A
Contraindications: Anemia not due to iron deficiency;
parenteral iron therapy; in patients receiving repeated Administration: Best absorbed on an empty stomach but
blood transfusions; hemochromatosis; hemosiderosis may be taken after food to reduce GI adverse effects.

Dose: Dilute with water liquid preparations containing iron

Iron-deficiency anemia, by mouth, ADULT, elemental iron, salts, and if possible swallow through a drinking straw to
100–200 mg daily in divided doses. prevent teeth discoloration.
Prevention of iron-deficiency anemia (in those at risk), by
mouth, ADULT (woman), elemental iron 60 mg daily; Pregnancy Category: C
CHILD >5 years, elemental iron 30 mg daily; CHILD <5
years, elemental iron 2 mg/kg daily (maximum, 30 mg). ATC Code: Not available

NOTE: For women and children >5 years, folic acid may also
be given.
Rx FERROUS SALT + FOLIC ACID
Precautions:
WARNING: May exacerbate GI bleeding. Use with Oral: 60 mg elemental iron + 400 micrograms folic acid per
caution in patients with GI disorders. tablet / capsule / film-coated tablet

A two-component, nutritional supplement of iron and folic

Not to be administered for longer than 6 months (monitor acid given during pregnancy.
closely for potential complications);
Transfusion-dependent anemia; Indications: Prevention of iron and folic acid deficiencies,
Peptic ulcer; especially in pregnancy; nutritional supplement during
Regional enteritis; pregnancy.
Ulcerative colitis;
Intestinal strictures; NOTE: Low doses of folic acid in combination preparations
Diverticula; are inadequate for the treatment of megaloblastic
Pregnancy (avoid use in the first trimester; administer only anemia, overdose, and therapy with deferoxamine.
in women with low-normal hemoglobin).
Contraindications: Hemolytic anemia; hemochromatosis;
NOTE: In cases of overdose, initiate therapy with hemosiderosis; repeated blood transfusions of
deferoxamine. Before administration of deferoxamine, parenteral iron therapy; pernicious anemia
the stomach should be emptied by gastric lavage (with a
wide-bore tube), preferable within one hour of ingesting Dose:
a significant quantity of iron or if radiography reveals Prevention of iron and folate deficiencies in pregnancy, by
tablets in the stomach. mouth, ADULT, elemental iron, 100 mg + folic acid, 350–
400 micrograms daily throughout pregnancy.
Adverse Drug Reactions: Severe anemia, by mouth, ADULT, elemental iron, 120 mg
Common: Abdominal pain, black discoloration of feces, + folic acid 400 micrograms daily for 3 months; CHILD
constipation, diarrhea, nausea, vomiting 2–12 years, elemental iron 60 mg + folic acid, 400
Less Common: Black discoloration of teeth micrograms daily for 3 months; CHILD <2 years,
Rare: Anaphylaxis, GI erosion and perforation, elemental iron, 25 mg + folic acid 100–400 micrograms
hemosiderosis daily for 3 months.

Drug Interactions: Dose Adjustment:

Monitor closely with: Renal Impairment:
Decreases bioavailability of Methyldopa (interferes with Give iron supplementation when the patient is anemic, and
blood pressure control) iron saturation is <20%.

Avoid concomitant use with: Precautions:

Decreases absorption of Iron:
Antacids, e.g., Aluminum or Magnesium Hydroxide, WARNING: Iron salts can exacerbate GI bleeding; thus,
Calcium, Doxycycline, Food, e.g., eggs, milk, it should be used with caution in patients with GI
Tetracyclines, Zinc Salts disorders.

Decreases absorption of the following drugs: Transfusion-dependent anemia;

Bisphosphonates e.g., Alendronate, Doxycycline, Peptic ulcer, regional enteritis, ulcerative colitis, intestinal
Levothyroxine [administer at least 2 hours apart], strictures, diverticula;
Quinolones, e.g., Ciprofloxacin, Tetracyclines, Zinc Salts Pernicious anemia;
Elderly and children;
Pregnancy (avoid use in the first trimester; administer only
in women with low-normal hemoglobin).

39
 ALIMENTARY TRACT AND METABOLISM

Adverse Drug Reactions:

Common: Abdominal pain, black discoloration of feces, OTC MICRONUTRIENT POWDER
constipation, diarrhea, nausea, vomiting
Less Common: Black discoloration of teeth
A

Oral: per 1-gram sachet contains:

Rare: Anaphylaxis, bronchospasm, fever, GI erosion and
perforation, hemosiderosis, irritability, rash, sleep Vitamin A 400 micrograms RE
disturbance Vitamin C 30 mg
Vitamin D 5 micrograms
Drug Interactions: Vitamin E 5 mg a-TE
Monitor closely with: Vitamin B1 0.5 mg
Decreases bioavailability of Methyldopa (interferes with Vitamin B2 0.5 mg
blood pressure control) Vitamin B6 0.5 mg
Vitamin B12 0.9 micrograms
Avoid concomitant use with: Folic acid 150 micrograms
Decreases absorption of Iron: Niacin 6 mg
Antacids, e.g., Aluminum or Magnesium Hydroxide Iron 10 mg
(separate administration times as long as possible), Zinc 4.1 mg
Calcium, Doxycycline, Food, e.g., eggs, milk, Copper 0.56 mg
Tetracyclines e.g., Doxycyline, Zinc Salts Iodine 90 micrograms
Selenium 17 micrograms
Decreases absorption of the following drugs:
Bisphosphonates e.g., Alendronate, Doxycycline, Single-dose packets vitamins and minerals, in powder form,
Levothyroxine [administer at least 2 hours apart], which can be sprinkled onto any ready-to-eat semisolid
Quinolones, e.g., Ciprofloxacin, Levofloxacin, food.
Tetracyclines, Zinc Salts
Indications: Prevent vitamin and mineral deficiencies;
Decreases serum concentration of Folic Acid: improve iron status and reduce anemia among infants
Folic Acid Antagonists, e.g., Methotrexate, and children 6-23 months of age.
Pyrimethamine, Triamterene, Sulfonamides,
Trimethoprim Contraindications: Children with specific conditions, such as
HIV infection or TB (effects and safety of the intervention
Decreases therapeutic effect of the following drugs: have not been evaluated).
Bisphosphonates e.g., Alendronate, Quinolones, e.g.,
Ciprofloxacin, Levofloxacin, Tetracyclines e.g., Dose:
Doxycycline (anti-infective activity) Prevention of vitamin and mineral deficiencies, improving
iron status, and reducing anemia, by mouth, CHILD and
Administration: To be taken on an empty stomach, at least INFANT 6-23 months, 1 sachet daily, add a mixture of
1 hour before or 2 hours after meals. micronutrients in powder form to any semisolid food.

Avoid taking antacids or antibiotics within 2 hours before Precautions:

or after administration. Programs involving the use of multiple micronutrient
powders for fortification at home of foods should be
Pregnancy Category: A preceded by an evaluation of the nutritional status
among children <5 years of age, and existing measures
ATC Code: Not available to control anemia and vitamin A deficiency (e.g.,
hookworm control programs, provision of supplements,
and use of other products for home fortification of foods
and fortified complementary foods), to ensure that daily
micronutrient needs are met and not exceeded.

Adverse Drug Reactions:

Common: Diarrhea
Less Common to Rare: Darkening of the stools, staining of
child’s teeth

Drug Interactions: No information found.

Administration: At minimum, for a period of 2 months,

followed by a period of 3–4 months off supplementation
(so that use of the micronutrient powders is started every
6 months.

Pregnancy Category: Not available

ATC Code: Not available

40
ALIMENTARY TRACT AND METABOLISM

Reconstitute as per manufacturer’s instruction. After

OTHER ALIMENTARY TRACT AND reconstitution, visually inspect prior to administration.
METABOLISM PRODUCTS Slight flocculation (thin translucent fibers) may

A
occasionally occur after dilution. Do NOT use if there are
opaque particles or discoloration.
ENZYMES
Pregnancy Category: C
Rx IMIGLUCERASE
ATC Code: A16AB02

Inj.: 400 U powder, 20 mL vial (IV infusion)

ANTI-HYPOGLYCEMICS
NOTE: Special Category: Drug for Compassionate Use

An analogue of the enzyme β-glucocerebrosidase (β-D- Rx GLUCOSE (DEXTROSE)

glucosyl-N-acylsphingosine glucohydrolase), produced by
recombinant DNA technology. It is a lysosomal
glycoprotein enzyme, which catalyzes the hydrolysis of Inj.: 50%, 10 mL and 20 mL ampule (IV)
the glycolipid glucocerebroside to glucose and ceramide. 50%, 50 mL vial (IV)
50%, 10 mL, 20 mL, and 50 mL (85 Kcal) vial (IV)
Indication: Long-term enzyme replacement therapy in type
1 Gaucher disease that results in anemia, A sterile, hypertonic solution of glucose, which provides a
thrombocytopenia, bone disease, or hepatomegaly / source of calories in a minimal volume of water and is
splenomegaly. used in restoring blood glucose concentrations in the
Contraindications: No known contraindications treatment of hypoglycemia.

NOTE: Carefully re-evaluate treatment if there is Indications: Fluid replacement without significant
significant clinical evidence of hypersensitivity to the electrolyte deficit; management of severe hypoglycemia
product. in an adult who is unable to take oral food or fluids.

Dose: Contraindications: Hyperglycemia; use of hyperosmotic

NOTE: Individualize dose to each patient based on disease solutions in patients with anuria; diabetic coma; glucose-
severity and therapeutic goals. galactose malabsorption syndrome; dehydrated patients
with delirium; intracranial or intraspinal hemorrhage;
Enzyme replacement therapy, by IV infusion, ADULT, initially should not be used after ischemic attacks.
2.5 U/kg 3 times weekly to 60 U/kg once every 2 weeks.
Dose:
Dose Adjustment: No information available Fluid replacement, by IV infusion, ADULT and CHILD,
determined based on clinical data and, whenever
Precautions: possible, electrolyte monitoring.
Treatment of hypoglycemia, by IV infusion (50% glucose
WARNING: Hypersensitivity reactions have occurred in solution into a large vein), ADULT, 25-50 mL.
patients who developed IgG antibody to
imiglucerase. Dose Adjustment:
Renal Impairment:
Select doses with care.
Pulmonary hypertension and pneumonia (known
complications of Gaucher); Precautions:
Previous treatment with alglucerase; May result in hypophosphatemia, hypokalemia and
Carcinogenesis; hypomagnesemia;
Mutagenesis; Observe for signs of mental confusion and loss of
Fertility (effect on reproductive capacity not known); consciousness;
Children (use with caution). Prolonged use (may affect insulin production);
Diabetes mellitus.
STORAGE. Store products at 2–8oC (36–46oF).
Adverse Drug Reactions:
Adverse Drug Reactions: NOTE: Administration of glucose without adequate thiamine
Common: Hypersensitivity reactions (pruritus, flushing, levels may precipitate overt deficiency states e.g.,
urticaria, angioedema, chest discomfort, dyspnea, Wernicke's encephalopathy.
coughing, cyanosis, hypotension), anaphylactoid
reaction, nausea, abdominal pain, vomiting, diarrhea, Less Common: Pain at the injection site, phlebitis, tissue
rash, fatigue, headache, fever, dizziness, chills, necrosis, venous irritation, venous thrombosis.
backache, tachycardia. Rare: Dehydration, edema or water intoxication, fluid and
electrolyte imbalance, glycosuria, hyperglycemia,
Drug Interactions: No information available hypokalemia, hypomagnesemia, hypophosphatemia.
Administration: Administer via IV infusion over 1–2 hours.
Drug Interactions:

41
 ALIMENTARY TRACT AND METABOLISM

Monitor closely with: Drug Interactions:

Associated with lower fasting glucose and insulin: Avoid concomitant use with:
Magnesium salts Enhances therapeutic effect of Anticoagulants, e.g.,
A

Warfarin (anticoagulant effect)

Administration: Should be administered by IV infusion via a
large central vein (e.g., into a secure IV cannula in an Administration: Administer parenterally because glucagon is
antecubital vein) to minimize damage at the site of destroyed in the GI tract.
injection (e.g., thrombophlebitis). Do not administer Reconstitute as per manufacturer’s instructions. Use
glucose solutions through the same infusion equipment reconstituted glucagon immediately. Discard any unused
as whole blood since hemolysis and clumping may occur. portion.

Visually inspect parenteral products for particulate Do NOT use at concentrations greater than 1 mg/mL (1
matter and discoloration prior to administration. unit/mL).

NOTE: Rapid administration of hypertonic glucose solutions NOTE: Patients with Type 1 diabetes may have less of an
may produce substantial hyperglycemia and increase in blood glucose levels compared with a stable
hyperosmolar syndrome. Type 2 patient. Administer supplementary carbohydrate
as soon as possible, especially to pediatric patients.
Pregnancy Category: C
Pregnancy Category: B
ATC Code: Not available
ATC Code: Not available

Rx GLUCAGON

Inj.: 1 mg lyophilized powder (as hydrochloride) + solvent

(IM, IV, SC)

A polypeptide that is produced by α cells of islets of

Langerhans in the pancreas. It stimulates adenylate
cyclase to produce cAMP, promoting hepatic
glycogenolysis and gluconeogenesis, which causes an
increase in blood glucose levels. Glucagon is synthesized
using genetically altered Escherichia coli bacteria.

Indication: For life-threatening hypoglycemia

Contraindications: Pheochromocytoma; known

hypersensitivity to glucagon or any of its components

Dose:
Severe hypoglycemia, by IV, IM, or SC injection, ADULT ≥25
kg, initially 1 mg; if not responsive within 10 minutes,
administer IV glucose; repeat glucagon dose if
necessary; ADULT <25 kg, initially 0.5 mg; if not
responsive within 10 minutes, administer IV glucose;
repeat glucagon dose if necessary.

Precautions:

WARNING: Effective in treating hypoglycemia only if

sufficient liver glycogen is present.

Insulinoma;
Glucagonoma;
Pheochromocytoma;
Renal impairment;
Hepatic impairment;
Lactation (not known if excreted in breastmilk).

Adverse Drug Reactions:

Common: Nausea, vomiting, diarrhea, hypokalemia,
hypoglycemia
Less Common: Generalized allergic reactions

42
BLOOD AND BLOOD FORMING ORGANS

baseline INR is 1–1.3, initiate at 0.2 mg/kg (maximum

BLOOD AND BLOOD FORMING ORGANS 10 mg/dose); adjust dose based on INR to maintain INR
of 2–3; administer 0.09–0.33 mg/kg daily; INFANT <12
months, may require an average dose of 0.33 mg/kg
daily to maintain an INR of 2–3.
ANTITHROMBOTIC AGENTS

B
NOTE: Consistent anticoagulation may be difficult to
maintain in children <5 years.
VITAMIN K ANTAGONISTS
Overlapping parenteral anticoagulant and warfarin by at
least 5 days is necessary in the treatment of DVT/PE
Rx WARFARIN even if the INR is therapeutic earlier than 5 days.

Dose Adjustment:
Oral: 1 mg, 2.5 mg, and 5 mg tablet (as sodium salt)
Geriatric:
Initiate at ≤5 mg. Usual maintenance dose is 2–5 mg daily.
A coumarin derivative anticoagulant that exerts its effect by
May require lower doses to produce a therapeutic level
interfering with the hepatic synthesis of vitamin K-
of anticoagulation.
dependent coagulation factors II (prothrombin), VII, IX,
and X, as well as the anticoagulant proteins C and S.
Precautions:
Indications: Prophylaxis and treatment of thromboembolic WARNING: Administration of large loading doses (i.e.,
disorders (e.g., venous, pulmonary) and embolic >10 mg) is NOT recommended due to possible
complications arising from atrial fibrillation or cardiac increased risk of hemorrhage or necrosis.
valve replacement; adjunct to reduce risk of systemic
embolism (e.g., recurrent MI, stroke) after myocardial Can cause major or fatal bleeding. Perform regular
infarction; acute coronary syndrome. monitoring of international normalized ratio (INR) on
all treated patients. Drugs, dietary changes, and
Contraindications: Hemorrhagic tendencies (e.g., cerebral other factors affect INR levels achieved with warfarin
aneurysm, cerebrovascular hemorrhage, dissecting therapy. Instruct patients about prevention
aortic aneurysm, spinal puncture, other diagnostic or measures to minimize the risk of bleeding and to
therapeutic procedures with potential for significant report immediately to their healthcare provider signs
bleeding, history of bleeding disorders); recent or and symptoms of bleeding.
potential surgery of the eye or CNS; major regional or
lumbar block anesthesia or traumatic surgery resulting
in large, open surfaces; blood dyscrasias; severe Risk factors for bleeding include high intensity
uncontrolled or malignant hypertension; pericarditis or anticoagulation (INR >4), age (≥65 years), variable INRs,
pericardial effusion; bacterial endocarditis; history of GI bleeding, hypertension, cerebrovascular
unsupervised patients with conditions associated with a disease, serious heart disease, anemia, severe diabetes,
high potential for nonadherence; eclampsia or malignancy, trauma, renal insufficiency, polycythemia
pre­eclampsia; threatened abortion; pregnancy (except vera, vasculitis, open wound, history of PUD, indwelling
in women with mechanical heart valves at high risk for catheters, menstruating and postpartum women, drug-
thromboembolism). drug interactions, long duration of therapy, or known
genetic deficiency in CYP2C9 activity.
Dose: Anaphylaxis or hypersensitivity; skin necrosis or gangrene.
NOTE: Carefully individualize dose based on clinical and Artheroemboli or cholesterol microemboli;
laboratory findings (i.e., INR, hepatic function, cardiac Infection (use with caution in acute infection or active TB, or
function, age, nutritional status, concurrent therapy, risk any disruption of normal GI flora).
of bleeding, prior dose response, clinical situation). Dietary insufficiency (e.g. vitamin K deficiency);
Consider other patient related factors when determining Heparin-induced thrombocytopenia and DVT (limb
initial dose (e.g., age, body weight, concomitant ischemia, necrosis, and gangrene have occurred).
medications, comorbidities). Determine optimum dose Hepatic impairment; renal impairment; thyroid disease.
and duration of therapy by the condition being treated. Surgery (discontinue for approximately 5 days before
Adjust dosage in small increments and carefully monitor surgery; may reinstitute warfarin therapy ~12–24 hours
patient response. after surgery).
Patients with genomic variants in CYP2C9 and/or VKORC1.
Thrombosis or embolism, prevention and/or treatment, by Elderly (may be more sensitive to anticoagulant therapy;
mouth, ADULT, start with 2–5 mg once daily for 2 days or risk of bleeding complications has been associated with
for healthy individuals, 10 mg once daily for 2 days; lower increased age).
doses (e.g., 5 mg once daily) are recommended for Lactation (carefully monitor breastfeeding women to avoid
patients with confirmed heparin induced excessive anticoagulation; monitor nursing infants for
thrombocytopenia (HIT) once platelet recovery has bruising or bleeding).
occurred; in patients with acute venous
thromboembolism, initiation may begin on the first or Adverse Drug Reactions: Vasculitis, signs or symptoms of
second day of low molecular weight heparin or bleeding (e.g., dizziness, fatigue, fever, headache,
unfractionated heparin therapy; adjust dose according to lethargy, malaise, pain), alopecia, bullous eruptions,
INR results; maintenance dose, 2–10 mg daily; CHILD, if dermatitis, rash, pruritus, urticaria, abdominal pain,

43
 BLOOD AND BLOOD FORMING ORGANS

diarrhea, flatulence, gastrointestinal bleeding, nausea, Avoid concomitant use with:

taste disturbance, vomiting, hematuria, anemia, Counteracts anticoagulant effect of Warfarin:
retroperitoneal hematoma, unrecognized bleeding sites Estrogen Derivatives or Progestins (potential
(e.g., colon cancer), hepatitis (including cholestatic prothrombotic effects)
hepatitis), osteoporosis (potential association with long-
term use), paralysis, paresthesia, weakness, respiratory Decreases absorption of Warfarin:
B

tract bleeding, tracheobronchial calcification, Sucralfate [administer Warfarin at least 2 hours before
anaphylactic reaction, hypersensitivity / allergic or 6 hours after Sucralfate]
reactions, skin necrosis, gangrene, “purple toe” Decreases metabolism of Warfarin and increases PT/ INR:
syndrome. Acute alcoholism, strong CYP2C9 Inhibitors, Imatinib,
Sulfinpyrazone
Drug Interactions:
Monitor closely with: Decreases protein binding of Warfarin:
Decreases absorption of Warfarin: Sulfinpyrazone
Bile Acid Sequestrants, Lixisenatide
Decreases serum concentration of Warfarin:
Enhances anticoagulant effect of Warfarin: Carbamazepine, Dabrafenib, Enzalutamide, Sucralfate
Paracetamol, Agents with Antiplatelet Properties, e.g.,
P2Y12 Inhibitors, Amikacin, Amoxicillin, Bupropion. Enhances anticoagulant effect of Warfarin:
Cephalosporins e.g., Cefuroxime, Chloramphenicol, Allopurinol, Amiodarone, Androgens, Apixaban,
Chondroitin Sulfate, Cloxacillin, Systemic Cimetidine, Clopidogrel, Dabigatran Etexilate, Fibric Acid
Corticosteroids, COX-2 Inhibitors e.g., Celecoxib, Derivatives, Fosphenytoin, Imatinib, NSAID, Phenytoin,
Cyclophosphamide, Etoposide, Exenatide, Fibrates e.g., Salicylates [except Salsalate], Sorafenib, Streptokinase,
Fenofibrate, Gefitinib, Gemcitabine, Glucagon, Sulfonamide Derivatives
Glucosamine, HMG-CoA Reductase Inhibitors [except
Atorvastatin], Ifosfamide, systemic Ivermectin, Enhances therapeutic effect of Rivaroxaban (anticoagulant
Leflunomide, Levocarnitine, Mirtazapine, Multivitamins effect)
with Fluoride with ADE
Increases metabolism of Warfarin and decreases PT / INR:
Enhances anticoagulant effect of Warfarin: Chronic alcoholism, Barbiturates e.g., Phenobarbital,
Multivitamins and Minerals with AE, no Iron, Neomycin, strong CYP2C9 Inducers
Nonsteroidal Anti-Inflammatory Agents, Omega-3 Fatty
Acids, Orlistat, Other Anticoagulants, Penicillins [except Increases serum concentration of Warfarin:
Dicloxacillin, Nafcillin, Pentoxifylline, Proguanil, Amiodarone [reduce Warfarin dose by 30 to 50%],
Propacetamol, Quinidine, Quinine, Quinolone Antibiotics Capecitabine, Ceritinib, Fluconazole, systemic and
e.g. Levofloxacin, Salicylates, Selective Serotonin topical Fluorouracil, Fosphenytoin, systemic Fusidic Acid,
Reuptake Inhibitors e.g. Sertraline, Sugammadex, systemic Metronidazole, topical Miconazole, Phenytoin,
Sulfonylureas e.g., Gliclazide, Tetracycline Derivatives Sorafenib, Tamoxifen
e.g. Clarithromycin, Thrombolytic Agents e.g. Alteplase,
Thyroid Products, Tibolone, Tramadol, Tricyclic Reduces anticoagulant effect of Warfarin:
Antidepressants e.g., Amitriptyline, Vitamin E Antithyroid Agents e.g., PTU, Contraceptives, e.g.,
Estrogens, Progestins, Phytonadione, Sucralfate
Enhances therapeutic effect of Sulfonylureas e.g., Gliclazide
(hypoglycemic effect) FOOD/SUPPLEMENT INTERACTIONS.

Increases metabolism of Warfarin: Cranberry juice, Ginkgo biloba, herbs with anticoagulant or
Anticholinergic/Sedative combination, Bosentan, antiplatelet properties, e.g., alfalfa, anise, bilberry
Rifamycin Derivatives (bleeding) may increase warfarin effect.

Increases risk of adverse or toxic effects of Warfarin (may Vitamin K-rich foods, including green tea (Camellia
increase INR/ risk of bleeding): sinensis), chewing tobacco, a variety of oils (canola, corn,
Ampicillin, Clindamycin, Desvenlafaxine, Prostacyclin olive, peanut, safflower, sesame seed, soybean, or
Analogues e.g., Quinidine, Venlafaxine, Vitamin E sunflower, may decrease anticoagulant effects of
Warfarin.
Increases risk of adverse or toxic effects (bleeding effect) of
the following drugs: Administration: May be taken with or without food. Take at
Deferasirox, Deoxycholic Acid, Nintedanib, the same time each day. Maintain a consistent diet.
Obinutuzumab, Regorafenib, Iodine I131 Avoid drastic changes in diet which decrease efficacy of
warfarin. Consult prescriber before making changes in
Reduces anticoagulant effect of Warfarin: diet.
Azathioprine, Cloxacillin, Coenzyme Q-10, Dicloxacillin,
Flucloxacillin, Floxacillin, Mercaptopurine, Multivitamins NOTE: Instruct patients to report bleeding, accidents, or falls
and Minerals with ADEK, Folate, Iron as well as any new or discontinued medications, herbal
or alternative products used, or significant changes in
smoking or dietary habits. Unrecognized bleeding sites

44
BLOOD AND BLOOD FORMING ORGANS

(e.g., colon cancer) may be uncovered by patients <45 kg or >120 kg); Elderly; Pregnancy;
anticoagulation. Lactation.

Pregnancy Category: D (women with mechanical heart NOTE: Some products are derived from porcine intestinal
valves); X (other indications) mucosa.

B
ATC Code: B01AA03 Drug Interactions:
Monitor closely with:
Enhances anticoagulant effect of Heparins:
HEPARIN GROUP Agents with Antiplatelet Properties, e.g., P2Y12
Inhibitors, SSRIs e.g., Fluoxetine
Antithrombin III, Aspirin, NSAIDS, Omega-3 Fatty Acids,
GENERAL INFORMATION Other Anticoagulants, Pentoxifylline, Salicylates e.g.
Aspirin, Sugammadex, Thrombolytic Agents e.g.,
Heparin is a heterogenous mixture of sulfated Streptokinase, Tibolone, Vitamin E
mucopolysaccharides.
High-molecular-weight (HMW) heparin, also known as Increases risk of adverse or toxic effects (bleeding or
unfractionated heparin (UFH), are fractions of heparin antiplatelet effects) of Heparins:
with high affinity for antithrombin. UFH has a molecular 5­ASA Derivatives, Dextran, Dipyridamole,
weight range of 5,000–30,000. Hydroxychloroquine, Prostacyclin Analogues
In contrast, the shorter chain low-molecular-weight (LMW)
fractions of heparin inhibit activated factor X but have Increases risk of adverse or toxic effects of the following
less effect on thrombin than the HMW species. LMW drugs:
heparins, in comparison with UFH, may have equal Hyperkalemic effect: ACE Inhibitors e.g., Enalapril,
efficacy, increased bioavailability from the subcutaneous Aliskiren, Angiotensin II Receptor Blockers e.g., Losartan,
site of injection, and less frequent dosing requirements. Canagliflozin, Potassium salts (hyperkalemic effect),
Potassium-sparing Diuretics e.g., Spironolactone
Mode of Action: Heparin acts as an anticoagulant by Bleeding complications: Antithrombin III,
enhancing the inhibition rate of clotting proteases such injection site bruising and/or bleeding: Deoxycholic acid,
as antithrombin III, whose action inhibits the activity of Nintedanib, Obinutuzumab, Iodine I131
clotting factors IXa, Xa, and thrombin (factor IIa). GI ulceration or irritation and/or bleeding: Deferasirox
Indications: Management of acute coronary syndrome, Reduces anticoagulant effect of Heparins:
peripheral artery occlusive disease and thrombosis or Antihistamines e.g., diphenhydramine, Digitalis,
thromboembolism. Nicotine, Nitroglycerine, Tetracyclines
Precautions: Avoid concomitant use with:
Enhances anticoagulant effect of Heparins:
WARNING: Bleeding is the major adverse effect of Apixaban, Dabigatran Etexilate, Streptokinase
anticoagulants. Hemorrhage may occur at virtually
any site. At recommended doses, single injections Enhances therapeutic effects of Rivaroxaban
do NOT significantly influence platelet aggregation (anticoagulant effect)
or affect global clotting time.
Increases risk of adverse or toxic effects (bleeding) of
May contain benzyl alcohol as a preservative. Use Heparins:
in neonates, infants, and pregnant or nursing Herbs with anticoagulant or antiplatelet properties, e.g.,
mothers has been associated with the Alfalfa, Anise, Bilberry, Vorapaxar
development of gasping syndrome in newborns.
Reduces anticoagulant effect of Heparins:
May contain sodium metabisulfite, which may Estrogen Derivatives, Progestins,
cause allergic-type reactions, including
anaphylactic symptoms and life-threatening
asthmatic episodes.
Rx ENOXAPARIN
Bleeding (discontinue if bleeding occurs; protamine may be
considered as a partial reversal agent in overdose Inj.: 100 mg/mL, 0.2 mL, 0.4 mL, and 0.6 mL pre-filled
situations); Thrombocytopenia; Hyperkalemia; GI syringe (SC) (as sodium salt)
ulceration; Renal impairment; Hepatic impairment;
Prosthetic heart valves; Low weight patients (risk of A low molecular weight heparin (LMWH). LMWHs strongly
bleeding may be increased in women <45 kg and in men inhibit factor Xa but have a small effect on the activated
<57 kg); Obesity (consult with a specialist regarding partial thromboplastin time. Enoxaparin has an
dosing in bariatric surgery patients and other obese approximate anti-factor Xa activity of 100 units/mg.
patients who may require higher LMWH doses); Surgical
patients (discontinue use 12–24 hours prior to CABG Indications: Management of acute coronary syndrome (e.g.,
and dose with unfractionated heparin as per institutional unstable angina, non-ST-elevation myocardial infarction
practice); Extreme body weights (use with caution in (NSTEMI), ST-elevation myocardial infarction (STEMI)),

45
 BLOOD AND BLOOD FORMING ORGANS

peripheral artery occlusive disease and thrombosis / Dose Adjustment:

thromboembolism (e.g., deep vein thrombosis (DVT)). Geriatric:
Dose adjustment may be required if renal impairment is
Contraindications: Thrombocytopenia associated with a present.
positive in vitro test for antiplatelet antibodies in the In patients ≥75 years being treated for STEMI, administer a
presence of enoxaparin; active major bleeding; In lower dose of 0.75 mg/kg every 12 hours and omit IV
B

neonates, infants, and pregnant or nursing mothers. bolus dose.

Dose:
NOTE: 1 mg enoxaparin = 100 units anti-Xa activity Renal Impairment:
Weight-based doses (e.g., 1 mg/kg) are commonly Primarily eliminated via the renal route. Reduce doses and
rounded to the nearest 10 mg. frequently monitor anti-Xa levels as accumulation may
Deep Vein Thrombosis (DVT) prophylaxis in abdominal occur with repeated doses.
surgery, by SC injection, ADULT, 40 mg once daily, with For patients with CrCl <30 mL/minute, if used for DVT
initial dose given 2 hours prior to surgery; continue until prophylaxis in abdominal surgery, hip replacement, knee
risk of DVT has diminished, usually 7–10 days. replacement, or in medical patients during acute illness,
DVT prophylaxis in hip replacement surgery, by SC injection, by SC injection, 30 mg once daily.
ADULT, 30 mg twice daily (every 12 hours), with initial For patients with CrCl <30 mL/minute, if used for DVT
dose within 12–24 hours after surgery, and every 12 treatment, for both inpatient or outpatient treatment in
hours for at least 10 days or until risk of DVT has conjunction with warfarin, by SC injection, 1 mg/kg once
diminished or the patient is adequately anticoagulated daily.
on warfarin; or For patients with CrCl <30 mL/minute, if used for STEMI, by
40 mg once daily, with initial dose within 9–15 hours SC injection, ADULT ≥75 years, maintenance, 1 mg/kg
before surgery, and daily for at least 10 days (or up to 35 once daily;
days postoperatively) or until risk of DVT has diminished by IV bolus, ADULT <75 years, initially 30 mg with the first
or the patient is adequately anticoagulated on warfarin. dose of the SC maintenance regimen (maintenance, by
DVT prophylaxis in knee replacement surgery, by SC SC injection, 1 mg/kg once daily.
injection, ADULT, 30 mg every 12 hours, with initial dose For patients with CrCl <30 mL/minute, if used for unstable
within 12–24 hours after surgery, and every 12 hours for angina or NSTEMI, by SC injection, ADULT 1 mg/kg once
at least 10 days or until risk of DVT has diminished or the daily.
patient is adequately anticoagulated on warfarin.
DVT prophylaxis in medical patients with severely restricted Obesity:
mobility during acute illness, by SC injection, ADULT, 40 Use actual body weight to calculate dose. Dose capping is
mg once daily; continue until risk of DVT has diminished, not recommended. Twice daily dosing preferred.
usually 6–11 days [NOTE: Start warfarin on the first or
second treatment day and continue enoxaparin until INR CONVERSION:
is ≥2 for at least 24 hours (usually 5–7 days)]. Conversion from IV unfractionated heparin (UFH)
DVT, acute treatment in inpatients with or without infusion to SC enoxaparin: Calculate specific dose for
pulmonary embolism, by SC injection, ADULT, 1 mg/kg enoxaparin based on indication. Discontinue UFH and
per dose every 12 hours or 1.5 mg/kg every 24 hours. begin enoxaparin within 1 hour.
DVT, acute treatment in outpatients without pulmonary
embolism, by SC injection, ADULT, 1 mg/kg per dose Conversion from SC enoxaparin to IV UFH infusion:
every 12 hours. Discontinue enoxaparin, calculate specific dose for IV
STEMI, by SC injection, ADULT ≥75 years, initially 0.75 UFH infusion based on indication. Omit heparin bolus or
mg/kg every 12 hours, do NOT administer by IV bolus loading dose.
(maximum dose, 75 mg for first 2 doses), for
maintenance, after the first 2 doses, 0.75 mg/kg every Converting from SC enoxaparin dosed every 12 hours:
12 hours; Start IV UFH infusion 10–11 hours after last enoxaparin
by IV bolus, ADULT <75 years, initially 30 mg once by IV dose.
bolus plus 1 mg/kg once by SC injection, followed by 1
mg/kg by SC injection, every 12 hours (maximum, 100 Converting from SC enoxaparin dosed every 24 hours:
mg for the first 2 doses). Start IV UFH infusion 22–23 hours after last enoxaparin
STEMI, maintenance, by SC injection, dose.
1 mg/kg every 12 hours (administer the first
maintenance dose 12 hours after the second SC dose) Precautions:
[NOTE: Therapy may be continued for up to 8 days or until WARNING: NOT to be used interchangeably (unit for
revascularization. Unless contraindicated, all patients unit) with heparin or any other LMWH.
should receive aspirin (indefinitely) and clopidogrel. In
patients with STEMI receiving thrombolytics, initiate NOT recommended for use in patients with current
enoxaparin dosing between 15 minutes before and 30 heparin-induced thrombocytopenia (HIT) or HIT with
minutes after fibrinolytic therapy.]. thrombosis due to high cross-reactivity to heparin-
Unstable angina or NSTEMI, by SC injection, ADULT, 1 platelet factor-4 antibody.
mg/kg every 12 hours in conjunction with oral aspirin
therapy; continue for the duration of hospitalization, at
least 2 days for up to 8 days.

46
BLOOD AND BLOOD FORMING ORGANS

Indications: Prophylaxis and treatment of thromboembolic

Epidural or spinal hematomas may occur in patients disorders (e.g, venous thromboembolism, acute arterial
who are anticoagulated with LMWHs or heparinoids thrombosis); acute coronary syndrome (e.g., unstable
and are receiving neuraxial anesthesia or angina, non-ST-elevation myocardial infarction (NSTEMI),
undergoing spinal puncture. May result in long-term ST-elevation myocardial infarction (STEMI));
or permanent paralysis. anticoagulant for extracorporeal and dialysis

B
procedures.
Renal impairment; Hepatic impairment; Elderly (increased
injection-associated bleeding and serious adverse Contraindications: Severe thrombocytopenia; uncontrolled
reactions; increased incidence of bleeding with doses of active bleeding except when due to disseminated
1.5 mg/kg daily or 1 mg/kg every 12 hours). intravascular coagulation (DIC); not for use when
appropriate blood coagulation tests cannot be obtained
Adverse Drug Reactions: at appropriate intervals; neonates; infants; pregnant or
Common: Confusion, pain, nausea, diarrhea, major nursing mothers
hemorrhage (intracranial, retroperitoneal, or
intraocular), moderate thrombocytopenia, anemia, Dose:
bruise, hematuria, fever, and hematoma, irritation, STEMI, as adjunct to fibrinolysis with full-dose alteplase,
bruising, erythema, or pain at injection site, reteplase, or tenecteplase, by IV infusion, ADULT, initially
Less Common: Alopecia, anaphylaxis, anaphylactoid 60 units/kg (maximum, 4000 units), then 12 units/kg
reaction, eczematous rash (plaques), eosinophilia, every hour (maximum, 1000 units/hour) as continuous
epidural hematoma after spinal puncture, headache, IV infusion, check aPTT every 4–6 hours; adjust to target
hepatic injury (hepatocellular and cholestatic), of 1.5–2 times the upper limit of control (50–70
hyperkalemia, hypersensitivity angiitis, hypersensitivity seconds); continue for a minimum of 48 hours,
reaction, osteoporosis (long-term use), pruritic preferably for the duration of hospitalization (up to 8
erythematous rash (patches), pruritus, purpura, days) or until revascularization.
retroperitoneal hemorrhage, severe anemia Unstable angina or NSTEMI, by IV bolus, ADULT, initially 60
(hemorrhagic), skin necrosis, thrombocythemia, units/kg (maximum, 4000 units) followed by an initial IV
thrombocytopenia, thrombosis (prosthetic valve; infusion of 12 units/kg every hour (maximum, 1000
enoxaparin-induced thrombocytopenia), shock, urticaria, units/hour); check aPTT every 4–6 hours; adjust to target
vesiculobullous rash of 1.5–2 times the upper limit of control (50–70
Rare: Intracranial hemorrhage seconds); recommended duration is 48 hours or until
percutaneous coronary intervention is performed
Administration: Administer by deep SC injection alternating Anticoagulation, intermittent administration, by IV infusion,
between the left or right anterolateral and left or right ADULT, initially 10,000 units, then 50 to 70 units/kg
posterolateral abdominal wall. (5,000–10,000 units) every 4–6 hours.
Maintenance of line patency or line flushing, by IV infusion,
Do NOT administer intramuscularly. ADULT and CHILD, 100 units/mL; INFANT, 10 units/mL
Do NOT rub injection site to minimize bruising. [NOTE: Capped PVC catheters and peripheral heparin
Do NOT expel the air bubble from the syringe prior to locks require flushing more frequently (e.g., every 6–8
injection to avoid loss of drug from the 30 mg and 40 mg hours). The volume of heparin flush is similar or slightly
prefilled syringes. greater than the volume of catheter. Additional flushes
Do NOT mix with other infusions or injections. should be given when stagnant blood is observed in
catheter, after catheter is used for drug or blood
See General Information on Heparin Group under administration, and after blood withdrawal from
Antithrombotic Agents for further information. catheter.].
Thromboprophylaxis for venous thromboembolism
Pregnancy Category: B prevention, by SC injection, ADULT, 5,000 units every 8–
12 hours; in acutely ill hospitalized medical patients at
ATC Code: B01AB05 increased risk of thrombosis and selected surgical
patients; and for a minimum of 10–14 days is
recommended for patients undergoing total hip
HEPARIN SODIUM arthroplasty, total knee arthroplasty, or hip fracture
Rx (UNFRACTIONATED, surgery.
Treatment in venous thromboembolism (VTE), by IV or SC
BOVINE ORIGIN) injection, ADULT, For patients starting intravenous
unfractionated heparin (UFH), the initial bolus and initial
Inj.: 1,000 IU/mL and 5,000 IU/mL, 5 mL and 30 mL vial
rate of the continuous infusion should be weight-
(IV infusion, SC)
adjusted (bolus 80 units/kg, immediately followed by 18
units/kg/hour for venous thromboembolism (VTE); bolus
It is a sulfated mucopolysaccharide prepared from the lungs
70 units/kg immediately followed by 15 units/kg/hour
of oxen or the intestinal mucosa of oxen, pigs, or sheep. for cardiac or stroke patients). Subsequent dose
Heparin inhibits clotting of blood by enhancing the action
adjustment should be guided by monitoring with
of antithrombin III, which inhibits the activity of activated
activated partial thromboplastin time (aPTT) testing 6
clotting factors including thrombin (factor IIa) and
hours after UFH bolus/infusion is started with
activated factor X (factor Xa).
therapeutic aPTT range of 1.5 – 2.5 times control. For
outpatients with VTE treated with subcutaneous UFH,

47
 BLOOD AND BLOOD FORMING ORGANS

use weight-adjusted dosing (first dose 333 units/kg, conjunctivitis (allergic reaction), lacrimation, hematuria,
then 250 units/kg after 12 hours and every 12 hours asthma, hemoptysis, pulmonary hemorrhage, rhinitis,
thereafter with no need for monitoring. Unless there are allergic reactions, anaphylactoid reactions, heparin
contraindications or further plans for surgery, start resistance, hypersensitivity (including chills, fever, and
warfarin on the first or second treatment day and urticaria)
continue heparin until INR is ≥2 for at least 24 hours Less Common: Erythematous plaques, bronchospasm
B

(usually 5–7 days).

Prophylaxis for cardiac catheterization, arterial approach, by TEST INTERACTIONS. Increased thyroxine level (competitive
IV bolus, CHILD, 100 units/kg. protein binding), increased PT
Systemic heparinization, by IV infusion, CHILD, initially 75
units/kg given over 10 minutes; adjust dose to maintain Precautions:
aPTT of 60–85 seconds (assuming this reflects an anti- Thrombocytopenia; Elderly (has higher serum levels and
factor Xa level of 0.35–0.7 units/mL); clinical response, e.g., longer aPTTs).
For maintenance, CHILD >1 year, 20 units/kg per hour;
CHILD <1 year, 28 units/kg per hour. NOTE: NOT interchangeable with Heparin lock flush
solution.
Pediatric Protocol for Systemic Heparin Adjustment:
Obtain blood for aPTT 4 hours after heparin loading dose Administration:
and 4 hours after every infusion rate change. For IV administration by continuous IV infusion, infuse
Obtain daily CBC and aPTT after aPTT is therapeutic. via infusion pump. If preparing solution, mix thoroughly
prior to administration.

aPTT Time to For IV administration via heparin lock, inject via injection
Dose Adjustment cap using positive pressure flushing technique.
(seconds) repeat aPTT
50 units/kg bolus
4 h after rate For IV administration by central venous catheters, flush
<50 and increase rate by
change with heparin solution when newly inserted, daily at the
10%.
time of tubing change, after blood withdrawal or
Increase infusion 4 h after rate transfusion, and after an intermittent infusion through
50-59
rate by 10%. change an injectable cap. At least 10 mL of blood should be
60-85 Keep rate the same. Next day removed and discarded from a heparinized line before
blood samples are sent for coagulation testing.
Decrease infusion 4 h after rate
86-95
rate by 10%. change For SC administration, injection sites should be rotated,
Hold infusion for 30 usually left and right portions of the abdomen, above iliac
minutes and 4 h after rate crest.
96-120
decrease infusion change
rate by 10%. Do NOT administer by IM due to pain, irritation, and
Hold infusion for 60 hematoma formation.
minutes and 4 h after rate
>120
decrease infusion change NOTE:
rate by 15%. Do NOT use 100 unit/mL concentration to flush heparin
locks, IV lines, or intra­arterial lines in neonates or infants
Dose Adjustment: <10 kg as systemic anticoagulation may occur.
Geriatric:
Lower doses may be required. The 10 unit/mL flush concentration may inadvertently
cause systemic anticoagulation in infants <1 kg who
Renal and Hepatic Impairment: receive frequent flushes.
No dose adjustment required. Adjust therapeutic heparin
according to aPTT or anti-Xa activity. See General Information on Heparin Group under
Antithrombotic Agents for further information.
Adverse Drug Reactions:
Common: Allergic vasospastic reaction, chest pain, Pregnancy Category: C
hemorrhagic shock, shock, thrombosis, chills, fever,
headache, alopecia, unexplained bruising, cutaneous ATC Code: B01AB01
necrosis, dysesthesia pedis, eczema, urticaria, purpura,
adrenal hemorrhage, hyperkalemia, ovarian
hemorrhage, rebound hyperlipidemia on
discontinuation, constipation, hematemesis, nausea, Rx TINZAPARIN
tarry stools, vomiting, frequent or persistent erection,
bleeding from gums, epistaxis, hemorrhage, ovarian Inj.: 10,000 anti-Xa IU/mL, 0.35 mL and 0.45 mL pre-filled
hemorrhage, retroperitoneal hemorrhage, syringe (SC) (as sodium)
thrombocytopenia, liver enzymes increased, irritation, 10,000 anti-Xa IU/mL, 2 mL vial (SC) (as sodium)
erythema, pain, hematoma, and ulceration have been
rarely reported with deep SC injections, peripheral A low molecular weight heparin with anticoagulant
neuropathy, osteoporosis (chronic therapy), properties used in the prevention and treatment of

48
BLOOD AND BLOOD FORMING ORGANS

venous thromboembolism and to prevent clotting during dose as necessary in increments of 500 anti-Xa units based on
extracorporeal circulation. previous outcome];
For dialysis sessions ≤4 hours with hemorrhage risk,
Indications: Treatment of deep vein thrombosis (DVT) initially 2,250 anti-Xa units at beginning of dialysis [NOTE:
and/or pulmonary embolism (PE) (except in patients with Do NOT add to dialysis circuit. For subsequent dialysis sessions,
adjust dose as necessary to achieve plasma concentrations of
severe hemodynamic instability) ; prevention of venous
0.2­0.4 anti-Xa units/mL].

B
thromboembolism (VTE) following orthopedic surgery or
following general surgery in patients at high risk of VTE;
prevention of clotting in indwelling intravenous lines and Dose Adjustment:
extracorporeal circuit during hemodialysis (in patients Geriatric:
Use is not recommended in patients >70 years of age with
without high bleeding risk).
renal impairment.
Contraindications: Active bleeding; history of confirmed or
suspected immunologically mediated heparin-induced Renal Impairment:
thrombocytopenia (HIT) or positive in vitro platelet For patients with CrCl ≥30 mL/minute, no dose adjustment
aggregation test in the presence of tinzaparin; acute or needed provided it primarily undergoes renal
subacute endocarditis; generalized hemorrhage elimination.
tendency and other conditions involving increased risks For patients with CrCl <30 mL/minute, consider dose
of hemorrhage (e.g., severe hepatic insufficiency, reduction.
imminent abortion); hemophilia or major blood clotting
disorders; acute cerebral insult or hemorrhagic Hepatic Impairment:
cerebrovascular accidents without systemic emboli; No dosage adjustment needed provided it does not undergo
uncontrolled severe hypertension; diabetic or hepatic metabolism.
hemorrhagic retinopathy; injury or surgery involving the
brain, spinal cord, eyes or ears; spinal / epidural Precautions:
anesthesia in patients requiring treatment dosages of WARNING: Contraindicated in patients with HIT or HIT with
tinzaparin; use of multi-dose vials containing benzyl thrombosis due to high cross-reactivity to heparin-platelet
alcohol in children <2 years of age, premature infants, factor­4 antibody.
and neonates; pregnant or nursing mothers
Hepatic impairment (use with caution); Renal impairment
Dose: (use with caution); Elderly (increased sensitivity may be
NOTE: 1 mg of tinzaparin equals 70­120 units of anti-Xa possible due to a decline in renal function).
activity.
Adverse Drug Reactions:
DVT and/or PE, treatment, by SC injection, ADULT, 175 anti- Common: chest pain, angina pectoris, arrhythmia, coronary
Xa units/kg once daily (maximum, 18,000 anti-Xa thrombosis or MI, dependent edema, thromboembolism,
units/day), start warfarin on the first or second treatment fever, headache, pain, bullous eruption, erythematous
day and continue tinzaparin until INR is ≥2 for at least 24 rash, maculopapular rash, skin necrosis, nausea,
hours, usually 5–7 days [NOTE: May use body weight dosing abdominal pain, constipation, diarrhea, vomiting, urinary
using prefilled syringes]. tract infection, bleeding events, granulocytopenia,
DVT, prophylaxis in hip replacement surgery, by SC injection, thrombocytopenia, injection site hematoma or cellulitis,
ADULT, preoperative regimen, 50 anti-Xa units/kg given back pain, epistaxis, dyspnea, allergic reaction,
2 hours preoperatively followed by 50 anti-Xa units/kg neoplasm.
once daily for 7–10 days; Less Common: Agranulocytosis, angioedema,
postoperative regimen, 75 anti-Xa units/kg once daily, anaphylactoid reaction, hemoptysis, hypoaldosteronism,
with initial dose given postoperatively and continued for hyperkalemia, metabolic acidosis, ocular hemorrhage,
7–10 days [NOTE: Initiate of LMWH ≥12 hours preoperatively or osteopenia, osteoporosis, priapism, pruritus, rash, spinal
≥12 hours postoperatively, may extend duration up to 35 days]. epidural hematoma, Stevens-Johnson syndrome,
DVT, prophylaxis in knee replacement surgery, by SC thrombocytosis, toxic epidermal necrolysis, urticaria.
injection, ADULT, 75 anti-Xa units/kg once daily, with
initial dose given postoperatively and continued for 7–10 Administration: For SC use only.
days [NOTE: Initiate of LMWH ≥12 hours preoperatively or ≥12
hours postoperatively, may extend duration up to 35 days; may Administer by deep SC injection into the lower abdomen,
use body weight dosing using prefilled syringes]. outer thigh, lower back, or upper arm. Patient should be
DVT, prophylaxis in general surgery, by SC injection, ADULT, lying down or sitting. Vary injection site daily.
3,500 anti-Xa units once daily, with initial dose given 2
hours prior to surgery and then continued Do NOT rub the injection site to minimize bruising.
postoperatively for 7–10 days.
Anticoagulant in extracorporeal circuit during hemodialysis, May be administered by IV injection in hemodialysis
for stable patients with chronic renal failure, by IV bolus, patients.
ADULT, for dialysis session ≤4 hours and no hemorrhage
risk, initially 4,500 anti-Xa units at beginning of dialysis, Do NOT administer by IM route and avoid IM
typically achieves plasma concentrations of 0.5–1 anti- administration of other medications due to the risk of
Xa units/mL, may give larger bolus for dialysis sessions hematoma formation.
>4 hours; [NOTE: For subsequent dialysis sessions, may adjust

49
 BLOOD AND BLOOD FORMING ORGANS

See General Information on Heparin Group under Adverse Drug Reactions:

Antithrombotic Agents for further information. Common: Abdominal pain, asymptomatic blood loss, back
pain, increased bleeding time, diarrhea, dyspepsia,
Pregnancy Category: B dyspnea, epistaxis, fatigue, GI irritation, headache,
malaise, melena, nausea, vomiting.
ATC Code: B01AB10 Less Common: Anorexia, asthenia, confusion, dizziness,
B

fever, flushing, gastritis, hemorrhage rectum,

hemorrhoids, hyperglycemia, hypoglycemia (children),
PLATELET AGGREGATION INHIBITORS, EXCLUDING hypotension, myalgia, palpitations, syncope,
HEPARIN tachycardia, thirst, tinnitus, vertigo.
Rare: Arrhythmia, convulsions, deafness, edema, GI ulcer
and perforation, intracranial hemorrhage,
Rx ASPIRIN hypersensitivity reactions (including Stevens-Johnson
syndrome); interstitial nephritis, iron-deficiency anemia,
Oral: 80 mg, 100 mg, 300 mg, and 325 mg tablet myocarditis, paresthesia, renal insufficiency, seizures,
thrombocytopenia, toxic epidermal necrolysis.
An irreversible, cyclo-oxygenase (COX) inhibitor, which
inhibits platelet aggregation. It is useful in the long-term Drug Interactions:
management and prevention of MI and stroke, Monitor closely with:
Enhances therapeutic effects of the following drugs:
Indications: Primary prevention of acute MI and stroke in Oral Hypoglycemics (hypoglycemic effect), Phenytoin,
patients with risk factors; secondary prevention of Valproic Acid
thrombotic cardiovascular or cerebrovascular disease,
and following bypass surgery; management of acute MI Increases risk of adverse or toxic effects of the following
and acute ischemic stroke. drugs:
Anticoagulant Therapy, e.g., Heparin, Warfarin
Contraindications: Children and adolescents <16 years (risk (bleeding), Corticosteroids (GI bleeding and ulceration),
of Reye’s syndrome); active peptic ulceration or bleeding Valproic Acid (increases effects on blood coagulation
GI ulcers; hemophilia and other bleeding disorders; and platelet function)
aspirin-sensitive asthma; thrombocytopenia; ulcerative
colitis; lactating mothers; acute hemorrhagic stroke or Avoid concomitant use with:
intracerebral bleeding. Increases excretion of Aspirin by alkaline urine:
Antacids, e.g., Aluminum and Magnesium Hydroxide
Dose:
Acute ischemic infarction, by mouth, ADULT, 80–100 mg Increases risk of adverse or toxic effects of the following
once daily. drugs:
Transient ischemic attack (early specific treatment), by ACE Inhibitors, e.g., Enalapril (renal impairment with
mouth, ADULT, 50–325 mg once daily. Aspirin doses of >300 mg daily), NSAIDs, e.g., Ibuprofen,
Prophylaxis of myocardial infarction or cerebrovascular Naproxen (gastric ulceration)
disease, by mouth, ADULT, 80–100 mg once daily.
Treatment of acute MI, by mouth, ADULT, 160–300 mg Reduces therapeutic effect of the Aspirin:
once daily. NSAIDs, e.g., Ibuprofen, Naproxen (anti-platelet activity
of low-dose aspirin)
Dose Adjustment:
Renal Impairment: Reduces therapeutic effect of the following drugs:
For mild-to-moderate impairment (CrCl >10 mL/min), dose ACE Inhibitors, e.g., Enalapril (hyponatremic and
adjustments are not necessary. hypotensive effect), Diuretics, e.g., Spironolactone
For severe impairment, use is not recommended. (inhibition of renal prostaglandins), NSAIDs, e.g.,
Ibuprofen, Naproxen (cardioprotective effect)
Hepatic Impairment:
Avoid use in severe liver disease. Administration: Take tablets from packaging just before use.
Should be taken with food or immediately after meals.
Precautions:
Gastritis and GI bleeding; Asthma; Urticaria; Allergic Pregnancy Category: C; D in 3rd trimester
disease; Uncontrolled hypertension; Dehydration; Gout;
Renal impairment (avoid use); hepatic impairment; ATC Code: B01AC06
G6PD-deficiency; Elderly; Pregnancy (use in third
trimester may lead to impaired platelet function and risk
of hemorrhage, delayed onset and increased duration of
labor with increased blood loss; avoid analgesic doses in
the last few weeks; with high doses, closure of fetal
ductus arteriosus in utero and possibly persistent
pulmonary hypertension in the newborn; risk of
kernicterus in jaundiced neonates; risk of Reye’s
syndrome).

50
BLOOD AND BLOOD FORMING ORGANS

epistaxis, esophageal hemorrhage, esophagitis, facial

Rx CILOSTAZOL edema, fever, furunculosis, gastric ulcer, gastritis,
gastroenteritis, gingival hemorrhage, gout,
Oral: 50 mg and 100 mg tablet hematemesis, hemorrhage, hemorrhage (eye),
50 mg (20% w/w) powder, 0.25 g sachet hemoptysis, hyperuricemia, hypotension, insomnia, iron
100 mg (20% w/w) powder, 0.5 g sachet deficiency anemia, malaise, melena, myocardial

B
infarction, neck stiffness, neuralgia, nodal arrhythmia,
A quinolinone derivative selective phosphodiesterase (PDE) orthostatic hypotension, ostealgia, otalgia, pelvic pain,
type III inhibitor with antiplatelet and vasodilating peptic ulcer, periodontal abscess, pneumonia,
activity. It prevents the degradation of cyclic adenosine- polycythemia, purpura, rectal hemorrhage, retinal
3′,5′-monophosphate (cAMP) in platelets and blood hemorrhage, retroperitoneal hemorrhage, sinusitis, skin
vessels resulting in arterial vasodilation and inhibition of hypertrophy, supraventricular tachycardia, syncope,
platelet aggregation. tinnitus, tongue edema, urinary frequency, urticaria,
vaginal hemorrhage, vaginitis, varicose veins,
Indication: Reduction of symptoms of intermittent vasodilation, ventricular premature contractions,
claudication. ventricular tachycardia, xeroderma.
Rare: Abnormal hepatic function tests, agranulocytosis,
Contraindications: Heart failure; hemostatic disorders or aplastic anemia, cerebrovascular accident, chest pain,
active pathologic bleeding, such as bleeding peptic ulcer coronary thrombosis (stent), fixed drug eruption,
or intracranial bleeding. gastrointestinal hemorrhage, granulocytopenia,
hematoma (extradural), hemorrhagic diathesis, hepatic
Dose: insufficiency, hot flash, hyperglycemia, increased blood
Intermittent claudication, by mouth, ADULT, 100 mg twice pressure, interstitial pneumonitis, intracranial
daily in combination with Aspirin or Clopidogrel. hemorrhage, jaundice, leukopenia, pain, pulmonary
hemorrhage, pruritus, prolonged Q­T interval on ECG,
NOTE: Discontinue treatment if symptoms are not improved Stevens-Johnson syndrome, subdural hematoma,
after 3 months of therapy. thrombocytopenia, thrombosis, torsade de pointes.

Dose Adjustment: Drug Interactions:

Renal Impairment: NOTE: Cilostazol is a weak inhibitor of CYP3A4.
In patients with CrCl <25 mL/minute, use is
contraindicated. Severe. Monitor closely with:
In patients with end-stage renal disease (ESRD) and on Enhances therapeutic effect of Cilostazol:
dialysis, dose adjustment has not been studied, antiplatelet effect: Agents with Antiplatelet Properties,
however, high protein binding makes removal by dialysis e.g., P2Y12 Inhibitors, NSAIDs, SSRIs; Glucosamine;
unlikely. Multivitamins / Fluoride with Vitamins ADE;
Multivitamins / Minerals with Vitamins ADEK, Folate,
Hepatic Impairment: Iron; Multivitamins / Minerals with Vitamins AE, no Iron;
Use with caution in patients with moderate to severe Omega­3 Fatty Acids; Vitamin E; Pentoxifylline,
impairment. Dose adjustment has not been studied. Prostacyclin Analogues
anticoagulant effect: Other Anticoagulants, Thrombolytic
Concomitant Medications: Agents
CYP2C19 Inhibitors, e.g., Fluconazole, Omeprazole and
Strong or Moderate CYP3A4 Inhibitors, e.g., Diltiazem, Increases risk of adverse or toxic effects of Cilostazol:
Erythromycin, Itraconazole, Ketoconazole, ADULT, 50 mg Anagrelide, Ibrutinib
Cilostazol twice daily.
Increases risk of adverse or toxic effects of the following
Precautions: drugs:
Cardiovascular effects; Cardiovascular disease; Hemostatic Bleeding: Deoxycholic Acid, Obinutuzumab, Salicylates
disorders (avoid use); Hematologic effects; Hepatic (bleeding), Iodine I131
impairment; Renal impairment; Elderly (must be
evaluated for cardiac status; CHF is common among Avoid concomitant use with:
elderly); Lactation Decreases serum concentration of Cilostazol:
Dabrafenib
Adverse Drug Reactions:
Common: Headache, abnormal stools, diarrhea, increased Enhances anticoagulant effect of Cilostazol:
susceptibility to infection, rhinitis, peripheral edema, Dabigatran Etexilate
palpitations, tachycardia, dizziness, vertigo, dyspepsia,
nausea, abdominal pain, flatulence, back pain, myalgia, Enhances therapeutic effect of Rivaroxaban (Anticoagulant
pharyngitis, cough. effect)
Less Common: Albuminuria, amblyopia, anemia, anorexia,
anxiety, arthralgia, asthma, atrial fibrillation, atrial flutter, Increases risk of adverse or toxic effects of Cilostazol:
blindness, bursitis, cardiac arrest, cardiac failure, Herbs with anticoagulant or antiplatelet properties, e.g.,
cerebral infarction, chills, cholelithiasis, colitis, Alfalfa, Anise, Bilberry (bleeding); Grapefruit Juice;
conjunctivitis, cystitis, diabetes mellitus, diplopia, Stiripentol
duodenal ulcer, duodenitis, ecchymoses, edema,

51
 BLOOD AND BLOOD FORMING ORGANS

Increases risk of adverse or toxic effects of Apixaban Transient ischemic attack, early specific treatment), by
(bleeding) mouth, ADULT, 75 mg once daily.

Increases serum concentration of Cilostazol: Dose Adjustment:

Fusidic Acid (systemic), Grapefruit Juice Renal Impairment:
For mild-to-moderate impairment, dose adjustment is not
B

Increases serum concentration of Dabigatran Etexilate required.

For severe impairment, refer patient to a specialist.
FOOD INTERACTION. A high-fat meal may increase peak concentration
by 90% and increase AUC by 25% Precautions:
WARNING: CYP2C19 Inhibition and Poor Metabolizers:
Administration: Administer 30 minutes before or 2 hours
Effectiveness depends on activation to active
after meals (breakfast and dinner).
metabolite by cytochrome P450 system, principally
CYP2C19. May be less effective in poor metabolizers
Pregnancy Category: C
lacking CYP2C19. Poor metabolizers exhibit higher
cardiovascular event rates after acute coronary
ATC Code: B01AC23
syndrome or percutaneous coronary intervention at
recommended doses. >50% of Asians have CYP2C19
genetic variants that inhibit Clopidogrel metabolism.
Rx CLOPIDOGREL Use of CYP2C19 inhibitors (Proton Pump Inhibitors)
or use in poor metabolizers may decrease
antiplatelet effect.
Oral: 75 mg tablet
Patients at risk of increased bleeding from trauma,
A thienopyridine-derived, platelet aggregation inhibitor that surgery, or other pathological conditions;
has no effect on prostaglandin metabolism unlike patients taking medications that increase
aspirin. It is used as an alternative for patients who are risk of bleeding; patients allergic to aspirin
unable to take aspirin in the treatment of thrombosis. who are undergoing PCI; History of bleeding or
hemostatic disorders; bleeding diathesis; ulcers; renal
Indications: Prevention of atherothrombotic events in: impairment; hepatic impairment; Surgery (may need to
peripheral arterial disease, or within 35 days of MI, or discontinue 5-10 days before surgical procedure);
within 6 months of ischemic stroke; in acute coronary Pregnancy (avoid use if possible).
syndrome without ST-segment elevation (unstable
angina or non-Q wave MI), including patients undergoing Adverse Drug Reactions:
stent placement following percutaneous coronary Common: Abdominal pain, bleeding, chest pain,
intervention (in combination with aspirin); in acute MI depression, diarrhea, dyspepsia, flu-like syndrome,
with ST-segment elevation, and in combination with ASA hemorrhage, rhinitis, upper respiratory tract infection,
in medically-treated patients eligible for thrombolytic urinary tract infection, urticaria.
therapy; in patients with atrial fibrillation where oral Less Common: Constipation, dizziness, flatulence, gastritis,
anticoagulation is unsuitable; neurologic indications; GI ulcer, headache, leukopenia, nausea, paresthesia,
transient ischemic attack and acute ischemic cerebral pruritus, rash, vomiting
infarction (for early specific treatment or secondary Rare: Acute liver failure, agranulocytosis, angioedema,
prevention of ischemic stroke). aplastic anemia, bronchospasm, colitis, confusion,
exfoliative dermatitis, hallucinations, hepatitis,
Contraindications: Severe liver impairment; intracranial hypersensitivity-like reactions, hypotension, interstitial
hemorrhage, peptic ulcer or other pathological bleeding; pneumonitis, lichen, myalgia, neutropenia, pancreatitis,
breastfeeding. Stevens-Johnson syndrome (SJS), stomatitis,
Dose: thrombocytopenia, thrombotic thrombocytopenic
Acute coronary syndrome, unstable angina or NSTEMI, by purpura, vasculitis
mouth, ADULT, 300 mg loading dose, then 75 mg daily
in combination with aspirin 75–100 mg daily. Drug Interactions:
Acute coronary syndrome, STEMI, by mouth, ADULT, 75 mg NOTE: CYP2C19 enzyme metabolizes Clopidogrel to its
daily (in combination with aspirin 162–325 mg daily, active metabolite. Combining Clopidogrel with CYP2C19
then 81–162 mg daily). Inhibitors (e.g. Omeprazole) of may decrease its efficacy.
Acute ischemic infarction and secondary prevention of
acute ischemic stroke, by mouth, ADULT, 75 mg once Monitor closely with:
daily. Enhances therapeutic effect of Clopidogrel:
Coronary artery disease, by mouth, ADULT, 75 mg once Carbamazepine. Rifampin
daily.
Recent MI, stroke, or established peripheral arterial Increases risk of adverse or toxic effects when used in
disease, by mouth, ADULT, 75 mg daily [NOTE: combination with the following drugs:
Recommended as alternative to aspirin, or Anticoagulants, e.g., Warfarin (bleeding); Aspirin
concomitantly with aspirin if patient is not at increased (unusual bleeding, severe abdominal pain, weakness,
risk for bleeding but at high risk for cardiovascular black stools); drugs which can affect the clotting process,
disease]. e.g. NSAIDs, other Antiplatelets (bleeding; inhibits
platelet aggregation)

52
BLOOD AND BLOOD FORMING ORGANS

Vitamins ADEK, Folate, Iron; Multivitamins/ Minerals

Reduces therapeutic effect of Clopidogrel: with Vitamins AE, no Iron; Omega­3 Fatty Acids;
Atorvastatin (blood clotting), Clarithromycin, Pentoxifylline; Prostacyclin Analogues; Vitamin E
Erythromycin, Isoniazid
Enhances therapeutic effect of Dipyridamole:
Avoid concomitant use with: Hypotensive effect: Barbiturates e.g., Phenobarbital;

B
Reduces antiplatelet effect of Clopidogrel by reducing Nicorandil; Risperidone
formation of its active metabolite:
Proton Pump Inhibitors, e.g., Omeprazole, Esomeprazole Enhances therapeutic effect of Beta Blockers (bradycardic
effect) [except Levobunolol, Metipranolol]
Administration: May be taken with or without food. Increases risk of adverse or toxic effects of Dipyridamole:
Ibrutinib; Other Hypotensive Agents
Pregnancy Category: B
Increases risk of adverse or toxic effects of the following
ATC Code: B01AC04 drugs:
Bleeding: Deoxycholic Acid; Obinutuzumab; Salicylates
e.g. Aspirin; Iodine 131; Ibritumab
Orthostatic hypotensive effect: Duloxetine
Rx DIPYRIDAMOLE Levodopa

Oral: 25 mg tablet Reduces therapeutic effect of Acetylcholinesterase

Inhibitors e.g. Physiostigmine
A non-nitrate coronary vasodilator that inhibits platelet
aggregation. It inhibits phosphodiesterase and Avoid concomitant use with:
adenosine reuptake. Enhances therapeutic effect of Rivaroxaban (anticoagulant
effect)
Indications: Secondary prevention of stroke in patients with
a history of non-cardioembolic ischemic stroke or TIA Increases risk of adverse or toxic effects of Adenosine
(preferably with aspirin); to decrease thrombosis after (cardiovascular effects; Apixaban (bleeding)
artificial heart valve replacement (with warfarin).
Increases risk of adverse or toxic effects of Dipyridamole:
Dose: Herbs with anticoagulant or antiplatelet properties, e.g.,
Adjunctive therapy for prophylaxis of thromboembolism with Alfalfa, Anise, Bilberry (bleeding)
cardiac valve replacement, by mouth, ADULT, 75–200
mg 4 times daily. Increases serum concentration of the following drugs:
Afatinib (reduce Afatinib by 10mg if not tolerated);
Colchicine (increase distribution into certain tissues,
Dose Adjustment: e.g., brain); Dabigatran Etexilate [active metabolites];
Geriatric: Doxorubicin (conventional); Everolimus [reduce doses if
Avoid use due to risk of orthostatic hypotension. used for subependymal giant cell astrocytoma or renal
cell carcinoma]; Pazopanib; Silodosin; Topotecan;
Precautions: Vincristine (liposomal)
Cardiovascular disease (use with caution in patients with
hypotension, unstable angina, and/or recent MI); hepatic Administration: Administer with water 1 hour before meals.
impairment; Elderly (use with caution); Lactation (use
with caution). NOTE: Preferably used in combination with aspirin. When
used concomitantly with aspirin, consider the cautions,
Adverse Drug Reactions: precautions, and contraindications associated with
Common: Dizziness, headache, skin rash, pruritus, aspirin.
abdominal distress, diarrhea, vomiting, hepatic
insufficiency. Pregnancy Category: B
Less Common: Alopecia, arthritis, cholelithiasis, dyspepsia,
fatigue, hepatitis, hypersensitivity reaction, hypotension, ATC Code: B01AC07
laryngeal edema, malaise, myalgia, nausea, palpitations,
paresthesia, tachycardia, thrombocytopenia.

Drug Interactions:
Monitor closely with:
Enhances anticoagulant effect of Dipyridamole:
Other Anticoagulants e.g., Warfarin, Heparin;
Thrombolytic Agents e.g., Streptokinase

Enhances antiplatelet effect of Dipyridamole:

Agents with Antiplatelet Properties, e.g., P2Y12
Inhibitors, NSAIDs, SSRIs; Glucosamine; Multivitamins/
Fluoride with Vitamins ADE; Multivitamins/ Minerals with

53
 BLOOD AND BLOOD FORMING ORGANS

ENZYMES Rare: Anaphylaxis, other hypersensitivity reactions.

Drug Interactions:
HUMAN RECOMBINANT TISSUE Monitor closely with:
Rx TYPE PLASMINOGEN ACTIVATOR Increases risk of adverse or toxic effects of Alteplase:
(ALTEPLASE) Orolingual angioedema: ACE Inhibitors e.g. Enalapril
B

Hemorrhage: Anticoagulants e.g., Warfarin; Antiplatelet

Inj.: 50 mg powder (IV infusion) Agents, e.g., Aspirin; Clopidogrel; Dipyridamole, GP
IIb/IIIa Inhibitors e.g. Abciximab
A recombinant DNA-derived form of human tissue-type
plasminogen activator (t-PA) used as a thrombolytic Administration:
agent. The agent t-PA promotes thrombolysis by forming Reconstitution of 50-mg vial:
the active proteolytic enzyme plasmin, which is capable Use a large-bore needle, e.g., 18-gauge. Do NOT prime
of degrading fibrin, fibrinogen, and factors V, VIII, and XII. needle with air. Dilute contents of vial with SWFI supplied
by manufacturer. Direct the stream of sterile water into
Indication: Management of acute ischemic stroke (within 0– the lyophilized cake. Slight foaming is normal. Allow to
4.5 hours of symptom onset). stand until bubbles dissipate. The resulting
concentration is 1 mg/mL.
Contraindications: Active internal bleeding; history of Start IV infusion as soon as possible after the
cerebrovascular accident; recent (within 2 months) thrombolytic event, preferably within 6 hours. Administer
intracranial or interspinal surgery or trauma; intracranial drug as reconstituted or further diluted with an equal
neoplasm; arteriovenous malformation; bleeding volume of NS or D5W to yield 0.5 mg/mL. Administer 5
disorders; severe uncontrolled hypertension; likelihood mg as an initial bolus over 1 minute, then give the
of left heart thrombus; acute pericarditis; bacterial remainder of the 0.75 mg/kg dose over 60 minutes.
endocarditis; severe liver dysfunction; age >75; Follow infusion with an IV flush of 30–50 mL of NS or
pregnancy; septic thrombophlebitis; concomitant use of D5W.
oral anticoagulants.
Do NOT exceed a total dose of 100 mg (higher doses
Dose: have been associated with intracranial bleeding).
NOTE: Each 1 mg of Alteplase provides 580,000 units of
human recombinant tissue plasminogen activator Do NOT use if vacuum in vial has been broken.
activity.
NOTE: Spontaneous bleeding occurs twice as often with
Acute ischemic stroke or thrombotic stroke, by IV infusion, Alteplase than Heparin. Avoid invasive procedures. IM
ADULT, 0.9 mg/kg over 60 minutes with 10% of dose as injections are contraindicated. Avoid physical
an initial bolus over 1 minute (maximum, 90 mg). manipulation of patient during thrombolytic therapy to
prevent bruising.
Precautions:
Pregnancy Category: C
WARNING: Avoid administration of Aspirin or IV
Heparin within the first 24 hours after treatment. if ATC Code: B01AD02
heparin is required for other indications, do NOT
exceed 10,000 units per day (SC).

If bleeding occurs, stop the infusion, then resume

Rx STREPTOKINASE
when bleeding stops. Report any signs of bleeding.
Inj.: 1,500,000 IU powder, vial (IV infusion)
Stop therapy immediately if dysrhythmias occur.
A derivative of the beta-hemolytic streptococci. It promotes
thrombolysis by activating the conversion of
Recent major surgery (within 10 days); risk of bleeding from plasminogen to plasmin, the enzyme that degrades
venipuncture or invasive procedures; cerebral vascular fibrin, fibrinogen, and other procoagulant proteins. It
disease; acute stroke; recent GI or GU bleeding; recent decreases blood and plasma viscosity and erythrocyte
trauma; Conditions in which thrombolysis might give rise aggregation tendency, thus increasing perfusion of
to embolic complications such as enlarged left atrium collateral blood vessels.
with atrial fibrillation; Hypertension; Hemorrhagic
ophthalmic conditions; External chest compression; Indications: Management of acute myocardial infarction
Recent or concurrent use of drugs that increase risk of (within 12 hours of onset) with persistent ST-segment
bleeding; Elderly; Children; Lactation. elevation or left bundle-branch block; for the lysis of
acute arterial thrombi or emboli; management of
Adverse Drug Reactions: extensive acute proximal deep vein thrombosis (DVT)
Common: Internal and superficial bleeding (cerebral, and acute massive pulmonary embolism (PE).
retroperitoneal, GU, GI), hemorrhage at injection site,
increased blood pressure, decreased pulse, coronary Contraindications: Hypersensitivity to Anistreplase aside
artery reperfusion events (e.g., rhythm disorders, from Streptokinase; recent internal bleeding; recent
nausea, vomiting, headache, muscle pain, fever. stroke, intracranial or intraspinal surgery or head trauma

54
BLOOD AND BLOOD FORMING ORGANS

(within 2 months); recent major or invasive operation tachycardia, chills, fever, headache, malaise,
(within 6–10 days); intracranial neoplasm or other ecchymoses, pruritus, rash, urticaria, diarrhea, epigastric
neoplasm with risk of hemorrhage, arteriovenous pain, gastrointestinal hemorrhage, nausea, vomiting,
malformation, or aneurysm; known bleeding diathesis; genitourinary hemorrhage, angioedema, bleeding at
spontaneous fibrinolysis and extensive clotting injection site, back pain, muscle pain, weakness, eye
disorders; severe uncontrolled hypertension (systolic BP hemorrhage, periorbital edema, bronchospasm,

B
>200 mmHg and/or diastolic BP >100 mmHg); dyspnea, epistaxis, pulmonary edema.
hypertensive retinopathy (grade III or IV); acute Less Common: Agitation, allergic reactions, anaphylactic
pancreatitis; severe renal impairment; severe hepatic shock, anaphylactoid reactions, anaphylaxis, arthritis,
impairment; endocarditis or pericarditis; concurrent oral cardiac arrest, cardiac tamponade, confusion, dizziness,
anticoagulant therapy (INR >1.3). embolism, erysipelas-like rash, Guillain-Barré syndrome,
hemarthrosis, hemiparesis, intracranial hemorrhage,
Dose: iridocyclitis, iritis, laryngeal edema, major hemorrhage,
ST-elevation myocardial infarction (STEMI), by IV infusion, mitral valve insufficiency, myocardial rupture,
ADULT, 1.5 million units over 1 hour; may administer noncardiogenic pulmonary edema, paralysis, pericardial
second dose if re-occlusion occurs within 5 days of initial effusion, pericardial epistaxis, polyneuropathy,
dose. pulmonary embolism, respiratory arrest, respiratory
Deep vein thrombosis, by IV infusion, ADULT, 250,000 units depression, retroperitoneal hemorrhage, serum
over 30 minutes, followed by 100,000 units/hour for sickness, shock, splenic rupture, thrombolytic drug-
24–72 hours; induced cholesterol embolism, uveitis, vasculitis.
alternative (high-dose) regimen, day 1, initially 250,000
units over 30 minutes followed by 1.5 million units/hour Drug Interactions:
for up to a maximum of 6 hours; days 2 and 3, if needed, Monitor closely with:
may repeat infusion of 1.5 million units/hour for 6 hours Enhance therapeutic effect of Streptokinase:
once daily. Anticoagulant effect: Agents with antiplatelet properties,
Pulmonary embolism, by IV infusion, ADULT, initially e.g., P2Y12 inhibitors, NSAIDs, SSRIs; Other
250,000 units over 30 minutes, followed by 100,000 Anticoagulants
units/hour for 24–72 hours; Hypotensive effect: Barbiturates e.g. Phenobarbital;
alternative accelerated regimen, 1.5 million units Nicorandil
administered over 2 hours.
Peripheral arterial thrombosis or embolism, by IV infusion, Enhances therapeutic effect of the following drugs:
ADULT, initially, 250,000 units over 30 minutes, followed Dabigatran Etexilate (anticoagulant effect); Risperidone
by 100,000 units/hour for 24 to 72 hours. (hypotensive effect)

Dose Adjustment: Increases risk of adverse or toxic effects of the following

Renal and Hepatic Impairment: drugs:
For patients with severe impairment, use is contraindicated. Orthostatic hypotensive effect: Duloxetine; Hypotensive
Agents
Precautions: Bleeding: Levodopa, Prostacyclin Analogues, Salicylates
Recent intubation; Previous puncture of non-compressible e.g. Aspirin
vessels; cerebrovascular disease; Recent
gastrointestinal or genitourinary bleeding (within 10 Avoid concomitant use with:
days); Recent trauma (within 10 days), including CPR; Increases risk of adverse or toxic effects of Streptokinase:
High likelihood of left heart thrombus, e.g., mitral Herbs with anticoagulant or antiplatelet properties, e.g.,
stenosis with atrial fibrillation; Undergoing trans-lumbar Alfalfa, Anise, Bilberry (bleeding)
aortography; Subacute bacterial endocarditis; Active
tuberculosis or severe bronchitis; Hemostatic defects Reduces therapeutic effect of Streptokinase:
including ones caused by renal or hepatic dysfunction; Aprotinin
Diabetic hemorrhagic retinopathy or other hemorrhagic
ophthalmic conditions; With indwelling urethral catheter; Reduces therapeutic effect of the following drugs:
Septic thrombophlebitis or occluded AV cannula at Aprotinin; Heparin (anticoagulant effect); Vitamin K
seriously infected site any condition where bleeding Antagonists, e.g., Warfarin (anticoagulant effect)
constitutes a significant hazard or would be particularly
difficult to manage because of location; Anaphylaxis; Administration: Temporarily loosen the needle from syringe
Arrhythmias; Bleeding (discontinue if serious bleeding to remove any residual vacuum while adding the diluent
occurs; hold heparin therapy prior to initiation of to ensure powder is completely dissolved. After
streptokinase until aPTT is <2 times the normal control reconstitution withdraw entire contents of vial and add to
value); Hypotension; Elderly (use with caution in patients appropriate diluent for infusion.
>75 years; may increase bleeding risk); Pregnancy;
obstetrical delivery or abortion. May have a slight yellow color in solution due to the
presence of albumin.
Adverse Drug Reactions:
Common: Angina pectoris, arrhythmias, development of Pregnancy Category: C
anti-streptokinase antibodies, bradycardia, cardiogenic
shock, CHF, flushing, hypotension, myocardial ATC Code: B01AD01
reinfarction, pericarditis, recurrent ischemia,

55
 BLOOD AND BLOOD FORMING ORGANS

OTHER ANTITHROMBOTIC AGENTS

Hemorrhage may occur at any site. Risk appears
increased by several factors including renal
Rx FONDAPARINUX dysfunction, age (>75 years), and weight (<50 kg).

Inj.: 2.5 mg/0.5 mL solution (as sodium salt)

B

Bleeding; thrombocytopenia; Hepatic impairment; Renal

A synthetic activated factor X (Xa) inhibitor used as an impairment; Patients <50 kg (use with caution; dose
anticoagulant. It increases the affinity of antithrombin III reduction recommended); Elderly (use with caution ;
for factor Xa, a key enzyme in the coagulation cascade. increased risk of bleeding in patients >75 years of age);
Lactation (use with caution).
Indications: Management of unstable angina (UA) or non-ST
segment elevation myocardial infarction (NSTEMI); Adverse Drug Reactions:
management of ST segment elevation myocardial Common: Anemia, hypotension, insomnia, dizziness,
infarction (STEMI). confusion, increased wound secretion, skin blister,
Contraindications: Severe renal impairment; body weight hypokalemia, thrombocytopenia, purpura, hematoma,
<50 kg; active major bleeding; bacterial endocarditis; minor or major hemorrhage, postoperative hemorrhage,
Thrombocytopenia associated with a positive in vitro test postoperative wound infection, epistaxis.
for antiplatelet antibodies in the presence of Less Common: Anaphylactoid reaction, anaphylaxis,
Fondaparinux. angioedema, catheter site thrombosis, elevated aPTT
associated with bleeding, epidural hematoma,
Dose: hemorrhagic death, injection site reaction (bleeding, skin
NOTE: PT and aPTT are insensitive measures of rash, pruritus), intracranial hemorrhage, reoperation due
Fondaparinux activity. If unexpected changes in to bleeding, spinal hematoma, thrombocytopenia,
coagulation parameters or major bleeding occur, severe thrombocytopenia (<50,000/mm3).
discontinue fondaparinux.
Drug Interactions:
UA or NSTEMI, by SC injection, ADULT, 2.5 mg once daily for Monitor closely with:
the duration of hospitalization or up to 8 days, initiate as Enhances anticoagulant effect of Fondaparinux:
soon as possible after presentation. Agents with Antiplatelet Properties, e.g., P2Y12
STEMI, by IV injection, ADULT, 2.5 mg once; Inhibitors, NSAIDs, SSRIs; Omega-3 Fatty Acids; Other
for subsequent doses, starting the following day, by SC Anticoagulants; Salicylates e.g. Aspirin; Sugammadex;
injection, 2.5 mg once daily for the duration of the Thrombolytic Agents; Tibolone; Vitamin E (increases
hospitalization up to 8 days, or until revascularization overall risk for bleeding)
[NOTE: Discontinue Fondaparinux 24 hours prior to
CABG surgery and administer UFH instead, as per Increases risk of adverse or toxic effects of Fondaparinux:
institutional practice]. Ibrutinib; Prostacyclin Analogues

Dose Adjustment: Increases risk of adverse or toxic effects of the following

Renal Impairment: drugs:
For CrCl >50 mL/minute, no dose adjustment is necessary, Deferasirox (GI ulceration or irritation; GI bleeding;);
however, total clearance is reduced ~25%. Deoxycholic Acid (bleeding or bruising in the treatment
For CrCl of 30–50 mL/minute, use with caution. Total area)
clearance ~40% lower compared to normal renal
function. When used for thromboprophylaxis, reduce Increases risk of adverse or toxic effects of the following
dose 50% or use low-dose heparin. drugs:
For CrCl <30 mL/minute, use is contraindicated. Bleeding: Nintedanib; Obinutuzumab; Iodine I131

Hepatic Impairment: Avoid concomitant use with:

For severe impairment, use with caution. Monitor closely for Enhances anticoagulant effect of the following drugs:
signs of bleeding. Apixaban; Dabigatran Etexilate; Rivaroxaban

Precautions: Increases risk of bleeding of Fondaparinux:

Herbs with anticoagulant or antiplatelet properties, e.g.,
WARNING: Epidural or spinal hematomas may occur in Alfalfa, Anise, Bilberry;
patients who are anticoagulated with low molecular
weight heparins, heparinoids, or fondaparinux and Reduces anticoagulant effect of Fondaparinux:
are receiving neuraxial anesthesia or undergoing Estrogen Derivatives, Progestins [except Tibolone]
spinal puncture. This may result in long­term or
permanent paralysis. Monitor patients frequently for Administration: Initiate therapy 6–8 hours following surgery.
signs and symptoms of neurologic impairment. If When used for DVT prophylaxis, early initiation (before 6
neurologic compromise is noted, urgent treatment is hours after orthopedic surgery) has been associated with
necessary. increased bleeding.

For STEMI, administer via IV route. Administer initial dose

as IV push or mix in NS and infuse over 1–2 minutes.

56
BLOOD AND BLOOD FORMING ORGANS

Flush tubing with NS after infusion to ensure complete Hematuria, by mouth, ADULT, 1–1.5 g every 8–12 hours
administration. daily until macroscopic
hematuria is no longer present.
If to be administered via SC route, alternate injection
sites. Administer according to recommended regimen. Dose Adjustment:
Do NOT expel air bubble from syringe before injection. Pediatric:

B
Limited data suggest that dosing instructions for adults can
Do NOT administer with other agents that increase the be used for children.
risk of hemorrhage unless they are essential for the Geriatric:
management of the underlying condition. No dose reduction necessary, unless there is
evidence of renal failure.
Do NOT administer via IM route.
Renal Impairment:
CONVERSION. To convert from IV UFH infusion to SC Fondparinux, Reduce doses because of risk of drug accumulation.
calculate specific dose for Fondaparinux based on indication.
Discontinue UFH and begin Fondaparinux within 1 hour.
To convert from SC Fondaparinux to IV UFH infusion, discontinue Precautions:
Fondaparinux, calculate specific dose for IV UFH infusion based on For prolonged treatment, perform an ophthalmological
indication. Omit Heparin loading dose. examination, including visual acuity, color vision,
eyeground, and visual fields, before and at regular
For SC Fondaparinux dosed every 24 hours, start IV UFH infusion intervals during treatment; Hematuria caused by
22–23 hours after last Fondaparinux dose.
diseases of the renal parenchyma; High risk for
thrombosis; Genitourinary effect; Irregular menstrual
Pregnancy Category: B bleeding (use is not recommended); Indissoluble clots
may develop in body cavities,
ATC Code: B01AX05 such as pleural space, joint spaces and urinary tract
(e.g., renal pelvis, bladder) due to
extravascular clots, which may be resistant to physiologic
ANTIHEMORRHAGICS fibrinolysis; Children (limited use in children, principally
in tooth extraction); Pregnancy (use only if clearly
needed); Lactation (exercise caution when administering
ANTIFIBRINOLYTICS to breastfeeding women).

Adverse Drug Reactions:

Rx TRANEXAMIC ACID Common: Abdominal pain, anemia, arthralgia, back pain,
diarrhea, fatigue, headache, muscle cramps and
spasms, nausea, nasal and sinus symptoms, vomiting.
Oral: 250 mg and 500 mg capsule
Rare: Allergic skin reactions, diarrhea, hypersensitivity
500 mg tablet
reactions, hypotension, thrombosis, thromboembolic
Inj.: 100 mg/mL, 2.5 mL and 5 mL ampule (IM, IV)
events (e.g., deep vein thrombosis, pulmonary
embolism); transient disturbance of color vision.
A competitive inhibitor of plasminogen activity used as an
anti-fibrinolytic agent
Drug Interactions:
Monitor closely with:
Indication: Treatment and control of excessive bleeding in
Enhances therapeutic effect of Tranexamic Acid:
various surgical and medical, obstetric and gynecologic,
Tretinoin (systemic) (thrombogenic effect)
and dental
conditions.
Reduces therapeutic effect of the following drugs:
Fibrinolytic Preparations e.g., Streptokinase (counteracts
Contraindications: History or risk of thrombosis, unless
thrombolytic effect)
concomitant treatment with anticoagulants; active
thromboembolic disease (e.g., deep vein thrombosis,
Avoid concomitant use with:
pulmonary embolism, cerebral thrombosis); acquired
Enhances therapeutic effect of Tranexamic Acid:
disturbances of color vision; subarachnoid hemorrhage.
Contraceptives, e.g., Estrogens, Progestins
(thrombogenic effect)
Dose:
Menorrhagia or menometrorrhagia, by mouth, ADULT,
Enhances therapeutic effect of the following drugs:
1–1.5 g every 6–8 hours for 3–4 days (maximum, 4 g
Anti-Inhibitor Coagulant Complex, human (thrombogenic
daily).
effect)
Dental surgery, by mouth, ADULT, 25 mg/kg 2
hours before surgery, then 25 mg/kg 3 or 4 times daily
Administration:
for 6–8 days.
For oral route, may be taken with or without food.
Epistaxis, by mouth, ADULT, 1.5 g every 8 hours for 4–10
Capsules must be swallowed whole. Do NOT chew,
days.
break, or crush.
Gastrointestinal hemorrhage, by IV injection, ADULT, initially
1 g every 4 hours for a maximum of 3 days, followed by
For intravenous route, administer by direct IV injection at
an oral dose of 1.5 g every 6 hours for a maximum of 4
a maximum rate of 100 mg/minute. Use plastic syringe
days.

57
 BLOOD AND BLOOD FORMING ORGANS

only for IV push. Dilute loading doses in 50–250 mL and Adverse Drug Reactions:
administer over 5–30 minutes. Common: Antibody development
Less Common: Hypersensitivity reaction
Pregnancy Category: B
Drug Interactions: No known significant interactions
ATC Code: B02AA02
B

Administration: Administer via IV route at a rate of 1–2

mL/minute.
VITAMIN K AND OTHE RHEMOSTATICS
Prior to reconstitution, warm vial and diluent to room
temperature. Gently swirl vial in a circular motion after
BLOOD COAGULATION FACTORS adding diluent until dissolved.
Rx FACTOR VIII CONCENTRATE
Do NOT administer in the same tubing or container with
other medicinal products.
Inj.: 100 IU/g lyophilized powder, vial + diluent (IV)
Pregnancy Category: C
A plasma protein fraction that contains the glycoprotein
coagulation factor VIII together with varying amounts of ATC Code: B02BD02
von Willebrand factor. Factor VIII is required for clot
formation and maintenance of hemostasis. It acts by
activating factor X, a coagulation factor necessary in
thrombin and eventual fibrin formation. FACTOR IX COMPLEX CONCENTRATE
Rx (COAGULATION
Indication: Treatment of bleeding episodes in adults with FACTORS II, VII, IX, X)
acquired hemophilia A.
Inj.: 100 IU/mL, 5 mL and 10 mL vial (IV)
NOTE: Not indicated for the treatment of congenital 500 IU lyophilized powder vial + diluent (IV)
hemophilia A or von Willebrand disease.
A sterile lyophilized concentrate derived from human
Contraindication: Life-threatening hypersensitivity reactions plasma. It is also known as prothrombin complex
to antihemophilic factor or any component of the concentrate and is composed of several Vitamin K-
formulation (including traces of hamster proteins). dependent clotting factors including factor IX, factor II
(prothrombin), factor X, and low levels of factor VII.
Dose:
NOTE: Individualize dose, dosing frequency, and duration Indication: Prevention and control of bleeding in patients
based on location and severity of bleeding, target factor with factor IX deficiency (hemophilia B).
VIII levels, and clinical condition of the patient. Plasma
levels of factor VIII should not exceed 200% of normal or NOTE: NOT indicated for the treatment of other factor
200 units/dL. deficiencies, hemophilia A patient with inhibitors to
factor VIII, or bleeding caused by low levels of liver-
Acquired hemophilia A, mild to moderate hemorrhage, by IV dependent coagulation factors.
injection, ADULT, initially 200 units/kg to achieve factor
VIII plasma level 50–100% of normal; titrate subsequent Contraindications: Hypersensitivity reactions to factor IX
doses to maintain recommended factor VIII trough levels complex or any component of the formulation; known
and individual clinical response; dose every 4–12 hours; allergy to heparin; history of heparin-induced
adjust frequency based on clinical response or factor VIII thrombocytopenia.
levels.
Acquired hemophilia A, major hemorrhage, by IV injection, Dose:
ADULT, initially 200 units/kg to achieve factor VIII NOTE: Dosage is expressed in units of factor IX activity.
plasma level 100–200% of normal for acute bleed or Individualize doses based on severity of factor IX
50–100% of normal after acute bleed is controlled, if deficiency, extent and location of bleeding, and clinical
required of normal; titrate subsequent doses to maintain status of patient. Closely monitor factor IX level to
recommended factor VIII trough levels and individual determine proper dosage.
clinical response; dose every 4–12 hours; adjust
frequency based on clinical response or factor VIII levels. When multiple doses are required, administer at 24-hour
intervals unless otherwise specified.
Precautions:
Antibody formation (suspect an anti-porcine factor VIII Control or prevention of bleeding in patients with factor IX
antibody if the plasma factor VIII level does not increase deficiency, by IV injection, ADULT and CHILD,
as expected or if bleeding is not controlled after
administration); Hypersensitivity reactions (discontinue
immediately if allergic or anaphylactic-type reactions
occur); Lactation (use with caution).

58
BLOOD AND BLOOD FORMING ORGANS

Indication Bebulin Profilnine or until healing

has been
Usually 50–75 Maintenance achieved
units/kg as a dose, 30–50
single infusion units/kg every
1 hour prior to 16–24 hours
Dental surgery,
surgery [raise for 7–10 days

B
single tooth
factor IX level following
to 40–60% of surgery or until
normal on day healing has
of surgery] been achieved
[raise factor IX
Replacement
level to 50% of
therapy may be
normal
required for up
immediately
to 1 week
Dental surgery, prior to
[raise factor IX
multiple teeth procedure; Typical dose,
level to 40–
maintain factor 50–75
60% of normal
IX levels at 30 units/kg [raise
on day of
to 50% of factor IX level
surgery]
normal] to 40–60% of
Initially 30–50
Indication Bebulin Profilnine normal on day
units/kg prior
Initially 20–30 of surgery]
Initially 25–35 to surgery
units/kg every Then lower
units/kg for 1 [raise factor IX
16–24 hours dose to usually
Minor day [raise level to 30–
for 1–2 days 26–65
bleeding, e.g., factor IX level 50% of normal]
for minor units/kg for 1–
early to 20% of Maintenance
hemorrhage or 2 weeks or
hemarthrosis, normal] dose, 30–50
until until adequate
minor units/kg every
hemorrhage Minor surgical wound healing
epistaxis, [NOTE: A single 16–24 hours
stops and procedures [decrease
gingival dose is usually for 7–10 days
healing has factor IX level
bleeding, mild sufficient, but following
been achieved to 20 to 40% of
hematuria a second dose surgery or until
[raise factor IX normal during
healing is
may be given initial postop
level to 20– achieved
after 24 hours] period]
30% of normal] [maintain
Give preop
Initially, 20–30 factor IX levels
Moderate dose 1 hour
units/kg every at 30 to 50% of
bleeding, e.g., prior to
16–24 hours normal]
severe joint surgery,
Initially 50–65 for 2–7 days
bleeding, early initially every
units/kg for 2 for moderate
hematoma, 12 hours, then
days, or until hemorrhage,
major open every 24 hours
adequate or until
bleeding, postop
wound healing hemorrhage
minor trauma,
[raise factor IX stops and
minor
level to 40% of healing has
hemoptysis,
normal] been achieved
hematemesis,
[raise factor IX
melena, major
level to 20–
hematuria
30% of normal]
Initially 30–50
units/kg every
16–24 hours
(maintenance
Major
Initially 75–90 dose, 20
bleeding, e.g.,
units/kg for 2– units/kg) [raise
severe
3 days or until factor IX level
hematoma,
adequate to 30–50% of
major trauma,
wound healing normal]
severe
[raise factor IX Following this
hemoptysis,
level to ≥60% treatment
hematemesis,
of normal] period,
melena
maintain factor
IX levels at
20% of normal
for 3–10 days,

59
 BLOOD AND BLOOD FORMING ORGANS

Indication Bebulin Profilnine Precautions:

Typical initial WARNING: Factor IX complex (factors II, IX, X) contains
dose, 75–90 low or nontherapeutic levels of factor VII component.
units/kg [raise Do NOT confuse with prothrombin complex
factor IX level concentrate (factors II, VII, IX, X, protein C, protein S),
to ≥60% of which contains therapeutic levels of factor VII.
B

normal on day
of surgery]
Antibody formation; Thrombotic events; Hepatic impairment
Adjust dose to
(use with caution)
typically 25–
75 units/kg for
Adverse Drug Reactions:
1–2 weeks
Common: Flushing, thrombosis, chills, fever, headache,
[decrease Initially 30–50
lethargy, somnolence, rash, urticaria, nausea, vomiting,
factor IX level units/kg prior
disseminated intravascular coagulation, paresthesia,
to 20–60% of to surgery
dyspnea, anaphylactic shock, development of clotting
normal during [raise factor IX
factor antibodies, heparin-induced thrombocytopenia.
initial postop level to 30–
period] 50% of normal]
Administration: Administer by IV infusion. Infuse solution at
Adjust dose to Maintenance
room temperature at 2 mL/minute for Bebulin or 10
typically 25– dose, 30–50
mL/minute for Profilnine.
35 units/kg units/kg every
Major surgical
during late 16–24 hours
procedures Prior to reconstitution, bring diluent (SWFI) and Factor IX
postop period for 7–10 days
Concentrate to room temperature. Do NOT exceed 37°C
(≥3 weeks) and following
[98.6°F]. Gently rotate or agitate to dissolve. Do NOT
continue until surgery or until
shake. Use reconstituted solution within 3 hours. Do NOT
adequate healing is
refrigerate. Vials are intended for single use. Discard
wound healing achieved
unused portion.
is achieved [maintain
[further factor IX levels
Do NOT mix with other drugs or solvents.
decrease to at 30–50% of
maintain a normal]
Do NOT exceed the recommended infusion rates to
factor IX level
prevent vasomotor reactions due to rapid administration.
of 20% of
Slowing the rate of infusion, changing the lot of
normal]
medication, or administering antihistamines may relieve
Give preop
some adverse reactions.
dose 1 hour
prior to
NOTE: [Bebulin] Reconstituted product should be a
surgery,
colorless to slightly yellowish and clear to slightly turbid
initially every
solution.
12 hours, then
every 24 hours
[Profilnine] A few particles may remain in solution
postop
following reconstitution. The Mix2Vial set will remove the
particles and the labeled potency will not be reduced.
Formula for units required to raise blood level %:
NOTE: Larger doses may be required, especially if treatment Pregnancy Category: C
is delayed.
ATC Code: B02BD04
[Bebulin] factor IX 1 unit/kg will increase the plasma factor
IX level by 0.8%
Number of Factor IX units required =
body weight (kg) x desired factor IX increase (as % of
normal) x 1.2 units/kg
[Profilnine] factor IX 1 unit/kg will increase the plasma
factor IX level by 1%
Number of factor IX units required =
bodyweight (kg) x desired factor IX increase (as % of
normal) x 1 unit/kg

Dose Adjustment:
Hepatic Impairment:
No dose adjustment required. Monitor factor IX levels.

60
BLOOD AND BLOOD FORMING ORGANS

Dose:
ANTIANEMIC PREPARATIONS NOTE: Dose is expressed in terms of mg of elemental iron.
Each 5-mL vial contains 100 mg elemental iron (20
mg/mL). Most CKD patients require a minimum
IRON PREPARATIONS cumulative dose of 1,000 mg elemental iron
administered over sequential sessions to achieve a

B
favorable hemoglobin or hematocrit response. Patients
OTC FERROUS SALT may then continue to require therapy at the lowest dose
necessary to maintain target levels of hemoglobin,
Oral: Tablet (equivalent to 60 mg elemental iron) hematocrit, and iron storage parameters within
Oral drops, 15 mL and 30 mL (equivalent to 15 mg acceptable limits.
elemental iron/0.6 mL)
Syrup, 60 mL (equivalent to 30 mg elemental iron/5 NDD-CKD, by slow IV injection, ADULT, 200 mg undiluted
mL) over 2–5 minutes on 5 different occasions within a 14-
day period for a total cumulative dose of 1,000 mg;
NOTE: The elemental iron content of a ferrous salt depends patients weighing less than 70 kg may require a longer
on the type of preparation as follows: infusion time.
Ferrous fumarate 33% HDD-CKD, by slow IV injection, ADULT, 100 mg undiluted
Ferrous gluconate 12% over 2–5 minutes; or
Ferrous lactate 19% by IV infusion, ADULT, 100 mg diluted in a maximum of
Ferrous sulfate, hydrated 20% 100 mL of 0.9% NaCl over a period of at least 15 minutes
Ferrous sulfate, desiccated 32% per consecutive hemodialysis session for a total
cumulative dose of 1,000 mg.
An essential trace element required for the formation of PDD-CKD, by IV injection, ADULT, 2 infusions of 300 mg over
hemoglobin and for the efficient oxygen transport in the 1.5 hours 14 days apart followed by one 400 mg infusion
blood. over 2.5 hours 14 days later for a total cumulative dose
of 1,000 mg in 3 divided doses within a 28-day period
Indications: Treatment of iron-deficiency anemia and in (dilute each dose in a maximum of 250 mL of 0.9%
people on hemodialysis who are receiving erythropoietin NaCl).
(supplement and prophylaxis); hematinic.
Precautions:
Dose:
Iron-deficiency anemia, by mouth, ADULT, elemental iron, WARNING: Iron sucrose should only be administered
100–200 mg daily in divided doses. when personnel and resuscitative interventions are
Prevention of iron-deficiency anemia (in at risk population), immediately available for the treatment of
by mouth, ADULT (female), elemental iron 60 mg daily; anaphylaxis and other serious hypersensitivity
CHILD >5 years, elemental iron, 30 mg daily; CHILD <5 reactions.
years, elemental iron, 2 mg/kg daily (maximum, 30 mg).
Hypersensitivity reactions; hypotension; Children; Lactation
NOTE: May also administer Folic Acid in women and children (use with caution).
>5 years. Adverse Drug Reactions:
Common: Dysgeusia, hypotension, nausea, dizziness,
See Ferrous Salts under Mineral Supplements in Chapter 1: diarrhea, vomiting, headache, pruritus, extremity pain,
Alimentary Tract and Metabolism for other information. arthralgia, back pain, muscle cramp, injection site
reactions, chest pain, peripheral edema.
ATC Code: B03AA02, B03AA03, B03AA07 Rare: Severe, life-threatening allergic reactions (loss of
consciousness, collapse, difficulty breathing or
convulsions), severe hypotension.
Rx IRON SUCROSE Drug Interactions:
Avoid concomitant use with:
Inj.: 20 mg/mL, 5 mL ampule (contains 100 mg elemental Reduces absorption of the following drugs:
iron) Oral Iron Preparations, concomitantly administered

Indication: Management of iron-deficiency anemia in non- Administration: Administered only by slow IV injection or IV
dialysis-dependent chronic kidney disease (NDD-CKD) infusion. Discard unused portion
patients, rhemodialysis dependent chronic kidney
disease (HDD-CKD) patients receiving erythropoietin, Inspect visually for clarity, particulate matter, precipitate,
and peritoneal dialysis dependent chronic kidney discoloration and leakage prior to administration.
disease (PDD-CKD) patients receiving erythropoietin.
When prepared as an infusion, use immediately. Do NOT
Contraindications: Iron overload; anemia not caused by iron store.
deficiency.
Do NOT mix iron sucrose with other medications or add
to parenteral nutrient solutions for IV infusion.

61
 BLOOD AND BLOOD FORMING ORGANS

NOTE: Administer with caution due to limited excretion. VITAMIN B12 AND FOLIC ACID
Excess tissue iron can be hazardous. Withhold
administration of IV iron formulations if patients VITAMIN B12 (CYANOCOBALAMIN AND ANALOGUES)
demonstrate transferrin saturation >50% and/or serum
ferritin >800 nanograms/mL.
Rx MECOBALAMIN
B

Avoid paravenous infiltration. If this occurs, discontinue

infusion immediately. Apply ice to cause local
vasoconstriction and decrease fluid absorption. Do NOT Oral: 500 micrograms tablet
massage area. Inj.: 500 micrograms/mL, 1mL ampule (IM, IV)

Monitor patients for signs and symptoms of A form of Vitamin B12, a water-soluble vitamin It acts as
hypersensitivity during and after administration for at coenzymes in nucleic acid synthesis.
least 30 minutes and until clinically stable following
completion of the infusion. Indications: Symptomatic treatment of peripheral
neuropathy associated with vitamin B12 deficiency (e.g.,
Guide for Dilution: numbness, pain, paralysis), including diabetic
Nominal Volume neuropathy and polyneuropathy; management of
Dose Volume of megaloblastic anemia associated with vitamin B12
concentration of iron
(mg Fe) diluent deficiency.
per mL sucrose
Hemodialysis-Dependent Chronic Kidney Disease
Patients (HDD-CKD) Dose:
Peripheral neuropathy, by mouth, ADULT, 500 micrograms
1 mg/mL (when
3 times daily;
maximum Maximum:
by IV or IM injection, ADULT, 500 micrograms 3 times
100 mg volume of 5 mL 100 mL
weekly.
diluent is used) 0.9% NaCl
Megaloblastic anemia, by IV or IM injection, ADULT, initially
500 micrograms 3 times weekly; 500 micrograms every
Non-Dialysis-Dependent Chronic Kidney Disease 1–3 months as maintenance dose after approximately 2
Patients (NDD-CKD) months of treatment).
2 mg/mL (when Administration: For IM or IV use. Administer immediately
Maximum:
maximum after removing from package to limit direct exposure to
500 mg 25 mL 250 mL
volume of light.
0.9% NaCl
diluent is used)
Peritoneal Dialysis-Dependent Chronic Kidney Disease For IM route, avoid multiple injections at the same site.
Patients (PDD-CKD) Do NOT inject near highly innervated regions.
1.2 mg/mL
(when NOTE: Do NOT use for more than 1 month without clear
300 mg maximum 15 mL signs of clinical improvement. Avoid long term use in
volume of patients regularly exposed to mercury or mercury
Maximum:
diluent is used) compounds.
250 mL
1.6 mg/mL
0.9% NaCl
(when See Mecobalamin under Vitamins in Chapter 1: Alimentary
400 mg maximum 20 mL Tract and Metabolism for other information.
volume of
diluent is used) Pregnancy Category: C

Pregnancy Category: B ATC Code: B03BA05

ATC Code: B03AE10

FOLIC ACID AND DERIVATIVES

Rx FOLIC ACID

Oral: 400 micrograms, 800 micrograms, 1 mg, and 5 mg

tablet/capsule
2.5 mg/mL pediatric drops
5 mg/5mL syrup

Also known as Vitamin B9, it is reduced in the body to

tetrahydrofolate, which is a coenzyme for various
metabolic processes, including the synthesis of purine
and pyrimidine nucleotides needed in DNA synthesis. It
is also involved in some amino acid conversions, and in
the formation and utilization of formate.

62
BLOOD AND BLOOD FORMING ORGANS

Indications: Treatment of megaloblastic and macrocytic OTHER ANTIANEMIC PREPARATIONS

anemias due to folate deficiency; used in diarrhea in
pediatric patients.
EPOETIN ALFA (RECOMBINANT
Rx
Dose: HUMAN ERYTHROPOIETIN)
Anemia, by mouth, ADULT, 0.4 mg daily; PREGNANT and
Inj.: 2,000 IU/0.5 mL, pre-filled syringe (IV, SC)

B
LACTATING WOMEN, 0.8 mg daily; CHILD <4 years, up to
0.3 mg daily; INFANT, 0.1 mg daily. 4,000 IU/0.4 mL, pre-filled syringe (IV, SC)
4,000 IU/mL, 1 mL vial (IV, SC)
Administration: May be administered by deep IM injection, 10,000 IU/mL, pre-filled syringe (IV, SC)
IV injection, or IV infusion. A glycosylated protein hormone and a hematopoietic growth
For IV injection or infusion, administer ≤5 mg undiluted factor that regulates erythropoiesis by stimulating the
over ≥1 minute; or dilute ≤5 mg in 50 mL of NS or D5W differentiation and proliferation of erythroid precursors,
and infuse over 30 minutes. May be added to IV the release of reticulocytes into the circulation, and the
maintenance solutions and given as an infusion. synthesis of cellular hemoglobin. It has the same
pharmacological actions as endogenous erythropoietin.
See Folic Acid under Vitamins in Chapter 1: Alimentary Tract
and Metabolism for other information. Indications: Treatment of anemia due to concurrent
myelosuppressive chemotherapy, chronic kidney
Pregnancy Category: A disease (CKD), or associated with HIV (zidovudine)
therapy; reduction of allogeneic RBC transfusion for
ATC Code: B03BB01 elective, noncardiac, nonvascular surgery.

NOTE: NOT indicated for use in cancer patients receiving

hormonal therapy, therapeutic biologic products, or
Rx FOLIC ACID + FERROUS SALT radiation therapy unless also receiving concurrent
myelosuppressive chemotherapy.
Oral: 400 micrograms folic acid + 60 mg elemental iron per
tablet / capsule / FC tablet Contraindications: Serious allergic reactions to epoetin alfa
or any component of the formulation; uncontrolled
A two-component, nutritional supplement of iron and folic hypertension; pure red cell aplasia (PRCA) that begins
acid given during pregnancy. after treatment with epoetin alfa or other epoetin protein
drugs; neonates, infants, pregnant women, and nursing
Indication: Prevention of iron and folic acid deficiencies, women (multi-dose vials).
especially in pregnancy.
Dose:
Dose: NOTE: Initiate treatment when hemoglobin is <10 g/dL.
Prevention of iron and folate deficiencies in pregnancy, by Reduce dose or interrupt treatment if hemoglobin
mouth, ADULT, 100 mg elemental iron + 350 to 400 approaches or exceeds 11 g/dL.
micrograms folic acid daily throughout pregnancy. Anemia associated with CKD patients on dialysis, by IV or SC
injection, ADULT, initially 50–100 units/kg 3 times a
Administration: To be taken on an empty stomach, at least week; CHILD 1 month–16 years, initially 50 units/kg 3
1 hour before or 2 hours after meal. Avoid taking times a week; if hemoglobin does not increase by >1
antacids or antibiotics within 2 hours before or after g/dL after 4 weeks, increase dose by 25%; if hemoglobin
taking it. increases >1 g/dL in any 2-week period, reduce dose by
≥25%.
See Ferrous Salt + Folic Acid under Mineral Supplements in Anemia associated with CKD patients not on dialysis, by IV
Chapter 1: Alimentary Tract and Metabolism for other or SC injection, ADULT, initially 50–100 units/kg 3 times
information. a week (use only if rate of hemoglobin decline would
likely result in RBC transfusion and desire is to reduce
Pregnancy Category: A risk of alloimmunization and/or other RBC transfusion-
related risks); reduce dose or interrupt treatment if
ATC Code: B03BB51 hemoglobin exceeds 10 g/dL; if hemoglobin does not
increase by >1 g/dL after 4 weeks, increase dose by
25%; if hemoglobin increases >1 g/dL in any 2-week
period, reduce dose by ≥25%.
Anemia due to chemotherapy in cancer patients (only if
anticipated duration of myelosuppressive chemotherapy
is at least 2 additional months), by SC injection, ADULT,
initially 150 units/kg 3 times a week or 40,000 units
once weekly until completion of chemotherapy; titrate
dose to use the minimum effective dose that will
maintain a hemoglobin level sufficient to avoid RBC
transfusions; discontinue erythropoietin following
completion of chemotherapy; ADOLESCENT and CHILD
≥5 years, initially 600 units/kg once weekly until

63
 BLOOD AND BLOOD FORMING ORGANS

completion of chemotherapy; titrate dosage to use the Pregnancy (does not cross human placenta;
minimum effective dose that will maintain hemoglobin polyhydramnios and intrauterine growth retardation
level sufficient to avoid RBC transfusions; discontinue have been reported; hypospadias and pectus excavatum
erythropoietin following completion of chemotherapy. have been reported with first trimester exposure;
Anemia due to Zidovudine in HIV-infected patients (serum menstruation may resume following treatment with
erythropoietin levels ≤500 milliunits/mL and zidovudine recombinant erythropoietin in amenorrheic
B

doses ≤4200 mg/week), by IV or SC injection, ADULT, premenopausal women; if needed, only use single dose
initially 100 units/kg 3 times a week; if hemoglobin does preparations); Lactation (use with caution).
not increase after 8 weeks, increase dose by 50–100
units/kg at 4– to 8-week intervals until hemoglobin Adverse Drug Reactions:
reaches a level sufficient to avoid RBC transfusion Common: Hypertension, fever, headache, pruritus, rash,
(maximum dose, 300 units/kg); withhold dose if nausea, vomiting, injection site reactions, arthralgia,
hemoglobin exceeds 12 g/dL, may resume treatment cough, deep vein thrombosis, edema, thrombosis, chills,
with a 25% dose reduction once hemoglobin <11 g/dL; depression, dizziness, insomnia, dysphagia, urticaria,
discontinue if hemoglobin increase is not achieved with hyperglycemia, hypokalemia, stomatitis, weight loss,
300 units/kg for 8 weeks; titrate dose to use the leukopenia, clotted vascular access, muscle spasm,
minimum effective dose that will maintain a hemoglobin myalgia, pulmonary embolism, bone pain, respiratory
level sufficient to avoid RBC transfusions; hemoglobin congestion, upper respiratory infection.
levels should not exceed 12 g/dL); CHILD 8 months to Less Common: Anaphylactic reaction, angioedema,
17 years, 50–400 units/kg 2–3 times a week; titrate bronchospasm, erythema, hypersensitivity reactions,
dosage to use the minimum effective dose that will hypertensive encephalopathy, MI, microvascular
maintain a hemoglobin level sufficient to avoid RBC thrombosis, neutralizing antibodies, porphyria, pure red
transfusions; hemoglobin levels should not exceed 12 cell aplasia (PRCA), renal vein thrombosis, retinal artery
g/dL). thrombosis, seizure, stroke, tachycardia, temporal vein
Surgery patients (perioperative hemoglobin should be >10 thrombosis, thrombophlebitis, transient ischemic attack,
g/dL and ≤13 g/dL), by SC injection, ADULT, initially 300 tumor progression.
units/kg daily for 15 days (10 days before surgery, the
day of surgery, and 4 days after surgery); or Drug Interactions:
600 units/kg once weekly for 4 doses (21, 14, and 7 Monitor closely with:
days before surgery, and on the day of surgery). Decreases bleeding time:
Desmopressin
Dose Adjustment:
Renal Impairment: Increases sensitivity of erythroid progenitors:
For CKD patients, use the minimum effective dose that will Androgens e.g. testosterone
maintain a hemoglobin level sufficient to avoid RBC
transfusions and evaluate patient for other causes of Administration: For IV or SC administration. Do NOT shake.
anemia. For patients with CKD on hemodialysis, IV route is
Dose reduction is recommended. Do NOT increase dose preferred. May be administered into the venous line at
more frequently than every 4 weeks. Dose decreases the end of the dialysis procedure.
may occur more frequently. Avoid frequent dosage
adjustments. Discontinue therapy if responsiveness For other patient populations, SC route is preferred.
does not improve. Usually administered undiluted, although may use a 1:1
Adjustments in dialysis parameters may be needed. dilution with bacteriostatic NS (contains benzyl alcohol).

Oncology: Pregnancy Category: C

Use lowest dose needed to avoid RBC transfusions. Use
ESAs only for treatment of anemia from concomitant ATC Code: B03XA01
myelosuppressive chemotherapy.

Precautions: EPOETIN BETA

Rx
WARNING: Erythropoiesis-stimulating Agents (ESAs) (RECOMBINANT ERYTHROPOIETIN)
increase the risk of death, myocardial infarction
(MI), stroke, venous thromboembolism, thrombosis Inj.: 2,000 IU/0.3 mL, pre-filled syringe with needle (IV,
of vascular access. SC)
5,000 IU/0.3 mL, pre-filled syringe with needle (IV,
SC)
Cardiovascular events; hypertension (use with caution); 10,000 IU/0.6 mL, pre-filled syringe (IV, SC)
Perisurgery patients; Pure red cell aplasia or PRCA
(discontinue treatment in patients with PRCA secondary A glycosylated protein hormone and a hematopoietic growth
to neutralizing antibodies to erythropoietin; do not switch factor that regulates erythropoiesis by stimulating the
to another ESA in patients who develop antibody- differentiation and proliferation of erythroid precursors,
mediated anemia); Severe anemia or acute blood loss; the release of reticulocytes into the circulation, and the
Hypersensitivity; Chronic kidney disease; Seizures; synthesis of cellular hemoglobin. It has the same
Elderly (decreased endogenous erythropoietin in elderly pharmacological actions as endogenous erythropoietin.
with normocytic or iron deficiency anemias or those with
a serum hemoglobin concentration <12 g/dL);

64
BLOOD AND BLOOD FORMING ORGANS

Indication: Treatment of symptomatic anemia associated

with chemotherapy in patients treated for non-myeloid Based on Response to Therapy:
malignancies and anemia associated with chronic renal HEMOGLOBIN
failure (CRF). DOSE ADJUSTMENT
INCREASE
≥1 g/dL but <2 g/dL
Contraindications: Hypersensitivity to Epoetin beta or any (hemoglobin ≤12 Continue initial dose

B
component of the formulation; uncontrolled g/dL)
hypertension; use in autologous blood donors with MI or Consider doubling initial
stroke in the past month, with unstable angina, or with <1 g/dL dose (maximum dose:
increased deep venous thrombosis (DVT) risk factors. 60,000 units weekly)
<1 g/dL after 8
Dose: Discontinue therapy
weeks of therapy
Note: Individualize dose and use the lowest dose necessary
to control symptoms of anemia and avoid hemoglobin >2 g/dL in 4 weeks
Reduce dose by 25% to
>12 g/dL. Hemoglobin target range is 10–12 g/dL. >12 g/dL and ≤13
50%
g/dL
Anemia associated with CRF, by IV injection, ADULT, initially Temporarily discontinue
40 units/kg 3 times per week; may increase dose to 80 therapy; once hemoglobin
>13 g/dL
units/kg 3 times per week based on hemoglobin ≤12 g/dL, reinitiate at
response after 4 weeks; may further increase dose by 20 25% of previous dose
units/kg 3 times per week every 4 weeks, if necessary
(maximum dose, 720 units/kg per week); Precautions:
by SC injection, ADULT, 20 units/kg 3 times per week or WARNING: Avoid all admixtures. Compatibility has not
60 units/kg per week divided into 7 daily doses; may been studied.
increase dose every 4 weeks by 60 units/kg per week if
hemoglobin response is <0.25 g/dL per week (maximum Cardiovascular events; electrolyte disturbance; Pure red cell
dose, 720 units/kg per week); maintenance, after aplasia (patients with a sudden loss of response should
reaching hemoglobin target, reduce weekly dose to ½ of be evaluated for PRCA with associated neutralizing
the previously administered dose and titrate every 12 antibodies to erythropoietin); Hypertension or
weeks as needed until stable hemoglobin response is cardiovascular disease (use with caution; rapid rise of
achieved. hemoglobin is associated with development or
Anemia associated with chemotherapy in cancer patients, exacerbation of hypertension; hypertensive
by SC injection, ADULT, initially 30,000 units/week or encephalopathy, e.g. sudden headache, confusion, gait
450 units/kg per week given once weekly or in divided instability, or seizure has been reported and requires
doses administered 3 times weekly or once daily for 7 immediate intervention); Cancer; Chronic hepatic failure;
days (maximum dose, 60,000 units/week); after 4 chronic renal failure; Myelodysplastic syndromes (MDS)
weeks, adjust initial dose based on change in (use caution in patients with refractory anemia with
hemoglobin. excess blasts in transformation); Seizures (use with
Treatment for increasing yield of autologous blood, by IV caution); Severe anemia or acute blood loss;
injection, ADULT, 200–800 units/kg twice weekly Thrombocytosis (use with caution); Pregnancy (does not
(maximum, 1,600 units/kg per week); cross placenta; polyhydramnios and intrauterine growth
by SC injection, ADULT, 150–600 units/kg twice per retardation have been reported with use in women with
week (maximum, 1,200 units/kg per week). chronic kidney disease; hypospadias and pectus
excavatum have been reported with first trimester
Dose Adjustment: exposure; menstruation may resume in amenorrheic
Renal Impairment: premenopausal women; multi-dose formulations
Use with caution in patients with nephrosclerosis who have containing benzyl alcohol are contraindicated for use in
not initiated dialysis. Avoid concomitant therapy with pregnant women, use single dose preparations);
aluminum-containing products. Lactation (use with caution).
Oncology:
Use lowest dose needed to avoid symptoms of anemia and Adverse Drug Reactions:
RBC transfusions. Common: hypertension, thromboembolism, headache.
Less Common: Hypertensive crisis, hypertensive
encephalopathy, injection site reaction, iron deficiency,
non-immunologic anaphylaxis or anaphylactoid reaction,
pruritus, pure red cell aplasia (PRCA), rash, seizure,
thrombocytosis, thrombosis of dialysis shunt, urticaria.

Drug Interactions:
Monitor closely with:
Enhance therapeutic effect of Epoetin Beta:
Nandrolone (erythropoiesis-stimulating effect)

Enhance therapeutic effect of the following drugs:

65
 BLOOD AND BLOOD FORMING ORGANS

Thrombogenic effect: Lenalidomide Thalidomide Hemolytic disease of the newborn, by IV infusion, INFANT, 1
(thrombogenic effect) g/kg per dose of 25% albumin prior to or during
Administration: May be administered by IV or SC route. exchange transfusion.

Dissolve powder with full contents in accompanying Dose Adjustment:

solvent ampule. Swirl vial gently until dissolved. Do NOT Renal Impairment:
B

shake. Solution should be clear, colorless, and In chronic renal insufficiency, receiving albumin solution
practically free of particles. Use a 26-gauge needle to may be at risk for accumulation of aluminum and
withdraw appropriate amount for a single injection. potential toxicities.
Replace needle before injection. Use appropriate size for
injection. Precautions:
WARNING: Parenteral product may contain aluminum.
SC route is the preferred route of administration except Toxic aluminum concentrations may be seen with
in patients with CRF on hemodialysis. high doses, prolonged use, or renal dysfunction.

For IV route, administer over a period of 2 minutes. IV is Monitor for adequate hydration electrolytes level in patients
the preferred route in CRF patients on hemodialysis. May receiving hyperosmotic solutions of albumin; Anaphylaxis
be injected into the venous line at the end of the dialysis (discontinue immediately if allergic or anaphylactic
procedure. In patients treated for increasing autologous reactions are suspected); Hemodynamic effects (closely
blood, administer after blood is donated. monitor hemodynamic parameters); Hypervolemia or
hemodilution (use with caution; adjust rate of
NOTE: Multi-dose vials contain preservative. administration per hemodynamic status and solution
concentration; observe for signs of hypervolemia, such
Pregnancy Category: Not available as pulmonary edema); Cardiovascular disease (avoid
rapid infusions; may cause circulatory overload and
ATC Code: B03XA01 pulmonary edema; discontinue at first signs of
cardiovascular overload); Hepatic impairment; Renal
impairment; Critical illness; sodium restricted patients
(use with caution); Premature neonates; Lactation (use
BLOOD SUBSTITUTES AND PERFUSION with caution).
SOLUTIONS
Adverse Drug Reactions:
NOTE: All plasma fractions should comply with the WHO Common: Anaphylactoid reactions, fever, chills, rash,
requirements for the Collection, Processing and nausea, vomiting, tachycardia, hypotension.
Quality Control of Human Blood and Blood Products) Less Common: Anaphylaxis, urticaria, pruritus,
angioneurotic edema, erythema or flushing, dysguesia,
BLOOD AND RELATED PRODUCTS increased salivation, hyperhidrosis, headache,
confusion, loss of consciousness, pulmonary edema,
dyspnea, bronchospasm.
Rx ALBUMIN, HUMAN Rare: Hemolysis

Drug Interactions:
Inj.: 20%, 50 mL and 100 mL bottle (IV, IV infusion) Monitor closely with:
25%, 50 mL and 100 mL bottle (IV, IV infusion) Increase risk of adverse or toxic reactions of the following
25%, 50 mL plastic bag (IV, IV infusion) drugs:
ACE Inhibitors (flushing, hypotension) [for patients
A protein colloid prepared as a sterile solution of serum undergoing therapeutic plasma exchange with human
albumin by fractionating pooled plasma from healthy albumin replacement, withhold ACE inhibitors at least 24
human donors. Albumin is the major protein involved in hours prior to plasma exchange]
maintaining colloid osmotic pressure in the blood. It is
used to restore effective plasma circulating volume and Administration: For IV administration only. Use within 4
colloid osmotic pressure. hours after entering package. Discard unused portion. In
emergencies, may administer as rapidly as necessary to
Indication: Management of neonatal hyperbilirubinemia improve clinical condition.
associated with hemolytic disease of the newborn.
Do NOT use sterile water to dilute albumin solutions, as
Contraindications: Patients at risk of volume overload (e.g., this has been associated with hypotonic-associated
patients with renal impairment, severe anemia, heart hemolysis. Do NOT use with ethanol or protein
failure); dilution with sterile water for injection. hydrolysates as precipitation may form.

Dose: Do NOT use solution if it is turbid or contains a deposit.

NOTE: Dose depends on the size of the patient, the severity Use within 4 hours after opening vial. Discard unused
of trauma or illness, and on continuing fluid and protein portion.
losses. Determine dose required based on measures of
adequacy of circulating volume and NOT plasma albumin
levels.

66
BLOOD AND BLOOD FORMING ORGANS

After initial volume replacement: Do NOT use if crystalline precipitate forms. Discard
5% albumin: Do not exceed 2–4 mL/minute in patients partially used containers. Do NOT add any drugs to
with normal plasma volume or 5–10 mL/minute in dextran solution. Flush tubing well or change IV tubing
patients with hypoproteinemia. If unavailable, it may be before infusing blood after dextran to prevent blood
prepared by diluting 25% human albumin with NS or coagulation.
D5W.

B
Monitor central venous pressure during the initial period
25% albumin: Do not exceed 1 mL/minute in patients of infusion to detect fluid overload. Stop immediately if
with normal plasma volume or 2–3 mL/minute in signs of anaphylactic reactions, or oliguria, or renal
patients with hypoproteinemia. May by diluted with NS or failure appear. Maintain hematocrit at 30% or higher and
D5W. observe for signs of bleeding complications.

NOTE: Rapid infusion may cause vascular overload. Pregnancy Category: C

Pregnancy Category: C ATC Code: B05AA05

ATC Code: B05AA01

Rx HYDROXYETHYL STARCH
DEXTRAN, HIGH MOLECULAR
Rx Inj.: 6% solution, 250 mL and 500 mL bottle (IV infusion)
WEIGHT (DEXTRAN 70)
Inj.: 6% dextran 70 in 0.9% sodium chloride, 500 mL A nonprotein synthetic colloid used for the prevention or
bottle (IV infusion) treatment of hypovolemia. Derived from corn starch
6% dextran 70 in 5% dextrose, 500 mL bottle (IV composed it expand circulating blood volume by an
infusion) amount approximately equal to the volume infused.

A nonprotein colloid and plasma volume expander used in Indication: Blood volume expander used in treatment of
the management of hypovolemic shock. It reduces blood hypovolemia.
viscosity, interferes with fibrin polymerization, has an
antiplatelet effect, and inhibits sludging or aggregation Contraindications: Renal failure with oliguria or anuria (not
of red blood cells. related to hypovolemia) ; any fluid overload condition
(e.g., pulmonary edema, CHF) ; pre­existing coagulation
Indication: Blood volume expander used in treatment of or bleeding disorders; critically ill adult patients,
shock or impending shock when blood or blood products including patients with sepsis or burns; severe liver
are not available. disease; lactic acidosis; leukapheresis.

NOTE: NOT a substitute for blood or blood components. Dose:

NOTE: Determine daily dose and rate of infusion based on
Contraindications: Hypersensitivity with dextran or any the amount of blood lost, maintenance or restoration of
component of the formulation; severe heart failure; hemodynamics, and amount of hemodilution.
bleeding disorders; renal failure
Administer lowest effective dose for the shortest period
Dose: possible. Do NOT administer etherified starches for more
Volume expansion or shock, by IV infusion, ADULT, initially than 24 hours. With severe dehydration, administer
500–1,000 mL at a rate of 20–40 mL/minute for not crystalloid first.
longer than 3 days (maximum dose, 20 mL/kg during the
first 24-hour period and 10 mL/kg daily thereafter). Plasma volume expansion, by IV infusion, ADULT, 500–
1,000 mL or 20 mL/kg daily (maximum, 1,500 mL or 50
Precautions: mL/kg daily); titrate to individual colloid needs,
Renal impairment; hemorrhage; chronic liver disease; hemodynamics, and hydration status.
patients at risk of developing pulmonary edema or heart
failure; Lactation (use with caution). Dose Adjustment:
Renal Impairment:
Adverse Drug Reactions: Avoid use in patients with pre­existing renal dysfunction.
Common: Hypersensitivity reactions (fever, nasal Discontinue use at the first sign of renal injury.
congestion, joint pains, urticaria, hypotension,
bronchospasm) Hepatic Impairment:
Less Common: Nausea, vomiting Use with caution.
Rare: Severe anaphylactic reactions

Drug Interactions:
Monitor closely with:
Enhances anticoagulant effect of Heparin

Administration: For IV infusion only.

67
 BLOOD AND BLOOD FORMING ORGANS

Precautions: intravascular space where they exert osmotic pressure to

WARNING: Etherified starches are associated with maintain circulatory volume.
increased bleeding. Avoid in patients with
coagulation disorders. Indications: Prophylaxis and treatment of absolute and
relative hypovolemia (e.g., following shock due to
Hydroxyethyl starch (HES) solutions have been hemorrhage or trauma, perioperative blood losses,
associated with mortality and renal injury requiring
B

burns, sepsis); prophylaxis of hypotension (e.g., with

renal replacement therapy in critically ill patients. induction of epidural or spinal anesthesia);
Avoid use in critically ill adult patients, including those hemodilution; extracorporeal circulation (heart-lung
with sepsis or burns, as well as patients admitted to machine, hemodialysis).
the ICU.
Contraindications: Hypervolemia; hyperhydration; severe
Anaphylactoid reactions (patients allergic to corn may be cardiac insufficiency; severe disturbance of blood
allergic to hetastarch); Bleeding (not recommended as a coagulation.
cardiac bypass pump prime; monitor the coagulation
status in patients undergoing open heart surgery in Dose:
association with cardiopulmonary bypass; may cause NOTE: Determine infusion rate and duration of
coagulation abnormalities in conjunction with a administration based on individual requirements. Adjust
reversible, acquired von Willebrand-like syndrome rate and duration to the current requirement by
and/or factor VIII deficiency when used over a period of monitoring the usual circulation parameters.
days); Fluid overload; Hematologic reactions; Hepatic
impairment; Renal impairment; Critically-ill patients Hypovolemia or hypotension, prophylaxis, by IV infusion,
(avoid use in patients with pre­existing renal dysfunction ADULT, 500–1,000 mL.
and discontinue use at the first sign of renal injury; Mild hypovolemia, treatment, by IV infusion, ADULT, 500–
monitor renal function in all patients for at least 90 days); 1,000 mL.
Lactation (use with caution). Hypovolemia, by IV infusion, ADULT, 500–1000 mL.
Severe hypovolemia, treatment, by IV infusion, ADULT,
Adverse Drug Reactions: 1,000–2,000 mL;
Common: Hypersensitivity reactions (including anaphylactic Severe hypovolemia, emergencies with vital indications, by
reactions), pruritus, hemodilution, decreased plasma rapid IV infusion, ADULT, 500 mL.
proteins and hematocrit. Hemodilution, isovolemic, by IV infusion, ADULT, not more
than 20 mL/kg body weight daily.
Drug Interactions: Incompatibilities can occur on mixing with Extracorporeal circulation, by IV infusion, ADULT, 500–
other medicaments. 1,500 mL.
Administration: Administer by IV infusion only. NOTE: Infuse the first 20–30 mL slowly under close
Administration rates vary depending on the extent of observation to allow early recognition of allergic
blood loss, age, and clinical condition of patient. Do NOT reactions (e.g., anaphylactic, anaphylactoid).
exceed 1.2 g/kg per hour (20 mL/kg per hour).
Precautions:
Do NOT use if crystalline precipitate forms or appears as Hypernatremia (use with great caution; additional sodium is
a turbid deep brown solution. administered with modified fluid gelatin); States of
May be administered via infusion pump or pressure dehydration; Disturbance of blood coagulation; Renal
infusion. If administered by pressure infusion, air should insufficiency; Hepatic impairment
be withdrawn or expelled from bag prior to infusion to .
prevent air embolus. Adverse Drug Reactions:
Less Common: Transient mild nausea or abdominal pain,
Do NOT administer with blood through the same transient mild rise of body temperature.
administration set. Change IV tubing or flush copiously Rare: Anaphylactoid reactions, tremor, hypotension,
with NS before administering blood through the same hypertension, wheezing, dyspnea, hypoxia, urticarial
line. Change IV tubing at least every 24 hours. reactions, sweating, chills, pyrexia.
Pregnancy Category: C Drug Interactions: Incompatibilities can occur on mixing with
other medicaments.
ATC Code: B05AA07
Administration: Administer by IV route. Warm solution to
body temperature prior to administration by pressure
MODIFIED FLUID GELATIN infusion.
Rx (POLYMERISATE OF DEGRADED
SUCCINYLATED GELATIN) Administer by rapid IV infusion under external pressure
in emergency situations. Remove all air from containers
Inj.: 3% and 4% solution, 500 mL bottle (IV infusion) with air space before starting the infusion to prevent air
embolism during infusion.
A sterile non-pyrogenic solution for infusion of succinylated
gelatin used as colloidal plasma substitutes. They Do NOT use if solution is not clear or the container or its
contain large molecules that do not readily leave the closure show visible signs of damage.

68
BLOOD AND BLOOD FORMING ORGANS

Pregnancy Category: No information available Precautions:

WARNING: Preterm infants and low birth weight
ATC Code: B05AA06 infants have poor clearance of IV lipid emulsion
and increased free fatty acid plasma levels
following lipid emulsion infusion. Deaths in preterm
I.V. SOLUTIONS FOR PARENTERAL NUTRITION infants after infusion of IV lipid emulsions have

B
been reported.
ALL-IN-ONE ADMIXTURES Special clinical monitoring is required at the beginning of IV
Rx (3 IN 1 SOLUTIONS / infusion (serum triglyceride level should not exceed 2
DUAL ENERGY SOLUTIONS) mmoL/L in 5–6 hours after the administration). Carefully
monitor serum glucose level, electrolytes, osmolarity,
Solution: Volume 400 – 2500 mL fluid balance, acid-base status, liver enzyme level
Concentration Variable [alkaline phosphatase, alanine aminotransferase (ALT),
Protein 3-6 g/100 mL and aspartate aminotransferase (AST) during
Carbohydrates 6–15 g/100 mL administration. Should any abnormal sign occur, the
Lipid 2–5 g/100 mL infusion must be stopped.
Calories Variable For long-term administration, consider additional
Electrolytes Variable administration of trace elements (e.g., copper, zinc) due
to increased urinary excretion accompanying IV
A sterile, nonpyrogenic emulsion of essential amino acids, administration of amino acids. Monitor blood cell count
electrolytes, dextrose, and lipid for central venous and coagulation during long-term administration.
administration, in a three-chamber bag. Disorders of lipid metabolism (induced by renal failure,
pancreatitis, impaired liver function, hypothyroidism
Indications: Supply of water, proteins, electrolytes, essential accompanied by hypertriglyceridemia); sepsis; lactic
amino acids & calories to patients by TPN when oral or acidosis, insufficient cellular oxygen supply, increased
enteral nutrition is unfeasible, insufficient, or serum osmolarity; patients who need a fluid
contraindicated; prevention of essential fatty acid resuscitation; patients with a tendency toward electrolyte
deficiency; treatment of negative nitrogen balance in retention.
adult patients. Renal failure (carefully monitor phosphate and potassium
intake to prevent hyperphosphatemia or hyperkalemia).
Contraindications: Hypersensitivity to eggs, soy protein, fat Patients under malnutrition state (monitor patients carefully
emulsion, amino acids, or glucose; hyperlipemia; severe and fine tune of the amount of additional solutions,
liver insufficiency; blood coagulation disorders; electrolytes, vitamins, and minerals required).
congenital disorder of amino acid metabolism; severe Elderly (adjust dose; reduced physiological activities).
renal insufficiency without hemofiltration or dialysis;
acute shock; hyperglycemia requiring insulin over 6 units Adverse Drug Reactions:
hourly; elevated serum levels including electrolytes. Common: Transient increase in body temperature.
Less Common: Shivering, chillness, nausea, vomiting.
Dose: Rare: Thrombophlebitis, hypersensitivity reactions (e.g.,
NOTE: Individualize dose and infusion rate based on the anaphylactic reaction, rash, urticaria), respiratory
ability to eliminate fat and metabolize glucose. symptoms (hyperventilation), hypertension or
Determine bag size with regard to the clinical condition hypotension, hemolysis, increased reticulocytes,
of the patient, the body weight and the nutritional abdominal pain, headache, fatigue, penile stiffness.
requirements.
Drug Interactions:
Normal nutritional state or under mild catabolic stresses, by Monitor closely with:
IV drip infusion, ADULT, 0.7–1 g/kg (nitrogen 0.1–0.15 Interferes with lipase system:
g/kg) daily of amino acids. Heparin (increases plasma lipolysis due to transient
Moderate to high catabolic stresses, by IV drip infusion, release of lipoprotein lipase; transient decrease of
ADULT, 1–2 g/kg (nitrogen 0.15–0.3 g/kg); generally, triglyceride clearance rate at initial administration),
0.7–1 g/kg daily of total amino acid (nitrogen 0.1–0.15 Insulin
g/kg) into peripheral or central veins; do not exceed a
rate of 3.7 mL/kg per hour (equivalent to 0.25 g glucose, General incompatibilities:
0.09 g amino acids, and 0.13 g lipids per kg); Glucose in solution (may form precipitates)
recommended infusion period is 12–24 hours or as
prescribed by the physician. Reduces therapeutic effect of Coumarin Derivatives:
Vitamin K1 [in soybean oil]
Dose Adjustment:
Geriatric: Administration: The solution is for IV infusion ONLY into a
Administer more slowly or at reduced dose. central vein.

Correct any state of electrolyte imbalance prior to initial

administration. Observe strict aseptic procedures during
insertion and manipulation to catheters to avoid
contamination.

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 BLOOD AND BLOOD FORMING ORGANS

Inspect the bag prior to activation. Use only if glucose Dose Adjustment:
solution and amino acid solution with electrolytes are The dosage should be adjusted according to patient’s
transparent, and fat emulsion is homogeneous. Discard clinical condition, body weight, and age.
the bag if there is evidence of damage to the bag, if more
than one chamber is white, if the solution is yellow, or if Use in Elderly:
any seal is broken. Reduce the dose by decreasing the infusion rate.
B

Mix the contents of each chamber thoroughly right

before use by inverting the bag upside down to ensure a Precautions:
homogenous admixture. Ensure the vertical seals Use in caution in patients with bacteremia, dehydration,
between chambers are broken and the contents of all hepatic dysfunction, renal failure, severe burns, cardiac
three chambers are mixed together prior to infusion. failure, reduced urine output due to obstructive
uropathy, diabetes mellitus, diabetes insipidus, severe
Ensure that precipitates have not formed during the acidosis, pancreatic disorders, history of allergic
mixing or addition of additives and that the emulsion has reactions and known hypersensitivity to any component
not separated. Separation of the emulsion can be visibly of the formulation.
identified by a yellowish streaking or the accumulation of
yellowish droplets in the mixed emulsion. If any of those Adverse Drug Reactions:
mentioned are observed, discard the admixture. Clinically Significant: Acidosis, shock and anaphylactoid
reactions, and hyperglycemia.
Consume solution within 24 hours unless specifically Less Common: Rash, pruritus, hyperkalemia,
stated that it is stable for a longer time. Discard any hyperglycemia, nausea, and vomiting.
remaining mixture after administration. Frequency Unknown: Facial flushing, hypernatremia,
hypercalcemia, abdominal pain, diarrhea, anorexia,
Do NOT inject with same syringe containing blood at the abnormal liver function tests, chest discomfort,
same time to minimize risk of false coagulation reaction. palpitation, cerebral edema, pulmonary edema,
peripheral edema, water intoxication, chills, fever, feeling
Use a dedicated line without any connections. Multiple of warmth, headache.
connections could result in air embolism due to residual
air being drawn from the primary container before Drug Interactions:
administration of the fluid from the secondary container Reduces the effects of the following:
is completed. Antiparkinsonian agents e.g. Levodopa, Warfarin
Enhances the effects of:
NOTE: Use of a vented IV administration set with the vent in Digitalis agents
the open position could result in air embolism.
Administration: Infuse via central vein; do not infuse via
Do NOT use administration sets and lines that contain di- peripheral vein.
2-ethylhexyl phthalate (DEHP) or administration sets that
contain polyvinyl chloride (PVC) components as these Pregnancy Category: C
contain DEHP as a plasticizer.
ATC Code: B05BA
Pregnancy Category: Not available

ATC Code: B05BA10 AMINO ACID + GLUCOSE +

Rx
ELECTROLYTES + VITAMIN B1
AMINO ACID + CARBOHYDRATE + Inj: Solution for peripheral venous infusion, 500 mL and
Rx
MULTIVITAMINS + ELECTROLYTES 1000 mL

Inj: Solution for IV injection/infusion set, 1000 mL The upper chamber contains an amino acid solution with
electrolytes and the lower chamber contains a glucose
Indications: Provision of water, electrolytes, calories, amino solution with electrolytes and vitamin B1.
acids and vitamin in patients who require central venous Indications: Provision of amino acids, electrolytes, vitamin
nutrition because oral or enteral nutrition is inadequate B1 and water via peripheral vein to patients with mild
or not possible. hypoproteinemia or mild malnutrition due to inadequate
oral intake, before and after surgery.
Contraindications: Abnormal electrolyte metabolism;
hepatic dysfunction; serious renal dysfunction; abnormal Contraindications: Hepatic coma or at risk of developing
amino acid metabolism; hemophilia; hypersensitivity to hepatic coma; serious renal dysfunction or azotemia;
any component of the formulation. congestive heart failure; severe acidosis; abnormal
electrolyte metabolism; reduced urine output due to
Dose: obstructive uropathy; abnormal amino acid metabolism;
Parenteral nutrition, by IV infusion, ADULT, 2000 mL via known hypersensitivity to thiamine chloride
central vein over 24 hours. hydrochloride.

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BLOOD AND BLOOD FORMING ORGANS

Dose: Precautions:
Mild hypoproteinemia or mild malnutrition, by IV infusion, Exercise caution against volume overload; Monitor
ADULT, 500 mL per dose infused via peripheral vein at periodically for signs of hyperosmolarity, hyperglycemia,
infusion rate of 500 mL administered over 120 minutes. glycosuria, and hypertriglyceridemia; Essential fatty acid
Maximum dose: 2500 mL per day. deficiency syndrome (may be prevented or corrected by
appropriate treatment with IV fat emulsions).

B
Dose Adjustment:
Use in Elderly: Adverse Drug Reactions:
Reduce the dose by decreasing the infusion rate under Common: Acidosis, alkalosis, hypophosphatemia,
careful supervision. hypocalcemia, rebound hypoglycemia, electrolyte
imbalance, hyperammonemia, nausea, vomiting, chills,
Precautions: flushing, sensation of warmth, headache, dizziness.
Use in caution in patients with hepatic dysfunction, renal
dysfunction, cardiovascular dysfunction, acidosis, and Drug Interactions: No information available
diabetes mellitus.
Administration: To be administered by IV route.
Adverse Drug Reactions:
Common: Vascular pain and phlebitis. Use only if bottle and seal are undamaged and solution
Less Common: Nausea, vomiting, chest discomfort is clear with vacuum present. Do NOT expose to light
Rare: Rash, palpitations, cerebral, pulmonary, and before using. Once closure is penetrated, transfer
peripheral edema, hyperkalemia, water intoxication, contents promptly, total time not to exceed 4 hours.
acidosis, chills, fever, sensation of warmth, and fever.
Initiation and termination of infusions of TPN fluids must
Drug Interactions: be gradual to permit adjustment of endogenous insulin
No information provided in the manufacturer’s labeling. release.

Administration: Immediately before use, break the center NOTE: Dose on the first day should be approximately half
seal between the two chambers and mix solutions the anticipated optimal dose and increased gradually to
thoroughly. The usual infusion rate in adults is 500 mL minimize glycosuria.
administered over 120 minutes.
Withdraw administration gradually to avoid rebound
Pregnancy Category: C hypoglycemia.

ATC Code: B05BA Pregnancy Category: Not available

ATC Code: B05BA01

AMINO ACIDS,
Rx
CRYSTALLINE STANDARD
COMBINED GLUCOSE-AMINO
Rx
Inj.: 3.5%, 500 mL bottle (IV infusion) ACID SOLUTIONS
5%, 100 mL, 250 mL, and 500 mL bottle (IV infusion)
6%, 100 mL and 250 mL bottle (IV infusion) Inj.:
7%, 8.5%, 10%, and 11.4%, 100 mL, 500 mL, and 1 Volume 100 mL and 500 mL
L bottle (IV infusion) Concentration variable
8% (as branched chain), 500 mL bottle (IV infusion) Glucose (sorbitol) 25-50 g
9.12%, 20 mL ampule and 200 mL bottle (IV infusion) Protein 20-30 g
10%, 100 mL and 500 mL bottle (IV infusion) Calories 300-450 kcal
Electrolytes variable
A sterile, clear, nonpyrogenic solution of essential and
nonessential amino acids for intravenous infusion in The solution provides carbohydrate calories and crystalline
parenteral nutrition following appropriate dilution. amino acids to stimulate protein synthesis, limit protein
catabolism, minimize liver glycogen depletion, and
Indications: Treatment of negative nitrogen balance when promote wound healing.
adequate nutrition by mouth or gastroduodenal tube is
impossible or undesirable; prevention of nitrogen loss. Indication: IV nutritional therapy to prevent nitrogen loss or
treat negative nitrogen balance in patients with
Contraindications: Hepatic coma; severe renal failure; adequate stores of body fat, in whom, for short periods
metabolic disorders involving impaired nitrogen of time, oral nutrition cannot be tolerated, is undesirable,
utilization. or inadequate.

Dose: Dose depends on metabolic status and clinical Contraindications: Hypersensitivity to one or more amino
response of the patient as therapy proceeds. Accompany acids in the solution; allergy to corn or corn products;
administration with other calorie sources in the form of hepatic coma; metabolic disorders involving impaired
carbohydrate or fat to ensure protein is utilized for nitrogen utilization; intracranial or intraspinal
protein synthesis. Doses which achieve nitrogen hemorrhage; severe dehydration; severe liver disease.
equilibrium or positive balance are the most desirable.

71
 BLOOD AND BLOOD FORMING ORGANS

Dose: Total daily dose depends on the daily protein SOYA BEAN + MEDIUM CHAIN
requirements and on the patient’s metabolic and clinical Rx TRIGLYCERIDES + OLIVE OIL +
response. Providing adequate calories in the form of
hypertonic dextrose may require the administration of PURIFIED FISH OIL
exogenous insulin to prevent hyperglycemia and
glycosuria. Administer 5% dextrose solution when Inj: 20 mg/mL (20%) emulsion for IV infusion, 250 mL
B

hypertonic dextrose infusions are abruptly discontinued

to prevent rebound hypoglycemia. A sterile, non-pyrogenic, white, homogenous lipid emulsion
consists of a mixture of soybean oil, medium-chain
Precautions: triglycerides, olive oil, and fish oil.

WARNING: Administration by central venous catheter Indications: Used for parenteral nutrition when oral or
should be used only by those familiar with this enteral nutrition is impossible, insufficient or
technique and its complications. contraindicated.

Contraindications: Known hypersensitivity to fish, egg,

Renal impairment (may induce a rise in BUN; perform
soybean, or peanut protein, or to any active ingredients
appropriate laboratory tests periodically; a modest rise in
or excipients of the product; severe hyperlipidemia or
BUN normally occurs as a result of increased protein
severe disorders of lipid metabolism characterized by
intake; discontinue infusion if BUN levels exceed normal
hypertriglyceridemia.
postprandial limits); Hepatic insufficiency; Diabetic or
prediabetic patients (take special care when
Dose:
administering glucose); Pulmonary disease, or with
The dose depends on the patient’s individual energy
cardiac insufficiency (use with caution to avoid excessive
requirements influenced by age, body weight, tolerance,
fluid accumulation); Severe renal failure and in
clinical status, and the ability to eliminate and
conditions where potassium retention is present (use
metabolize lipids.
with great care); Metabolic or respiratory alkalosis;
Increased level or impaired utilization of acetate (e.g.,
Dose Adjustment:
severe hepatic insufficiency) (use with great care);
Hepatic Impairment
Hyperammonemia.
Use in caution in patients with hepatic impairment.
Adverse Drug Reactions: Nausea, erythema, extravasation,
Precautions:
infection at the injection site, phlebitis extending from
May cause death after infusion in preterm infants,
the injection site, venous thrombosis, warm sensation,
hypersensitivity reactions, increased risk of catheter-
hyperglycemia, hyperosmolar syndrome, hypervolemia,
related infections, fat overload syndrome, refeeding
diuresis, fever, flushing, glycosuria.
syndrome, aluminum toxicity, parenteral nutrition-
associated liver disease, and hypertriglyceridemia.
Drug Interactions:
Monitor closely with:
Adverse Drug Reactions:
Reduces nitrogen-sparing effects of amino acids:
Common: Nausea.
Tetracycline.
Less Common: Vomiting, hyperglycemia, flatulence, pyrexia,
abdominal pain, increased blood triglycerides,
Administration: Administer by IV route. Hypertonic
hypertension, sepsis, dyspepsia, UTI, anemia, and
admixtures may be administered by continuous IV
device-related infection.
infusion through a central venous catheter with the tip
Rare: Dyspnea, leukocytosis, diarrhea, pneumonia,
located in the superior vena cava.
cholestasis, dysgeusia, increased blood alkaline
phosphatase, tachycardia, headache, pruritus, dizziness,
Inspect visually for particulate matter and discoloration
rash and thrombophlebitis.
prior to administration.
Drug Interactions:
Administration time for a single bottle and set should
No drug interaction studies have been performed. However,
NEVER exceed 24 hours.
vitamin K1 content of soybean oil and olive oil may
counteract the anticoagulant activity coumarin and
Solutions administrated to children by peripheral vein
coumarin derivatives including warfarin.
should NOT exceed twice the normal serum osmolarity
(718 mOsmol/L).
Administration: For central or peripheral intravenous
infusion.
Pregnancy Category: C
Pregnancy Category: C
ATC Code: B05BA10
ATC Code: B05BA02

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BLOOD AND BLOOD FORMING ORGANS

I.V. SOLUTIONS AFFECTING THE ELECTROLYTE 5% DEXTROSE

BALANCE Rx
IN 0.3% SODIUM CHLORIDE
DEXTROSE PREPARATIONS IN SODIUM CHLORIDE Inj.: 250 mL, 500 mL, and 1 L bottle / bag (IV infusion)

General Information Composition:

B
Dextrose 50 g/L
Sterile preparations containing dextrose for IV Na+ 51 mmol/L
administration. Cl- 51 mmol/L

Contraindications: Known hypersensitivity to corn or corn A sterile, non-pyrogenic, large-volume parenteral solution,
products; where the administration of sodium or chloride which contains 0.3% of sodium chloride and 5% dextrose
could be clinically detrimental. in water for injection; a source of electrolytes, water, and
calories for patients.
Dose:
Dose is dependent on age, weight, and clinical condition of Indication: Initial fluid replacement therapy for patients
patient. Select dose and constant infusion rate with having elevated serum sodium and conditions where
caution in pediatric patients, particularly neonates and fluid loss exceeds electrolyte loss.
low birth weight infants, because of the increased risk of
hyperglycemia or hypoglycemia. Adverse Drug Reactions:
Dose of sodium chloride is dependent on degree of sodium Rare: Sodium accumulation, water retention
depletion (e.g., moderately severe hyponatremia (serum
sodium, 125–129 mmol/L) or profound hyponatremia See General Information on Dextrose Preparations in
(serum sodium <125 mmol/L); on severity of symptoms Sodium Chloride under Blood Substitutes and Perfusion
(e.g., moderate or severe); and time of development of Solutions – I.V. Solutions affecting the Electrolyte
hyponatremia (acute, where hyponatremia is Balance in Chapter 02: Blood and Blood Forming Organs
documented to exist <48 hours). for other information.

Dose Adjustment: Pregnancy Category: C

Renal Impairment:
Take care in dose selection due to an increased risk of ATC Code: B05BB02
adverse effects.

Precautions: 5% DEXTROSE
Rx
IN 0.45% SODIUM CHLORIDE
WARNING: Mix infusion solutions thoroughly after
adding concentrated electrolytes to avoid possible
Inj.: 250 mL, 500 mL, and 1 L bottle / bag (IV infusion)
toxicity.
Composition:
Cardiovascular condition, cirrhotic disease, and nephrotic Dextrose 50 g/L
disease, and in patients receiving corticosteroid therapy; Na+ 77 mmol/L
Solutions containing dextrose should be used with Cl- 77 mmol/L
caution in patients with overt or known diabetes mellitus
and carbohydrate intolerance for any reason; clinical A sterile, non-pyrogenic, large-volume parenteral solution,
evaluation and periodic laboratory examinations are which contains 0.45% of sodium chloride and 5%
necessary; Cardiovascular effects. dextrose in water for injection, intended for intravenous
administration.
Drug Interactions:
Monitor closely with: Indications: For parenteral replenishment of fluid, minimal
Increases risk of hypertension and edema of the following carbohydrate calories, and sodium chloride as required
drugs due to sodium and water retention: by the clinical condition of the patient.
Corticosteroids
Adverse Drug Reactions: Febrile response, infection at the
Administration: Adjust rate of administration according to site of injection, venous thrombosis or phlebitis
tolerance. Too rapid infusion of hypertonic solutions may extending from the site of injection, extravasation,
cause local pain and venous irritation. hypervolemia.

Inspect visually for particulate matter and discoloration Administration: Intended only as a single-dose injection.
prior to administration. Do NOT administer unless Contains no bacteriostatic agent, antimicrobial agent, or
solution is clear, and container is undamaged. added buffer. Discard unused portion.

See General Information on Dextrose Preparations in

Sodium Chloride under Blood Substitutes and Perfusion
Solutions – I.V. Solutions affecting the Electrolyte

73
 BLOOD AND BLOOD FORMING ORGANS

Balance in Chapter 02: Blood and Blood Forming Organs NOT for use the treatment of severe potassium
for other information. deficiency, lactic acidosis, or severe metabolic acidosis.

Pregnancy Category: C Contraindications: Known hypersensitivity to sodium

lactate; allergy to corn or corn products.
ATC Code: B05BB02
B

Dose: Dose is dependent on age, weight, and clinical

condition of patient.
5% DEXTROSE
Rx Dose Adjustment:
IN 0.9% SODIUM CHLORIDE
Geriatric:
Start at the low end of the dosing range, reflecting the
Inj.: 250 mL, 500 mL, and 1 L bottle / bag (IV infusion)
greater frequency of decreased hepatic, renal, or cardiac
function, and of concomitant disease or drug therapy.
Composition:
Dextrose 50 g/L
Renal and Hepatic Impairment:
Na+ 154 mmol/L
Select dose with care due to increased risk of adverse
Cl- 154 mmol/L
effects, e.g., sodium and potassium retention.
A sterile, non-pyrogenic, large-volume parenteral solution,
Precautions:
which contains 0.9% of sodium chloride and 5% dextrose
in water for injection; a source of electrolytes, water, and WARNING: Mix infusion solutions thoroughly after adding
calories for patients. concentrated electrolytes to avoid possible toxicity.

Indications: Initial fluid and electrolyte replacement therapy Hypersensitivity (immediately stop infusion if any signs or
in conditions with combined water and sodium depletion; symptoms of a suspected hypersensitivity reaction
vehicle for IV drug administration. develop); Electrolyte imbalance; Hyperkalemia or
conditions predisposing to hyperkalemia; alkalosis or
Adverse Drug Reactions: risk for alkalosis; Conditions that may cause sodium
Rare: Sodium accumulation, water retention and/or potassium retention, fluid overload, or edema;
Cardiac disease; hypervolemia; overhydration; Impaired
See General Information on Dextrose Preparations in glucose tolerance or diabetes mellitus; Severe renal
Sodium Chloride under Blood Substitutes and Perfusion impairment; Conditions associated with increased
Solutions – I.V. Solutions affecting the Electrolyte lactate levels or impaired lactate utilization, such as
Balance in Chapter 02: Blood and Blood Forming Organs severe hepatic insufficiency; Substantially hypertonic
for other information. solutions (administer hyperosmolar solutions with
caution, if at all, to patients with hyperosmolar states);
Pregnancy Category: C Solutions containing calcium salts should be used with
caution in patients with hypercalcemia or conditions
ATC Code: B05BB02 predisposing to hypercalcemia, such as severe renal
impairment and granulomatous diseases associated
with increased calcitriol synthesis such as sarcoidosis,
5% DEXTROSE calcium renal calculi; Elderly; children and newborns
Rx
IN LACTATED RINGER’S
Adverse Drug Reactions:
Inj.: 250 mL, 500 mL, and 1 L bottle / bag (IV infusion) Less Common: Pain and inflammation at the injection site,
phlebitis, tissue necrosis, venous irritation, venous
Composition: thrombosis.
Dextrose 50 g/L Rare: Angioedema, anxiety, blood pressure decreased,
Na+ 130 mmol/L bronchospasm, chest discomfort and pain, cough,
K+ 4 mmol/L decreased heart rate, dysgeusia, dyspnea, edema,
Ca++ 1.22 – 1.5 mmol/L erythema, flushing, headache, hyperkalemia,
Cl- 109 mmol/L hypersensitivity reactions, including anaphylactic and
Lactate 28 mmol/L anaphylactoid reactions; hypesthesia, nausea,
A sterile, non-pyrogenic solution, which contains 5% paresthesia, pruritus, pyrexia, rash, respiratory distress,
dextrose and lactated ringer’s solution, in a single-dose tachycardia, throat irritation, urticaria.
container for IV administration and can produce a
metabolic alkalinizing effect. Drug Interactions:
Monitor closely with:
Indications: Source of water, electrolytes, and calories; Alters renal clearance of the following drugs:
alkalinizing effect. Acidic Drugs, e.g., Salicylates, Barbiturates (increased
renal clearance)
NOTE: Capable of inducing diuresis depending on the Basic Drugs, e.g., Sympathomimetics (decreased renal
clinical condition of the patient. clearance)
Lithium (increased renal clearance)

74
BLOOD AND BLOOD FORMING ORGANS

Increases risk of adverse or toxic effects of the following Dose Adjustment:

drugs: Renal Impairment:
Corticosteroids (sodium and fluid retention) Select doses with care due to an increased
risk of adverse effects, e.g., sodium and potassium
Increases risk of adverse or toxic effects of the following retention.
drugs:

B
Drugs which can cause hyperkalemia, e.g., Potassium- Precautions:
sparing Diuretics, Angiotensin II Receptor Antagonists, WARNING: Mix infusion solutions thoroughly after
ACE Inhibitors, Immunosuppressants (hyperkalemia) adding concentrated electrolytes to avoid possible
Thiazide Diuretics (hypercalcemia) toxicity.
Vitamin D (hypercalcemia)
High volume infusion must be used under specific
Avoid concomitant use with: monitoring in patients with cardiac or pulmonary failure,
Increases risk of adverse or toxic effects of Ceftriaxone in patients presenting edema, ascitic cirrhosis or renal
(Ceftriaxone-Calcium Salt precipitation in the insufficiency; Closely monitor patient’s clinical status
bloodstream) and laboratory parameters, including plasma electrolyte
levels of sodium, chloride, potassium, magnesium and
Administration: Administer via IV route. calcium; Sodium content (administer carefully to
patients with hypertension, heart failure, peripheral or
Inspect visually for particulate matter and discoloration pulmonary edema, impaired renal function, pre-
prior to administration. Do NOT administer unless eclampsia, aldosteronism, or other conditions
solution is clear, and container is undamaged. associated with sodium retention); Potassium content
(administer with caution to patients with cardiac
Do NOT connect flexible plastic containers in series to diseases or conditions that can lead to hyperkalemia
avoid air embolism due to possible residual air contained such as renal or adrenocortical insufficiency, acute
in the primary container. Pressurizing IV solutions dehydration, or extensive tissue destruction as occurs
contained in flexible plastic containers to increase flow with severe burns); Calcium content (Calcium Chloride is
rates can result in air embolism if the residual air in the an irritant; administer with caution to prevent
container is not fully evacuated prior to administration. extravasation; administer with caution to patients with
impaired renal function, or disease associated with
Do NOT administer simultaneously with citrate elevated Vitamin D concentrations, such as sarcoidosis
anticoagulated or preserved blood through the same or to patients receiving Digitalis therapy); Magnesium
administration set to prevent likelihood of coagulation. content (use with caution in patients with renal
impairment, severe heart rate disorders, and myasthenia
Pregnancy Category: C gravis; monitor for clinical signs of excess magnesium,
particularly when being treated for eclampsia; use with
ATC Code: B05BB02 caution when administered after neuromuscular block
during the postoperative period since magnesium salts
can lead to a recurarisation effect); Acetate content (may
cause metabolic alkalosis; not suitable as treatment for
Rx ACETATED RINGER’S SOLUTION severe metabolic or respiratory acidosis).

Inj.: 500 mL and 1 L bottle / bag (IV infusion) Adverse Drug Reactions:
Common: Overhydration, heart failure in patient with
Composition: cardiac disorder, pulmonary edema, febrile reaction,
Na+ 130 mmol/L infection at the site of injection, local pain or reaction,
K+ 4 mmol/L vein irritation, venous thrombosis or phlebitis extending
Ca++ 3 mmol/L from the site of injection, extravasation.
Cl- 109 mmol/L Rare: Hypersensitivity reactions, allergic reactions or
Acetate 28 mmol/L anaphylactic or anaphylactoid symptoms, tachycardia,
bradycardia, chest tightness, chest pain, localized or
A sterile, non-pyrogenic, lactate-containing solution, generalized urticaria, pruritus.
which serves as a source of water and electrolytes.
Drug Interactions:
Indication: For fluid and electrolyte replacement therapy. Monitor closely with:
Alters renal clearance of the following drugs:
Contraindications: Extracellular hyperhydration; Bicarbonates (increased renal elimination of certain
hypervolemia. drugs, e.g., quinidine, salicylates, lithium; decreased
elimination of sympathomimetics).
Dose: Dose is dependent on age, weight, and
clinical and biological (acid-base balance) conditions of Increases risk of adverse or toxic effects of the following
patient and concomitant therapy. drugs:
Potassium and or sodium retention: ACE Inhibitors e.g.,
Captopril; Cyclosporine; Corticosteroids e.g. Prednisone;
Digitalis Glycosides e.g. Digoxin; Potassium-sparing
Diuretics e.g. Spironolactone

75
 BLOOD AND BLOOD FORMING ORGANS

Tacrolimus BALANCED MULTIPLE

Rx
MAINTENANCE SOLUTON
Avoid concomitant use with:
Increases risk of adverse or toxic effects of the following
Inj.: with 5% dextrose, 250 mL and 500 mL (infants) and
drugs:
1 L (children and adults), bottle / bag (IV infusion)
Suxamethonium (hyperkalemia; intensifies negative
B

effect on cardiac rhythm); Potassium (hyperkalemia;

Composition:
intensifies negative effect on cardiac rhythm)
INFANTS CHILDREN
& ADULTS
Potentiates therapeutic effects of Neuromuscular Blockers,
Dextrose 50 g/L 50 g/L
e.g., Suxamethonium, Vecuronium, Tubocurarine:
Na+ 25-30 mmol/L 40-50 mmol/L
Magnesium Salts
K+ 20-25 mmol/L 13-30 mmol/L
Mg++ 1.35-1.65 mmol/L 1.65 mmol/L
Administration: Administer via IV route.
Cl- 22 mmol/L 40 mmol/L
Acetate 23 mmol/L 16 mmol/L
Inspect visually for particulate matter and discoloration
prior to administration. Do NOT administer unless
A sterile, nonpyrogenic, hypertonic solution of balanced
solution is clear, and container is undamaged.
maintenance electrolytes and 5% dextrose injection in
water for injection.
Administer with sterile equipment using aseptic
technique. Prime equipment with the solution to prevent
Indication: Fluid and electrolyte maintenance therapy.
air entering the system.
Contraindications: Hyperkalemia; oligo-anuric renal failure.
Do NOT connect flexible plastic containers in series to
avoid air embolism due to possible residual air contained
Dose: Dose is dependent on age, weight, and degree of fluid
in the primary container before the administration of the
and electrolyte loss.
fluid from the secondary container is completed.
Pressurizing IV solutions contained in flexible plastic
Dose Adjustment:
containers to increase flow rates can result in air
Renal Impairment:
embolism if the residual air in the container is not fully
Select doses with care due to an increased risk of adverse
evacuated prior to administration. Avoid using a vented
effects, e.g., sodium and potassium retention.
IV administration set with the vent in the open position
to prevent air embolism.
Precautions:
Do NOT administer simultaneously with citrate WARNING: Mix infusion solutions thoroughly after
anticoagulated or preserved blood through the same adding concentrated electrolytes to avoid possible
administration set to prevent likelihood of coagulation. toxicity.

Do NOT administer via the same infusion system as Hypersensitivity reactions; CHF; renal insufficiency; clinical
concomitant blood transfusion because of the risk of states with edema with sodium retention.
coagulation Administration of the solution can cause fluid and/or solute
Due to its iso-osmolality, this solution can be overloading resulting in dilution of serum electrolyte
administered through a peripheral vein. Use only if the concentration, overhydration, congested states or
solution is clear, without visible particles and if the pulmonary edema; Clinical evaluation and periodical
container is undamaged. Administer immediately laboratory determinations are necessary to monitor
following the insertion of infusion set. Do NOT remove changes in fluid balance, electrolyte concentration, and
unit from overwrap until ready for use. The inner bag acid-base balance during prolonged therapy or whenever
maintains the sterility of the product. Discard after single the patient’s condition warrants such evaluation.
use. Discard any unused portion. Do not reconnect
Adverse Drug Reactions: Febrile response, infection at the
partially used bags.
site of injection, venous thrombosis or phlebitis
NOTE: Additives may be introduced before or during infusion extending from the site of injection, extravasation,
through the injection site. When additive is used, verify hypervolemia
isotonicity prior to administration. Thorough and careful NOTE: May occur because of the solution or the technique
aseptic mixing of any additive is mandatory. Solutions during administration.
containing additives should be used immediately and not
stored. Adding other medication or using an incorrect Drug Interactions: No information available
administration technique might cause fever reactions
due to the possible introduction of pyrogens. Stop NOTE: Additives may be incompatible. Consult with
infusion immediately in case of adverse reaction. pharmacist.
Pregnancy Category: C Administration: Administer by IV infusion. Contains no
bacteriostat, antimicrobial agent, or added buffer and is
ATC Code: B05BB01 intended only for use as a single-dose injection. Discard
unused portion.

76
BLOOD AND BLOOD FORMING ORGANS

When introducing additives, use aseptic technique, mix Drug Interactions:

thoroughly, and do not store. Monitor closely with:
Increases risk of hypertension and edema of the following
Select dose and constant infusion rate of IV dextrose with drugs due to sodium and water retention:
caution in pediatric patients, particularly neonates and Corticosteroids e.g. prednisone
low birth weight infants, because of the increased risk of

B
hyperglycemia or hypoglycemia. Administration: Administer via IV infusion.

Pregnancy Category: C Inspect visually for particulate matter and discoloration

prior to administration. Do NOT administer unless
ATC Code: B05BB02 solution is clear, and container is undamaged.

Pregnancy Category: C
BALANCED MULTIPLE
Rx ATC Code: B05BB02
REPLACEMENT SOLUTON
Inj.: 500 mL and 1 L bottle / bag (IV infusion)
BALANCED MULTIPLE
Composition: Rx REPLACEMENT SOLUTION
Na+ 140-145 mmol/L WITH pH 7.4
K+ 4-5 mmol/L
Mg++ 1-1.65 mmol/L Inj.: 500 mL and 1 L bottle / bag (IV infusion)
Cl- 98-127 mmol/L
Acetate 24-50 mmol/L Composition:
Plus 5% dextrose (50 g/L) Na+ 140 mmol/L
K+ 5 mmol/L
A sterile, non-pyrogenic solution consisting of balanced Mg++ 3 mmol/L
electrolytes with 5% dextrose in water for injection. Cl- 98 mmol/L
Acetate 50 mmol/L
Indications: Acute fluid and electrolyte replacement therapy;
fluid replacement in hyperchloremic acidosis. A sterile, nonpyrogenic, isotonic solution of balanced
Contraindications: Not to be used for fluid and electrolyte electrolytes in water for injection, administered by IV
maintenance therapy; hyperkalemia, hypermagnesemia; infusion for parenteral replacement of acute losses of
metabolic alkalosis. extracellular fluid.

Dose: Dose is dependent on age, weight, and degree of fluid Indications: Replacement of acute losses of extracellular
and electrolyte loss. fluid volume in surgery, trauma, burns, or shock; adjunct
to restore a decrease in circulatory volume in patients
Dose Adjustment: with moderate blood loss.
Renal Impairment:
Select doses with care due to an increased risk of adverse NOTE: NOT intended to supplant transfusion of whole blood
effects, e.g., sodium and potassium retention. or packed red cells in the presence of uncontrolled
hemorrhage or severe reductions of red cell volume.
Precautions:
WARNING: Mix infusion solutions thoroughly after NOT intended to correct acidosis or large deficits of
adding concentrated electrolytes to avoid possible individual electrolytes, nor to replace blood or plasma
toxicity. expanders when these are indicated.

Hypersensitivity reactions; CHF; renal insufficiency; clinical Contraindications: Hypernatremia or hyperchloremia and
states with edema with sodium retention; Administration related conditions (hypermagnesemia,
of the solution can cause fluid and/or solute overloading hyperphosphatemia, edema, certain cardiac diseases).
resulting in dilution of serum electrolyte concentration,
overhydration, congested states or pulmonary edema; Dose: Dose is dependent on age, weight, and degree of fluid
Clinical evaluation and periodical laboratory and electrolyte loss.
determinations are necessary to monitor changes in fluid
balance, electrolyte concentration, and acid-base Dose Adjustment:
balance during prolonged therapy or whenever the Geriatric:
patient’s condition warrants such evaluation. Select doses with caution. Begin at the low end of the dosing
range.
Adverse Drug Reactions: Febrile response, infection at the
site of injection, venous thrombosis or phlebitis Precautions:
extending from the site of injection, extravasation, Can cause fluid and/or solute overloading resulting in
hypervolemia. dilution of serum electrolyte concentrations,
overhydration, congested states, or pulmonary edema;
NOTE: May occur because of the solution or the technique Clinical evaluation and periodic laboratory
during administration.

77
 BLOOD AND BLOOD FORMING ORGANS

determinations are necessary to monitor changes in fluid ISOTONIC ELECTROLYTE SOLUTION

balance, electrolyte concentrations and acid-base Rx
FOR IV INFUSION
balance during prolonged parenteral therapy or
whenever the condition of the patient warrants such
Inj: 1 L bottle
evaluation; Sodium content (use with caution in CHF,
concomitant corticosteroid use, severe renal
Composition:
B

insufficiency, and clinical states with edema with sodium

Sodium chloride - 6.80 g
retention); Potassium content (use with caution in
Potassium chloride - 0.30 g
hyperkalemia, severe renal failure, and potassium
Calcium chloride dehydrate - 0.37 g
retention); Acetate content (use with caution in
Magnesium chloride hexahydrate - 0.20 g
metabolic or respiratory alkalosis and severe hepatic
Sodium acetate trihydrate - 3.27 g
insufficiency); Renal impairment (monitor renal function
Malic acid - 0.67 g
during fluid replacement); Elderly (have been shown to
secrete higher levels of ADH; increased risk for
An isotonic electrolyte solution resembling human plasma.
developing fluid overload and dilutional hyponatremia).
Indications: Use in the replacement of extracellular fluid
Adverse Drug Reactions: Febrile response, infection at the
losses in the case of isotonic dehydration, where acidosis
site of injection, venous thrombosis or phlebitis
is present or imminent.
extending from the site of injection, extravasation,
hypervolemia
Contraindications: Hypervolemia; severe congestive heart
NOTE: May occur because of the solution or the technique failure, renal failure with oliguria or anuria; severe
during administration. general edema; hyperkalemia; hypercalcemia; metabolic
alkalosis.
If an adverse reaction occurs, discontinue the infusion,
evaluate the patient, institute appropriate therapeutic Dose:
countermeasures, and save the remainder of the fluid for The dosage depends on the age, weight, clinical and
examination, if deemed necessary. biological conditions of the patient and concomitant
therapy.
Drug Interactions:
Monitor closely with: Dose Adjustment:
Increases risk of hypertension and edema of the following No dosage adjustments provided in the manufacturer’s
drugs due to sodium and water retention: labeling.
Corticosteroids e.g. Prednisone
Precautions:
NOTE: Additives may be incompatible. Consult with pharmacist. Use in caution in patients with mild to moderate cardiac
insufficiency, peripheral or pulmonary edema or
Administration: Administer by IV infusion. Contains no extracellular hyperhydration, hypernatremia,
bacteriostat, antimicrobial agent, or added buffer hyperchloremia, hypertonic dehydration, hypertension,
(except for pH adjustment) and is intended only for use impaired renal function, present or imminent eclampsia,
as a single-dose injection. Discard unused portion. aldosteronism or other conditions or treatment
associated with sodium retention;
Inspect visually for particulate matter and discoloration Use in caution in patients with cardiac disease, or conditions
prior to administration. Do NOT administer unless predisposing to hyperkalemia such as renal or
solution is clear, and container is undamaged. adrenocortical insufficiency, acute dehydration, or
extensive tissue destruction as occurs with severe burns;
Determine the amount to be infused based on May cause extravasation due to calcium content and should
replacement of losses of extracellular fluid volume in the be given cautiously in patients with impaired renal
individual patient. Up to 3 times the volume of estimated function or diseases associated with elevated vitamin D
blood loss during and after surgery can be given to concentrations such as sarcoidosis.
correct circulatory volume when there is only a moderate
loss of blood. Adverse Drug Reactions:
Less Common: Adverse reactions associated to the
Pregnancy Category: C technique of administration including febrile response,
infection at the injection site, local pain or reaction, vein
ATC Code: B05BB02 irritation, vein irritation, venous thrombosis or phlebitis
extending from the site of injection and extravasation.
Rare: Urticaria due to intravenous administration of
magnesium salts.

Drug Interactions:
Monitor closely with:
Corticosteroids- may be associated with sodium and water
retention, with increased risk of edema and
hypertension.
Digoxin- enhanced hypercalcemia, which can lead to cardiac
arrhythmia.

78
BLOOD AND BLOOD FORMING ORGANS

Drugs that can cause hyperkalemia (e.g., suxamethonium, Small and/ or debilitated patients:
potassium-sparing diuretics or tacrolimus) - increased Consider giving 500 mg/kg.
risk of hyperkalemia.
Vitamin D- may induce hypercalcemia. Precautions:

Administration: The solution is administered IV; do not WARNING: Use caution in patients with underlying
renal disease. May be used to reduce the incidence

B
administer unless the solution is clear and container is
undamaged. of acute tubular necrosis when administered prior
to revascularization during kidney transplantation.
Pregnancy Category: C
Carefully monitor fluid balance, electrolytes, renal function,
ATC Code: B05BB01 and vital signs during infusion to prevent fluid and
electrolyte imbalance, including circulatory overload and
tissue dehydration; Extravasation (vesicant at
I.V. SOLUTIONS PRODUCING OSMOTIC DIURESIS concentrations >5%; ensure proper catheter or needle
position prior to and during IV infusion); fluid or
electrolyte loss (close medical supervision and dose
Rx MANNITOL evaluation are required; adjust dose to avoid
dehydration); Nephrotoxicity (use caution in patients
Inj.: 20%, 250 mL and 500 mL bottle (IV) taking other nephrotoxic agents, with sepsis or
pre­existing renal disease; maintain serum osmolality
A hexahydric alcohol related to mannose that acts as an less than 320 mOsm/L to minimize adverse effects;
osmotic agent with little energy value. When given discontinue if evidence of acute tubular necrosis occurs);
parenterally, it raises the osmotic pressure of the Cerebral edema; cardiovascular status should also be
plasma, thus drawing water out of body tissues and evaluated; Lactation (use with caution).
producing an osmotic diuresis.
Adverse Drug Reactions:
Indications: To reduce cerebral edema; to reduce increased Common: Fluid and electrolyte imbalance including
intraocular pressure; to promote urinary excretion of circulatory overload and acidosis (large doses), nausea,
toxic substances. vomiting, thirst, headache, dizziness, chills, fever,
tachycardia, chest pain, hyponatremia, dehydration,
blurred vision, urticaria, hypotension or hypertension,
NOTE: NOT recommended to be used for the prevention of
hypersensitivity reactions, extravasation (leading to
acute renal failure and/or promotion of diuresis.
edema and skin necrosis), thrombophlebitis.
Rare: Acute renal failure (large doses)
Contraindications: Hypersensitivity to mannitol or any
component of the formulation; severe renal disease
Drug Interactions:
(anuria); severe dehydration; active intracranial bleeding
Monitor closely with:
except during craniotomy; progressive heart failure,
Enhances therapeutic effect of Mannitol:
pulmonary congestion, or renal dysfunction after
Barbiturates (hypotensive effect)
administration; severe pulmonary edema or congestion.
Brimonidine, topical (hypotensive effect)
MAO Inhibitors (hypotensive effect)
Dose:
Nicorandil (hypotensive effect)
Increased intracranial pressure, cerebral edema, by IV
Pentoxifylline (antihypertensive effect)
injection, ADULT, 0.25–2 g/kg per dose, may repeat
Phosphodiesterase-5 Inhibitors (antihypertensive effect)
every 6–8 hours, as needed to maintain a serum
Prostacyclin Analogues (hypotensive effect)
osmolality <300-320 mOsm/kg; CHILD, 0.25–1 g/kg per
dose administered over 30–60 minutes, repeat as
Enhances therapeutic effect of the following drugs:
needed to maintain a serum osmolality <300–320
Alfuzosin (hypotensive effect), Other Antihypertensives
mOsm/kg.
(hypotensive effect), Herbs with hypertensive properties
Reduction of intraocular pressure, by IV injection, ADULT,
(hypotensive effect), Risperidone (hypotensive effect)
0.25–2 g/kg administered over 30–60 minutes 1–1.5
hours prior to surgery; CHILD, 1 to 2 g/kg or 30–60 g/m2
Increases risk of adverse or toxic effects of Mannitol:
administered over 30–60 minutes 1–1.5 hours prior to
Opioid Analgesics, Other Hypotensive Agents, MAO
surgery.
Inhibitors [except Linezolid, Tedizolid] (orthostatic
Reduction of intraocular pressure, traumatic hyphema, by IV
hypotensive effect)
injection, ADULT, 1.5 g/kg administered over 45 minutes
twice daily for IOP >35 mmHg; may administer every 8
Increases risk of adverse or toxic effects of the following
hours; CHILD, 1.5 g/kg administered over 45 minutes
drugs:
twice daily for IOP >35 mmHg; may administer every 8
Duloxetine (orthostatic hypotensive effect)
hours in patients with extremely high pressure.
Levodopa (orthostatic hypotensive effect)
Dose Adjustment:
Reduces therapeutic effect of Mannitol:
Geriatric:
Herbs with hypertensive properties (antihypertensive
Consider initiation at lower end of dosing range.
effect)
Methylphenidate (antihypertensive effect)

79
 BLOOD AND BLOOD FORMING ORGANS

Avoid concomitant use with: Dose: For use as an irrigant during ocular surgery, consult
Increases risk of adverse or toxic effects of the following specialized references for proper use during various
drugs: ocular surgery types.
Aminoglycosides (nephrotoxic effect)
Obinutuzumab [withhold Mannitol 12 hours prior to Precautions:
Obinutuzumab infusion until 1 hour after the end of the WARNING: Open under aseptic conditions only.
B

infusion] (hypotensive effect)

Rituximab (hypotensive effect)
Corneal clouding and edema; Diabetes (use with caution in
Sodium Phosphates (nephrotoxic effect; risk of acute
patients undergoing vitrectomy).
phosphate nephropathy)
Adverse Drug Reactions: Corneal swelling or bullous
Administration: For IV administration. Determine
keratopathy (prolonged procedures), inflammatory
concentration and rate of administration based on
reactions (post-operative), corneal edema (post-
indication or severity or adjust to urine flow.
operative), corneal decompensation (post-operative)
Inspect for crystals prior to administration. If crystals are NOTE: Use proper solution in accordance to the surgical
present, re-dissolve by warming solution. Use filter type procedure to prevent cytotoxic effects.
administration set for infusion solutions containing
≥20% Mannitol. Drug Interactions: No information found
Do NOT administer until adequacy of renal function and Administration: Use according to standard format for each
urine flow is established. Use 1–2 test doses to assess surgical procedure. For single patient use only. This
renal response. solution contains no preservative. Discard unused
portion.
Do NOT administer electrolyte-free mannitol solutions
with blood. NEVER add to whole blood for transfusion or Use an administration set with an air-inlet in the plastic
administer through the same set by which blood is being spike since the bottle does not contain a separate airway
infused to prevent crenation and agglutination of RBC. tube. Follow directions of the administration set to be
used. Remove blue flip-off cap. Clean and disinfect the
Pregnancy Category: C rubber stopper using a sterile alcohol wipe. Insert the
spike aseptically into the bottle through the target area
ATC Code: B05BC01 of the rubber stopper. Allow the fluid to flow and remove
air from the tubing before irrigation.
IRRIGATING SOLUTIONS Do NOT use unless product is clear, seal is intact,
vacuum is present, and container is undamaged. Do NOT
INTRAOCULAR IRRIGATING use if product is discolored or contains a precipitate.
Rx SOLUTION
Pregnancy Category: C
(BALANCED SALT SOLUTION)
ATC Code: B05CX10
Solution: 15 mL, 250 mL, and 500 mL bottle

Composition:
Sodium chloride 0.64% PERITONEAL DIALYTICS
Potassium chloride 0.075%
Calcium chloride 0.048%
Magnesium chloride
Rx PERITONEAL DIALYSIS SOLUTION
(hexahydrate) 0.03%
Sodium acetate 0.39% Solution: Sterile with 1.5%, 2.3%, and 4.25% dextrose, 2
Sodium citrate 0.17% L and 5 L bottle/bag
Water for injection to make 100%
Content per liter:
A sterile, isotonic, balanced salt solution for use in irrigating Glucose monohydrate 16.5 g
tissues of the eyes. (equivalent to 15.0 g glucose)
Fructose up to 0.75 g
Indications: Extraocular and intraocular irrigating solution Sodium chloride 5.786 g
during ocular surgical procedure involving the anterior Sodium (S) – lactate solution 7.85 g
chamber (e.g., cataract and glaucoma surgeries) and (equivalent to 3.925 g sodium (S) – lactate)
vitreous cavity (e.g., vitrectomy); for perfusion of the eye Calcium chloride dihydrate 183.8 mg
with an expected maximum duration of <60 minutes. Magnesium chloride hexahydrate 101.7 mg

Contraindications: No information available A sterile, nonpyrogenic solution containing electrolytes at a

concentration close to the electrolytic composition of
plasma and glucose in varying concentrations or other
suitable osmotic agents. It is used for peritoneal dialysis,

80
BLOOD AND BLOOD FORMING ORGANS

a procedure for removing toxic substances and Administration: For intraperitoneal infusion only. Do NOT
metabolites normally excreted by the kidneys, and for administer by IV infusion.
aiding in the regulation of fluid and electrolyte balance.
Observe aseptic technique throughout the procedure.
Indications: Correct acid and electrolyte imbalance, and The drained fluid should be inspected for the presence
fluid overload; remove metabolites in renal failure. of fibrin or cloudiness, which may indicate the presence

B
of peritonitis. Discard any unused solution.
Contraindications: Known hypersensitivity to corn or corn
products; abdominal sepsis; previous abdominal Prior to use, check for leaks by squeezing the inner bag
surgery; severe inflammatory bowel disease; presence of firmly. If leaks are found, do NOT use solution as sterility
abdominal devices; pre-existing severe lactic acidosis; may be impaired. Check to see that solution is clear and
uncorrectable mechanical defects that prevent effective free of foreign matter. Solutions that are cloudy,
peritoneal dialysis or increase the risk of infection; discolored, contain visible particulate matter, or show
documented loss of peritoneal function or extensive evidence of leakage should not be used or discarded.
adhesions that compromise peritoneal function.
Heating the dialysis solution to 37°C while in the over
Dose: Individualized according to clinical condition and pouch may decrease discomfort and heat loss and
based on blood chemistry results. increase urea clearance compared to solution at room
Precautions: temperature. Use only dry heat (e.g. heating pad,
Encapsulating Peritoneal Sclerosis; azotemic diabetics warming plate). Do NOT heat solutions in water or in a
(carefully monitor insulin requirements during and microwave oven due to the potential for patient injury or
following dialysis); Improper clamping or priming discomfort.
sequence may result in infusion of air into the peritoneal
cavity; Abdominal conditions, including disruption of the When introducing additives, refer to directions for use
peritoneal membrane and diaphragm by surgery or from accompanying drugs to obtain full information on
congenital anomalies or trauma until healing is additives, and use aseptic techniques. Mix thoroughly.
complete, abdominal tumors, extensive adhesions, Do NOT store.
bowel distension, undiagnosed abdominal disease,
abdominal wall infection, hernias or burns, fecal fistula, NOTE: 1,000–2,000 international units of heparin per liter
colostomy or ileostomy, frequent episodes of of solution may be added to the dialysis solution to
diverticulitis, inflammatory or ischemic bowel disease, prevent catheter blockage in patients with peritonitis, or
tense ascites, obesity, and large polycystic kidneys, or when the solution drainage contains fibrinous or
other conditions that compromise the integrity of the proteinaceous material.
abdominal wall, abdominal surface, or intra-abdominal
cavity (perform peritoneal dialysis with great care); Aortic Pregnancy Category: C
graft replacement and severe pulmonary disease
(perform peritoneal dialysis with caution); Protein, amino ATC Code: B05DA (isotonic), B05DB (hypertonic)
acids, water-soluble vitamins, and other medicines may
be lost during peritoneal dialysis and may require
replacement (carefully monitor patients to avoid over- I.V. SOLUTIONS ADDITIVES
and under-hydration); Routine periodic evaluation of
blood chemistries, serum electrolyte concentrations, and
hematologic factors, as well as other indicators of patient Rx 0.9% SODIUM CHLORIDE
status, should be performed for stable patients
undergoing maintenance peritoneal dialysis.
Inj.: 2 mL, 2.5 mL, 5 mL, 10 mL, and 20 mL ampule
50 mL, 100 mL, 200 mL, 500 mL, and 1 L bottle /
Adverse Drug Reactions: Abdominal pain, bleeding,
bag (IV infusion)
peritonitis, catheter blockage, difficulty in fluid removal,
ileus, electrolyte and fluid imbalances, hypovolemia,
Solution: 1 L bottle solution for irrigation
hypervolemia, hypertension, hypotension,
hyperphosphatemia, muscle cramping, fungal
Composition:
peritonitis, bacterial peritonitis, catheter-related
Na+ 154 mmol/L
infection, hypervolemia, fluid retention, hypokalemia,
Cl- 154 mmol/L
hyponatremia, dehydration, hypochloremia, dyspnea,
sclerosing encapsulating, peritonitis, peritoneal cloudy
A sterile, non-pyrogenic, isotonic solution of sodium chloride
effluent, vomiting, diarrhea, nausea, constipation,
in water for injection.
abdominal distension, abdominal discomfort, Stevens-
Johnson syndrome, urticaria, rash, pruritus, myalgia,
Indications: Fluid and electrolyte replacement
musculoskeletal pain, muscle spasms, generalized
therapy in conditions where water and sodium losses are
edema, pyrexia, malaise, infusion site pain, catheter-
in isotonic proportion; vehicle for IV
related complication.
drug administration; priming and rinsing fluid
for hemodialysis; lavage in surgical patients.
Drug Interactions:
NOTE: Additives may be incompatible. Consult with
Contraindication: Where the administration of
pharmacist familiar with peritoneal dialysis.
sodium or chloride could be clinically detrimental.

81
 BLOOD AND BLOOD FORMING ORGANS

Dose:
NOTE: Individualize fluid administration based on calculated Rx 5% DEXTROSE IN WATER
maintenance or replacement fluid requirements.
Inj.: 250 mL, 500 mL, and 1 L bottle / bag (IV infusion and
Fluid and electrolyte replacement, by IV infusion, as vehicle for IV medications)
ADULT and CHILD, determined based on clinical and,
B

whenever possible, electrolyte A sterile, non-pyrogenic solution of dextrose that is

monitoring. See under Sodium Chloride. indicated for use in adults and children as a
Dose of sodium chloride is dependent on degree of sodium source of calories and water of hydration.
depletion (i.e., moderately severe hyponatremia where
serum sodium is between 125-129 mmol/L or profound Indications: Replacement therapy in conditions
hyponatremia where serum sodium is <125 mmol/L); on mainly due to water losses; elevated serum sodium; IV
severity of symptoms (i.e., moderately or severely infusion to keep vein open for IV drug administration.
symptomatic); and on time of development of
hyponatremia (acute, where hyponatremia is Contraindication: Known hypersensitivity to corn
documented to exist <48hrs). or corn products.
IMPORTANT NOTE: Sodium deficit must be corrected Dose:
gradually in stages. Avoid overtly rapid correction to For replacement therapy, by IV infusion, depending
prevent development of Osmotic Demyelination on requirement, with average dose 1,000–2,000
Syndrome (previously named Central Pontine mL/day (flow rate up to 120 drops/minute, 360
Myelinosis). The rate of correction of hyponatremia mL/hour).
should not be more than 10 mmol/L (or 10 mEq/L) in
24 hours, or 18 mmol/L (or 10 mEq/L) in 48 hours. Dose Adjustment:
Renal Impairment:
Dose Adjustment: Select doses with care due to an increased risk of adverse
Renal Impairment: effects.
Select doses with care due to an increased risk of adverse
effects. Precautions:
Precautions: WARNING: Mix infusion solutions thoroughly after adding
concentrated electrolytes to avoid possible toxicity.
WARNING: Mix infusion solutions thoroughly after adding
concentrated electrolytes to avoid possible toxicity.
Fluid and/or solute overload; prolonged infusion of isotonic
or hypotonic dextrose in water; Hyponatremia; fluid
Impaired renal function, cardiac failure, hypertension,
retention; DM or carbohydrate intolerance (use with
peripheral and pulmonary edema, and toxemia during
caution); Contains aluminum which may be toxic,
pregnancy (restrict intake); Cardiac, cirrhotic, or
particularly in those with impaired kidney function, e.g.,
nephrotic patients.
premature neonates.
Adverse Drug Reactions: Air embolization, febrile response,
Adverse Drug Reactions: Febrile response, infection at the
local tenderness, tissue necrosis or infection at the site
site of injection, venous thrombosis or phlebitis
of injection, venous thrombosis or phlebitis extending
extending from the sit
from the site of injection, extravasation, hypervolemia
e of injection, extravasation, hypervolemia.
NOTE: may occur because of the solution or the technique
NOTE: May occur because of the solution, added drugs or
during administration.
the technique of reconstitution or administration.
Drug Interactions: No information found
Rare: Edema, sodium accumulation
Administration: Adjust rate of administration according to
Drug Interactions:
tolerance. Too rapid infusion may cause local pain and
Monitor closely with:
venous irritation. Use largest peripheral vein and a small-
Increases risk of hypertension and edema of the following
bore needle.
drugs due to sodium and water retention:
Corticosteroids
Inspect visually for particulate matter and discoloration
prior to administration.
Administration: For single use only. Contamination may lead
to injury, illness or death.
Pregnancy Category: C
Inspect visually for particulate matter and discoloration
ATC Code: Not available
prior to administration.

Pregnancy Category: C

ATC Code: B05XA03

82
BLOOD AND BLOOD FORMING ORGANS

Hyperosmolar syndrome (excessively rapid

Rx 10% DEXTROSE IN WATER administration), hypovolemia, dehydration, mental
confusion, and/or loss of consciousness, diuresis (too
Inj.: 250 mL, 500 mL, and 1 L bottle / bag (IV infusion) rapid infusion), hyperglycemia (too rapid infusion),
3 mL ampule (as solvent) glycosuria (too rapid infusion), hyperosmolar coma (too
rapid infusion)

B
A sterile, non-pyrogenic, hypertonic solution of Dextrose,
USP in water for injection for intravenous administration NOTE: If an adverse reaction occurs, discontinue the
after appropriate admixture or dilution. infusion, evaluate the patient, institute appropriate
therapeutic countermeasures and save the remainder of
Indications: Source of water and calories; parenteral the fluid for examination, if deemed necessary.
nutrient, indicated as a caloric component in a
parenteral nutrition regimen; used with an appropriate Drug Interactions:
protein (nitrogen) source in the prevention of nitrogen Monitor closely with:
loss or in the treatment of negative nitrogen balance in Increases risk of hypertension and edema of the following
patients where: drugs due to sodium and water retention:
(1) alimentary tract cannot or should not be used, Corticosteroids
(2) GI absorption of protein is impaired, or
(3) metabolic requirements for protein are substantially NOTE: Additives may be incompatible. Consult a pharmacist.
increased, as with extensive burns. If additives are to be introduced, use aseptic technique.

Contraindications: Intracranial or intraspinal hemorrhage; Administration: For IV administration only. Contains no

severe dehydration; anuric; hepatic coma. bacteriostat, antimicrobial agent or added buffer. For
use only as a single-dose injection following admixture or
Dose: Dose is usually dependent upon the age, weight, and dilution.
clinical condition of the patient, as well as laboratory
determinations. Inspect visually for particulate matter and discoloration
prior to administration. Do NOT administer unless
NOTE: Use with caution in infants of diabetic mothers, solution is clear and seal is intact.
except as may be indicated in hypoglycemic neonates.
Prior to administration, dilute to a concentration which,
Precautions: when administered with an amino acid (nitrogen) source,
will result in an appropriate calorie-to-gram nitrogen
WARNING: Contains aluminum that may be toxic. May ratio, and which has an osmolarity consistent with the
reach toxic aluminum levels with prolonged use if route of administration.
kidney function is impaired.

Administration by central venous catheter should NOTE: Unless appropriately diluted, hypertonic dextrose
be used only by those familiar with this technique infusion into a peripheral vein may result in vein
and its complications. irritation, vein damage, and thrombosis. Strongly
hypertonic nutrient solutions should be administered
through an indwelling IV catheter with the tip located in
Overt or subclinical diabetes mellitus or carbohydrate a large central vein such as the superior vena cava.
intolerance (use with caution); hyperglycemia and
glycosuria (slow the infusion rate to minimize these Use a final filter during administration. Slowly inject the
conditions; monitor blood and urine glucose); vitamin B- solution at a rate not exceeding 0.5 g/kg body weight per
complex deficiency; Acute ischemic stroke (do not use hour.
after acute ischemic strokes); cardiac insufficiency (use
with caution to avoid circulatory overload); Hypokalemia; NOTE: About 95% of the dextrose is retained when infused
IV injections can cause fluid and/or solute overload at a rate of 0.8 g/kg/hour.
resulting in dilution of serum electrolyte concentrations,
overhydration, congested states, or pulmonary edema; Do NOT administer by SC or IM route.
Clinical evaluation and periodic laboratory
determinations are necessary to monitor changes in fluid Do NOT administer simultaneously with blood through
balance, electrolyte concentrations, and acid-base the same administration set because of the possibility of
balance during prolonged parenteral therapy, or pseudo-agglutination or hemolysis.
whenever the condition of the patient warrants such
evaluation; Elderly and children (administer with NOTE: All injections in plastic containers are intended for IV
caution); premature neonates. administration using sterile equipment. Replace IV
administration apparatus at least once every 24 hours.
Adverse Drug Reactions: Febrile response, infection at the
site of injection, venous thrombosis or phlebitis Interruption or rapid cessation of hypertonic dextrose
extending from the site of injection, extravasation, therapy may result in a hypoglycemic reaction. Titrate
hypervolemia [NOTE: May occur because of the solution or the with a dilute dextrose solution until the patient has
technique of administration]. reached glucose equilibrium.

Pregnancy Category: C

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 BLOOD AND BLOOD FORMING ORGANS

ATC Code: Not available hours or follow with an infusion (maximum dose, 500
mg/kg daily).
Daily maintenance calcium, by IV administration, INFANT
and CHILD ≤25 kg, 1–2 mEq/kg daily, CHILD 25–45 kg,
Rx CALCIUM GLUCONATE 0.5–1.5 mEq/kg daily; CHILD >45 kg, 0.2–0.3 mEq/kg
daily or 10–20 mEq daily.
B

Inj.: 10%, 10 mL ampule/vial (IV)

10%, 20 mL and 25 mL bottle (IV) Precautions:

The calcium salt of gluconic acid, produced as an oxidation WARNING: May cause asystole when given by rapid IV
product of glucose. Calcium is an essential element for administration.
regulating the excitation threshold of nerves and
muscles, for blood clotting mechanisms, cardiac function Cardiovascular effects (monitor cardiac rate); Concomitant
(rhythm, tonicity, contractility), maintenance of renal digitalis therapy; Sarcoidosis or renal or cardiac disease
function, for body skeleton and teeth, as well as in (use with caution); history of lithiasis; renal impairment;
regulating storage and release of neurotransmitters and Immobilized patients (use with caution); Premature
hormones, regulating amino acid uptake and absorption neonates; Lactation (use with caution).
of vitamin B12, gastrin secretion, and in maintaining
structural and functional integrity of cell membranes and NOTE: Supersaturated solutions are prone to precipitation.
capillaries. Calcium gluconate increases cardiac muscle If crystallization has occurred, warm in a 60°C water
tone and force of systolic contractions (positive inotropic bath for 15–30 minutes with occasional shaking. Cool to
effect). body temperature before use.

Indications: Treatment of conditions arising from calcium Adverse Drug Reactions:

deficiencies such as hypocalcemic tetany, hypocalcemia Common: Tingling sensation, sensations of heat waves
related to hypoparathyroidism, and hypocalcemia due to (peripheral vasodilation), fainting, constipation, chalky
rapid growth or pregnancy; to antagonize cardiac toxicity taste, increased gastric acid secretion, hypotension,
in patients not receiving digitalis. bradycardia, cardiac arrhythmias, cardiac arrest, pain
and burning at IV site, severe venous thrombosis,
Contraindications: Ventricular fibrillation; metastatic bone extravasation (with necrosis and sloughing)
disease; injection into myocardium; renal calculi;
hypercalcemia and predisposition to hypercalcemia (e.g., Drug Interactions:
hyperparathyroidism, certain malignancies); above Monitor closely with:
normal serum calcium levels; concomitant Decreases absorption of the following drugs:
administration of ceftriaxone in neonates. Magnesium, Quinolone

Dose: Dose depends on the individual requirements of the Avoid concomitant use with:
patient. Decreases therapeutic effect of the following drugs:
Tetracycline (forms Tetracycline-Calcium complex),
NOTE: 1 g calcium gluconate = 90 mg (4.5 mEq, 9.3%) Calcium Channel Blockers, e.g., Verapamil
elemental calcium.
Increases risk of adverse or toxic effects of the following
Severe hypermagnesemia, severe hyperkalemia, by IV drugs:
administration, ADULT, 10 mL of 10% solution over 2 Ceftriaxone Sodium Injection (may form precipitates),
minutes, repeated every 10 minutes if needed. Digitalis Glycosides e.g digoxin (arrhythmias)
Hypermagnesemia, by IV administration, ADULT, 1,000–
2,000 mg (10–20 mL) single dose at a rate not Administration: For IV use only. No preservative added.
exceeding 0.5–2 mL/min; CHILD and NEONATE, 0.5 Discard unused portion.
mL/kg of 10% solution single dose.
Hyperkalemia, by IV administration, ADULT, 500 to 3,000 Inspect visually for particulate matter and discoloration.
mg (5–30 mL) single dose at a rate not to exceed 0.5–2 Use only if solution is clear and seal intact.
mL/min; CHILD and NEONATE, 0.5 mL/kg of 10%
solution single dose. For direct IV administration, administer undiluted at a
Hypocalcemic tetany, severe acute hypocalcemia, by IV rate of 0.5 mL or a fraction thereof over 1 minute. Do
administration, ADULT, 2.25 mmoL over 10 minutes by NOT exceed 2 mL/minute.
slow IV injection, followed by 58–77 mL 10% solution in
0.5–1 L of 5% dextrose solution as continuous IV For intermittent or continuous IV administration,
infusion; CHILD and NEONATE, 0.5 mL/kg of 10% administer diluted in 1,000 mL of NS slowly. Do NOT
solution as a single dose (maximum, 20 mL of 10% exceed 200 mg/minute, through a small-bore needle
solution). into a large vein to avoid possibility of extravasation and
Hypocalcemia secondary to citrated blood infusion, by IV resultant necrosis.
administration, ADULT, 0.45 mEq elemental calcium for
each 100 mL citrated blood infused Do NOT administer by SC or IM injection as this may
Tetany, by IV administration, CHILD and INFANT, 100–200 cause severe necrosis and sloughing. IM injection may
mg/kg per dose over 5–10 minutes; may repeat after 6 cause local necrosis and abscess formation.

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BLOOD AND BLOOD FORMING ORGANS

NOTE: Injection should be stopped if patient complains of LACTATED RINGER’S SOLUTION

any discomfort. Patient should be advised to remain in Rx
(RINGER’S LACTATE)
bed for at least 15–30 minutes following injection,
depending on response.
Inj.: 500 mL and 1 L bottle / bag (IV infusion)
Avoid scalp veins in children. Avoid rapid infusion. High
Composition:

B
concentrations of calcium suddenly reaching the heart
Na+ 130 mmol/L
can cause fatal cardiac arrest.
K+ 4 mmol/L
Ca ++ 1.22 – 1.5 mmol/L
Pregnancy Category: B; C
Cl- 109 mmol/L
Lactate 28 mmol/L
ATC Code: Not available
A sterile, non-pyrogenic, lactate-containing solution, which
serves as a source of hydration and electrolytes and
produces a metabolic alkalinizing effect.
Rx GLUCOSE (DEXTROSE)
Indications: Fluid and electrolyte replacement
therapy in the presence of acidosis; IV infusion in the
Inj.: 50%, 50 mL vial (IV) initial management of the injured or wounded;
50%, 10 mL and 20 mL ampule (IV) hypovolemic shock
50%, 10 mL, 20 mL, and 50 mL (85 Kcal) vial (IV)
Contraindications: Metabolic and respiratory
A sterile, hypertonic solution of glucose, which provides alkalosis; hypocalcemia; hypochlorhydria; lactic acidosis;
calories in a minimal volume of water and is used in anuria; oliguria; hyperkalemia; increased BUN; cardiac
restoring blood glucose concentrations in the treatment failure.
of hypoglycemia.
Dose: Dose is dependent on age, weight, and
Indication: Fluid replacement without significant electrolyte clinical condition of patient.
deficit.
Dose Adjustment:
Contraindications: Hyperglycemia; diabetic coma; use of Renal Impairment:
hyperosmotic solutions in patients with anuria; glucose- Select dose with care due to an increased
galactose malabsorption syndrome; dehydrated patients risk of adverse effects, e.g., sodium and potassium
with delirium; intracranial or intraspinal hemorrhage; retention.
following ischemic attacks.
Precautions:
Dose:
Fluid replacement, by IV infusion, ADULT and CHILD, WARNING: Mix infusion solutions thoroughly after
determine dose based on clinical data and, whenever adding concentrated electrolytes to avoid possible
possible, electrolyte monitoring. toxicity.

Administration: Administer via a large vein (e.g., into a Avoid simultaneous administration with blood;
secure IV cannula in an antecubital vein). hyperkalemia; hypernatremia; hyperchloremia; cardiac
diseases; alkalosis; increased blood glucose; hepatic
Inspect visually for particulate matter and discoloration. impairment; conditions which may cause potassium or
Use only if solution is clear and seal intact. sodium retention, fluid overload or edema, e.g., renal
impairment, hypervolemia, overhydration; There is risk
See Glucose (Dextrose) under Antihypoglycemics in Chapter for hyponatremia due to lower sodium
01: Alimentary Tract and Metabolism for other content compared to 0.9% NaCl or Balanced
information. Multiple Replacement Solution.
Pregnancy Category: C Adverse Drug Reactions:
Less Common: Pain and inflammation at the injection site,
ATC Code: Not available phlebitis, tissue necrosis, venous irritation, venous
thrombosis.
Rare: Angioedema, anxiety, blood pressure decreased,
bronchospasm, chest discomfort and pain, cough,
decreased heart rate, dysgeusia, dyspnea, edema,
erythema, flushing, headache, hyperkalemia,
hypersensitivity reactions, including anaphylactic and
anaphylactoid reactions; hypesthesia, nausea,
paresthesia, pruritus, pyrexia, rash, respiratory distress,
tachycardia, throat irritation, urticaria.

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 BLOOD AND BLOOD FORMING ORGANS

Drug Interactions: infused over at least 8–12 hours (maximum rate, 100
Monitor closely with: mL per hour); CHILD, up to 4 g/kg daily (60% of
Alters renal clearance of the following drugs: nonprotein calories) infused over at least 8–12 hours
(maximum rate, 100 mL/hour); PREMATURE NEONATE,
Increased renal clearance: Acidic Drugs, e.g., Salicylates, initially 0.25–0.5 g/kg daily; increase by 0.25–0.5 g/kg
Barbiturates; Lithium daily (maximum dose, 3–4 g/kg daily; maximum rate,
B

0.15 g/kg per hour).

Decreased renal clearance: Basic Drugs, e.g.,
Sympathomimetics Dose Adjustment:
Renal Impairment:
Increases risk of adverse or toxic effects of the following Normal renal function required. Reduce dose.
drugs:
Hyperkalemia: Drugs which can cause hyperkalemia, Precautions:
e.g., Potassium-sparing Diuretics, Angiotensin II Jaundice (use with caution); Pulmonary disease; Liver
Receptor Antagonists, ACE Inhibitors, disease; Anemia; blood coagulation disorders;
Immunosuppressants thrombocytopenia; Diabetes mellitus; History of gastric
Hypercalcemia; Thiazide Diuretics, Vitamin D ulcer or when there is any danger of fat embolism; Renal
impairment; Premature neonates (use with caution).
Avoid concomitant use with:
Increases risk of adverse or toxic effects of the following Adverse Drug Reactions:
drugs: Common: Hypersensitivity reactions, irritation at infusion
Ceftriaxone (Ceftriaxone-Calcium salt precipitation in the site, thrombocytopenia (neonates), hypercoagulability,
bloodstream) increased liver function tests (transient), hyperlipidemia,
sepsis, cholestatic jaundice, hepatomegaly, kernicterus
Administration: For IV administration. Rare: Shock

Inspect visually for particulate matter and discoloration. Drug Interactions: No information available
Use only if solution is clear and seal intact.
Administration: Do NOT use if oil appears to be separating
Pregnancy Category: C out of the emulsion.

ATC Code: B05XA30 Pregnancy Category: B (Soyacal®); C (others)

ATC Code: Not available

Rx LIPIDS

Inj.: 10%, 100 mL, 200 mL, and 500 mL bottle (IV
Rx MAGNESIUM SULFATE
infusion)
20%, 100 mL, 250 mL, and 500 mL bottle (IV Inj.: 250 mg/mL, 2 mL and 10 mL ampule (IM, IV) and 10
infusion) mL, 20 mL and 50 mL vial (IV) (as heptahydrate)
500 mg/mL, 2 mL and 10 mL ampule (IM, IV) (as
An isotonic nutrient containing emulsified fat particles used heptahydrate)
as a source of calories and essential fatty acids.
A sterile preparation that contains magnesium as
Indications: Parenteral nutrition; prevention of essential heptahydrate.
fatty acid deficiency; source of essential fatty acids and
additional calories in high-density form to patients Indications: For parenteral nutrition; treatment and
receiving prolonged TPN therapy who cannot tolerate prevention of hypomagnesemia; pediatric acute
high dextrose concentrations or when fluid intake must nephritis; treatment of cardiac arrhythmias (VT/VF)
be restricted as in renal failure, CHF, and ascites. caused by hypomagnesemia; prevention and control of
seizures in women with severe preeclampsia.
Contraindications: Any condition that disturbs normal fat
metabolism (e.g., pathologic hyperlipemia, lipoid Contraindications: Heart block; myocardial infarction;
nephrosis, acute pancreatitis with hyperlipemia); bone hypermagnesemia; deranged
marrow dyscrasias; allergy to egg yolk phospholipids. renal function; myasthenia gravis; IV use for
pre­eclampsia or eclampsia during the 2 hours prior to
Dose: delivery.
Prevention of essential fatty acid deficiency, by IV infusion,
ADULT, 500 mL 10% solution or 250 mL 20% solution Dose:
infused over 8–12 hours twice a week (maximum rate, NOTE: Individualize dose based on patient requirement and
100 mL/hour); CHILD, 0.5–1 g/kg infused slowly over 8– response. Discontinue as soon as desired response is
12 hours twice a week (maximum dose, 3–4 g/kg daily; obtained.
maximum rate, 0.25 g/kg per hour).
Calorie source in fluid-restricted patients, by IV infusion, Total Parenteral Nutrition, by IV injection, ADULT, 0.5 to 3 g
ADULT, up to 2.5 g/kg daily (60% of nonprotein calories) daily.

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BLOOD AND BLOOD FORMING ORGANS

Hypomagnesemia seizures, mild, by IV or IM injection, Avoid concomitant use with:

ADULT, 1 g every 6 hours for 4 doses. Decreases absorption of Magnesium Sulfate:
Hypomagnesemia seizures, mild, by IV or IM injection, Alpha-Lipoic Acid
ADULT, 250 mg/kg infused over 4 hours.
Hypomagnesemia seizures, by IV injection, CHILD, 20–100 Decreases absorption of the following drugs:
mg/kg every 4–6 hours, or as needed. Alpha-Lipoic Acid, Multivitamins / Fluoride with ADE

B
Hypomagnesemia seizures, severe, by IV or IM injection, (fluoride absorption) [separate administration by at least
ADULT, 1–2 g/hour for 3–6 hours, then 0.5–1 g/hour as 1 hour]
needed based on serum magnesium levels.
Decreases serum concentration of the following drugs:
Dose Adjustment: Bisphosphonate Derivatives [except Pamidronate,
Geriatric and Renal Impairment: Zoledronic Acid], Deferiprone, Dolutegravir,
Reduce dose. Up to 50% of an IV dose may be eliminated in Eltrombopag, Gabapentin, Levothyroxine, Multivitamins
the urine. / Fluoride with ADE, Quinolone Antibiotics, Raltegravir
For patients with renal disease, Do NOT exceed 20 g every
48 hours for patients with renal disease. Enhances therapeutic effect of the following drugs:
Gabapentin (CNS depressant effect)
Precautions:
Increases serum concentration of Magnesium Sulfate:
WARNING: Toxicity causes loss of deep tendon
Alfacalcidol, Calcitriol (systemic)
reflexes, followed by respiratory depression and
ultimately respiratory arrest. If deep tendon Administration: Administer at a concentration not exceeding
reflexes are absent, withhold further doses until
20%. Dilute according to manufacturer’s instructions.
reflexes return. Toxicity can be reversed with
calcium gluconate.
For IM route, solutions may need dilution prior to
administration. 25% or 50% for adults or ≤20% for
Magnesium is excreted by the kidney. Monitor children.
regularly serum levels in women with oliguria (urine
output <100 mL/4 hours). If repeated seizures For IV route, solutions must be diluted to ≤20% for IV
occur despite magnesium, other pre-hospital infusion and may be administered by IV push, IVPB, or
options include administering diazepam. continuous IV infusion.

Myasthenia gravis or other neuromuscular disease (use For IV push, dilute first and do not administer faster than
with extreme caution); Renal impairment (use with 150 mg/minute.
caution); Electrolyte abnormalities; Magnesium toxicity;
Pregnancy (monitor mother and fetus closely; do not use May be administered over 1–2 minutes in patients with
for longer than 5–7 days to prevent adverse fetal persistent pulseless VT or VF with known
events). hypomagnesemia. Administer over 15 minutes in
patients with torsade de pointes.
Adverse Drug Reactions:
Common: Flushing, nausea, vomiting Maximum rate of infusion is 1 g/hour in asymptomatic
Less Common: Dizziness, drowsiness, headache, thirst patients. For doses <6 g, infuse over 8–12 hours. For
Rare: Arrhythmias, cardiac arrest, coma, confusion, larger doses, infuse over 24 hours.
loss of tendon reflexes, muscle weakness, If patient is severely symptomatic or has conditions such
respiratory depression as preeclampsia or eclampsia, more aggressive therapy
(≤4 g over 4-5 minutes) may be required.
Drug Interactions:
Monitor closely with: Pregnancy Category: A
Enhances therapeutic effect of Magnesium Sulfate:
Aminoglycosides (additive neuromuscular blocking ATC Code: B05XA05
effect)

Enhances therapeutic effect of the following drugs:

Calcium Channel Blockers (hypotensive effect)
Rx POTASSIUM CHLORIDE
CNS Depressants, e.g., Barbiturates, Opiates, General
Aesthetics (CNS depressant effects) Oral: 600 mg tablet
Neuromuscular Blocking Agents, e.g., Tubocurarine, 750 mg durules (equiv. to approximately 10 mEq
Vecuronium, Succinylcholine (neuromuscular blocking potassium)
effect) 1 mmol/mL syrup, 30 mL and 60 mL
Inj.: 2 mEq/mL, 2 mL and 5 mL ampule (IV infusion)
Increases risk of adverse or toxic effects of Magnesium 2 mEq/mL, 10 mL and 20 mL vial (IV infusion)
Sulfate:
Calcium Channel Blockers A sterile preparation that contains potassium chloride,
utilized for the treatment of hypokalemia.

87
 BLOOD AND BLOOD FORMING ORGANS

Indications: Prophylaxis and treatment of potassium Potassium intoxication: Areflexia (absence of reflexes),
deficiency states; for parenteral nutrition. cardiac arrest, cardiac arrhythmias, ECG abnormalities,
heart block, hypotension, mental confusion, muscular or
Contraindications: Any disease or condition in which high respiratory paralysis, paresthesias of the extremities,
potassium levels may occur through potassium retention weakness; progression of side effects may cause death.
or other processes (e.g., acute dehydration, Potassium deficit: Disruption of neuromuscular function,
B

adrenocortical insufficiency); adynamia episodica intestinal ileus, dilatation.

hereditaria (periodic loss of strength or weakness);
anuria; azotemia; crush syndrome; heat cramps; Drug Interactions:
hyperkalemia from any cause; oliguria; patients taking Monitor closely with:
digoxin with severe or complete heart block; Increases risk of adverse or toxic effects of the following
postoperative oliguria; renal failure; severe hemolytic drugs:
reactions. Hyperkalemia: ACE Inhibitors, e.g., Captopril, Enalapril,
Lisinopril; Angiotensin Receptor Blockers, e.g., Losartan,
Dose: Valsartan; Potassium-sparing Diuretics, e.g.,
NOTE: Dose and rate of administration are dependent on specific Spironolactone
patient condition.
Administration: For IV infusion only. Infuse at a rate not
IV additive solution, by IV injection, ADULT, 40–100 mEq/L exceeding 10 mEq/hour. Adult patients with severe
or more daily (maximum, 150 mEq/L daily); maintenance potassium depletion may be able to tolerate 20
dose, 20–30 mEq/L. mEq/hour.
Replacement in hypokalemia, IV additive solution, by IV
injection, CHILD and INFANT, 40–50 mEq/L. Each individual dose must be diluted in a larger volume
Severe acute hypokalemia, by IV injection, ADULT, of suitable IV solution and given as an infusion. Add the
serum potassium level >2.5 mEq/L, 40 mEq/L for not desired amount to 100–1,000 mL IV solution. 40 mEq/L
more than 10 mEq/hour (maximum dose, 200 mEq/24 is preferred to lessen irritation to veins. Usual maximum
hours); concentration is 80 mEq/1000 mL.
serum potassium level <2 mEq/L, 40 mEq/L at a rate of After adding potassium chloride, invert bag or bottle
up to 40 mEq/hr (maximum dose, 400 mEq/24 hours). several times to ensure even distribution and to avoid
layering of potassium. NEVER add potassium chloride to
Dose Adjustment: an IV bag or bottle, which is hanging. Use only clear
Geriatric: solutions.
Initiate at the lower end of the dosing range based on
potential for decreased organ function and concomitant In severe hypokalemia, solutions without dextrose are
disease or drug therapy. preferred.
Renal Impairment: NEVER administer by IV push or in concentrated
Reduce dose. Do NOT use in patients with kidney failure. amounts by any route.
Precautions: Take extreme care to prevent extravasation and
WARNING: Concentrated solutions must be diluted before infiltration. At first sign, discontinue infusion and select
administration. Direct injection of concentrated solutions another site.
can be instantly fatal. Too rapid infusion may cause fatal
hyperkalemia. Rapid IV infusion or bolus may cause fatal NOTE: Potassium phosphate is preferred for specific
arrhythmia and cardiac arrest. intracellular deficiency not caused by alkalosis.

Impaired renal function or adrenal insufficiency; severe Pregnancy Category: C

hepatic insufficiency and metabolic or respiratory
alkalosis (use with caution); cardiac disease (cardiac ATC Code: B05XA01
monitoring recommended); Potassium depletion (treat
cause of potassium depletion in addition to giving
potassium); Alkalizing potassium, e.g., acetate, citrate
(preferred for potassium-deficient patients with renal Rx POTASSIUM PHOSPHATE
tubular acidosis); May contain aluminum (may reach
toxic levels in impaired kidney function); Administration Inj.: 224 mg monobasic potassium phosphate equivalent
of IV solutions can cause fluid and/or solute overload, to 3 mmol phosphorus and 4.4 mEq potassium per
resulting in dilution of serum electrolyte concentrations, 236 mg dibasic-potassium phosphate anhydrous per
overhydration, congested states, or pulmonary edema; mL in 5 mL vial (IV)
Premature neonates.
A sterile preparation that contains potassium phosphate,
Adverse Drug Reactions: utilized for the treatment of hypophosphatemia.
Common: Abdominal pain, diarrhea, nausea, vomiting,
extravasation, fever, hyperkalemia, hypervolemia, Indication: For parenteral nutrition to prevent or correct
infection or pain at the site of injection, phlebitis, venous hypophosphatemia in patients with restricted or no oral
thrombosis. intake.

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BLOOD AND BLOOD FORMING ORGANS

Contraindications: Any disease with high phosphate or low by the pharmacist to avoid a precipitate of calcium
calcium levels; hyperkalemia; severe renal impairment; phosphate.
infected phosphate renal calculi.
NOTE: Rapid infusion may cause phosphate or potassium
Dose: intoxication. Serum calcium may be reduced rapidly,
NOTE: Dose is dependent on individual needs of the patient. causing hypocalcemic tetany.

B
TPN, by IV injection, ADULT and CHILD, 10–15 mM (310– Potassium phosphate will be further limited by the
465 mg) of phosphorus/liter of TPN solution to maintain maximum rate for potassium. Consider potassium
normal serum phosphate (1 mM equals 31 mg); INFANT, content.
1.5–2 mM/kg daily.
Acute hypophosphatemia, by IV injection, ADULT and CHILD, Pregnancy Category: C
0.08–0.32 mM/kg as loading dose, equally distributed
over 6 hour; maintain pediatric patients with 0.5–1.5 ATC Code: B05XA06
mM/kg every 24 hours and adults with 48.4–64.5 mM
every 24 hours.

Dose Adjustment: Rx SODIUM BICARBONATE

Geriatric:
Initiate doses at the lower end of the dosing range based on Oral: 325 mg and 650 mg tablet
the potential for decreased organ function and Inj.: 1 mEq/mL, 10 mL vial (pediatric), 50 mL and 100 mL
concomitant disease or drug therapy. ampule / vial (adult) (IV infusion)
Precautions: A sterile preparation that contains sodium bicarbonate,
Rapid infusion may cause phosphate, sodium, or potassium utilized as an alkalizing agent.
intoxication. Serum calcium may be reduced, rapidly
causing hypocalcemic tetany; Cardiac disease, renal Indications: Systemic alkalinizer to correct metabolic
disease, and digitalized patients (use with caution). acidosis; buffer for acidic parenteral solutions to prevent
acidosis; for parenteral nutrition.
Adverse Drug Reactions:
Common: Hyperphosphatemia, hypocalcemia, ectopic Contraindications: Diuretics known to produce
calcification, hypotension, organ damage, acute renal hypochloremic alkalosis; edema; hypertension;
failure, tissue calcification, nausea, vomiting, diarrhea, hypocalcemia; hypochloremia; hypernatremia; impaired
abdominal pain, flatulence, bradycardia, hyperkalemia, renal function; metabolic alkalosis; respiratory alkalosis
weakness, dyspnea. or acidosis; any situation where administration of sodium
Potentially fatal: Acute renal failure, arrhythmia, chest could be clinically detrimental.
pain, decreased urine output, dyspnea, edema, mental Dose:
confusion, paralysis, paresthesias, phlebitis, tetany. NOTE: Doses are adjusted according to pH, PaCO2,
calculated base deficit, clinical response, and fluid
Drug Interactions: limitations of the patient.
Monitor closely with:
Alters absorption of the following drugs:
Cardiac arrest, by IV injection, ADULT, initially 1 mEq/kg of
Aluminum, Calcium, or Magnesium Salts (decreased
7.5% or 8.4% solution initially, then 0.5 mEq/kg every 10
absorption due to phosphate binding)
minutes, depending on arterial blood gas determinations
(8.4% solutions contain 50 mEq/50 mL), given over 1–2
Increases risk of adverse or toxic effects of the following
minutes; CHILD, 0.5–1 mEq/kg of 4.2% solution every
drugs:
10 minutes, depending on arterial blood gas
Hyperkalemia: ACE Inhibitors, e.g., Enalapril; Potassium-
determinations, given over 1–2 minutes.
sparing Diuretics
Metabolic acidosis, by IV infusion, ADULT, 2–5 mEq/kg over
Hyperphosphatemia: Vitamin D (hyperphosphatemia)
4–8 hours; CHILD and INFANT, 2 to 3 mEq/kg daily of
4.2% solution over 4–8 hours.
Increases therapeutic effect of Digitalis

Administration: For IV infusion. Infuse slowly. Equally Amount (mEq NaHCO3) = (base deficit)(0.3)(BW in kg)
distribute desired dose over 6 hours. May also Amount (mEq NaHCO3)=(27 mEq HCO3/L)(0.3)(BW in kg)
administer up to 15 mM over 2 hours, up to 30 mM over
4 hours, and up to 45 mM over 6 hours. Dose Adjustment:
Geriatric, Renal and Hepatic Impairment:
Dilute in a larger volume of suitable IV solution prior to Dose adjustment may be required.
administration. Soluble in most commonly used IV
solutions except protein hydrolysate. Mix thoroughly. Administration: Give 4.2% (0.5 mEq/mL) and 5% (0.595
mEq/mL) NaHCO3 solutions undiluted. Dilute 7.5%
When adding an additive, consult a pharmacist. Specific (0.892 mEq/mL) and 8.4% (1 mEq/mL) solutions with
conditions may apply. TPN solutions requiring the compatible IV solutions. Dilute to at least 4.2% for infants
addition of phosphates and calcium salts must be mixed and children. Give a bolus dose only in emergency
situations. The usual rate is 2–5 mEq/kg over 4–8 hours.

89
 BLOOD AND BLOOD FORMING ORGANS

Do not exceed 50 mEq/hour. Stop infusion immediately hypertension, peripheral and pulmonary edema, or
if extravasation occurs. Flush IV line thoroughly before toxemia of pregnancy; Seizures or neurologic deficit
and after administration. (requires aggressive therapy); IV administration can
cause fluid and/ or solute overloading resulting in
WARNING: Rapid or excessive administration may dilution of other electrolyte concentration, overhydration,
produce alkalosis, hypokalemia, and hypocalcemia. congested states or pulmonary edema; excessive
B

Cardiac arrhythmias may result from an intracellular administration of potassium-free solutions may result in
shift of potassium. Many other complications may significant hypokalemia; Premature neonates.
arise from electrolyte imbalance.
Adverse Drug Reactions: Air embolization, febrile response,
See Sodium Bicarbonate under Antacids in Chapter 1: local tenderness, tissue necrosis or infection at the site
Alimentary Tract and Metabolism for other information. of injection, venous thrombosis or phlebitis extending
from the site of injection, extravasation [NOTE: May occur
Pregnancy Category: C because of the solution, added drugs or the technique of
reconstitution or administration].
ATC Code: B05XA02
Rare: Edema, sodium accumulation

Drug Interactions:
Rx SODIUM CHLORIDE Monitor closely with:
Increases risk of hypertension and edema of the following
drugs due to sodium and water retention:
Inj.: 2.5 mEq/mL, 20 mL and 50 mL vial Corticosteroids e.g. Prednisone
A sterile, non-pyrogenic, concentrated solution of Administration: Administer based on calculated dose
sodium chloride administered to replenish electrolytes. requirements for each patient. Must be diluted before
infusion to avoid a sudden increase in the plasma-
Indication: Hyponatremia with overt manifestations. sodium level. Too rapid administration should be avoided
[see Important Note under Dose].
Contraindications: Where the administration of Inspect visually for particulate matter and discoloration
sodium or chloride could be clinically detrimental (e.g., prior to administration. Do NOT use unless the solution
hypernatremia); fluid retention; hypertension; CHF. is clear, and seal is intact. Discard unused portion.
Dose: Dose is dependent on degree of sodium depletion Pregnancy Category: C
(i.e., moderately severe hyponatremia where serum
sodium is between 125–129 mmol/L or profound ATC Code: B05XA03
hyponatremia where serum sodium is <125 mmol/L); on
severity of symptoms (i.e., moderately or severely
symptomatic); and on time of development of
hyponatremia (acute, where hyponatremia is Rx STERILE WATER FOR INJECTION
documented to exist <48hrs).
Inj.: 2 mL, 5 mL, 10 mL, and 20 mL ampule
IMPORTANT NOTE: Sodium deficit must be corrected
50 mL, 100 mL, 500 mL, and 1 L bottle / bag (no
gradually in stages. Avoid overtly rapid correction to
preservative)
prevent development of Osmotic Demyelination
Syndrome (previously named Central Pontine
A sterile, nonpyrogenic water for injection that does
Myelinosis). The rate of correction of hyponatremia
not contain any antimicrobial agent or other
should not be more than 10 mmol/L (or 10 mEq/L) in 24
added substances, such as buffer, and is
hours, or 18 mmol/L (or 10 mEq/L) in 48 hours.
supplied in single-dose containers to dilute or
dissolve drugs for injection.
Dose Adjustment:
Renal Impairment:
Indication: For dissolving or diluting medicines that are
Select doses with caution due to potential to
intended for parenteral injection.
result in sodium retention and increased risk
of adverse effects.
NOTE: Use in accordance with the instructions set by the
manufacturer of the drug.
Precautions:
Contraindications: No information found
WARNING: Contains aluminum, which may be toxic. May
reach toxic aluminum levels with prolonged use,
Dose: Volume to be used for any drug for injection is based
especially if kidney function is impaired.
on the vehicle concentration, dose, and route of
administration as recommended by the drug
Monitor fluid balance, electrolyte concentration, and manufacturer.
acid-base balance; observe for hypernatremia, water
retention and pulmonary edema; restrict in patients with
renal insufficiency or failure, cardiac failure,

90
BLOOD AND BLOOD FORMING ORGANS

Precautions: without copper supplementation contraindicated in

WARNING: IV administration without a solute may copper-deficient patients.
result in hemolysis.
Dose: Dose is dependent on clinical condition of patient.
Should be made isotonic prior to use; not for direct infusion;
not for non-automated admixture preparations; Dose Adjustment:

B
Neonates and very small infants. Geriatric:
Use with caution. Use lower end of the dosing range,
NOTE: Upon reconstitution of medicines, label to indicate considering decreased organ function and concomitant
that no antimicrobial or other substance has been disease or drug therapy.
added, and that it is not suitable for IV injection without Renal Impairment:
first having been made approximately isotonic by the Reduce or omit dose.
addition of a suitable solute.
Precautions:
Adverse Drug Reactions: Febrile response, local tenderness, Assess possibility of diabetes mellitus when giving
abscess, tissue necrosis or infection at the site of chromium supplements to maintain normal glucose
injection, venous thrombosis or phlebitis extending from metabolism; Selenium enhances vitamin E and
the site of injection, extravasation. decreases the toxicity of mercury, cadmium, and arsenic;
Biliary tract obstruction; Wilson’s disease; Impaired
NOTE: May occur because of the solution, added drugs, or kidney function; Aluminum content; Premature
the technique reconstitution or administration neonates; Lactation (use manganese with caution).

Drug Interactions: May be incompatible with some drugs for Adverse Drug Reactions:
injection in a given vehicle, or when combined in the Rare: Toxicity; anaphylaxis (due to iodine)
same vehicle.
Drug Interactions:
Administration: Inspect reconstituted drugs for clarity and NOTE: Therapeutic serum levels of copper and zinc will
freedom from unexpected precipitation or discoloration decrease if not given together.
prior to administration.
Do NOT use for IV injection unless the osmolar Administration: Must be added to daily volume of IV infusion
concentration results in an isotonic admixture. fluids including TPN. Administer properly diluted at rate
prescribed for IV infusion fluids or TPN.
Do NOT use unless the solution is clear and intact. mix
thoroughly and use promptly after diluting or dissolving Do NOT administer by direct IV.
drugs.
If additives are to be added, consult with pharmacist;
Do NOT store reconstituted solutions of drugs for specific conditions may apply.
injection, unless otherwise directed. Do NOT reuse
single-dose containers. Pregnancy Category: C

Do NOT heat over 66°C (150°F). ATC Code: Not available

Pregnancy Category: No information found

VITAMINS INTRAVENOUS (IV),
ATC Code: Not available Rx
FAT-SOLUBLE
Inj.: Contains vitamins A, D, E, and K, 10 mL ampule (IV)
Rx TRACE ELEMENTS
Organic substances that are essential for normal
metabolism and thus must be provided in the diet in
Inj.: Contains Zn, Cu, Mn, Mg, Mb, etc., 10 mL ampule (IV small quantities because these substances are not
nutrition) synthesized in the human body.
Fat soluble vitamins include Vitamins A, D, E, and K. They
A sterile solution containing basic elements present in the present a potential harm as they can be stored in
human body in specific amounts required to initiate, massive degree and many patients may take more than
facilitate, or maintain appropriate body systems. Trace the prescribed dose. Overdosing may cause toxic effects
elements, or microminerals, are inorganic compounds because they are metabolized very slowly.
that aid physiological processes of the body such as
building and regulation. Indications: Daily multivitamin maintenance supplement for
patients receiving parenteral nutrition; situations, which
Indication: Nutritional supplement to IV solutions given for may provoke a stress response and alteration in the
total parenteral or central nutrition. body’s metabolic demands; dietary supplement when
oral administration is contraindicated, not possible, or
Contraindications: Hypersensitivity to any component insufficient; treatment for specific deficiency states.
(especially iodides); manganese contraindicated in
presence of high manganese levels; molybdenum

91
 BLOOD AND BLOOD FORMING ORGANS

Contraindications: Hypersensitivity to any ingredient; needs; for inborn errors of metabolism; treatment for
hypervitaminosis; pregnancy (vitamin A doses > RDA); specific deficiency states.
hypercalcemia; signs of vitamin D toxicity.
Contraindications: Hypersensitivity to any ingredient;
Dose: Dose is dependent on the clinical condition of the hypervitaminosis; patients with hyperoxaluria; G6PD
patient. Multiples of the daily dose may be given for 2 or deficiency; diabetes mellitus; hemochromatosis; renal
B

more days in patients with multiple vitamin deficiencies impairment; pregnancy; lactation.
or markedly increased requirements. Individual
components may be indicated in specific or long- Dose: Dose is dependent on the clinical condition of the
standing deficiencies. patient. Multiples of the daily dose may be given for 2 or
more days in patients with multiple vitamin deficiencies
Precautions: or markedly increased requirements. Individual
Do not wait for the development of clinical signs of vitamin components may be indicated in specific or long-
deficiency before initiating vitamin therapy; may contain standing deficiencies.
aluminum; Hypersensitivity reactions; elevated Vitamin E
blood levels; Renal failure or liver disease (use with Precautions:
caution); Impaired kidney function; Premature neonates Do not wait for the development of clinical signs of vitamin
deficiency before initiating vitamin therapy; may contain
Adverse Drug Reactions: aluminum; Preparations containing Vitamin C must be
Rare: Agitation, allergic reactions, anxiety, diplopia, protected from light; Hypersensitivity reactions;
dizziness, erythema, fainting, headache, pruritus, rash, Megaloblastic anemia (requires blood draws for the
vitamin A and D hypervitaminosis detection of folic acid and cyanocobalamin deficiencies
prior to administration); pernicious anemia; diabetes
Drug Interactions: mellitus and hypoglycemic states; impaired kidney
Avoid concomitant use with: function; Premature neonates.
Decreases therapeutic effect of Warfarin (anticoagulant
effect) Adverse Drug Reactions:
Rare: Agitation, allergic reactions, anxiety, diplopia,
Administration: Most may be reconstituted with 5 mL of dizziness, erythema, fainting, headache, pruritus, rash.
SWFI or supplied diluent. All preparations must be
further diluted in at least 500 mL but preferably 1,000 Drug Interactions:
mL of IV fluids. Monitor closely with:
Bleomycin – inactivated in vitro by ascorbic acid (Vitamin C)
Do NOT use if any crystals have formed. Vitamin A may and riboflavin (Vitamin B2)
adhere to plastic, resulting in inadequate vitamin A Chloramphenicol – hematologic response to vitamin B12
administration in the doses recommended. therapy in patients with pernicious anemia may be
inhibited
If additives are to be added, consult with pharmacist. Erythromycin, kanamycin, streptomycin, doxycycline,
Specific conditions may apply. lincomycin – thiamine, riboflavin, pyridoxine,
niacinamide, and ascorbic acid may decrease their
Pregnancy Category: C (product-specific) antibiotic activity
Hydralazine, isoniazid (INH) – may increase pyridoxine
ATC Code: B05XC requirements
Levodopa – pyridoxine may reduce effectiveness of
levodopa
VITAMINS, INTRAVENOUS (IV), Methotrexate – folic acid may decrease the patient’s
Rx response to methotrexate therapy
WATER-SOLUBLE
Phenytoin – folic acid may lower serum concentration of
phenytoin, resulting in increased seizure frequency;
Inj.: Contains vitamin B complex and vitamin C, 1 mL vial
monitor serum levels of both drugs; may decrease serum
and 2 mL ampule (IV)
folic acid concentrations; avoid during pregnancy
Organic substances that are essential for normal
Administration: Most may be reconstituted with 5 mL of
metabolism and thus must be provided in the diet in
SWFI or supplied diluent. All preparations must be
small quantities because these substances are not
further diluted in at least 500 mL but preferably 1,000
synthesized in the human body.
mL of IV fluids. Do not use if any crystals have formed.
Water soluble vitamins include vitamins C, B1, B2, B6, B12,
If additives are to be added, consult with pharmacist.
biotin, folic acid, niacin, and pantothenic acid. Water-
Specific conditions may apply.
soluble vitamins, are metabolized rapidly and any excess
is excreted in the urine. Except for niacin and pyridoxine,
Pregnancy Category: C
overdosage seldom causes toxic effects in individuals
with normal renal function.
ATC Code: B05XC
Indications: Daily multivitamin maintenance supplement for
patients receiving parenteral nutrition; dietary
supplement in a variety of circumstances where vitamin
deficiencies are likely to occur; for increased tissue

92
BLOOD AND BLOOD FORMING ORGANS

HEMODIALYTICS AND HEMOFILTRATES

Rx HEMODIALYSIS SOLUTIONS
Preparations:
Acid Concentrate

B
Composition (g/L):
Glucose 0 – 49.50 g
Sodium chloride 216.19– 270.80 g
Potassium chloride 5.25 – 6.7 g
Calcium chloride 6.47 – 9.9 g
Magnesium chloride 3.58 – 4.75 g
Glacial acetic acid 8.1 – 8.46 g
Purified water 1,000 mL

Sodium bicarbonate for Hemodialysis

Sodium bicarbonate, 650 g powder

A clear, sterile solution of electrolytes with a concentration

close to the electrolytic composition of plasma.

Indications: Remove metabolites in renal failure; correct

electrolyte and acid-base abnormalities in End-Stage
Renal Disease (ESRD).

Dose: Dose depends on the clinical condition of the patient,

as well as the patient’s fluid, electrolyte, acid-base, and
glucose balance.

Precautions:
Monitor hemodynamic fluid, electrolyte and acid-base
balance throughout the procedure. Citrate, when used as
an anticoagulant, contributes to the base load, and can
reduce plasma calcium levels; Abnormalities in plasma
concentration of potassium, calcium, glucose, and
phosphate; Cardiovascular disease, especially those
using cardiac glycoside medications (carefully monitor
plasma levels of calcium, potassium, and magnesium).

Adverse Drug Reactions:

Common: Thrombophlebitis

Drug Interactions: No information found

NOTE: The blood concentrations of certain drugs may need

to be monitored and appropriate therapy implemented to
correct for removal during treatment.

Administration: Aseptic technique should be used

throughout administration. Take necessary precautions
during dilution and use to avoid microbial contamination.
Use diluted solutions immediately after preparation.
Discard any unused solution.
Hemodialysis solutions are usually prepared by diluting a
concentrated solution with water of suitable quality
because of the large volume used. In certain
circumstances, it may be necessary to use sterile
solutions.

Pregnancy Category: C

ATC Code: B05ZA

93
 CARDIOVASCULAR SYSTEM

Precautions:
CARDIOVASCULAR SYSTEM WARNING: Fatal arrhythmia may follow overdose.
Maintain heart rate above 60 beats/minute and
early signs of toxicity should be carefully
monitored.
CARDIAC THERAPY
Acute myocarditis, such as rheumatic carditis; advanced
CARDIAC GLYCOSIDES heart failure; severe pulmonary disease; sick sinus
C

syndrome; recent MI; Fever and hyperthyroidism;

Hypomagnesemia, hypokalemia;
Rx DIGOXIN hypercalcemia, hypoxia; Hypothyroidism; Renal impairment;
Elderly; Pregnancy (may need dose adjustment); lactation
Oral: 250 micrograms tablet (amount in breastmilk too small to be harmful)
50 micrograms/mL elixir, 60 mL
Inj.: 250 micrograms/mL, 2 mL ampule (IM, IV) Adverse Drug Reactions:
Common: Abdominal pain, agitation, anorexia, blurred
A cardiac glycoside obtained from the leaves of Digitalis vision, confusion, depression, diarrhea, dizziness,
lanata. Digoxin inhibits the Na+-K+-ATPase pump and drowsiness, nausea, nightmares, visual disturbances,
consequently increases the force of cardiac contraction vomiting
and slows the heart rate. Less Common: Acute psychosis, amnesia, atrial or
ventricular extrasystoles, delirium, fatigue,
Indication: For rate control in chronic atrial fibrillation and gynecomastia, hallucinations, headache, heart block,
atrial flutter. intestinal ischemia, paroxysmal atrial tachycardia and
fibrillation; shortened QRS complex
Contraindications: Ventricular tachycardia or fibrillation; Rare: Arrhythmias, rash, seizures, thrombocytopenia,
hypertrophic obstructive cardiomyopathy (unless there is xanthopsia (yellow vision)
concomitant atrial fibrillation and heart failure);
permanent or even intermittent second-degree and third- Drug Interactions:
degree atrioventricular block without a cardiac Monitor closely with:
pacemaker; pre-excited atrial fibrillation/atrial flutter or Alters absorption of Digoxin:
antidromic atrioventricular reentrant tachycardia Acarbose (decreased absorption); Macrolides, e.g.,
associated with Wolff-Parkinson-White (WPW) syndrome; Azithromycin, Clarithromycin, Erythromycin (increased
arrhythmias caused by cardiac glycoside intoxication absorption)

Dose: Enhances therapeutic effect of Digoxin:

Atrial fibrillation or flutter, by mouth, ADULT, Amiodarone (slowing cardiac conduction), Beta
Rapid Oral Loading: 750–1,500 micrograms as a single- Blockers, e.g., Atenolol, Propranolol (slow
dose; where there is less urgency or greater risk of atrioventricular conduction), Diltiazem (additive negative
toxicity, e.g., elderly, oral loading dose is given in divided effects on heart rate and cardiac conduction)
doses 6 hours apart, with half of the total dose given as
the first dose; assess clinical response before each Avoid concomitant use with:
additional dose; Decreases serum concentration of Digoxin:
Slow Oral Loading: 250–750 micrograms daily for 1 Antacids, e.g., Aluminum or Magnesium Hydroxide,
week followed by appropriate maintenance dose; Rifampicin, Salbutamol
Maintenance Dose: 3.4–5.1 micrograms/kg daily or
125–500 micrograms daily; increase dose gradually Reduces therapeutic effect of Digoxin by reducing its
every 2 weeks based on clinical responses, toxicity, and absorption:
serum drug levels. Bile Acid Binding Resins

Dose Adjustment: Increases serum concentration of Digoxin, increasing its risk

Geriatric: of adverse or toxic effects:
Use lower doses due to the tendency to develop impaired Verapamil (additive negative effects on heart rate and
renal function and lean body mass, which can lead to cardiac conduction)
digoxin toxicity.
Loading Dose: by mouth, 125–250 micrograms every 4–6 Administration: To be taken 1 hour before or 2 hours after
hours, to a maximum of 500 micrograms; eating food. For meals high in fiber, take it 2 hours before
Maintenance Dose: by mouth, 62.5–125 micrograms once or 2 hours after eating food.
daily.
IM route is generally not preferred due to severe injection
Renal Impairment: site pain.
For mild-to-moderate renal impairment, reduce dose.
For severe impairment, refer patient to a specialist. Avoid rapid IV administration (increased risk of
arrhythmias);
Hypomagnesemia, hypokalemia, hypercalcemia, hypoxia,
hypothyroidism: Reduce dose Pregnancy Category: C

94
CARDIOVASCULAR SYSTEM

ATC Code: C01AA05 hypotonia and bradycardia after paracervical block);

lactation

ANTIARRHYTHMICS Adverse Drug Reactions:

Common: Blurred vision, chest pain, confusion,
CLASS I ANTIARRHYTHMICS disturbances in vision, dizziness, drowsiness, dyspnea,
flushing, headache, lightheadedness, nausea,
paresthesia, tinnitus, tremors
Rx LIDOCAINE Less Common: Arrhythmias, bradycardia, cardiac arrest,

C
coma, heart block, hypotension, muscle twitching,
recurrence of SVT, respiratory depression, restlessness,
Inj.: 20 mg/mL (as hydrochloride), 2 mL, 5 mL, 20 mL, and seizures
50 mL ampule / vial (IM, IV) Rare: Bronchospasm, convulsions, hypersensitivity
reactions, paraplegia, unconsciousness
A class IB antiarrhythmic agent that acts by blocking fast
sodium channels, thereby inhibiting the rapid Drug Interactions:
depolarization (phase 0) of fast response cardiac action Monitor closely with:
potentials while decreasing the effective refractory Increases risk of adverse or toxic effects of Lidocaine by
period. increasing its serum concentration:
Beta Blockers e.g., Metoprolol
Indications: Management of pulseless ventricular fibrillation
or ventricular tachycardia; emergency treatment of Avoid concomitant use with:
ventricular arrhythmia Decreases therapeutic effect of Lidocaine:
Diuretics, e.g. Furosemide, Hydrochlorothiazide
Contraindications: Adjacent skin infection or inflamed skin
to the proposed site of injection; concomitant therapy Decreases therapeutic effect of the following drugs:
with anticoagulants or an abnormal bleeding tendency; Antiarrhythmics, e.g., Amiodarone, Sotalol, Disopyramide
severe anemia or heart disease; spinal/epidural
anesthesia in dehydrated or hypovolemic patients Increases risk of adverse or toxic effects of the following
drugs:
Dose: Bupivacaine (Bupivacaine toxicity), Drugs which
Pulseless ventricular fibrillation or ventricular tachycardia, depresses cardiac contractility and conduction (heart
by IV injection, ADULT, 1–1.5 mg/kg repeated as failure; significant bradyarrhythmia)
necessary (maximum dose, 3 mg/kg);
for ventricular arrhythmias in more stable patients, usual Administration: For IV or IM use only.
loading dose, 50–100 mg at 25 to 50 mg/minute, may
repeat once or twice up to a maximum of 200–300 mg Pregnancy Category: B
in 1 hour, followed by 1–4 mg/minute via continuous IV
infusion, may need to reduce dose if the infusion is ATC Code: C01BB01
longer than 24 hours.
Emergency treatment of ventricular arrhythmias, by IM
injection, ADULT, 300 mg injected into the deltoid CLASS II ANTIARRHYTHMICS
muscle, repeat after 60–90 minutes, if necessary.

Dose Adjustment: Rx ESMOLOL

Geriatric and Debilitated Patients:
Reduce doses commensurate with age and physical status.
Inj.: 10 mg/mL (as hydrochloride), 10 mL vial (IV)
100 mg/mL, 10 mL vial (IV)
Renal and Hepatic Impairment:
Reduce dose during prolonged infusion (>24 hours) or
repeated IV doses. A class II antiarrhythmic agent that competitively blocks
response to beta1-adrenergic stimulation with little or no
Precautions: effect to beta2-receptors except at high doses. Esmolol
Severe bradycardia, heart block or impaired cardiac does not exhibit intrinsic sympathomimetic activity and
conduction; severe shock; respiratory impairment; renal membrane stabilizing activity.
impairment; hepatic impairment; epilepsy; porphyria;
neuromuscular diseases, e.g., myasthenia gravis; Indications: Treatment of supraventricular tachycardia
neurological disease (SVT); treatment of atrial fibrillation or flutter; treatment
Solutions containing epinephrine should be used with of intraoperative and postoperative tachycardia
caution for ring block of digits or appendages to prevent
risk of ischemic necrosis Contraindications: Any supraventricular tachyarrhythmia
conducted across an accessory pathway (WPW
Elderly (increased sensitivity); children <6 months (more
Syndrome-associated tachyarrhythmias including
sensitive to toxic effects)
preexcited atrial fibrillation/atrial flutter, antidromic
Pregnancy (avoid large doses during third trimester to
diminish risk of neonatal respiratory depression, atrioventricular reentrant tachycardia).

95
 CARDIOVASCULAR SYSTEM

Dose: NOTE: Esmolol is a vesicant. Ensure proper needle or

Intraoperative and postoperative tachycardia, immediate catheter placement prior to and during infusion to avoid
control, by IV injection, ADULT, initially 1 mg/kg bolus extravasation. If extravasation occurs, stop infusion
over 30 seconds, followed by 150 micrograms/kg per immediately and disconnect (leave cannula or needle in
minute, if necessary (maximum dose, 300 place) and gently aspirate extravasated solution then
micrograms/kg per minute). elevate extremity. Do NOT flush the line.
Intraoperative and postoperative tachycardia, gradual
control, by IV injection, ADULT, initially 0.5 mg/kg bolus See General Information on Beta Blocking Agents, Selective
over 1 minute, followed by an infusion of 50 under Beta Blocking Agents in Chapter 3: Cardiovascular
C

micrograms/kg per minute for 4 minutes, may be System for other information.
continued at 50 micrograms/kg per minute (if response
is inadequate, titrate dose upward at 50 micrograms/kg Pregnancy Category: C
per minute increments, increase no more frequently than
every 4 minutes (maximum dose, 300 micrograms/kg ATC Code: C07AB09
per minute); may administer an optional loading dose of
0.5 mg/kg over 1 minute prior to each increase in
infusion rate.
Supraventricular tachycardia, by IV injection, ADULT, Rx METOPROLOL
optional loading dose, 0.5 mg/kg over 1 minute, followed
by 50 micrograms/kg per minute infusion for 4 minutes; Oral: 50 mg and 100 mg tablet (as tartrate)
continue infusion at 50 micrograms/kg per minute (if
response is inadequate, increase dose in 50 A selective inhibitor of beta1­adrenergic receptors that
micrograms/kg per minute increments, for no more competitively blocks beta1­receptors, with little or no
frequently than every 4 minutes (maximum dose, 200 effect on beta2­receptors. Metoprolol does not exhibit
micrograms/kg per minute); any membrane stabilizing activity or intrinsic
for a more rapid response, re-bolus with a second 0.5 sympathomimetic activity.
mg/kg loading dose over 1 minute, and increase the
maintenance infusion to 100 micrograms/kg per minute Indications: Atrial fibrillation or flutter; supraventricular
for 4 minutes; tachycardia (SVT)
a third, final 0.5 mg/kg loading dose may be
administered, if necessary, prior to increasing infusion Contraindications: Any supraventricular tachyarrhythmia
rate of 150 micrograms/kg per minute; after 4 minutes, conducted across an accessory pathway (WPW
(maximum infusion rate, 200 micrograms/kg per Syndrome-associated tachyarrhythmias including
minute; usual dose, 50–200 micrograms/kg per minute; preexcited atrial fibrillation/atrial flutter, antidromic
maintenance infusions may be continued for up to 48 atrioventricular reentrant tachycardia).
hours).
Perioperative tachycardia, by IV injection, ADULT, initially Dose:
1.5 mg/kg bolus (maximum dose, 100 mg) over 30 Atrial fibrillation or flutter (ventricular rate control), and SVT,
seconds, followed by 150 micrograms/kg per minute maintenance, by mouth, ADULT, 25–100 mg twice daily.
infusion; adjust infusion rate as needed to maintain
desired heart rate (maximum rate, 300 micrograms/kg Dose Adjustment:
per minute). Renal Impairment:
Atrial fibrillation or atrial flutter, by IV injection, ADULT, 0.5 For mild-to-moderate impairment, no dose adjustment
mg/kg over 1 minute, followed by 50 micrograms/kg per necessary.
minute infusion for 4 minutes; continue infusion at 50 For severe impairment, refer patient to a specialist.
micrograms/kg per minute; if response is inadequate, re-
bolus with a second 0.5 mg/kg loading dose over 1 Hepatic Impairment:
minute, and increase the maintenance infusion to 100 For mild-to-moderate impairment, dose reduction may be
micrograms/kg per minute for 4 minutes; repeat if warranted.
necessary, until target heart rate or safety end point For severe impairment, refer patient to a specialist.
begins to occur, then omit subsequent loading dose and
decrease dosing increment of maintenance infusion to Precautions:
≤25 micrograms/kg per minute (usual effective dose is Major surgery. Do NOT routinely withdraw CHRONIC beta blocker
50–200 micrograms/kg per minute; doses as low as 25 therapy prior to surgery. Use of high-dose extended-release
micrograms/kg per minute may be adequate). metoprolol in patients naive to beta blocker therapy undergoing
non-cardiac surgery has been associated with bradycardia,
hypotension, stroke, and death. Chronic beta-blocker therapy
Dose Adjustment: should not be routinely withdrawn prior to major surgery.
Geriatric:
Dose reductions may be necessary. See General Information on Beta Blocking Agents, Selective
under Beta Blocking Agents in Chapter 3: Cardiovascular
Administration: For IV administration only. Administer System for other information.
loading doses over 30 seconds to 1 minute depending
on how urgent the need for effect. Pregnancy Category: C
Avoid infusion into small veins or through a butterfly ATC Code: C07AB02
catheter to prevent thrombophlebitis.

96
CARDIOVASCULAR SYSTEM

Diabetes (may potentiate and/or mask signs and symptoms

Rx PROPRANOLOL of hypoglycemia); thyroid disease (may mask signs of
hyperthyroidism; carefully manage and monitor; abrupt
Oral: 10 mg and 40 mg tablet (as hydrochloride) withdrawal may exacerbate symptoms of
hyperthyroidism or precipitate thyroid storm)
A non-selective beta-adrenergic blocker (class II Pheochromocytoma (adequate alpha-blockade is required
antiarrhythmic) that competitively blocks response to prior to use of any beta blocker)
beta1­ and beta2­adrenergic stimulation. It decreases Hepatic impairment; renal impairment (may have increased
heart rate, myocardial contractility, blood pressure, and side effects)

C
myocardial oxygen demand. Psoriasis; myasthenia gravis; psychiatric disease (may
cause or exacerbate CNS depression)
Indication: Management of supraventricular Smokers (may decrease plasma levels of propranolol by
tachyarrhythmia increasing metabolism)
Elderly (bradycardia may be observed more frequently)
Contraindications: Uncompensated congestive heart failure Pregnancy (may cause pharmacologic effects, such as
(unless the failure is due to tachyarrhythmias being bradycardia, in the fetus and newborn infant)
treated with propranolol); cardiogenic shock; severe
sinus bradycardia; sick sinus syndrome or heart block NOTE: Do NOT withdraw abruptly. Gradually tapered over 1–
greater than first degree (except in the presence of a 2 weeks to avoid acute tachycardia, hypertension,
functioning artificial pacemaker); bronchial asthma; for and/or ischemia. Severe exacerbations of angina,
any supraventricular tachyarrhythmia conducted across ventricular arrhythmias and myocardial infarction have
an accessory pathway (WPW Syndrome-associated been reported following abrupt withdrawal of beta
tachyarrhythmias including preexcited atrial blocker therapy. Temporary but prompt resumption of
fibrillation/atrial flutter, antidromic atrioventricular beta blocker therapy may be indicated with worsening of
reentrant tachycardia). angina or acute coronary insufficiency.

Dose: Adverse Drug Reactions:

Tachyarrhythmias, by mouth, ADULT, 10–30 mg every 6–8 Common: Cold extremities, angina pectoris, AV conduction
hours; usual maintenance dose, 10–40 mg 3 or 4 times disturbance, bradycardia, cardiogenic shock, congestive
daily for rate control in patients with atrial fibrillation. heart failure, hypotension, ineffective myocardial
contractions, syncope, sleep disorder, agitation, fatigue,
Dose Adjustment: dizziness, nightmares, irritability, drowsiness, amnesia,
Geriatric: catatonia, cognitive dysfunction, confusion,
Dose reduction may be necessary. hypersomnia, lethargy, paresthesia, psychosis, vertigo,
Administer 10 mg twice daily initially; increase dose every changes in nails, contact dermatitis, dermal ulcer,
3–7 days (usual dose range, 10–320 mg daily given in eczematous rash, erosive lichen planus, hyperkeratosis,
1–2 divided doses). pruritus, skin rash, hyperglycemia, hyperkalemia,
hyperlipidemia, diarrhea, abdominal pain, hypoglycemia,
Precautions: decreased appetite, constipation, stomach discomfort,
immune thrombocytopenia, anorexia,
WARNING: Exacerbations of angina pectoris and
thrombocytopenia, oculomucocutaneous syndrome,
myocardial infarction (MI) have occurred following
arthropathy, conjunctival hyperemia, decreased visual
abrupt discontinuation of beta blockers. Gradually
acuity, polyarthritis, mydriasis, increased blood urea
reduce the dose over a period of 1–2 weeks and
nitrogen, bronchiolitis, bronchospasm, dyspnea,
monitor the patient. If angina or acute coronary
bronchitis, pulmonary edema, wheezing, ulcer
insufficiency develops, promptly resume therapy
Less Common: Abdominal cramps, agranulocytosis,
temporarily, and take other measures appropriate
alopecia, arterial insufficiency, arterial mesenteric
for the management of unstable angina. Avoid
thrombosis, decreased heart rate, depression, emotional
abrupt discontinuation to prevent coronary artery
lability, epigastric distress, erythema multiforme,
disease.
erythematous rash, exfoliative dermatitis, fever,
Anaphylactic reactions (patients may become more hallucination, hypersensitivity reaction, impotence,
sensitive to repeated challenges; treatment of insomnia, ischemic colitis, lassitude, lupus-like
anaphylaxis, e.g., epinephrine, may be ineffective or syndrome, myotonia, myopathy, nausea,
promote undesirable effects) nonthrombocytopenic purpura, peripheral arterial
Bronchospastic disease (monitor closely) disease, Peyronie's disease, pharyngitis, psoriasiform
Conduction abnormality (consider pre­existing conditions eruption, purpura, Raynaud's phenomenon, second-
such as sick sinus syndrome before initiating) degree atrioventricular block, slightly clouded
Heart failure (monitor for worsening of the condition); sensorium, Stevens-Johnson syndrome, systemic lupus
Peripheral vascular disease (PVD) and Raynaud's disease erythematosus, temporary amnesia, tingling of
(can precipitate or aggravate symptoms of arterial extremities, toxic epidermal necrolysis, urticaria, visual
insufficiency); disturbance, vivid dream, vomiting, weakness,
Prinzmetal variant angina (unopposed alpha1-adrenergic xerophthalmia
receptors mediate coronary vasoconstriction and can Rare: Carpal tunnel syndrome, oliguria, proteinuria,
worsen anginal symptoms; avoid beta­blockers without interstitial nephritis
alpha1­adrenergic receptor blocking activity)

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 CARDIOVASCULAR SYSTEM

Drug Interactions: effects of epinephrine), Alpha1 Blocker e.g. Tamsulosin

Monitor closely with: (orthostatic hypotensive effect), Alpha2­agonists [except
Enhances therapeutic effect of Propranolol: Apraclonidine] (rebound hypertension; may enhance
Bradycardic effect: Acetylcholinesterase Inhibitors e.g. sinus node dysfunction), Amifostine (hypotensive
Neostigmine, Amiodarone (may induce cardiac arrest), effect), Grass Pollen Allergen Extract / 5 Grass Extract
Bretylium, Dipyridamole, Disopyramide, Regorafenib, (may inhibit the ability to effectively treat severe allergic
Reserpine, Ruxolitinib, Tofacitinib, Other Bradycardia- reactions with epinephrine), Methacholine,
causing Agents Obinutuzumab (hypotensive effect), Rituximab
Antihypertensive effect: Phenothiazine Antipsychotic (hypotensive effect)
C

Agents, Barbiturates e.g Phenobarbital, Brimonidine

(topical), Calcium Channel Blockers (Non- Increases serum concentration of Propranolol:
Dihydropyridine e.g. Verapamil), Diazoxide, Lacidipine, Abiratone Acetate, Dronedarone, Fluvoxamine,
Molsidomine, Nicorandil, Nifedipine (also negative Panobinostat
inotropic effect), Pentoxifylline, Phosphodiesterase-5
Inhibitors, Prostacyclin Analogues e.g., Epoprostenol, Increases serum concentration of the following drugs:
Propafenone (possesses independent beta-blocking Afatinib, Bosutinib, Colchicine (may increase distribution
activity), Anilidopiperidine Opioids e.g., Fentanyl to certain tissues, e.g., brain), Dabagitran Etexilate
(bradycardic and hypotensive effects), [active metabolites], Doxorubicin (Conventional),
Edoxaban, Everolimus, Pazopanib, Rizatriptan [reduce
Enhances therapeutic effect of the following drugs: dose to 5 mg when used concomitantly], Silodosin,
Bretylium (AV blockade), Cardiac Glycosides (bradycardic Tizanidine, Topotecan, Vemurafenib, Vincristine
effect), Disopyramide (negative inotropic effect), (Liposomal)
Fingolimod (bradycardic effect), Insulin (hypoglycemic
effect), Ivabradine (bradycardic effect), Lacosamide (AV Reduces therapeutic effect of the following drugs:
blocking effect), Midodrine (bradycardic effect), Other Beta2­agonists e.g Salbutamol (bronchodilatory effect),
Antihypertensives (antihypertensive effect), Theophylline Derivatives e.g., Aminophylline
Sulfonylureas (hypoglycemic effect) (bronchodilatory effect)

Increases metabolism of Propranolol: Administration: To be taken on an empty stomach.

CYP1A2 Inducers, CYP2D6 Inducers
NOTE: Do NOT withdraw abruptly, particularly in patients
Increases risk of adverse or toxic effects of Propranolol: with CAD. Gradually taper dose to avoid acute
MAO Inhibitors (orthostatic hypotensive effect) tachycardia, hypertension, and/or ischemia.

Increases risk of adverse or toxic effects of the following Pregnancy Category: C

drugs:
Cholinergic Agonists (potential for cardiac conduction ATC Code: C07AA05
abnormalities and bronchoconstriction), Duloxetine
(orthostatic hypotensive effect), Levodopa (orthostatic
hypotensive effect), MAO Inhibitors [except Linezolid, CLASS III ANTIARRHYTHMICS
Tedizolid] (orthostatic hypotensive effect), Other
Antihypertensive Agents
Rx AMIODARONE
Reduces therapeutic effect (anti-hypertensive effect) of
Propranolol: Oral: 200 mg tablet (as hydrochloride)
Methylphenidate (antihypertensive effect), NSAIDS Inj.: 50 mg/mL (as hydrochloride), 3 mL ampule (IV)
(antihypertensive effect)
A class III antiarrhythmic agent with alpha- and beta-
Avoid concomitant use with: blocking properties, that acts by inhibiting adrenergic
Enhances therapeutic effect of Propranolol: stimulation. Amiodarone affects sodium, potassium, and
Alpha2­agonists [except Apraclonidine] (AV blocking calcium channels and prolongs the action potential
effect), Dronedarone (bradycardic effect), Rivastigmine duration and refractory period in myocardial tissue. It
(bradycardic effect) also decreases AV conduction and sinus node function.
Enhances therapeutic effect of the following drugs: Indications: Management of life-threatening recurrent
Alpha / Beta-Agonists, Direct-Acting (vasopressor effect) ventricular fibrillation (VF) or recurrent hemodynamically-
Ceritinib (bradycardic effect), Ergot Derivatives e.g., unstable ventricular tachycardia (VT); supraventricular
Ergotamine (vasoconstricting effect) arrhythmias
Increases metabolism of Propranolol: Contraindications: Severe sinus-node dysfunction causing
CYP1A2 Inducers, CYP2D6 Inducers marked sinus bradycardia; second- and third-degree
heart block; bradycardia causing syncope; cardiogenic
Increases risk of adverse or toxic effects of the following shock
drugs:
Alpha / Beta-Agonists, Direct-Acting (reduced beta-
adrenoceptor-mediated effects, including anaphylactic

98
CARDIOVASCULAR SYSTEM

Dose: Precautions:
Recurrent life-threatening ventricular arrhythmias,
prevention, by mouth, ADULT, 800–1,600 mg daily in 1– WARNING: For use only in patients with indicated life-
2 doses for 1–3 weeks; when adequate arrhythmia threatening arrhythmias due to the risk for
control is achieved, decrease to 600–800 mg daily in 1– substantial, potentially fatal toxicity (e.g.,
2 doses for 1 month (maintenance, 300 mg daily). pulmonary toxicity, overt liver disease).
Pulseless VT or VF, by IV push, I.O., ADULT, initially 300 mg
rapid bolus; if condition continues or recurs, administer Bradycardia or hypotension (infusion-rate related);
supplemental dose of 150 mg, preferably undiluted Proarrhythmic effects

C
(maximum recommended total daily dose, 2.2 g); once Arrhythmias (hospitalize patients when amiodarone is
spontaneous circulation returns, administer by IV initiated), Wolff-Parkinson-White (WPW) syndrome
infusion of 1 mg/minute for 6 hours, then 0.5 mg/minute Cardiac devices, e.g., implantable defibrillators (chronic
for 18 hours); CHILD, 5 mg/kg rapid bolus (maximum, therapy may increase defibrillation threshold)
300 mg per dose); may repeat twice up to a maximum Myocardial infarction
total dose of 15 mg/kg during acute treatment. Dermatologic toxicity (may cause life-threatening or fatal
Stable VT, by IV infusion, ADULT, 150 mg over 10 minutes, cutaneous reactions, including SJS and TEN)
then 1 mg/minute for 6 hours, followed by 0.5 photosensitivity (blue-gray discoloration of exposed skin
mg/minute; continue this rate for at least 18 hours or may occur during long-term treatment)
until complete transition to oral (total infusion duration, Hepatotoxicity
24 hours). Neurotoxicity (peripheral neuropathy has been reported);
Breakthrough stable VT, by IV infusion, ADULT, 150 mg ocular effects (may cause optic neuropathy and/or optic
supplemental doses in 100 mL D5W or NS over 10 neuritis resulting in visual impairment; permanent
minutes [NOTE: Mean daily doses >2.1 g/day have been blindness has occurred; corneal microdeposits
associated with hypotension.]
commonly occur and may cause reversible visual
Atrial fibrillation, pharmacologic cardioversion, by mouth,
disturbances)
ADULT, 600–800 mg daily in divided doses to a total of
Pulmonary toxicity (hypersensitivity pneumonitis, or
10 g, then 200 mg daily as maintenance dose (usual
interstitial or alveolar pneumonitis, and abnormal
maintenance dose, 100 mg daily); or
diffusion capacity without symptoms may occur; acute-
800 mg daily for 14 days, followed by 600 mg daily for
onset pulmonary injury has occurred; most fatalities due
the next 14 days, then 300 mg daily for the remainder of
to sudden cardiac death occurred when amiodarone was
the first year, then 200 mg daily thereafter; or
discontinued)
10 mg/kg daily for 14 days, followed by 300 mg daily for
Thyroid effects (may cause hyper­ or hypothyroidism;
4 weeks, then 200 mg daily as maintenance dose;
myxedema has been reported and may be fatal; thyroid
by IV infusion, ADULT, 150 mg over 10 minutes, then 1
mg/minute for 6 hours, then 0.5 mg/minute for 18 nodules and thyroid cancer have been reported)
Electrolyte imbalance (correct hypokalemia,
hours, or change to oral dosing.
hypomagnesemia, or hypocalcemia prior to use and
Maintenance of sinus rhythm, by mouth, ADULT, 400 to 600
throughout therapy)
mg daily in divided doses for 2–4 weeks followed by a
Surgical patients (may enhance myocardial depressant and
maintenance dose of 100–200 mg once daily.
conduction effects of halogenated inhalational
Prevention of postoperative atrial fibrillation and atrial
anesthetics; adult respiratory distress syndrome (ARDS)
flutter associated with cardiothoracic surgery, by mouth,
has been reported postoperatively)
ADULT, 200 mg 3 times daily for 7 days prior to surgery,
Elderly (use is associated with thyroid disease, pulmonary
followed by 200 mg daily until hospital discharge;
abnormalities, and QT-interval prolongation)
by IV injection, ADULT, 150 mg loading dose, followed by
Lactation (excreted in breastmilk; not recommended for
0.4 mg/kg per hour for 3 days prior to surgery and for 5
nursing mothers).
days postoperative; after surgery, infuse 1,000 mg over
24 hours for 2 days.
Adverse Drug Reactions:
Supraventricular tachycardia, pharmacologic cardioversion,
by mouth, ADULT, 600–800 mg daily in divided doses to
Common: Hypotension, bradycardia, AV block, cardiac
arrest, cardiac arrhythmia, cardiac failure, ventricular
a total of 10 g, then 200 mg daily as maintenance;
tachycardia, asystole, atrial fibrillation, cardiogenic
by IV infusion, ADULT, 150 mg over 10 minutes, then 1
shock, torsade de pointes, ventricular fibrillation,
mg/minute for 6 hours, then 0.5 mg/minute for 18
atrioventricular dissociation, cardiac conduction
hours, or change to oral dosing.
disturbance, edema, flushing, peripheral
thrombophlebitis, pulseless electrical activity (PEA),
Dose Adjustment:
abnormal gait, ataxia, dizziness, fatigue, involuntary
Geriatric:
Select doses with caution. Begin at low end of dosage range body movements, malaise, peripheral neuropathy,
memory impairment, paresthesia, altered sense of
and titrate slowly to evaluate response.
smell, headache, insomnia, sleep disorder, blue-gray
A maintenance dose of 100 mg daily is commonly used
skin pigmentation, skin photosensitivity, hypothyroidism,
especially for the elderly or patients with low body mass.
decreased libido, hyperthyroidism nausea, vomiting,
anorexia, constipation, altered salivation, dysgeusia,
Hepatic Impairment:
abdominal pain, diarrhea, blood coagulation disorder,
Dose adjustment may be necessary. Decrease dose or
discontinue Amiodarone once hepatic enzymes exceed 3 hepatic disease, tremor, corneal deposits, visual halos,
visual disturbance, optic neuritis, photophobia,
times the normal or double in a patient with an elevated
pulmonary toxicity, pulmonary edema, hypersensitivity
baseline.

99
 CARDIOVASCULAR SYSTEM

pneumonitis, interstitial pneumonitis, pulmonary Decreases metabolism of the following drugs:

fibrosis, fever Cyclosporine (Systemic), HMG-CoA Reductase Inhibitors
Less Common: Acute renal failure, adult respiratory distress [except Pitavastatin, Pravastatin; limit Simvastatin adult
syndrome, agranulocytosis, alopecia, anaphylactic maximum dose to 20 mg daily; limit Lovastatin adult
shock, anaphylactoid reaction, anaphylaxis, maximum dose to 40 mg daily], Tamoxifen, Tegafur
angioedema, aplastic anemia, back pain, bronchiolitis
obliterans organizing pneumonia, bronchospasm, Decreases serum concentration of Amiodarone:
bullous dermatitis, cholestasis, cholestatic hepatitis, Dabrafenib, Fosphenytoin, Mitotane, Rifampin [including
confusion, cough, delirium, demyelinating its active metabolite, desethylamiodarone],
C

polyneuropathy, disorientation, DRESS syndrome, drug-

induced Parkinson disease, dyspnea, eczema, Decreases serum concentration of the following drugs:
eosinophilic pneumonia, epididymitis, erythema Artesunate, Tamoxifen, Tegafur
multiforme, exfoliation of skin, exfoliative dermatitis,
fever, hallucination, hemolytic anemia, hemoptysis, Enhances therapeutic effect of Amiodarone:
hepatic cirrhosis, hepatic failure, hepatitis, QTc prolonging effect: Azithromycin (Systemic),
hepatotoxicity (idiosyncratic), hypoesthesia, Fosphenytoin
hypotension, hypoxia, impotence, increased intracranial Bradycardic effect: Non-Dihydropyrdine Calcium Channel
pressure, injection site reaction, jaundice, Blockers e.g., Diltiazem, Daclatasvir
leukocytoclastic vasculitis, malignant neoplasm of skin, Arrhythmogenic effect: Fingolimod
pulmonary mass, myasthenia, myopathy, neutropenia,
optic neuropathy, pancreatitis, pancytopenia, pleural Enhances therapeutic effect of Amiodarone:
effusion, pleurisy, prolonged QT interval, pruritus, QTc prolonging effect: Ivabradine, Lopinavir,
pseudotumor cerebri, pulmonary alveolar hemorrhage, Mifepristone, Other QTc-prolonging Agents, Saquinavir,
pulmonary infiltrates, pulmonary phospholipidosis, renal Bradycardic effect: Sofosbuvir
insufficiency, respiratory arrest, respiratory distress
syndrome, respiratory failure, rhabdomyolysis, SIADH, Enhances therapeutic effect of the following drugs:
sinoatrial arrest, sinus node dysfunction, skin carcinoma, Antiarrhythmic Agents, Class Ia (QTc prolonging effect),
skin granuloma, skin rash, skin sclerosis, spontaneous Ceritinib (bradycardic effect), Flecainide [when used
ecchymoses, Stevens-Johnson syndrome, superior vena concomitantly, decrease Flecainide dose by 50%] (QTc
cava syndrome, thrombocytopenia, thyroid cancer, prolonging effect), Vitamin K Antagonists, e.g., Warfarin
thyroid nodule, thyrotoxicosis, tissue necrosis at injection (anticoagulant effect)
site, toxic epidermal necrolysis, urticaria, vasculitis,
vortex keratopathy, wheezing, xerostomia Increases bioavailability of Amiodarone:
Grapefruit Juice
Drug Interactions:
Monitor closely with: Increases risk of adverse or toxic effects of the following
Decreases absorption of Amiodarone: drugs:
Orlistat Loratadine (QT interval prolongation and torsade de
pointes), Propafenone (cardiac conduction and
Decreases metabolism of Tramadol repolarization)

Enhances therapeutic effect of Amiodarone: Increases serum concentration of Amiodarone:

Bretylium (bradycardic and AV blocking effects), Cimetidine, Fusidic Acid (Systemic) Idelalisib, Indinavir,
Lidocaine (arrhythmogenic effect), Ruxolitinib Lopinavir, Nelfinavir, Ritonavir, Saquinavir, Tipranavir
(bradycardic effect)
Tofacitinib (bradycardic effect) Increases serum concentration of the following drugs:
Afatinib [reduce Afatinib dose by 10 mg if not tolerated],
Enhances therapeutic effect of the following drugs: Antiarrhythmic Agents, Class Ia e.g. Procainamide,
Beta Blockers [except Levobunolol, Metipranolol] Artesunate, Bosutinib, Cardiac Glycosides e,g, Digoxin
(bradycardic effect), Bradycardia-causing Agents [when used concomitantly, reduce Cardiac Glycosides
(bradycardic effect), Lacosamide (AV blocking effect) dose by 30-50% or reduce frequency of administration],
Colchicine (may increase colchicine distribution into
Increases risk of adverse or toxic effects of Amiodarone: certain tissues, e.g., brain), Dabigatran Etexilate,
Cyclophosphamide (pulmonary toxicity), Porfimer Doxorubicin (Conventional), Everolimus, Flecainide
(photosensitizing effect), Telaprevir, Verteporfin [when used concomitantly, decrease Flecainide dose by
(photosensitizing effect) 50%], Lomitapide [limit maximum dose to 30 mg daily],
Loratadine, Metoprolol, Pazopanib, Pimozide,
Reduces therapeutic effect of the following drugs: Propafenone, Silodosin, Thioridazine, Tizanidine [if
Codeine, Tramadol (opioid-like effects) concomitant use cannot be avoided, initiate Tizanidine
at an adult dose of 2 mg and increase in 2–4 mg
Avoid concomitant use with: increments based on patient response], Topotecan,
Decreases bioavailability of Amiodarone: Vincristine (Liposomal), Vitamin K Antagonists, e.g.,
Bile acid sequestrants Warfarin

Decreases metabolism of Amiodarone: Reduces therapeutic effect of the following drugs:

Grapefruit Juice Agalsidase Alfa, Agalsidase Beta, Sodium Iodide I131

100
CARDIOVASCULAR SYSTEM

Administration: fibrillation/atrial flutter, antidromic atrioventricular

For oral administration, administer consistently with reentrant tachycardia); Lown-Ganong-Levine syndrome);
meals. Take in divided doses with meals if GI upset concurrent use of IV beta-blocking agents; ventricular
occurs or if taking large daily doses. If GI intolerance tachycardia.
occurs with single-dose therapy, use twice daily dosing.
Dose:
For IV infusions >1 hour, use concentrations ≤2 mg/mL PSVT prophylaxis, by mouth, ADULT, 240–480 mg daily in
unless a central venous catheter is used. Use only 3–4 divided doses.
volumetric infusion pump to prevent underdosage. Atrial fibrillation (rate control), by IV injection, ADULT, initially

C
Administer through an IV line located as centrally as 0.075–0.15 mg/kg IV bolus over 2 minutes (usual dose,
possible. 5–10 mg) ; if no response, administer an additional 10
mg after 15–30 minutes; if patient responds to the initial
For IV infusions >2 hours, administer in a non-PVC or repeat bolus dose, administer continuous infusion
container (e.g., glass, polyolefin). PVC tubing is initially at 5 mg/hour; titrate to goal heart rate;
recommended for administration regardless of infusion by mouth, ADULT, as immediate-release tablet, 240-480
duration. Flush with saline prior to and following infusion mg daily in 3–4 divided doses;
to prevent incompatibilities with heparin. as MR tablet, 180–480 mg once daily.
SVT, by IV injection, ADULT, 2.5–5 mg over 2 minutes; a
For continuous IV infusions, use an in­line filter to reduce second dose of 5–10 mg (approximately 0.15 mg/kg)
the incidence of phlebitis. Adjust administration rate to may be given 15–30 minutes after the initial dose if
urgency. Give more slowly when perfusing arrhythmia is patient tolerates, but does not respond to initial dose
present. Slow the infusion rate if hypotension or (maximum total dose, 20–30 mg); CHILD 1–15 years,
bradycardia develops. 0.1–0.3 mg/kg per dose over 2 minutes (maximum, 5
mg per dose); may repeat dose in 30 minutes if
NOTE: IV administration at lower flow rates, i.e., pediatric inadequate response (maximum for second dose, 10
use, and higher concentrations than recommended may mg).
result in leaching of plasticizers (DEHP) from IV tubing.
DEHP may adversely affect male reproductive tract NOTE: Verapamil is NOT included in the Pediatric Advanced
development. Life Support (PALS) tachyarrhythmia algorithm.

Pregnancy Category: D Dose Adjustment:

Renal Impairment: Use with caution and monitor ECG.
ATC Code: C01BD01 Reduced renal clearance of verapamil and its
metabolite, norverapamil, in advanced renal failure.
Initiate at 100 mg daily at bedtime.
CLASS IV ANTIARRHYTHMICS
NOTE: NOT removed by hemodialysis.

Rx VERAPAMIL Hepatic Impairment:

In patients with liver cirrhosis, administer 20% and 50%
of normal dose for oral and IV administration,
Oral: 80 mg tablet (as hydrochloride) respectively. Initiate at 100 mg daily at bedtime. Monitor
240 mg MR tablet (as hydrochloride) [for ECG.
maintenance therapy]
Inj.: 2.5 mg/mL (as hydrochloride), 2 mL ampule (IV) For patients with severe impairment, administer 30% of the
normal dose.
A non-dihydropyridine calcium channel blocker that acts
during depolarization by inhibiting calcium ions from Precautions:
entering “slow channels” or select voltage-sensitive Conduction abnormalities (can cause first-degree AV block
areas of vascular smooth muscle and myocardium. or sinus bradycardia); hypotension or syncope
Verapamil produces relaxation of coronary vascular (symptomatic hypotension with or without syncope rarely
smooth muscle and coronary vasodilation, which occur; blood pressure must be lowered at a rate
increases myocardial oxygen delivery in patients with appropriate for the patient's clinical condition);
vasospastic angina and slows automaticity and arrhythmia (severe hypotension likely to occur upon
conduction of AV node. administration); heart failure (avoid use; can exacerbate
condition); hypertrophic cardiomyopathy (use with
Indications: Paroxysmal supraventricular tachycardia (PSVT) caution in patients with outflow tract obstruction)
prophylaxis; atrial fibrillation (rate control); ventricular Attenuated neuromuscular transmission (dose reduction
tachycardia may be required); gastrointestinal effects (use MR
Contraindications: Severe left ventricular dysfunction; tablets with caution in patients with severe GI narrowing)
hypotension (systolic pressure <90 mm Hg); cardiogenic Hepatic impairment (monitor hemodynamics and ECG);
shock; sick sinus syndrome; second- or third-degree AV increased hepatic enzymes; renal impairment (monitor
block without a cardiac pacemaker; atrial flutter or hemodynamics and ECG, particularly if with concomitant
fibrillation; accessory bypass tract; any supraventricular hepatic impairment)
tachyarrhythmia conducted across an accessory Elderly (may experience a greater hypotensive response;
pathway (Wolff-Parkinson-White syndrome-associated constipation may be more of a problem in the elderly;
tachyarrhythmias including pre-excited atrial

101
 CARDIOVASCULAR SYSTEM

may not be bioequivalent in the elderly); children (avoid Enhances therapeutic effect of the following drugs:
IV use in neonates and young infants due to severe Beta Blockers [except Levobunolol] (antihypertensive
apnea, bradycardia, hypotensive reactions, and cardiac effect); Cardiac Glycosides (AV blocking effect);
arrest; use with caution in children as myocardial Diazoxide (antihypertensive effect); Fingolimod
depression and hypotension may occur) (bradycardic effect); Herbs with Hypotensive Properties
Pregnancy (may cause adverse effects, including (antihypertensive effect); Lacosamide (AV blocking
bradycardia, heart block, and hypotension in fetus, and effect); MAO Inhibitors [except Linezolid, Tedizolid]
maternal toxicity; crosses the placenta; fetal monitoring (antihypertensive effect)
is recommended); lactation excreted in breastmilk; not
C

recommended in nursing mothers) Enhances therapeutic effect of the following drugs:

Midodrine (bradycardic effect); Neuromuscular-blocking
Adverse Drug Reactions: Agents; Nondepolarizing (neuromuscular blocking
Common: Headache, gingival hyperplasia, constipation, effect); Nitroprusside (antihypertensive effect);
peripheral edema, hypotension, CHF, pulmonary edema, Salicylates (anticoagulant effect)
AV block, bradycardia, flushing, fatigue, dizziness,
lethargy, pain, sleep disturbance, rash, dyspepsia, Increases bioavailability of the following drugs:
nausea, diarrhea, myalgia, paresthesia, dyspnea, flu­like Fexofenadine
syndrome, abdominal discomfort, alopecia, angina,
arthralgia, atrioventricular dissociation, blurred vision, Increases metabolism of Verapamil:
bruising, cerebrovascular accident, chest pain, Barbiturates
claudication, confusion, diaphoresis, ECG abnormal,
equilibrium disorders, erythema multiforme, exanthema, Increases risk of adverse or toxic effects of Verapamil:
extrapyramidal symptoms, galactorrhea, Clonidine (sinus node dysfunction)
hyperprolactinemia, gastrointestinal distress, Other Antihypertensive Agents
gynecomastia, hyperkeratosis, impotence, insomnia,
macules, MI, muscle cramps, palpitation, psychosis, Increases risk of adverse or toxic effects of the following
purpura (vasculitis), shakiness, somnolence, spotty drugs:
menstruation, Stevens-Johnson syndrome, syncope, Atosiban (pulmonary edema and/or dyspnea); Beta
tinnitus, urination increased, urticaria, weakness, Blockers [except Levobunolol] (bradycardia; heart
xerostomia failure); Duloxetine (orthostatic hypotensive effect);
Less Common: Bronchospasm, laryngeal spasm, Flecainide (impairment of myocardial contractility and
depression, diaphoresis, itching, muscle fatigue, AV nodal conduction); Levodopa (orthostatic hypotensive
respiratory failure, rotary nystagmus, seizure, sleepiness, effect); Lithium (neurotoxic effect); Magnesium Salts;
urticaria, vertigo, asystole, eosinophilia, EPS, exfoliative MAO Inhibitors [except Linezolid, Tedizolid] (orthostatic
dermatitis, GI obstruction, hair color change, paralytic hypotensive effect)
ileus, Parkinsonian syndrome, pulseless electrical
activity, shock, ventricular fibrillation Reduces therapeutic effect of Verapamil:
Calcium Salts; Herbs with Hypertensive Properties
Drug Interactions: (antihypertensive effect); Methylphenidate
NOTE: Verapamil may inhibit CYP1A2 (weak), CYP2C9 (antihypertensive effect)
(weak), CYP2D6 (weak), CYP3A4 (moderate), and P-
glycoprotein. Reduces therapeutic effect of the following drugs:
Clopidogrel, Metformin
Monitor closely with:
Decreases metabolism of the following drugs: Avoid concomitant use with:
Pimecrolimus, Tacrolimus Decreases metabolism of Verapamil:
Cyclosporine, Systemic; Macrolide
Enhances therapeutic effect of Verapamil: Antibiotics [except Azithromycin, Fidaxomicin,
Anti-hypertensive effect: Alpha1 Blockers e.g. Alfuzosin Spiramycin]; Protease Inhibitors; Antifungal Agents,
Anilidopiperidine Opioids e.g., Fentanyl (bradycardic); Systemic Azole Derivatives [except Fluconazole
Barbiturates e.g. (antihypertensive effect), Bretylium
(bradycardic effect; AV blockade); Brimonidine, Topical Decreases metabolism of the following drugs:
(antihypertensive effect); Clonidine (AV blocking effect); Buspirone, Cyclosporine (Systemic)
Magnesium Salts (antihypertensive effect), Molsidomine
(antihypertensive effect); Nicorandil (antihypertensive Decreases serum concentration of Verapamil:
effect); Other Antihypertensives (antihypertensive Carbamazepine, Dabrafenib, Mitotane, Phenytoin,
effect); Other Bradycardia-causing Agents (bradycardic Rifamycin Derivatives, St John’s Wort
effect); Other Calcium Channel Blockers
(antihypertensive effect); Pentoxifylline Enhances therapeutic effect of Verapamil:
(antihypertensive effect); Phosphodiesterase-5 Antifungal Agents, Systemic Azole Derivatives [except
Inhibitors (antihypertensive effect); Prostacyclin Fluconazole, Isavuconazonium Sulfate] (negative
Analogues (antihypertensive effect); Quinidine inotropic effect); Dantrolene (negative inotropic effect);
(antihypertensive effect); Regorafenib (bradycardic Ivabradine (QTc-prolonging effect); Telithromycin
effect); Ruxolitinib (bradycardic effect); Tofacitinib (bradycardic and antihypertensive effects)
(bradycardic effect)

102
CARDIOVASCULAR SYSTEM

Enhances therapeutic effect of the following drugs: OTHER ANTIARRHYTHMIC AGENTS

Amiodarone (bradycardic effect); Ceritinib (bradycardic
effect); Dronedarone (AV-blocking and other
electrophysiologic effects); Ivabradine (bradycardic Rx ADENOSINE
effect)
Inj.: 3 mg/mL, 2 mL vial (IV)
Increases metabolism of Verapamil:
Nafcillin
A class V antiarrhythmic agent that slows conduction time
through the AV node, interrupting the re­entry pathways

C
Increases risk of adverse or toxic effects of Verapamil:
through the AV node, thus restoring normal sinus rhythm.
Dantrolene (hyperkalemic effect); Protease Inhibitors (AV
nodal blockade)
Indications: Treatment of paroxysmal supraventricular
tachycardia (PSVT), including accessory bypass tracts
Increases risk of adverse or toxic effects of the following
(Wolff-Parkinson-White syndrome); pharmacologic stress
drugs:
agent in myocardial perfusion thallium­201 scintigraphy.
Amifostine (hypotensive effect); Amiodarone (sinus
arrest); Antifungal Agents, Systemic Azole Derivatives
Contraindications: Patients with second- or third-degree AV
[except Fluconazole, Isavuconazonium Sulfate];
block, sick sinus syndrome, and symptomatic
Disopyramide (potential for profound depression of
bradycardia but without a cardiac pacemaker; known or
myocardial contractility); Obinutuzumab (hypotensive
suspected bronchoconstrictive or bronchospastic lung
effect); Oxycodone; Rituximab (hypotensive effect)
disease; asthma.
Increases serum concentration of Verapamil:
Dose:
Cimetidine, Conivaptan, CYP3A4 Inducers; Fusidic Acid,
PSVT, by rapid IV push, ADULT and CHILD ≥50 kg, initially 6
Systemic; Grapefruit Juice; Idelalisib; Mifepristone,
mg over 1–2 seconds via a peripheral line; if not effective
Protease Inhibitors; Stiripentol
within 1–2 minutes, administer 12 mg; may repeat 12
mg bolus if needed (maximum single dose, 12 mg);
Increases serum concentration of the following drugs:
follow each dose with 20 mL normal saline flush (reduce
Afatinib [reduce Afatinib by 10 mg if not tolerated];
initial dose to 3 mg if concomitantly on carbamazepine
Avanafil [when used concomitantly, limit Avanafil dose to
or dipyridamole, or has a transplanted heart, or if
50 mg per 24-hour period]; Budesonide (Systemic);
administered via central line); INFANT and CHILD
Carbamazepine; Cilostazol [reduce Cilostazol dose to 50
<50 kg, initially 0.05–0.1 mg/kg over 1–2 seconds via a
mg twice daily]; Colchicine (may increase colchicine
peripheral line (maximum initial dose, 6 mg); if
distribution into certain tissues, e.g., brain); Dabigatran
conversion of PSVT does not occur within 1–2 minutes,
Etexilate [active metabolites]; Dapoxetine (limit
increase dose by 0.05–0.1 mg/kg; repeat until sinus
Dapoxetine dose to 30 mg daily); Dofetilide,
rhythm is established or to a maximum single dose of 0.3
Domperidone; Doxorubicin, Conventional Dronedarone,
mg/kg or 12 mg; follow each dose with 20 mL normal
Eletriptan, Eplerenone, Everolimus, Fentanyl,
saline flush.
Fosphenytoin, Halofantrine, Ivabradine, Ivacaftor,
SVT treatment in pediatric advanced life support, by IV
Lovastatin [initiate Lovastatin at 10 mg daily; do not
injection, CHILD, initially 0.1 mg/kg (maximum initial
exceed 20 mg daily]; Oxycodone [including active
dose, 6 mg); if not effective within 1–2 minutes,
metabolite, Oxymorphone]; Pazopanib, Phenytoin,
administer 0.2 mg/kg (maximum single dose, 12 mg);
Pimozide; Ranolazine [limit Ranolazine dose to a
follow each dose with ≥5 mL normal saline flush.
maximum of 500 mg twice daily]; Rivaroxaban, Silodosin,
Pharmacologic stress testing, by continuous IV infusion,
Simeprevir; Simvastatin [if concomitant use cannot be
ADULT, 140 micrograms/kg per minute for 6 minutes
avoided, limit Simvastatin to 10 mg daily]; Suvorexant,
using syringe or volumetric infusion pump via peripheral
Tizanidine [if concomitant use cannot be avoided, initiate
line (total dose, 840 micrograms/kg); inject thallium–
Tizanidine at 2 mg and increase in 2–4 mg increments
201 at midpoint of infusion (3 minutes).
based on patient response]; Tolvaptan, Topotecan,
Ulipristal, Vindesine; Zopiclone [if concomitant use
Dose Adjustment:
cannot be avoided, initiate Zopiclone dose at not more
Heart Transplant Recipients:
than 3.75 mg]
Reduce dose.
Reduces therapeutic effect of Verapamil:
Yohimbine (antihypertensive effect)
Precautions:
Atrial fibrillation or flutter (especially in patients with PSVT
Administration:
and underlying Wolff-Parkinson-White syndrome);
For IV route, administer for over 2 minutes. Administer
Cardiovascular events (e.g. cardiac arrest, fatal and
for over 3 minutes in older patients.
nonfatal, myocardial infarction, cerebrovascular
accident, hemorrhagic and ischemic, and sustained
For oral route, take with food. Do NOT crush or chew MR
ventricular tachycardia requiring resuscitation;
tablets.
arrhythmia); conduction disturbances (may produce
first-, second-, or third-degree heart block; rare,
Pregnancy Category: C
prolonged episodes of asystole);
Hypertension; Hypotension; Pulmonary artery hypertension
ATC Code: C08DA01
Respiratory disease (dyspnea, bronchoconstriction, and
respiratory compromise have occurred)

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 CARDIOVASCULAR SYSTEM

Hypersensitivity (watch out for dyspnea, pharyngeal edema,

erythema, flushing, rash, or chest discomfort) Rx ATROPINE
Seizures (new-onset or recurrent seizures)
Electrolyte imbalance (correct hypokalemia or Oral: 600 micrograms (as sulfate) (equivalent to 500 mcg
hypomagnesemia prior to use and throughout therapy) atropine)
Heart transplant recipients (use with extreme caution; may Inj.: 1 mg/mL (as sulfate), 1 mL ampule (IM, IV, SC)
cause prolonged asystole)
Elderly (may be at increased risk of hemodynamic effects, An alkaloid from Atropa belladonna that competitively
bradycardia, and/or AV block; may be more sensitive to blocks acetylcholine action in central and peripheral
C

the effects of Adenosine) muscarinic autonomic receptors.

Lactation (not known if excreted in breastmilk; potential for
adverse reactions in the nursing infant) Indications: Adjunct chronotropic agent; bradycardia

Adverse Drug Reactions: Dose:

Common: Cardiac arrhythmia, chest pressure and Bradycardia, by IV injection, ADULT, 0.5 mg every 3-5
discomfort, atrioventricular block, depression of ST minutes (maximum dose, 3 mg or 0.04 mg/kg);
segment on ECG, hypotension, chest pain, palpitations, ADOLESCENT, CHILD, and INFANT, 0.02 mg/kg
headache, dizziness, nervousness, paresthesia, (maximum single dose, 0.5 mg); may repeat once in 3-5
numbness, apprehension, facial flushing, diaphoresis, minutes (maximum total dose, 1 mg).
gastrointestinal distress, nausea, neck discomfort, upper Stress echocardiography (adjunct chronotropic agent), by IV
extremity discomfort, dyspnea, hyperventilation injection, ADULT, 0.25–0.5 mg up to a total dose of 1–2
Less Common: Asystole (prolonged), atrial fibrillation, mg until 85% of target heart rate is achieved.
blurred vision, bradycardia, bronchospasm, burning
sensation, cardiac arrest (fatal and nonfatal), increased NOTE: May be ineffective in heart transplant recipients.
intracranial pressure, injection site reaction, loss of Use in children at doses <0.1 mg have been associated
consciousness, metallic taste, myocardial infarction, with paradoxical bradycardia.
respiratory arrest, seizure, torsade de pointes, transient
hypertension, ventricular arrhythmia, ventricular Administration: Administer undiluted by rapid IV injection.
fibrillation, ventricular tachycardia Slow injection may result in paradoxical bradycardia.

Drug Interactions: See Atropine under Drugs for Functional Gastrointestinal

Monitor closely with: Disorders – Anticholinergics in Chapter 1: Alimentary
Enhances therapeutic effect of Adenosine: Tract and Metabolism for other information.
Nicotine (AV-blocking and tachycardic effects)
Pregnancy Category: B/C (product-specific)
Increases risk for adverse or toxic effects of Adenosine:
Digoxin ATC Code: Not available

Avoid concomitant use with:

Increases risk of adverse or toxic effects of Adenosine:
Carbamazepine (risk of higher degree heart block), Rx MAGNESIUM SULFATE
Dipyridamole (cardiovascular effects)
Inj.: 250 mg/mL (as heptahydrate), 2 mL and 10 mL
Reduces therapeutic effect of Adenosine: ampule (IV)
Caffeine and Caffeine-containing Products, Theophylline 250 mg/mL (as heptahydrate), 10 mL, 20 mL, and 50
Derivatives e.g Aminophylline mL vial (IV)
500 mg/mL (as heptahydrate), 2 mL and 10 mL
Administration: Administer via rapid bolus IV or IV infusion ampule (IV)
only.
Indication: Ventricular arrhythmia
Administer IV push over 1–2 seconds via a peripheral IV
site as proximal as possible to trunk. Do NOT inject into Dose:
the lower arm, hand, lower leg, or foot. Follow each bolus NOTE: Individualize dose based on patient requirement and
with a rapid normal saline flush. Use separate syringes response. Discontinue as soon as desired response is
for Adenosine and NS flush, connected to a T-connector obtained.
or stopcock.
Torsade de pointes, ventricular fibrillation, or pulseless
Pregnancy Category: C ventricular tachycardia associated with torsade de
pointes, by IV injection, ADULT, 1–2 g over 15 minutes.
ATC Code: C01EB10
Dose Adjustment:
Geriatric:
Use with caution. Reduce dose of magnesium sulfate.
Renal Impairment:
Use with caution. Up to 50% of an IV dose may be eliminated
in the urine.

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CARDIOVASCULAR SYSTEM

Reduce dose. Do not exceed 20 g every 48 hours. Dose Adjustment:

Heart Failure:
Administration: For intravenous use. May be administered Reduce doses to minimize adverse effects (maximum dose,
via IV push, IVPB, or continuous IV infusion. 20 micrograms/kg per minute).

Do NOT administer at doses exceeding 20%. Precautions:

Arrhythmias (e.g. ventricular arrhythmias and sudden
For IV push, do NOT administer faster than 150 cardiac death; may increase ventricular response rate)
mg/minute. Administer over 1–2 minutes in patients Blood pressure effects (increase in blood pressure is more

C
with persistent pulseless VT or VF with known common due to augmented cardiac output; may also
hypomagnesemia. Administer over 15 minutes in cause hypotension due to peripheral vasodilation)
patients with torsade de pointes. Heart failure complications (increased risk of hospitalization
and death with prolonged use)
If patient is severely symptomatic, or has conditions such Tachycardia and ventricular ectopy (dose-related)
as preeclampsia or eclampsia, more aggressive therapy Aortic stenosis (renders therapy ineffective); electrolyte
(≤4 g over 4–5 minutes) may be required. imbalance (correct hypokalemia or hypomagnesemia
prior to use and throughout therapy to minimize the risk
See Magnesium Sulfate under I.V. Solutions Additives in of arrhythmias); hypovolemia; active myocardial
Chapter 2: Blood and Blood Forming Organs for other ischemia or recent myocardial infarction (can increase
information. myocardial oxygen demand)
Lactation (not known if excreted in breastmilk; use with
Pregnancy Category: D caution in nursing women)

ATC Code: Not available Adverse Drug Reactions:

Common: Ventricular premature contractions, angina
pectoris, chest pain, palpitations, hypotension,
CARDIAC STIMULANTS, EXCLUDING increased blood pressure, increased heart rate, localized
CARDIAC GLYCOSIDES phlebitis, ventricular ectopy (increased), headache,
paresthesia, nausea, local inflammation, local pain (from
infiltration), leg cramps, dyspnea, fever
Rx DOBUTAMINE Rare: Skin necrosis, thrombocytopenia

Drug Interactions:
Inj.: 50 mg/mL (concentrate, as hydrochloride), 5 mL Monitor closely with:
ampule (IV infusion) Decreases metabolism of Dobutamine:
2 mg/mL (as hydrochloride), 250 mL D5W (pre-mixed) COMT Inhibitors e.g. Entacapone
(IV)
Enhances therapeutic effect (hypertensive and tachycardic
A racemic mixture of dobutamine. It stimulates myocardial effects) of Dobutamine:
beta1­adrenergic receptors and some alpha1-receptors. Atomoxetine, Tedizolid
This results in increased contractility and heart rate, and
some peripheral vasodilation. Increases risk of adverse or toxic effects of the following
drugs:
Indications: For management of cardiogenic or vascular Doxofylline, Other Sympathomimetics
shock; inotropic agent; cardiac decompensation
Reduces therapeutic effect of Dobutamine:
Contraindications: Hypertrophic cardiomyopathy with Calcium Salts
outflow tract obstruction (formerly known as idiopathic
hypertrophic subaortic stenosis [IHSS]) Avoid concomitant use with:
Enhances therapeutic effect of Dobutamine:
Dose: Linezolid (hypertensive effect)
Immediate post­cardiac arrest care setting, based on Adult
Advanced Cardiovascular Life Support (ACLS) guidelines, Administration: For IV administration. Always administer via
by IV infusion, ADULT, initially 5–10 micrograms/kg per infusion device into a large vein.
minute; titrate to effect.
Cardiac output maintenance and post-resuscitation Pregnancy Category: B
stabilization, based on Pediatric Advanced Life Support
(PALS) guidelines, by IV injection, CHILD, 2–20 ATC Code: C01CA07
micrograms/kg per minute.
Cardiac decompensation, by IV infusion, ADULT, initially
0.5–1 micrograms/kg per minute; may initiate at higher
doses, e.g., 2.5 micrograms/kg per minute, depending
on severity of decompensation with titration to desired
response (maintenance dose, 2–20 micrograms/kg per
minute; maximum dose, 40 micrograms/kg per minute).

105
 CARDIOVASCULAR SYSTEM

(may reduce effectiveness and/or increase incidence of

Rx DOPAMINE adverse effects of dopamine)
Pulmonary hypertension (may be worsened due to
Inj.: 40 mg/mL (as hydrochloride), 5 mL vial / ampule (IV) dopamine-induced pulmonary vasoconstriction);
800 micrograms/mL (as hydrochloride), 250 mL D5W suppresses pituitary secretion of thyroid-stimulating
(pre-mixed) (IV) hormone, growth hormone and prolactin
1.6 mg/mL (as hydrochloride), 250 mL D5W (pre- Elderly; Pregnancy (limited human data available)
mixed) (IV)
Adverse Drug Reactions:
C

A direct-acting sympathomimetic, which acts on beta1 Common: Anginal pain, chest pain, dyspnea, ectopic beats,
receptors in cardiac muscles, leading to increased flushing, headache, hypotension with dizziness, nausea,
contractility with little effect on rate. Dopamine may be palpitations, peripheral vasoconstriction, vomiting,
given for short periods in the treatment of severe heart tachycardia
failure; it also causes renal vasodilation, thus preserving Less Common: Abnormal ventricular conduction,
renal perfusion and renal function. It also has peripheral bradycardia, extravasation (may cause necrosis and
vasoconstricting properties when given at higher doses. sloughing of surrounding tissue), fainting, gangrene,
hypertension, mydriasis, piloerection, uremia
Indications: Hypovolemic shock and hemorrhagic shock as Rare: Allergic reactions, ventricular arrhythmia
adjuvant therapy to volume replacement; cardiogenic
shock (where systolic BP <90 in adults); septic shock Drug Interactions:
Monitor closely with:
Contraindications: Ischemic heart disease; Enhances therapeutic effect of Dopamine:
tachyarrhythmias, ventricular fibrillation; MAO Inhibitors, e.g., Linezolid, Phenelzine,
pheochromocytoma; hyperthyroidism Tranylcypromine

Dose: Increases risk of adverse or toxic effects of Dopamine:

Hypovolemic and hemorrhagic shock as adjuvant therapy to Phenytoin (hypotension; bradycardia)
volume replacement, by IV infusion into a large vein,
ADULT, initially 5 micrograms/kg per minute, gradually Reduces therapeutic effect of Dopamine:
increase by 5–10 micrograms/kg per minute according Alpha-adrenergic Blocking Agents
to blood pressure, cardiac output, and urine output
(seriously-ill patients, up to 20 micrograms/kg per Avoid concomitant use with:
minute); CHILD, 2–10 micrograms/kg per minute Decreases serum concentration of Dopamine:
depending on patient response. Metoclopramide (inhibits GI absorption)

Dose Adjustment: Increases risk of adverse or toxic effects of Dopamine:

Renal and Hepatic Impairment: Vasoconstrictors, e.g., Ergot Alkaloids (peripheral
For mild-to-moderate impairment, dose reduction may be ischemia)
warranted. Use with caution
For severe impairment, refer patient to a specialist. Reduces therapeutic effect of Dopamine:
Beta-adrenergic Blocking Agents, e.g., Propranolol,
Precautions: Metoprolol (cardiac effects); Chlorpromazine
WARNING: This may cause peripheral ischemia in (hypertensive effects); Fluphenazine (hypertensive
patients with history of occlusive vascular disease effects); Haloperidol (hypertensive effects);
(e.g., atherosclerosis and Raynaud’s syndrome). In Vasoconstrictors, e.g., Ergot Alkaloids (peripheral
case of extravasation causing peripheral ischemia, vasoconstriction)
use phentolamine for local infiltration.
Administration: Administer via a large vein high up in the
NOTE: Dosage is critical – at low doses, it stimulates limb, preferably the arm, to avoid tissue necrosis.
myocardial contractility and increases cardiac output;
however, higher doses (more than 5 micrograms/kg per Dilute solution, usually to 1.6 or 3.2 mg/mL, in dextrose
minute) cause vasoconstriction, which increases blood 5% or sodium chloride 0.9% before administration. Pre-
pressure and may also cause worsening of heart failure. mixed dopamine solution is also available in
single/double concentration.
Close monitoring of arterial and venous pressure and
continuous ECG should be performed; treatment with Do NOT admix with alkaline solutions, such as sodium
sympathomimetics should be guided by hemodynamic bicarbonate to prevent drug inactivation.
monitoring (individualize treatment depending on clinical
response); use low dose in cardiogenic shock due to MI; Pregnancy Category: C
prolonged use of sympathomimetics may result in
diminution of therapeutic effect (downregulation of ATC Code: C01CA04
receptors; disproportionate increase in diastolic
pressure)
Correct hypovolemia before treatment and maintain blood
volume during treatment; correct hypoxia, hypercapnia,
and metabolic acidosis before or at the start of treatment

106
CARDIOVASCULAR SYSTEM

ischemia and necrosis (at infusion site), pulmonary

Rx EPINEPHRINE (ADRENALINE) edema, ventricular arrhythmias
Rare: Allergic reactions
Inj.: 1 mg/mL (as hydrochloride), 1 mL ampule (IV, IM, SC)
0.3 mg auto-injector (IM-preload), 0.3 mL preloaded Drug Interactions:
injection pen NOTE: Alpha-adrenergic blockers antagonize
vasoconstricting and hypertensive effects of
A direct-acting, mixed alpha- and beta-adrenoceptor epinephrine.
agonist; a sympathomimetic catecholamine, which is a

C
potent cardiac stimulant, peripheral vasoconstrictor and Monitor closely with:
bronchodilator. Increases therapeutic effect of Epinephrine:
Tricyclic Antidepressants (blocks catecholamine uptake)
NOTE: Vasodilator at low dose (beta2-receptors).
Vasoconstrictor at high dose (alpha-receptors). Increases risk of adverse or toxic effects of Epinephrine:
Drugs causing Potassium loss, [e.g., Corticosteroids,
Indications: Management of anaphylactic shock; may be Potassium-depleting Diuretics, Aminophylline,
used in cases of serious and fatal anaphylaxis; cardiac Theophylline (hypokalemia)], Oxytocin (hypertension),
arrest Tricyclic Antidepressants (arrhythmia)

Contraindications: Known hypersensitivity to epinephrine or Reverses therapeutic effect of Epinephrine:

any of the excipients; pheochromocytoma; use in local Ergot Alkaloids (pressor effect)
anesthesia of fingers, toes, ears, nose or genitalia;
shock; organic heart disease or cardiac dilatation; Avoid concomitant use with:
closed-angle glaucoma; labor Increases risk of adverse or toxic effects of Epinephrine:
Beta Blockers (hypertension followed by bradycardia)
NOTE: There are no absolute contraindications to the use of
epinephrine in life-threatening allergic reactions. Reduces therapeutic effect of Epinephrine:
Alpha Blockers (vasoconstricting and hypertensive
Dose: effects), Beta Blockers (prevents receptor activation)
Anaphylaxis, by IM or SC injection of 1:1,000 injection,
ADULT and ADOLESCENT, 500 micrograms (0.5 mL); Reduces therapeutic effect of Hypoglycemic Agents (loss of
CHILD 6–12 years, 250 micrograms (0.25 mL); CHILD 6 blood sugar control)
months to 6 years, 120 micrograms (0.12 mL); INFANT
<6 months, 50 micrograms (0.05 mL); by SC injection of Administration: Best administered by SC or IM injection into
1:1,000 injection, CHILD, 10 micrograms/kg (0.01 the anterolateral aspect of the middle third of the thigh
mL/kg), repeat if necessary at intervals of 20 minutes to for anaphylaxis or by IV injection for cardiac arrest or
4 hours depending on the response of the patient and emergency situations.
the severity of the condition (maximum single dose, 500
micrograms). Administer by slow IV injection only in severely ill patients
when there is doubt about the adequacy of circulation
Dose Adjustment: No information found and absorption from the IM site.

Precautions: Do NOT administer by intracardiac injection.

Cerebrovascular disease (increased risk of peripheral
ischemia or stroke); hypovolemia (correct before using Do NOT mix with alkaline solutions. Discard after 24
epinephrine); acidosis, hypercapnia, or hypoxia (may hours or if solution is discolored or contains precipitate.
reduce effectiveness and increase incidence of adverse
effects); heart diseases, e.g., ischemic heart disease, NOTE: If a central line is used, infusion pump is required. If
heart failure, other arrhythmias (increased risk of given through a peripheral line, each dose should be
arrhythmias, angina, and myocardial ischemia); aortic followed by a flush of 20 mL of IV fluid to ensure delivery
stenosis and hypertrophic cardiomyopathy (may of the drug to the central compartment.
increase outflow obstruction); arrhythmias; pulmonary
Pregnancy Category: C
hypertension (may worsen due to pulmonary
vasoconstriction).
ATC Code: C01CA24
Hyperthyroidism or diabetes mellitus (adverse reactions are
more likely to occur)
Elderly; Pregnancy (use with caution during second stage of
labor).

Adverse Drug Reactions:

Common: Anxiety, dizziness, dyspnea, fear, headache,
hyperglycemia, nausea, pallor, palpitations,
restlessness, sweating, tachycardia, tremor, vomiting,
weakness
Less Common: Angina, cerebral hemorrhage, excessive
increase in blood pressure, hypertension, peripheral

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 CARDIOVASCULAR SYSTEM

Extravasation (extravasation may cause severe ischemic

Rx NOREPINEPHRINE necrosis).
Pregnancy (animal reproduction studies have not been
Inj.: 1 mg/mL (as bitartrate), 2 mL and 4 mL ampule (IV conducted; norepinephrine is an endogenous
infusion) catecholamine and crosses the placenta);
1 mg/mL concentrate solution (as bitartrate), 10 mL Lactation (not known if excreted in breast milk; use with
ampule (IV infusion) caution when administering to nursing women).
2 mg/mL, solution for injection (as bitartrate), 4 mL
ampule Adverse Drug Reactions:
C

Common: Arrhythmias, bradycardia, peripheral ischemia,

A direct-acting, mixed alpha- and beta-adrenoceptor agonist anxiety, headache (transient), skin necrosis, dyspnea,
that stimulates beta1-adrenergic receptors and alpha- respiratory difficulty
adrenergic receptors causing increased contractility and
heart rate, as well as peripheral vasoconstriction. This Drug Interactions:
results in an increased systemic blood pressure and Monitor closely with:
coronary blood flow. Vasoconstricting effects on alpha- Decreases metabolism of Norepinephrine:
receptors are greater than the inotropic and chronotropic COMT Inhibitors e.g., Entacapone
effects on beta receptors.
Enhances therapeutic effect of Norepinephrine:
Indications: For cardiogenic or vascular shock, persists after MAO Inhibitors e.g., Selegeline (hypertensive effect;
adequate fluid volume replacement; severe hypotension; tachycardia)
first-choice vasopressor for the treatment of sepsis and
septic shock in adults Enhances therapeutic effect of the following drugs:
Atomoxetine (hypertensive and tachycardic effects),
Contraindications: Hypotension from hypovolemia except as Droxidopa (hypertensive effect)
an emergency measure to maintain coronary and
cerebral perfusion until volume could be replaced; Increases risk of adverse or toxic effects of the following
mesenteric or peripheral vascular thrombosis (unless drugs:
life-saving procedure); during anesthesia with Doxofylline, Sympathomimetics
cyclopropane or halothane (risk of ventricular
arrhythmias) Reduces diagnostic effect of Ioflupane I123

Dose: Reduces therapeutic effect of Norepinephrine:

NOTE: Norepinephrine dose is stated in terms of its base Alpha Blockers e.g., Phentolamine (vasodilating effect)],
form. Spironolactone (vasoconstricting effect)

Hypotension or shock, by continuous IV infusion, ADULT, Reduces therapeutic effect of Alpha Blockers e.g.,
initially 8-12 micrograms/minute, titrate to desired Phentolamine (vasoconstricting effect)
response (usual maintenance dose, 2–4
micrograms/minute); dosage range varies greatly Avoid concomitant use with:
depending on clinical situation; CHILD, initially 0.05–0.1 Enhances therapeutic effect of Norepinephrine:
micrograms/kg per minute; titrate to desired effect Beta Blockers (vasopressor effect), Ergot Derivatives
(maximum dose, 2 micrograms/kg per minute) [NOTE: If [except Ergoloid Mesylates] (hypertensive and
patient remains hypotensive despite large doses, vasoconstricting effects), Hyaluronidase
evaluate for occult hypovolemia, and provide fluid (vasoconstricting effect), Linezolid (hypertensive effect)
resuscitation as appropriate.] [reduce initial dose], Serotonin / Norepinephrine
Reuptake Inhibitors (tachycardic and vasopressor
effects), Tricyclic Antidepressants e.g., Amitryptilline
Post cardiac arrest care, by continuous IV infusion, ADULT,
(vasopressor effect)
initially 0.1–0.5 micrograms/kg per minute, titrate to
desired response.
Enhances therapeutic effect of Inhalational Anesthetics
e.g., Sevoflurane (arrhythmogenic effect)
Sepsis and septic shock, by continuous IV infusion, ADULT,
0.01–3 micrograms/kg per minute, titrate to desired
Reduces therapeutic effect of Norepinephrine:
response.
Beta Blockers e.g., Propranolol
Dose Adjustment: No information found
Reduces therapeutic effect of Iobenguane I123
Precautions:
Administration: For IV route, administer as a continuous
WARNING: If extravasation occurs, infiltrate the area infusion with the use of an infusion pump. Dilute prior to
with 5–10 mg Phentolamine diluted in 10–15 mL use. Administer via a central line.
of saline using a fine hypodermic needle.
Administer Phentolamine within 12 hours after Do NOT administer alkaline solutions, i.e., sodium
extravasation is noted to prevent sloughing or bicarbonate, through the same IV line as norepinephrine.
necrosis. Inactivation of norepinephrine may occur.

108
CARDIOVASCULAR SYSTEM

EXTRAVASATION MANAGEMENT: Norepinephrine is a Consider dose reduction. Significant accumulation of the

vesicant. Ensure proper needle or catheter placement active metabolites may occur with chronic use.
prior to and during infusion. Infuse into a large vein to Hepatic Impairment:
prevent extravasation. Avoid infusion into leg veins. If Consider dose reduction. Partially metabolized by the liver.
extravasation occurs, stop infusion immediately and
disconnect. Leave cannula or needle in place then gently Precautions:
aspirate extravasated solution. Do NOT flush the line. Long-term therapy (may develop nitrate tolerance;
Remove needle or cannula and elevate extremity. Initiate administer nitrate-free interval daily to prevent
phentolamine or alternative antidote. Apply dry warm tolerance).

C
compresses. Severe hepatic impairment; renal impairment;
hypothyroidism; recent history of MI; malnutrition;
Pregnancy Category: C hypothermia.
Pregnancy (may cross placenta; avoid medication unless
ATC Code: C01CA03 potential benefit outweighs risk).

Adverse Drug Reactions:

VASODILATORS USED IN Common: Dizziness, fainting, flushing, hypotension
CARDIAC DISEASES (including orthostatic hypotension), palpitations,
peripheral edema, tachycardia, throbbing headache
Less Common: Heartburn, hypoxemia, nausea, rash,
Rx ISOSORBIDE DINITRATE (ISDN) rebound angina, syncope, vomiting
Rare: Angle-closure glaucoma
Oral: 10 mg and 20 mg tablet Drug Interactions:
20 mg MR tablet / capsule Monitor closely with:
Sublingual: 5 mg tablet Enhances therapeutic effect of ISDN:
Inj.: 1 mg/mL, 10 mL ampule (IV) Drugs which reduce blood pressure (hypotensive effects)
An organic nitrate vasodilator with better stability in storage Reduces therapeutic effect of ISDN:
than nitroglycerin. It is useful in patients who require Atropine (failure to dissolve under the tongue owing to
nitrates infrequently because of its slower onset of action dry mouth)
but longer duration. Commonly used as a PRN drug.
Avoid concomitant use with:
Indication: Prophylaxis and treatment of angina Increases risk of adverse or toxic effects of ISDN:
Phosphodiesterase Inhibitors [e.g., Sildenafil
Contraindications: Hypotension; hypovolemia; hypertrophic (hypotension; MI)]
obstructive cardiomyopathy; aortic stenosis; cardiac
tamponade; constrictive pericarditis; mitral stenosis; Reduces therapeutic effect of ISDN:
marked anemia; head trauma; cerebral hemorrhage; Antagonism of hypotensive effect: Dexamethasone,
angle-closure glaucoma; GI hypermotility; malabsorption Hydrocortisone Ibuprofen, Oral Contraceptives,
syndrome Prednisolone
Dose: Administration:
Angina, acute attack, by sublingual route, ADULT, 2.5–5 mg, For oral administration, take on an empty stomach ½
repeated every 5–10 minutes as required for 3 doses hour before meals.
[NOTE: Inability to relieve chest pain after 3 doses may signal
acute MI, which will need immediate hospitalization. IV infusion
may be started, while awaiting transfer to the hospital, at 1 For sublingual tablets, sit or lie down before use since
mg/hour and titrated upward to 4 mg/hour.] the tablet may cause dizziness. Place the appropriate
Angina prophylaxis, by mouth, ADULT, dose under the tongue. Do NOT swallow. After the pain
as regular release tablet, initially 5–20 mg 2–3 times has been relieved, the patient may spit out or swallow
daily (maintenance dose, 10–40 mg 2–3 times daily; what is left of the tablet to avoid adverse effects, such as
maximum dose, 240 mg); headache.
as MR tablet, 40–80 mg 1–2 times daily, space twice
daily dose 6 hours apart (maximum dose, 160 mg daily) For IV infusion, mix 10 mL (equivalent to 10 mg) in 90
[NOTE: Provide nitrate-free interval daily (14 hours for regular mL NSS.
release and 18 hours for extended release) to avoid development
of tolerance.] Pregnancy Category: C
Acute angina, prevention before a precipitating activity, by
sublingual route, ADULT, 5–10 mg taken 10 minutes ATC Code: C01DA08
before activity.
Chronic angina, prevention, by mouth, ADULT, 5-20mg
(maintenance 10–40 mg) up to 3 times daily.

Dose Adjustment:
Renal Impairment:

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 CARDIOVASCULAR SYSTEM

ISOSORBIDE MONONITRATE Drug Interactions:

Rx Monitor closely with:
(ISMN)
Enhances therapeutic effect of ISMN:
Antihypertensive effect: Barbiturates e.g., Phenobarbital,
Oral: 40 mg tablet
Molsidomine, Nicorandil; Vasodilatory effect: Ethyl
30 mg and 60 mg MR tablet / capsule
alcohol
An antianginal agent that forms free radical nitric oxide.
Increases risk of adverse or toxic effects of ISMN:
Nitric oxide activates guanylate cyclase in smooth
Dapoxetine (orthostatic hypotension), Other
muscle which leads to smooth muscle relaxation and
C

Antihypertensive Agents
prominent vasodilator effect on the peripheral veins. It
also reduces cardiac oxygen demand by decreasing
Increases risk of adverse or toxic effects of the following
preload and afterload due to its vasodilatory effect. It
drugs:
likewise causes epicardial coronary arteries vasodilation.
Methemoglobinemia: Dapsone, (Topical), Nitric Oxide,
Prilocaine, Sodium Nitrite,
Indication: Prevention of angina pectoris
Orthostatic hypotension: Duloxetine, Levodopa,
Risperidone (hypotensive effect), Rosiglitazone
Contraindications: Hypersensitivity to organic nitrates;
(ischemia)
concurrent use with phosphodiesterase­5 inhibitors
Avoid concomitant use with:
Dose:
Decreases serum concentration of ISMN:
Angina, by mouth, ADULT,
CYP3A4 Inducers, Dabrafenib, Mitotane
as regular release tablet, initially 5–20 mg twice daily,
given 7 hours apart to decrease tolerance development;
Enhances therapeutic effect of ISMN:
patients initiating therapy with 5 mg twice daily should
Phosphodiesterase-5 Inhibitors e.g. Sildenafil
be titrated up to 10 mg twice daily in the first 2–3 days;
(vasodilatory effects)
as MR tablet, initially 30–60 mg once daily in the
morning; titrate upward as needed with at least 3 days
Enhances therapeutic effect of Riociguat (hypotensive
between increases (maximum single daily dose, 240
effect)
mg).
Increases serum concentration of ISMN:
Dose Adjustment:
CYP3A4 Inhibitors, Fusidic Acid (Systemic), Idelalisib,
Geriatric:
Mifepristone, Stiripentol
Start with lowest recommended adult dose. Administer first
dose in a physician's office to observe for maximal
Administration: Do NOT administer around-the-clock.
cardiovascular dynamic effects and adverse effects.
Adjust dose or change medication when reflux
For immediate release tablets, schedule twice daily
esophagitis occurs.
doses 7 hours apart (8 AM and 3 PM).
Precautions:
For MR tablets, administer once daily in the morning
Long-term therapy (may develop tolerance; administer
upon rising with a half-glassful of fluid. Do NOT chew or
nitrate-free interval daily to prevent tolerance)
crush MR tablets. MR tablets that are scored may be
Hypotension or bradycardia (may be accompanied by
split.
paradoxical bradycardia and increased angina pectoris;
increased risk of hypotension; orthostatic hypotension)
Pregnancy Category: B / C (product-specific)
Hypertrophic cardiomyopathy (may reduce preload,
exacerbate obstruction, and cause hypotension or
ATC Code: C01DA14
syncope and/or worsening of heart failure)
Increased intracranial pressure (may worsen clinical
outcomes in patients with neurologic injury)
Lactation (not known if excreted in breastmilk) NITROGLYCERIN
Rx
(GLYCERYL TRINITRATE)
Adverse Drug Reactions:
Common: Angina, flushing, headache, dizziness, fatigue, Inj.: 1 mg/mL, 10 mL and 25 mL ampule (IV infusion)
pain, emotional lability, pruritus, rash, nausea,
abdominal pain, diarrhea, upper respiratory infection, An antianginal agent which releases nitric oxide. Nitric oxide
cough, allergic reaction produces a more prominent vasodilator effect on the
Less Common: Amblyopia, anorexia, anxiety, apoplexy, peripheral veins than arteries. In turn, it reduces cardiac
arrhythmia, asthma, back pain, bradycardia, impaired oxygen demand by decreasing preload and afterload. It
concentration, depression, diaphoresis, dyspepsia, likewise causes epicardial coronary arteries vasodilation.
dyspnea, edema, hypertension or hypotension,
insomnia, MI, muscle cramps, neck pain, nervousness, Indication: Management of unstable angina
nightmares, orthostatic hypotension, pallor, palpitation,
paresthesia, prostatic disorder, restlessness, sinusitis, Contraindications: Concurrent use with PDE­5 Inhibitors or
susurrus aurium, tachycardia, taste disturbance, thirst, Riociguat; hypersensitivity to corn or corn products
tremor, vertigo, vomiting, xerostomia (solutions containing dextrose); constrictive pericarditis;
Rare: Methemoglobinemia pericardial tamponade; restrictive cardiomyopathy;

110
CARDIOVASCULAR SYSTEM

hypotension (SBP <90 mmHg or ≥30 mmHg below Increases risk of adverse or toxic effects of Nitroglycerin:
baseline); marked bradycardia or tachycardia; right Dapoxetine (orthostatic hypotension), Other
ventricular infarction Antihypertensive Agents

Dose: Increases risk of adverse or toxic effects of the following

Angina, by IV infusion, ADULT, 5 micrograms/minute, drugs:
increase by 5 micrograms/minute every 3–5 minutes Methemoglobinemia: Dapsone, (Topical), Nitric Oxide,
until 20 micrograms/minute; if no response at 20 Prilocaine, Sodium Nitrite,
micrograms/minute, may increase dose by 10–20 Orthostatic hypotension: Duloxetine, Levodopa

C
micrograms/minute every 3–5 minutes (maximum dose, Risperidone (hypotensive effect), Rosiglitazone
400 micrograms/minute). (ischemia)
Unstable angina, management, by IV infusion, ADULT,
initially 10 micrograms/minute, increase by 10 Reduces therapeutic effect of Heparin (anticoagulant
micrograms/minute every 3–5 minutes until relief of effect)
symptoms; if no response at 20 micrograms/minute,
may increase by 10 micrograms/minute and later by 20 Avoid concomitant use with:
micrograms/minute. Enhances therapeutic effect of ISMN:
Phosphodiesterase-5 Inhibitors e.g. Sildenafil
NOTE: If nitroglycerin is prescribed, advise the patient to (vasodilatory effects), Ergot Derivatives (vasodilatory
take 1 dose promptly in response to chest pain. effects)

Dose Adjustment: No information found Enhances therapeutic effect of Riociguat (antihypertensive

effects)
Precautions:
Long-term therapy (may develop hemodynamic and Increases serum concentration of Ergot Derivatives
antianginal tolerance; administer 10–12 hours nitrate-
free interval daily to prevent tolerance; gradually Administration: For IV administration, administer via
decrease dose to avoid withdrawal reaction). infusion pumps.
Headache (dose-related; may occur during initial dosing);
increased intracranial pressure (may precipitate or Prepare in glass bottles, EXCEL, or PAB containers.
aggravate increased intracranial pressure; may worsen Adsorption occurs to soft plastic (e.g., PVC). Use
clinical outcomes in patients with neurologic injury). administration sets intended for nitroglycerin.
Hypotension or bradycardia (severe hypotension and
orthostatic hypotension can occur; paradoxical Prepare a 100 micrograms/mL solution by withdrawing
bradycardia and increased angina pectoris can 25 mL D5W from a 250-mL bottle of D5W and replace
accompany hypotension) this volume with 25 mg (25 mL) of nitroglycerin.
Hypertrophic cardiomyopathy (may reduce preload,
exacerbating obstruction and cause hypotension or Prepare a 200 micrograms/mL solution by withdrawing
syncope and/or worsening of heart failure). 50 mL D5W from a 250-mL bottle of D5W and replace
Elderly (hypotension is enhanced due to decreased volume with 50 mg (50 mL) of nitroglycerin.
baroreceptor response, decreased venous tone,
hypovolemia, or other hypotensive drugs). Pregnancy Category: B / C (product-specific)
Lactation (not known if excreted in breastmilk; limited
information available; use with caution when ATC Code: C01DA02
administering to nursing women).

Adverse Drug Reactions: OTHER CARDIAC PREPARATIONS

Common: Bradycardia, flushing, hypotension, orthostatic
hypotension, peripheral edema, syncope, tachycardia,
headache, dizziness, lightheadedness, nausea, Rx TRIMETAZIDINE
vomiting, xerostomia, paresthesia, weakness, dyspnea,
pharyngitis, rhinitis, diaphoresis Oral: 35 mg tablet (as hydrochloride)
Less Common: Allergic reactions, anaphylactoid reaction,
blurred vision, cardiovascular collapse, crescendo A fatty acid oxidation (pFOX) inhibitor that exerts antianginal
angina, exfoliative dermatitis, pallor, palpitation, rash, and anti-ischemic effects by altering metabolism to
rebound hypertension, restlessness, shock, vertigo maintain intracellular ATP levels in ischemic regions
Rare: Methemoglobinemia without changing hemodynamic parameters.
Drug Interactions: Indication: Adjunctive treatment of symptomatic stable
Monitor closely with: angina
Enhances therapeutic effect of Nitroglycerin:
Antihypertensive effects: Alfuzosin, Barbiturates e.g. NOTE: NOT recommended as treatment for angina attacks
Phenobarbital, Molsidomine, Nicorandil or for use as initial treatment during acute coronary
syndrome.
Vasodilatory effect: Ethyl alcohol

111
 CARDIOVASCULAR SYSTEM

Contraindications: Parkinson disease; parkinsonian

symptoms; tremors, restless leg syndrome (RLS), or ANTIHYPERTENSIVES
other movement disorders; severe renal impairment
(CrCl <30 mL/minute)
AGENTS ACTING ON ARTERIOLAR
Dose: SMOOTH MUSCLE
Adjunct in treatment of symptomatic stable angina, by
mouth, ADULT, initially 20 mg 3 times daily (maximum
dose, 20 mg 3 times daily).
C

Rx HYDRALAZINE
NOTE: Discontinue treatment if lack of significant
antianginal response within 3 months of initiation. Oral: 25 mg and 50 mg tablet (as hydrochloride)
Inj.: 20 mg/mL (as hydrochloride), 1 mL ampule (IM, IV)
Dose Adjustment:
Renal Impairment: A direct vasodilator of arterioles with little effect on veins
In patients with CrCl of 30–60 mL/minute, initial and and decreased systemic resistance.
maximum dose is 20 mg twice daily.
In patients with CrCl <30 mL/minute, use is Indication: Management of moderate to severe
contraindicated. hypertension
Hepatic Impairment:
Use in hepatic impairment has not been studied. Contraindications: Mitral valve rheumatic heart disease
Precautions: Dose:
Extrapyramidal symptoms (new-onset or worsening of Hypertension, by mouth, ADULT, initially 10 mg 4 times daily
parkinsonian symptoms have been reported) for the first 2–4 days; increase to 25 mg 4 times daily for
Renal impairment (elimination is primarily renal; use with the rest of the first week; further increase gradually by
caution in mild renal impairment). 10–25 mg/dose every 2–5 days to 50 mg 4 times daily
Elderly (decreased renal function has been observed with (maximum dose, 300 mg daily in divided doses); CHILD,
increased Trimetazidine exposure; induced gait initially 0.75–1 mg/kg daily in 2–4 divided doses;
disturbances and/or hypotension may increase fall risk). increase over 3–4 weeks up to 7.5 mg/kg daily in 2–4
Lactation (not known if excreted in breastmilk; divided doses (maximum daily dose, 200 mg daily).
breast­feeding is not recommended). Acute hypertension, by IM or IV injection, CHILD, 0.1 to 0.2
mg/kg per dose every 4–6 hours as needed (maximum
Adverse Drug Reactions: dose, 20 mg), up to 1.7–3.5 mg/kg daily in 4–6 divided
Common: Dizziness, headache, pruritus, rash, urticaria, doses.
abdominal pain, diarrhea, dyspepsia, nausea, vomiting, Hypertensive emergency, by IM or IV injection, ADULT, 10–
weakness 20 mg every 4–6 hours as needed. [NOTE: NOT
Less Common: Acute generalized exanthematous recommended due to unpredictable and prolonged
pustulosis (AGEP), agranulocytosis, angioedema, antihypertensive effects.]
constipation, drowsiness, flushing, gait instability, Hypertensive emergency in pregnancy with systolic BP ≥160
extrasystoles, hepatitis, hypotension, insomnia, mmHg or diastolic BP ≥110 mmHg, by IM or IV injection,
movement disorders, palpitations, Parkinsonian ADULT, initially 5 or 10 mg, may repeat dose in 20–40
symptoms (tremor, akinesia, hypertonia), restless leg minutes with 5–10 mg if blood pressure continues to
syndrome (RLS), tachycardia, thrombocytopenia, exceed thresholds (maximum total cumulative dose, 20
thrombocytopenic purpura mg IV or 30 mg IM); after the initial dose, may initiate a
continuous infusion of 0.5–10 mg/hour instead of
Drug Interactions: intermittent dosing.
Avoid concomitant use with: Perioperative hypertension, by IV injection, ADULT, 3 to 20
Increases risk of adverse or toxic effects of Trimetazidine: mg every 20–60 minutes as needed. [NOTE: Lower end of
Metoclopramide (extrapyramidal symptoms) dosing range is preferred in the immediate perioperative period
and in patients with renal failure. Avoid use in perioperative
Administration: To be taken with food. hypertension, especially in patients with ischemic heart disease,
aortic dissection, or an intracranial process due to unpredictable
and prolonged antihypertensive effects.]
Pregnancy Category: C

ATC Code: C01EB15 Dose Adjustment:

Geriatric:
Use lower initial doses within the recommended dosage
range.

Renal Impairment:
For patients with CrCl of 10–50 mL/minute, administer
every 8 hours.
For patients with CrCl <10 mL/minute, administer every 8–
16 hours in fast acetylators and every 12–24 hours in
slow acetylators.

112
CARDIOVASCULAR SYSTEM

Precautions: TEST INTERACTION. Produces a positive direct Coombs’ Test,

Drug-induced lupus-like syndrome (dose-related); fluid or interfering with blood cross-matching.
sodium retention (drug-induced; may require addition or
increased dose of a diuretic); peripheral neuritis Administration: Food enhances bioavailability when taken
(associated with paresthesia, numbness, and tingling, orally. Administer consistently with regard to meals.
possibly due to an anti-pyridoxine effect).
Cardiovascular disease (increase in tachycardia may For IV route, administer as a slow IV push with a
increase myocardial oxygen demand); pulmonary maximum rate of 5 mg/minute.
hypertension (may cause hypotension); renal

C
impairment; hepatic impairment (undergoes extensive Pregnancy Category: C
hepatic metabolism).
Elderly. ATC Code: C02DB02
Pregnancy (crosses the placenta; may cause adverse
events); lactation (excreted into breastmilk; use with
caution in nursing mothers). NITROGLYCERIN
Rx
(GLYCERYL TRINITRATE)
Adverse Drug Reactions:
Common: Angina pectoris, flushing, orthostatic Inj.: 1 mg/mL, 10 mL and 25 mL ampule (IV)
hypotension, palpitations, paradoxical hypertension,
peripheral edema, tachycardia, vascular collapse, An antianginal agent that forms free radical nitric oxide,
anxiety, chills, depression, disorientation, dizziness, which activates guanylate cyclase in smooth muscle,
fever, headache, increased intracranial pressure, increasing cGMP, leading to dephosphorylation of
psychotic reaction, pruritus, rash, urticaria, anorexia, myosin light chains and smooth muscle relaxation. It
constipation, diarrhea, nausea, paralytic ileus, vomiting, produces a more prominent vasodilator effect on the
dysuria, impotence, agranulocytosis, eosinophilia, peripheral veins than arteries. It has blood pressure
erythrocyte count reduced, hemoglobin decreased, lowering effects and also reduces cardiac oxygen
hemolytic anemia, leukopenia, muscle cramps, demand by decreasing preload and afterload.
peripheral neuritis, rheumatoid arthritis, tremor,
weakness, conjunctivitis, lacrimation, dyspnea, nasal Indication: For coronary artery disease
congestion
Less Common: Diaphoresis, drug-induced lupus-like Dose:
syndrome, fever, arthralgia, splenomegaly, Coronary artery disease, by IV injection, ADULT, 5
lymphadenopathy, asthenia, myalgia, malaise, pleuritic micrograms/minute, increase by 5 micrograms/minute
chest pain, edema, positive ANA and LE cells, every 3–5 minutes until 20 micrograms/minute; if no
maculopapular facial rash, positive direct Coombs' test, response at 20 micrograms/minute, may increase dose
pericarditis, pericardial tamponade by 10-20 micrograms/minute every 3–5 minutes
Rare: Thrombocytopenia (maximum dose, 400 micrograms/minute).

Drug Interactions: See Nitroglycerin (Glyceryl Trinitrate) under Cardiac Therapy

Monitor closely with: – Vasodilators used in Cardiac Disease in Chapter 3:
Enhances antihypertensive effect of Hydralazine: Cardiovascular System for other information.
Alfuzosin, Barbiturates, Brimonidine (Topical), Diazoxide,
Herbs with hypotensive properties, Other Pregnancy Category: B / C (product-specific)
Antihypertensive Agents, Molsidomine, Nicorandil,
Pentoxifylline, Phosphodiesterase-5 Inhibitors, ATC Code: Not available
Prostacyclin Analogues

Increases risk of adverse or toxic effects of Hydralazine:

Orthostatic hypotension: Dapoxetine, Duloxetine, Other Rx SODIUM NITROPRUSSIDE
Antihypertensive Agents, Levodopa, MAO Inhibitors
[except Linezolid, Tedizolid] Inj.: 50 mg powder, ampule (IV infusion)
Increases risk of adverse or toxic effects of Risperidone A direct, short-acting vasodilating agent that acts directly on
(hypotensive effect) the venous and arteriolar smooth muscle causing
peripheral vasodilation. It does not affect other smooth
Reduces antihypertensive effect of Hydralazine: muscle tissue, such as the uterus or duodenum, and has
Methylphenidate, Nonsteroidal Anti-Inflammatory Agents no direct effect on vasomotor centers, sympathetic
e.g., Ibuprofen nerves, or adrenergic receptors.
Avoid concomitant use with: Indications: Management of hypertensive crisis; heart
Increases risk of adverse or toxic effects of the following failure and low-output syndromes; for controlled
drugs: hypotension during anesthesia
Hypotensive effect: Amifostine, Obinutuzumab,
Rituximab Contraindications: Inadequate cerebral circulation; use
during emergency surgery in patients near death;

113
 CARDIOVASCULAR SYSTEM

compensatory hypertension; congenital (Leber’s) optic Less Common: Angina, myocardial infarction, ataxia,
atrophy; tobacco amblyopia seizures, stroke, tinnitus, miosis, confusion,
hyperreflexia, nausea, retching, vomiting, nasal
Dose: stuffiness, diaphoresis, apprehension, headache,
Hypertensive crises, by IV infusion, ADULT and CHILD, 0.1– restlessness, muscle twitching, retrosternal discomfort,
10 micrograms/kg per minute (usual dose, 3 palpitation, dizziness, abdominal pain or cramps,
micrograms/kg per minute); start infusion at 0.25–0.3 bradycardia, tachycardia, ECG changes, rash, decreased
micrograms/kg per minute and gradually increase every platelet aggregation, ileus, increased intracranial
few minutes until adequate blood pressure control is pressure, flushing, venous streaking, irritation at the site
C

achieved (maximum rate, 10 micrograms/kg per of injection

minute); if well-tolerated, gradually reduce dose toward Rare: Methemoglobinemia, cyanosis, hyperthyroidism
normal in the next 24–48 hours.
Acute severe hypertension associated with preeclampsia, Drug Interactions:
by IV infusion, ADULT, 0.25 micrograms/kg per minute Monitor closely with:
(maximum dose, 5 micrograms/kg per minute) Enhances therapeutic effect of Alteplase (prolongs
fibrinolytic activity)
NOTE: Do NOT exceed 10 micrograms/kg per minute to
avoid excessive thiocyanate accumulation and to Avoid concomitant use with:
decrease the possibility of a precipitous drop in blood Increases risk of adverse or toxic effects of Sodium
pressure. Discontinue immediately if blood pressure is Nitroprusside:
not adequately controlled within 10 minutes following an Phosphodiesterase Inhibitors e.g., Sildenafil (severe
IV infusion of 10 micrograms/kg per minute. hypertension)

Replace with longer-acting antihypertensive agents as Enhances therapeutic effect of Sodium Nitroprusside:
soon as possible to minimize the duration of sodium Additive hypotensive effects: Antihypertensives,
nitroprusside therapy. Circulatory Depressants, Ganglionic-blocking Agents,
General Anesthetics, Negative Inotropic Agents
Dose Adjustment:
Renal Impairment: Administration: Administer by IV infusion only using a
For anuric patients, prolonged infusions should not exceed controlled-infusion device, micro-drip regulator, or
1 microgram/kg per minute to maintain <60 similar device that will allow precise measurement of the
micrograms/mL thiocyanate concentration. flow rate.

Precautions: Dilute concentrate prior to IV infusion. One vial

WARNING: Infusions at rates exceeding 2 containing 50 mg of the drug should be diluted in 250–
micrograms/kg per minute generate cyanogen 1,000 mL of 5% dextrose injection.
(cyanide radical) in amounts greater than can be Inspect visually for particulate matter and discoloration
effectively buffered by normally present prior to administration. The freshly prepared infusion
methemoglobin, which can result to cyanogen solution has a very faint brownish tint. Discard highly
toxicity. colored solutions or solutions containing particulate
matter.
Hypotension; cyanogenic effects (toxic effects may be rapid, For single use only. Do NOT add other drugs to the
serious, and possibly fatal; may manifest as venous infusion fluid for simultaneous administration.
hyperoxemia, lactic acidosis, air hunger, confusion, and
death) Sodium nitroprusside infusions at the maximum
Methemoglobinemia; thiocyanate accumulation (monitor recommended infusion rate of 10 micrograms/kg per
for manifestations of thiocyanate). minute should NEVER last longer than 10 minutes.
Cyanogen or low plasma vitamin B12 concentrations Immediately discontinue infusion if blood pressure has
Renal and hepatic impairment (use with caution; cyanide not been adequately controlled after 10 minutes.
may accumulate); hypothyroidism; hyponatremia;
ischemic heart disease. Protect from light by promptly wrapping the containers in
Increased intracranial pressure (use with extreme caution in aluminum foil or other opaque material. It is not
patients with preexisting increased intracranial necessary to cover the infusion drip chamber or IV
pressure); pulmonary disease (may reverse hypoxic tubing. If properly protected from light, diluted solutions
pulmonary vasoconstriction, which may exacerbate of the drug are stable for 24 hours.
intrapulmonary shunting, resulting in worsened
hypoxemia). Avoid extravasation. Adjust rate of administration to
Pregnancy (effects are unknown); lactation (not known if maintain the desired hypotensive effect based on
excreted in breastmilk; use with caution in nursing continuous monitoring of blood pressure.
mothers).
NOTE: Administer only when adequate facilities, equipment,
Adverse Drug Reactions: and personnel are available for close monitoring of blood
Common: Profound hypotension, accumulation of cyanogen pressure. The hypotensive effect of sodium nitroprusside
(cyanide radical), metabolic acidosis occurs rapidly and can produce precipitous decreases in

114
CARDIOVASCULAR SYSTEM

blood pressure. The possible sequelae of profound, Neutropenia and agranulocytosis

prolonged hypotension are serious. Obstructive sleep apnea
Surgery (excessive hypotension may occur during
Pregnancy Category: C anesthesia and after surgery)
Hypotension with the first dose, especially in patients on
ATC Code: C02DD01 diuretics, on a low-sodium diet, on dialysis, dehydrated,
or with heart failure.
Concomitant use of diuretics (see notes below)
Concomitant use of statins (increased risk of myopathy;
AGENTS ACTING ON THE

C
limit simvastatin dose to 20 mg daily if used
RENIN-ANGIOTENSIN SYSTEM concurrently).
Elderly (may be more predisposed to first dose hypotension,
hyperkalemia, and renovascular disease)
ACE INHIBITORS, PLAIN Pregnancy (use in first trimester may cause major
congenital malformations; use in second and third
GENERAL INFORMATION trimester may cause fetal renal dysfunction and
oligohydramnios, and subsequently fetal death);
Mode of Action: This drug class acts by inhibiting the lactation (avoid use in the first few weeks after delivery,
Angiotensin-Converting Enzyme (ACE), which produces particularly in preterm infants; risk of profound neonatal
two mechanisms to reduce blood pressure. First, by hypertension).
inhibiting the conversion of Angiotensin I to Angiotensin
II, a potent vasoconstrictor that stimulates the release of NOTE: Initiation of therapy in patients with ischemic heart
norepinephrine. Its other mechanism prevents the disease or cerebrovascular disease warrants close
breakdown of bradykinin, a vasodilator substance. observation due to the potential consequences posed by
falling blood pressure, e.g., MI, stroke. Fluid replacement
Precautions: may restore blood pressure, if needed. Discontinue
therapy if hypotension recurs.
WARNING: Overzealous treatment with ACE inhibitors
may lead to sudden hypotension, renal Concomitant use of ARB or renin inhibitor, e.g., Aliskiren,
insufficiency or failure, or hyperkalemia with the is associated with an increased risk of hypotension,
risk of arrhythmia. hyperkalemia, and renal dysfunction.

Drugs acting directly on the renin-angiotensin USE WITH DIURETICS. Initiate at very low doses to
system can cause injury and death to a developing minimize the risk of very rapid fall in blood pressure in
fetus. When pregnancy is detected, discontinue as volume-depleted patients. Discontinue or significantly
soon as possible. reduce high-dose diuretic therapy, e.g., with furosemide
at doses >80 mg daily, at least 24 hours before starting
NOTE: ACE inhibitors should be initiated with careful clinical enalapril (may not be possible in heart failure due to the
risk of pulmonary edema). If high-dose diuretic therapy
monitoring in those with severe heart failure or those:
cannot be stopped, medical supervision is advised for at
• Receiving multiple or high-dose diuretic therapy
least 2 hours after administration or until blood pressure
• With hypovolemia
is stable.
• With hyponatremia (plasma-sodium concentration <130
mmol/L)
• With hypotension (SBP <90 mmHg)
• With unstable heart failure Rx CAPTOPRIL
• Receiving high-dose vasodilator therapy
• Known vascular disease
Oral: 25 mg and 50 mg tablet
Cough (dry, hacking, non-productive, which usually occurs
An ACE inhibitor useful in treating hypertension, decreasing
within the first few months of treatment and should
morbidity and mortality in heart failure and left
generally resolve within 1-4 weeks after discontinuation
ventricular dysfunction after myocardial infarction, and
of the ACE inhibitor).
delaying the progress of diabetic nephropathy.
Angioedema (may occur rarely; may involve head and neck,
or the intestine); Peripheral vascular disease or
Indications: Management of mild-to-moderate essential
generalized atherosclerosis (risk of renovascular
hypertension (alone, or with thiazide-diuretic therapy)
disease)
and severe hypertension resistant to other treatment;
Collagen vascular disease (increased risk of
CHF with left ventricular dysfunction following MI;
agranulocytosis)
diabetic nephropathy (microalbuminuria >30 mg/day) in
Severe or symptomatic aortic stenosis (risk of hypotension);
type 1 diabetes
Hypertrophic cardiomyopathy
Renal impairment (increased risk hyperkalemia; may affect
Contraindications: Significant hyperkalemia; hypotension;
the excretion of ACE inhibitors); Hepatic impairment;
significant bilateral renal artery stenosis; angioedema;
jaundice or marked elevations of hepatic enzymes
pregnancy; concurrent use with Aliskiren in patients with
(discontinue use due to risk of hepatic necrosis); Renal
DM or renal impairment
artery stenosis

115
 CARDIOVASCULAR SYSTEM

Dose: Angiotensin II Receptor Blockers e.g., Losartan, Loop

NOTE Titrate dose according to patient's response. Use Diuretics e.g., Furosemide (severe hypotension with the
lowest effective dose. first ACE inhibitor dose), Drugs which reduce blood
pressure (ACE inhibitor-induced renal impairment),
Heart failure, by mouth, ADULT, initially 6.25–12.5 mg 3 Thiazide Diuretics (severe hypotension with the first ACE
times daily in conjunction with cardiac glycoside and inhibitor dose)
diuretic therapy (initial dose depends upon patient's fluid
or electrolyte status); increased at 2-week intervals to Avoid concomitant use with:
25–75 mg twice daily (target dose, 50 mg 3 times daily). Decreases serum concentration of Captopril:
C

Hypertension, by mouth, ADULT, initially 25 mg twice daily, Antacids, e.g., Aluminum or Magnesium Hydroxide
may increase by 12.5–25 mg per dose at 1- to 2-week
intervals up to a total dose of 150 to 200 mg daily in 2 Increases risk of adverse or toxic effects (hyperkalemia) of
divided doses. Captopril:
Hypertensive urgencies, by mouth, ADULT, 25 mg, may Selective and Non-selective NSAIDs, (also renal
repeat as required. impairment); Potassium Supplements; Drugs that cause
LV dysfunction following MI, by mouth, ADULT, initially 6.25 Potassium retention, e.g., Potassium-sparing Diuretics
mg; if tolerated, follow with 12.5 mg 3 times daily; then
increase to 25 mg 3 times daily during next several days Reduces therapeutic effect of Captopril:
and then gradually increase over next several weeks to Indomethacin, Selective and Non-Selective NSAIDs,
target dose of 50 mg 3 times daily (some dose schedules Salicylates (other beneficial pharmacodynamic effects
are more aggressive to achieve an increased goal dose desired for the treatment of CHF)
within the first few days of initiation).
Diabetic nephropathy, by mouth, ADULT, initially 25 mg 3 Administration: Take on an empty stomach.
times daily; may be taken with other antihypertensive
therapy if required to further lower blood pressure. Patient may feel dizzy when taking this medicine. Advise
the patient to get up gradually from sitting or lying
Dose Adjustment: position to minimize this effect, and to sit or lie down if
Geriatric: the patient becomes dizzy or light-headed.
Start treatment with lower doses.
See General Information on Agents Acting on the Renin-
Renal Impairment: Angiotensin System – ACE Inhibitors, Plain in Chapter 3:
For mild-to-moderate renal impairment, dose reduction is Cardiovascular System for information on Warnings and
warranted. Precautions.
For severe impairment, refer patient to a specialist.
Pregnancy Category: C in 1st trimester
Adverse Drug Reactions: D in 2nd & 3rd trimesters
Common: Cough, dizziness, dysgeusia, fatigue, headache,
hyperkalemia, hypersensitivity reactions, hypertension, ATC Code: C09AA01
malaise, nausea, rash
Less Common: Abnormal dreams, anaphylactoid reactions,
angina pectoris, anorexia, chest pain, congestive heart
failure, constipation, diarrhea, dry mouth, elevated Rx ENALAPRIL
hepatic aminotransferases, alkaline phosphatase and
serum bilirubin; fever, flushing, hoarseness, itching, Oral: 5 mg and 20 mg tablet (as maleate)
muscle cramps, MI, pallor, palpitations, Raynaud’s
syndrome, sore throat, stomatitis, tachycardia, taste An oral ACE inhibitor, is converted by hydrolysis in the body
disturbances, urticaria, vomiting to enalaprilat. Its effects are similar with captopril.
Rare: Acute renal failure, bronchospasm, cardiac arrest, Indications: Management of hypertension; heart failure;
cerebrovascular insufficiency, dyspnea, angioedema, acute coronary syndrome; post-myocardial infarction
erythema multiforme, exfoliative dermatitis, maintenance
gynecomastia, hepatitis, hemolytic anemia,
hyponatremia, impotence, neuropathy, myalgia, oliguria, Contraindications: Significant bilateral renal artery stenosis;
orthostatic hypotension, pancreatitis, pancytopenia, renovascular disease; pregnancy; significant
polyuria, proteinuria, psoriasis, renal insufficiency, hyperkalemia; hypotension; history of angioedema (ACEI-
serum sickness-like syndrome, rhythm disturbances, induced, hereditary or idiopathic); concurrent use of
Stevens-Johnson syndrome, syncope, toxic epidermal aliskiren in patients with DM or renal impairment
necrolysis, visceral angioedema
Dose:
Drug Interactions: Heart failure, adjunct or asymptomatic left ventricular
Monitor closely with: dysfunction, by mouth, ADULT, initially 2.5 mg once daily,
Enhances antihypertensive effect of Captopril: increased gradually over 2–4 weeks to 10–20 mg twice
Other antihypertensive agents e.g. diuretics, other drugs daily if tolerated.
which reduce blood pressure Hypertension, by mouth, ADULT, initially 5 mg once daily
(lower dose if used in addition to a diuretic); increased at
Increases risk of adverse or toxic effects of Captopril: intervals of 1–2 weeks up to a total dose of 20 mg daily
in 1 or 2 divided doses; CHILD, refer to a specialist.

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CARDIOVASCULAR SYSTEM

Dose Adjustment: ATC Code: C09AA02

Renal Impairment:
For mild-to-moderate impairment, dose reduction is
warranted. ACE INHIBITORS, COMBINATIONS
For severe impairment, refer patient to a specialist.

Hepatic Impairment: ENALAPRIL +

Rx
For mild-to-moderate impairment, no dose adjustment is HYDROCHLOROTHIAZIDE
needed.

C
For severe impairment, refer patient to a specialist. Oral: 20 mg enalapril + 12.5 mg hydrochlorothiazide tablet

Adverse Drug Reactions: Hydrochlorothiazide increases plasma renin activity,

Common: Blurred vision, cough, depression, dizziness, increases aldosterone secretion, and decreases serum
dyspnea, headache, hyperkalemia, hypertension potassium.
Less Common: Abnormal dreams, alopecia, anaphylactoid Enalapril blocks the renin-angiotensin-aldosterone axis and
reactions, angioedema, anorexia, chest pain, confusion, reverses the potassium loss associated with the diuretic.
diarrhea, drowsiness, dry cough, elevated hepatic
aminotransferases and bilirubin; dry mouth, fatigue, Indication: Treatment of hypertension
fever, flushing, hoarseness, hypotension, impotence,
insomnia, muscle cramps, nausea, nervousness, Contraindications: Hypersensitivity to other sulfonamide-
palpitations, rash, renal impairment, sweating, tinnitus, derived drugs; history of angioedema; idiopathic
urticaria, vertigo angioedema; anuria; diabetes; co-administration with a
Rare: Abdominal pain, agranulocytosis, allergic alveolitis, neprilysin inhibitor
aplastic anemia, arrhythmias, electrolyte disturbances,
exfoliative dermatitis, bronchospasm, GI angioedema, Dose:
gynecomastia, hepatitis, hemolytic anemia, Hypertension, by mouth, ADULT, 10–25 mg enalapril with
hypersensitivity-like reactions, hyponatremia, ileus, liver 12.5–50 mg hydrochlorothiazide daily as a single dose
damage, neuropathy, neutropenia, paresthesia, peptic or in 2 divided doses.
ulcer, pancreatitis, proteinuria, pulmonary infiltrates,
psoriasis, Raynaud’s syndrome, Stevens-Johnson Dose Adjustment:
syndrome, thrombocytopenia, toxic epidermal necrolysis, Renal Impairment:
visceral angioedema, vomiting In patients with severe impairment, use is not
recommended. Loop diuretics are preferred to thiazide
Drug Interactions: diuretics.
Monitor closely with:
Enhances therapeutic effect of Enalapril: Precautions:
Drugs which reduce blood pressure
WARNING: Fetal Toxicity. Drugs acting directly on the
renin-angiotensin system can cause injury and
Increases risk of adverse or toxic effects of Enalapril:
death to the developing fetus. When pregnancy is
Digoxin (cardiac toxicity), Loop Diuretics (profound
detected, discontinue as soon as possible.
diuresis; serious electrolyte disturbance), Potassium-
lowering Drugs (hypokalemia), Salbutamol
(hypokalemia) Hypotension (excessive hypotension and syncope has been
reported; in patients with CHF with or without associated
Avoid concomitant use with: renal insufficiency, excessive hypotension may be
Increases risk of adverse or toxic effects of the following associated with oliguria and/or progressive azotemia).
drugs: Anaphylactoid and related reactions (exacerbation or
Ibuprofen (nephrotoxicity) activation of systemic lupus erythematosus has been
Selective and Non- selective NSAIDs (nephrotoxicity) reported; may be subject to a variety of adverse
reactions, some serious; have been reported in patients
Reduces therapeutic effect of the following drugs: undergoing low-density lipoprotein apheresis with
Lidocaine, Metformin (antagonism of hypoglycemic dextran sulfate absorption).
effect), Selective and non-selective NSAIDs (renal Angioedema (angioedema of the face, extremities, lips,
function, diuretic and hypotensive effect) tongue, glottis, and/or larynx has been reported;
angioedema associated with laryngeal edema may be
Administration: Take once daily in the morning. If to be fatal; intestinal angioedema has been reported
taken twice daily, take the first dose in the morning and presenting with abdominal pain with or without nausea
the second dose before 6 in the evening. or vomiting).
Neutropenia or agranulocytosis (agranulocytosis and bone
See General Information on Agents Acting on the Renin- marrow depression has been reported; consider periodic
Angiotensin System – ACE Inhibitors, Plain in Chapter 3: monitoring of WBC counts).
Cardiovascular System for information on Warnings and Hepatic impairment (associated with a syndrome that starts
Precautions. with cholestatic jaundice and progresses to fulminant
hepatic necrosis, and sometimes, death; may precipitate
Pregnancy Category: B hepatic coma)
Renal disease (may precipitate azotemia).

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 CARDIOVASCULAR SYSTEM

Ophthalmic effects (can cause idiosyncratic reactions; Elderly (may be volume-depleted due to diuretic use and/or
acute myopia and secondary angle-closure glaucoma blunted thirst reflex resulting in inadequate fluid intake).
have been reported). Pregnancy (avoid use unless essential; may adversely affect
fetal and neonatal BP control and renal function)
Adverse Drug Reactions: Lactation (not known if excreted into breastmilk;
Common: Dizziness, headache, fatigue, cough, muscle information is limited).
cramps, nausea, asthenia, orthostatic effects,
impotence, diarrhea NOTE: Concomitant use of an ACE inhibitor or renin inhibitor,
Less Common: Syncope, chest pain, abdominal pain, e.g., Aliskiren, is associated with an increased risk of
C

orthostatic hypotension, palpitation, tachycardia, hypotension, hyperkalemia, and renal dysfunction.

vomiting, dyspepsia, constipation, flatulence, dry mouth,
insomnia, nervousness, paresthesia, somnolence, Drug Interactions:
vertigo, pruritus, rash, dyspnea, gout, back pain, Monitor closely with:
arthralgia, diaphoresis, decreased libido, tinnitus, Decreases metabolism of ARB:
urinary tract infection, angioedema, hypotension, cough Antifungal Agents, e.g., Azole Derivatives, (Systemic),
CYP2C8 Substrates, CYP2C9 Substrates
Administration: Take once daily in the morning. If to be
taken twice daily, take the first dose in the morning and Enhances therapeutic effect (antihypertensive effect) of
the second dose before 6 in the evening. ARB:
Alfuzosin, Barbiturates e.g. Phenobarbital, Brimonidine
See individual monographs for Enalapril under Agents (Topical), Canagliflozin, Diazoxide, MAO Inhibitors
Acting on the Renin-Angiotensin System – ACE [except Linezolid, Tedizolid], Molsidomine, Nicorandil,
Inhibitors, Plain in Chapter 3: Cardiovascular System and NSAIDs, Other Antihypertensive Agents, Pentoxifylline,
Hydrochlorothiazide under Diuretics – Thiazide Diuretics Phosphodiesterase-5 Inhibitors e.g. Sildenafil,
in Chapter 3: Cardiovascular System for other Prostacyclin Analogues e.g. Epoprostenol
information.
Increases risk of adverse or toxic effects of ARB:
Pregnancy Category: D Antifungal Agents, e.g., Azole Derivatives, (Systemic)
Hyperkalemic effect: Canagliflozin, Heparin, Eplerenone,
ATC Code: C09BA02; C03AX01 Nicorandil NSAIDS (also acute renal failure), Tolvaptan,
Trimethoprim
Orthostatic hypotension: Dapoxetine, MAO Inhibitors
ANGIOTENSIN II ANTAGONISTS, PLAIN [except Linezolid, Tedizolid]
First ARB dose hypotension: Loop diuretics, Thiazide
diuretics
GENERAL INFORMATION Other Antihypertensive Agents
Also known as Angiotensin Receptor Blockers (ARB), they
act by blocking the type 1 angiotensin II (AT1) receptors Increases risk of adverse or toxic effects of the following
on blood vessels and other tissues such as the heart, drugs:
which prevents the stimulation of vascular smooth
Ciprofloxacin (systemic) (arrhythmogenic effect),
muscle contraction.
Cyclosporine (systemic) (hyperkalemic effect),
Drospirenone (hyperkalemic effect), Duloxetine
Precautions: (orthostatic hypotension), Levodopa (orthostatic
WARNING: Fetal Toxicity. Drugs acting directly on the hypotension), Risperidone (hypotensive effect)
renin-angiotensin system can cause injury and
death to the developing fetus. When pregnancy is Reduces therapeutic effect of ARB:
detected, discontinue as soon as possible. Methylphenidate, Rifampicin

Peripheral vascular disease (patients may be more likely to Avoid concomitant use with:
have renal artery stenosis) Increases risk of adverse or toxic effects (hyperkalemia) of
Volume or sodium depletion (may activate the renin- ARB:
angiotensin system leading to excessive hypotension) Aliskiren (also hypotensive, and nephrotoxic effects),
Aortic or mitral valve stenosis and hypertrophic Potassium Supplements, Drugs that cause Potassium
cardiomyopathy; angioedema (may occur rarely; may retention, e.g., Potassium-sparing Diuretics,
involve head and neck or the intestine) Spironolactone
Hypotension (symptomatic hypotension may occur upon
initiation in patients who are salt- or volume-depleted); Increases risk of adverse or toxic effects (hypotensive
Heart failure effect) of the following drugs:
Hyperkalemia; renal function deterioration (increased risk ACE Inhibitors e.g. Enalapril, Amifostine [withhold ARB 24
of hyperkalemia); hours prior to Amifostine administration], Obinutuzumab
Hepatic impairment [withhold ARB 12 hours prior to Obinutuzumab infusion
Renal artery stenosis (avoid use in patients with unstented until 1 hour after the end of the infusion], Ramipril,
unilateral or bilateral renal artery stenosis). Rituximab, Sodium Phosphates (also nephrotoxic effect,
Surgical patients (if on chronic ARB therapy, intraoperative specifically acute phosphate nephropathy)
hypotension may occur with induction and maintenance
of general anesthesia).

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CARDIOVASCULAR SYSTEM

Increases serum concentration of the following drugs: See for General Information on Agents Acting on the Renin-
ACE Inhibitors e.g. Enalapril, Amodiaquine, Lithium, Angiotensin System – Angiotensin II Antagonists, Plain in
Ramipril [Ramiprilat] Chapter 3: Cardiovascular System for other information.

NOTE: Dual blockade of the Renin-Angiotensin-Aldosterone Pregnancy Category: D

system, i.e., ARB and ACEI combination, in patients with
established heart failure, atherosclerotic disease, or ATC Code: C09CA04
diabetes with end-organ damage is associated with
higher risk for hypotension, syncope, hyperkalemia, and

C
disordered renal function, including acute renal failure.
Rx LOSARTAN

Oral: 50 mg and 100 mg tablet (as potassium salt)

Rx IRBESARTAN
An angiotensin II type 1 (AT1) receptor blocker whose
Oral: 150 mg and 300 mg tablet efficacy in hypertension is similar to that of ACE
inhibitors, but is associated with a lower incidence of
An angiotensin receptor antagonist that binds to the AT1 side-effects, such as dry cough and angioedema.
angiotensin II receptor. It blocks the vasoconstrictor
effect of angiotensin II, as well as sodium and water Indications: Treatment of hypertension; treatment of
reabsorption which results in a decrease in blood diabetic nephropathy in patients with type 2 diabetes
pressure. mellitus (noninsulin dependent, NIDDM) and a history of
hypertension; risk reduction of stroke in patients with
Indication: Treatment of hypertension alone or in HTN and left ventricular hypertrophy (LVH)
combination with other antihypertensive agents
Contraindication: Concomitant use with aliskiren in patients
Contraindication: Concomitant use with aliskiren in patients with diabetes mellitus
with diabetes mellitus
Dose:
Dose: Hypertension, by mouth, ADULT, usual starting dose, 50 mg
Hypertension, by mouth, ADULT, 150 mg once daily; once daily; can be administered once or twice daily with
patients may be titrated to 300 mg once daily; usual a total daily dose ranging from 25–100 mg (usual initial
dosage range, 150–300 mg daily; target dose, 300 mg dose in patients receiving diuretics, or those with
once daily. intravascular volume depletion: 25 mg once daily).
Nephropathy in type 2 DM and hypertension, by mouth,
Dose Adjustment: ADULT, initial dose, 50 mg once daily; can be increased
Renal Impairment to 100 mg once daily based on BP response.
Use with caution. Dose adjustment is only required if patient Stroke reduction, HTN with LVH, by mouth, ADULT, 50 mg
is volume-depleted. once daily (maximum daily dose, 100 mg); may be in
combination with a thiazide diuretic.
Volume Depletion:
Start dose at 75 mg. Dose Adjustment:
Renal Impairment:
Adverse Drug Reactions: For severe impairment, refer patient to a specialist.
Common: Fatigue, diarrhea, dyspepsia, upper respiratory
infection, cough Hepatic Impairment:
Less Common: Abdominal distension, abnormal urination, For mild-to-moderate hepatic impairment, dose reduction is
angina, angioedema, arrhythmia, arthritis, bronchitis, warranted.
bursitis, cardiopulmonary arrest, cerebrovascular For severe impairment, refer patient to a specialist.
accident, chest pain (noncardiac), chills, congestion,
conjunctivitis, constipation, depression, dermatitis, Adverse Drug Reactions:
dyspnea, ear infection, ear pain, ecchymosis, epistaxis, Common: Dizziness, fatigue, headache, hyperkalemia,
erythema, facial edema, fever, flatulence, flushing, hypoglycemia, nausea, upper respiratory tract infections,
gastroenteritis, gout, hearing abnormality, heart failure, urinary tract infections
hepatitis, hypertension or hypotension, hypertensive Less Common: Abnormal liver function, angina, back pain,
crisis, jaundice, decreased libido, MI, muscle aches, decreased hemoglobin, diarrhea, dyspepsia, dyspnea,
muscle cramps, muscle weakness, numbness, edema, hypotension (first-dose), insomnia, malaise,
orthostatic hypotension, paresthesia, prostate disorder, muscle cramps, myalgia, nasal congestion, palpitation,
pruritus, pulmonary congestion, renal failure, impaired pharyngitis, pruritus, rash, sleep disorders
renal function, sexual dysfunction, sleep disturbance, Rare: Anaphylaxis, anemia, angioedema, atrial fibrillation,
somnolence, thrombocytopenia, TIA, tremor, upper cerebrovascular accidents, cough, depression, erectile
extremity edema, urticaria, vision disturbance, wheezing dysfunction, hepatitis, hyponatremia, pancreatitis,
Rare: Hyperkalemia, anemia, rhabdomyolysis purpura, renal impairment, rhabdomyolysis, syncope,
thrombocytopenia, vasculitis
Administration: May be administered with or without food.
Administration: May be taken with or without food.

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 CARDIOVASCULAR SYSTEM

The patient may feel dizzy when taking this medicine. hypotension, impotence, insomnia , malaise, MI,
Advise patient to get up gradually from sitting or lying migraine, muscle cramps, neoplasm, nervousness,
position to minimize this effect. and sit or lie down if the orthostatic hypotension, palpitation, paresthesia,
patient becomes dizzy or light-headed. pruritus, otitis media, renal dysfunction, renal failure,
rhabdomyolysis, rash, reflux, rhinitis, somnolence,
See for General Information on Agents Acting on the Renin- tachycardia, syncope, tendon pain, tendonitis,
Angiotensin System – Angiotensin II Antagonists, Plain in tenosynovitis, thrombocytopenia, tinnitus, toothache,
Chapter 3: Cardiovascular System for other information. urticaria, vertigo, vomiting, weakness, xerostomia
C

Pregnancy Category: C in 1st trimester; D in 2nd and 3rd Administration: May be administered without regard to
trimesters meals.

ATC Code: C09CA01 NOTE: May contain sorbitol (refer to product labelling prior
to administration in patients with fructose intolerance).

See for General Information on Agents Acting on the Renin-

Rx TELMISARTAN Angiotensin System – Angiotensin II Antagonists, Plain in
Chapter 3: Cardiovascular System for other information.
Oral: 40 mg and 80 mg tablet
Pregnancy Category: D
It blocks the vasoconstriction and the aldosterone secreting
effects of angiotensin II, resulting to a decrease in blood ATC Code: C09CA07
pressure.

Indications: Cardiovascular risk reduction in patients ≥55

years of age unable to take ACE inhibitors and who are
Rx VALSARTAN
at high risk of major cardiovascular events (e.g., MI,
stroke, death); treatment of hypertension, alone or in Oral: 80 mg and 160 mg tablet / film coated tablet
combination with other antihypertensive agents
A direct antagonist of the angiotensin II (AT2) receptors,
Contraindication: Concurrent use of aliskiren in patients displacing angiotensin II from the AT1 receptor. It
with diabetes produces its blood pressure lowering effects by
antagonizing AT1­induced vasoconstriction, aldosterone
Dose: release, catecholamine release, arginine vasopressin
Hypertension, by mouth, ADULT, initially 40 mg once daily; release, water intake, and hypertrophic responses.
usual dosage range, 40–80 mg daily.
Cardiovascular risk reduction, by mouth, ADULT, 80 mg Indications: Treatment of primary hypertension, alone or in
once daily. combination with other antihypertensive agents;
reduction of cardiovascular mortality in left ventricular
Dose Adjustment: dysfunction post-myocardial infarction; treatment of HF,
Hepatic Impairment: NYHA Class II–IV
Initiate therapy at a low dose, then titrate slowly with close
monitoring. Contraindication: Concomitant use with aliskiren in patients
with diabetes mellitus
Volume Depletion:
Initiate at a lower dose with close supervision. Dose:
Hypertension, by mouth, ADULT, initially 80 mg or 160 mg
Adverse Drug Reactions: once daily if not volume-depleted; dose may be
Common: Intermittent claudication, chest pain, increased to achieve desired effect; usual dosage range,
hypertension, peripheral edema, dizziness, fatigue, 80–320 mg daily; target dose, 160–320 mg daily
headache, pain, skin ulcer, diarrhea, abdominal pain, (maximum recommended dose, 320 mg daily); CHILD 6–
dyspepsia, nausea, urinary tract infection, back pain, 16 years, initially 1.3 mg/kg once daily (maximum dose,
myalgia, upper respiratory infection, sinusitis, cough, 40 mg daily); may increase dose to achieve desired
pharyngitis effect.
Less Common: Abnormal ECG, abnormal vision, abscess, Heart failure, by mouth, ADULT, initially 40 mg twice daily,
allergic reaction, anaphylaxis, anemia, angina, titrate dose to 80–160 mg twice daily, as tolerated
angioedema, anxiety, arthralgia, arthritis, asthma, atrial (maximum daily dose, 320 mg).
fibrillation, bradycardia, bronchitis, cerebrovascular Left ventricular dysfunction after MI, by mouth, ADULT,
disorder, CHF, conjunctivitis, constipation, cramps, initially 20 mg twice daily, titrate dose to target of 160
cystitis, depression, dermatitis, diabetes mellitus, mg twice daily as tolerated; may initiate ≥12 hours
diaphoresis, dyspnea, earache, eczema, edema, following MI.
enteritis, epistaxis, erectile dysfunction, erythema, facial
edema, fever, fixed drug eruption, flatulence, flushing, Dose Adjustment:
frequent urination, fungal infection, gastroenteritis, gout, Renal Impairment:
hemorrhoids, hepatic dysfunction, hyperkalemia, Use with caution in patients with CrCl <30 mL/min. Safety
hypersensitivity, hypoglycemia (diabetic patients), and efficacy have not been established.

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CARDIOVASCULAR SYSTEM

Adverse Drug Reactions: 2 weeks (maximum daily dose, 300 mg irbesartan + 25

Common: Hypotension, orthostatic hypotension, syncope, mg hydrochlorothiazide).
dizziness, fatigue, orthostatic dizziness, headache,
vertigo, hyperkalemia, diarrhea, abdominal pain, Dose Adjustment:
nausea, neutropenia, viral infection, arthralgia, back Renal Impairment:
pain, blurred vision, renal insufficiency, cough Use with caution in mild-to-moderate impairment.
Less Common: Alopecia, anaphylaxis, anemia, angioedema, Use is not recommended in severe impairment.
anorexia, anxiety, bullous dermatitis, chest pain,
constipation, drowsiness, dyspepsia, flatulence, Adverse Drug Reactions:

C
hypersensitivity reaction, impotence, insomnia, muscle Common: Edema, chest pain, tachycardia, dizziness,
cramps, myalgia, palpitation, photosensitivity, pruritus, fatigue, nausea, vomiting, abdominal pain, dyspepsia,
renal failure, rhabdomyolysis, skin rash, taste disorder, abnormal urination, musculoskeletal pain, flu-like
paresthesia, vasculitis, vomiting, weakness, xerostomia syndrome
Rare: Hepatitis, thrombocytopenia Less Common: Angioedema, hepatitis, hyperkalemia,
urticaria
Administration: Administer consistently with regard to
meals. Food decreases peak plasma concentration by Administration: Administer with or without food.
50% and extent of absorption by 40%. Avoid salt
substitutes which contain potassium. See individual monographs for Irbesartan and
Hydrochlorothiazide under Agents Acting on the Renin-
NOTE: May contain sorbitol (refer to product labelling prior Angiotensin System – Angiotensin II Antagonists, Plain
to administration in patients with fructose intolerance). and under Diuretics – Thiazide Diuretics, respectively in
Chapter 3: Cardiovascular System for other information.
See for General Information on Agents Acting on the Renin-
Angiotensin System – Angiotensin II Antagonists, Plain in Pregnancy Category: D
Chapter 3: Cardiovascular System for other information.
ATC Code: C09DA04; C03AX01
Pregnancy Category: D

ATC Code: C09CA03 LOSARTAN +

Rx
HYDROCHLOROTHIAZIDE
ANGIOTENSIN II ANTAGONISTS, Oral: 50 mg losartan + 12.5 mg hydrochlorothiazide tablet
COMBINATIONS
Losartan is an angiotensin II type 1 (AT1) receptor blocker
IRBESARTAN + whose efficacy in hypertension is similar to that of ACE
Rx inhibitors but is associated with a lower incidence of side
HYDROCHLOROTHIAZIDE
effects, such as dry cough and angioedema.
Oral: 150 mg irbesartan + 12.5 mg hydrochlorothiazide Hydrochlorothiazide inhibits sodium reabsorption in the
tablet distal tubules causing increased excretion of sodium and
water, as well as potassium and hydrogen ions.
Irbesartan is an angiotensin receptor antagonist that binds
Indications: Treatment of hypertension; to reduce the risk of
to the AT1 angiotensin II receptor, blocking the
vasoconstrictor effect of angiotensin II, as well as sodium stroke in patients with hypertension and left ventricular
and water reabsorption, resulting in a decrease in blood hypertrophy (LVH)
pressure
Hydrochlorothiazide inhibits sodium reabsorption in the Contraindications: Hypersensitivity to sulfonamide-derived
distal tubules causing increased excretion of sodium and drugs ; concomitant use with aliskiren in patients with
diabetes mellitus; anuria
water, as well as potassium and hydrogen ions.
Dose:
Indication: Treatment of hypertension
NOTE: Individualize doses. Combination product may be
Contraindications: Hypersensitivity to sulfonamide-derived substituted for individual components in patients
drugs concomitant use with aliskiren in patients with currently maintained on both agents separately or in
diabetes mellitus; anuria patients not adequately controlled with monotherapy.

Dose: Hypertension, replacement therapy, by mouth, ADULT, 1–2

NOTE: Maximum antihypertensive effects are attained tablets (50–100 mg losartan + 12.5–25 mg
within 2 to 4 weeks after initiation or a change in dose; hydrochlorothiazide) once daily, may titrate dose after
however, if necessary, carefully titrate dose as soon as approximately 3 weeks of therapy as necessary until
after 1 week of treatment. maximum daily dose is reached (maximum daily dose,
100 mg losartan + 25 mg hydrochlorothiazide).
Hypertension, by mouth, ADULT, initially 1 tablet (150 mg Severe hypertension, by mouth, ADULT, initially 1 tablet (50
Irbesartan + 12.5 mg hydrochlorothiazide) once daily; if mg losartan + 12.5 mg hydrochlorothiazide) once daily,
initial response is inadequate, may titrate dose after 1– may titrate dose after 2–4 weeks of therapy as
necessary until maximum daily dose is reached

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 CARDIOVASCULAR SYSTEM

(maximum daily dose, 2 tablets: 100 mg losartan + 25 inhibitors; concomitant use of aliskiren in patients with
mg hydrochlorothiazide). diabetes.
Hypertension with left ventricular hypertrophy, by mouth,
ADULT, 1 tablet (50 mg losartan + 12.5 mg Dose:
hydrochlorothiazide) once daily, may increase to 2 Heart failure, by mouth, ADULT, 100 mg tab twice daily
tablets (100 mg losartan + 12.5 mg hydrochlorothiazide initially, double the dose after 2-4 weeks until target dose
once daily). of 200 mg twice daily as tolerated.

NOTE: Initiate treatment with losartan monotherapy. If blood Dose Adjustment:

C

pressure reduction is inadequate, initiate losartan + Renal impairment:

hydrochlorothiazide combination. Mild to moderate- no dosage adjustment necessary.
Severe- reduce starting dose to 50 mg tab twice daily;
Dose Adjustment: double the dose every 2-4 weeks to target maintenance
Renal Impairment: dose of 200 mg twice daily as tolerated.
In severe impairment (CrCl ≤30 mL/min), use is not
recommended and is ineffective. Hepatic impairment:
Mild- no dosage adjustment necessary.
Hepatic Impairment: Moderate- reduce starting dose to 50 mg tab twice daily;
Use is not recommended as initial therapy. double the dose every 2-4 weeks to target maintenance
dose of 200 mg twice daily as tolerated.
Adverse Drug Reactions: Severe- use not recommended.
Common: Edema, palpitation, dizziness, skin rash,
abdominal pain, back pain, upper respiratory infection, Precautions:
cough, sinusitis May cause angioedema, hyperkalemia, hypotension, renal
Less Common: hypertension or hypotension, hyponatremia, function deterioration; use in caution in patients with
rhabdomyolysis, thrombocytopenia aortic or mitral stenosis, heart failure, hepatic
impairment, renal artery stenosis, and renal impairment.
Administration: May be administered without regard to
meals.
Adverse Drug Reactions:
See individual monographs for Losartan under Agents Common: Hypotension and hyperkalemia.
Acting on the Renin-Angiotensin System – Angiotensin II Less Common: Cough, dizziness, orthostatic hypotension,
Antagonists, Plain in Chapter 3: Cardiovascular System falls, decreased hematocrit and hemoglobin,
and Hydrochlorothiazide under Diuretics – Thiazide angioedema, and renal failure.
Diuretics in Chapter 3: Cardiovascular System for other Rare: Anaphylaxis, hypersensitivity, pruritus, and skin rash.
information.
Drug Interactions:
Pregnancy Category: D Monitor closely with:
Both drugs increase serum potassium:
ATC Code: C09DA01; C03AX01 Aspirin, Atenolol, Betaxolol, Bisoprolol, Candesartan,
Carvedilol, Celecoxib, Diclofenac, Digoxin, Esmolol,
Ibuprofen, Ketorolac, Losartan, Mefenamic Acid,
Naproxen, Potassium Chloride, Potassium Citrate,
Rx SACUBITRIL/VALSARTAN Propranolol, Spironolactone, Succinylcholine,
Telmisartan
Oral: 50 mg, 100 mg and 200 mg tablet
Decreases effects of sacubitril/valsartan:
Sacubitril is a prodrug that inhibits neprilysin leading to Aspirin, Celecoxib, Diclofenac, Ibuprofen, Ketoprofen,
increased natriuretic peptides, which promotes excretion Ketorolac, Mefenamic Acid, Naproxen.
of sodium by the kidneys; valsartan produces direct
antagonism of the angiotensin II receptors preventing Either drug increases the toxicity of the other:
vasoconstriction, aldosterone release, arginine Aspirin, Celecoxib, Diclofenac, Ibuprofen, Ketorolac,
vasopressin release, water intake, and hypertrophic Mefenamic Acid, Naproxen
responses.
Increases effects of sacubitril/valsartan
Indications: Reduce the risk of cardiovascular death and Atorvastatin, Carbamazepine, Carbidopa,
hospitalization for heart failure in patients with chronic Clarithromycin, Daclatasvir, Digoxin, Erythromycin,
heart failure (NYHA Class II-IV) and reduced ejection Levodopa, Paclitaxel, Rifampin, Simvastatin, Tacrolimus
fraction; usually administered in conjunction with other
heart failure therapies, in place of an angiotensin- Increases toxicity of sacubitril/valsartan
converting enzyme (ACE) inhibitor or other angiotensin II Enoxaparin, Heparin
receptor blocker (ARB). Increases the toxicity of the following:
Contraindications: Hypersensitivity to sacubitril, valsartan, Atorvastatin
or any component of the formulation; history of
angioedema related to previous ACE inhibitor or ARB Avoid concomitant use with:
therapy; concomitant use or use within 36 hours of ACE Either increases the toxicity of the other:

122
CARDIOVASCULAR SYSTEM

Captopril, Enalapril, Lithium Adverse Drug Reactions:

Common: Dizziness, fatigue, diarrhea, nausea, upper
Administration: Administer with or without food. respiratory tract infection, sinusitis, flu-like syndrome
Less Common: Abdominal pain, back pain, increased
Pregnancy Category: D bilirubin, bronchitis, dyspepsia, decreased hematocrit
and hemoglobin, hypokalemia, orthostatic hypotension,
ATC Code: C09DX04 pharyngitis, rash, tachycardia, vomiting
Rare: Rhabdomyolysis

C
TELMISARTAN + Administration: May be administered without regard to
Rx meals.
HYDROCHLOROTHIAZIDE
See individual monographs for Telmisartan under Agents
Oral: 40 mg telmisartan + 12.5 mg hydrochlorothiazide
Acting on the Renin-Angiotensin System – Angiotensin II
tablet
Antagonists, Plain in Chapter 3: Cardiovascular System
and Hydrochlorothiazide under Diuretics – Thiazide
Telmisartan is a nonpeptide AT1 angiotensin II receptor
Diuretics in Chapter 3: Cardiovascular System for other
antagonist that binds to the AT1 angiotensin II receptor
information.
preventing angiotensin II binding, thereby blocking the
vasoconstriction and the aldosterone secreting effects of
Pregnancy Category: D
angiotensin II, resulting to a decrease in blood pressure.
Hydrochlorothiazide inhibits sodium reabsorption in the
ATC Code: C09DA07; C03AX01
distal tubules causing increased excretion of sodium and
water, as well as potassium and hydrogen ions.

Indication: Treatment of hypertension VALSARTAN +

Rx
HYDROCHLOROTHIAZIDE
Contraindications: Hypersensitivity to sulfonamide-derived
drugs, or any component of the formulation; concomitant Oral: 80 mg valsartan + 12.5 mg hydrochlorothiazide tablet
use with aliskiren in patients with diabetes mellitus;
anuria Valsartan is a direct antagonist of the angiotensin II (AT1)
receptors, displacing angiotensin II from the AT1
Dose: receptor. It produces its blood pressure-lowering effects
NOTE: Combination product can be substituted for by antagonizing AT1­induced vasoconstriction,
individual titrated agents. Initiation of combination aldosterone release, catecholamine release, arginine
therapy when monotherapy has failed to achieve desired vasopressin release, water intake, and hypertrophic
effects. responses.

Do NOT use fixed-dose combination products as initial Hydrochlorothiazide inhibits sodium reabsorption in the
therapy. distal tubule causing increased excretion of sodium and
water, as well as potassium and hydrogen ions.
Hypertension, replacement therapy, by mouth, ADULT,
blood pressure not controlled by 80 mg telmisartan Indication: Treatment of hypertension
monotherapy, 1 tablet (80 mg telmisartan + 12.5 mg
hydrochlorothiazide) once daily, may titrate dose up to 2 Contraindications: Hypersensitivity to valsartan,
tablets (160 mg telmisartan + 25 mg hydrochlorothiazide, sulfonamide-derived drugs, or any
hydrochlorothiazide) if needed; component of the formulation; concomitant use with
blood pressure not controlled by 25 mg aliskiren in patients with diabetes mellitus; anuria
hydrochlorothiazide monotherapy, 1 tablet (80 mg
telmisartan + 12.5 mg hydrochlorothiazide) once daily, Dose:
may titrate dose up to 2 tablets (160 mg telmisartan + NOTE: Combination product can be substituted for
25 mg hydrochlorothiazide) if blood pressure remains individual titrated agents. Initiation of combination
uncontrolled after 2–4 weeks of therapy. therapy when monotherapy has failed to achieve desired
effects.
Dose Adjustment:
Renal Impairment: Do NOT use fixed-dose combination products as initial
If CrCl ≤30 mL/min, use is not recommended. therapy.

Hepatic Impairment: Hypertension, replacement therapy, by mouth, ADULT,

In mild-to-moderate impairment or biliary obstructive blood pressure not controlled by 80 mg valsartan
disorders, initiate at 40 mg telmisartan + 12.5 mg monotherapy, 1 tablet (80 mg valsartan + 12.5 mg
hydrochlorothiazide. hydrochlorothiazide) once daily, may titrate dose up to 2
In patients with severe hepatic impairment, use is not tablets (160 mg valsartan + 25 mg hydrochlorothiazide)
recommended. if needed;
blood pressure not controlled by 25 mg
hydrochlorothiazide monotherapy, 1 tablet (80 mg
valsartan + 12.5 mg hydrochlorothiazide) once daily,

123
 CARDIOVASCULAR SYSTEM

may titrate dose up to 2 tablets (160 mg telmisartan +

25 mg hydrochlorothiazide) if blood pressure remains BETA-BLOCKING AGENTS
uncontrolled after 2–4 weeks of therapy.

Dose Adjustment: ALPHA AND BETA BLOCKING AGENTS

Geriatric:
Use with caution. Monitor renal function.
Rx CARVEDILOL
Renal Impairment:
C

If CrCl ≤30 mL/min, use is not recommended. Oral: 6.25 mg and 25 mg tablet

Hepatic Impairment: A racemic mixture, carvedilol has non-selective beta-

In mild-to-moderate impairment or biliary obstructive adrenoreceptor and alpha-adrenergic blocking activity. It
disorders, initiate at 40 mg valsartan + 12.5 mg causes exercise-induced or beta-agonist-induced
hydrochlorothiazide. tachycardia, a reduction of cardiac output and reflex
In severe hepatic impairment, use is not recommended. orthostatic tachycardia, vasodilation, decreased
peripheral and renal vascular resistance, reduced
Adverse Drug Reactions: plasma renin activity, and increased levels of atrial
Common: Hypotension, dizziness, hypokalemia, natriuretic peptide
nasopharyngitis
Less Common: Anaphylaxis, increased appetite, Indication: Management of heart failure
bronchospasm, constipation, dehydration, depression,
dysuria, epistaxis, flushing, gout, decreased hematocrit Contraindications: Decompensated cardiac failure requiring
or hemoglobin, decreased libido, hyperkalemia, intravenous inotropic therapy; bronchial asthma or
neutropenia, orthostatic hypotension, photosensitivity, related bronchospastic conditions; second­ or third-
pruritus, syncope, vasculitis, abnormal vision, abdominal degree AV block, sick sinus syndrome, and severe
pain, anxiety, arthralgia, chest pain, cough, diarrhea, bradycardia (except in patients with a functioning
dyspepsia, dyspnea, fatigue, fever, flatulence, artificial pacemaker) ; cardiogenic shock; severe hepatic
hyperhidrosis, infection, insomnia, myalgia, nausea, impairment
palpitation, paresthesia, peripheral edema, pollakiuria,
postural dizziness, rash, somnolence, tachycardia, Dose:
tinnitus, vertigo, vomiting, weakness, xerostomia Heart failure, by mouth, ADULT, 3.125 mg twice daily for 2
Rare: Rhabdomyolysis weeks; if tolerated, may increase to 6.25 mg twice daily;
double the dose every 2 weeks to the highest dose
Administration: Administer with or without food. tolerated by patient.
Mild-to-moderate heart failure, by mouth, ADULT >85 kg,
See individual monographs for Valsartan under Agents maximum dose, 50 mg twice daily; ADULT <85 kg,
Acting on the Renin-Angiotensin System – Angiotensin II maximum dose, 25 mg twice daily.
Antagonists, Plain in Chapter 3: Cardiovascular System Severe heart failure, by mouth, ADULT, 25 mg twice daily
and Hydrochlorothiazide under Diuretics – Thiazide (maximum dose, 80 mg once daily).
Diuretics in Chapter 3: Cardiovascular System for other Left ventricular dysfunction following MI, by mouth, ADULT,
information. initially 3.125–6.25 mg twice daily; increase dose
incrementally at intervals of 3–10 days, based on
Pregnancy Category: D tolerance, to a target dose of 25 mg twice daily
(maximum dose, 50 mg twice daily).
ATC Code: C09DA03; C03AX01
NOTE: Use with caution in patients who require inotropes
during their hospital course. Increase dose gradually and
monitor for congestive signs and symptoms of HF making
every effort to achieve target.

Dose Adjustment:
Geriatric:
Lower initial dose and titrate to response. Dose reductions
may be necessary.
Patients with Hypotension or Syncope:
Lower initial dose and titrate to response. Lower blood
pressure at a rate appropriate for the patient's clinical
condition.

Precautions:
Anaphylactic reactions
Diabetes (may potentiate and/or mask signs and symptoms
of hypoglycemia)
Pheochromocytoma (adequate alpha-blockade should be
initiated prior to use of any beta­blocker).

124
CARDIOVASCULAR SYSTEM

Bradycardia (may occur; reduce dose if heart rate drops to Drug Interactions:
<55 beats/minute); Hypotension or syncope (may occur Monitor closely with:
within the first 30 days of therapy); Angina Decreases metabolism of Carvedilol:
Heart failure (may experience a worsening of renal function; Aminoquinolines e.g. Antimalarial drugs; Phenothiazine
worsening heart failure or fluid retention may occur Antipsychotic Agents, CYP2D6 Inhibitors (Moderate)
during upward titration).
Floppy iris syndrome (has been observed in cataract surgery Decreases metabolism of Phenothiazine Antipsychotic
patients who were on or were previously treated with Agents
alpha1 blockers);

C
Myasthenia gravis; peripheral vascular disease (may Enhances therapeutic effect of Carvedilol:
precipitate or aggravate symptoms of arterial Bradycardic effect: Acetylcholinesterase Inhibitors e.g.,
insufficiency). Neostigmine, Amiodarone, Anilidopiperidine Opioids e.g.,
Bronchospastic disease (use with caution and close Fentanyl (bradycardic effect; antihypertensive effect),
monitoring) Bretylium (also AV blockade), Cardiac Glycosides e.g.,
Hepatic impairment Digoxin, Dipyridamole, Disopyramide, Other Bradycardia-
Psoriasis (associated with induction or exacerbation of causing Agents, Regorafenib, Ruxolitinib, Tofacitinib
psoriasis)
Thyroid disease (may mask signs of hyperthyroidism; abrupt Antihypertensive effect: Anilidopiperidine Opioids e.g.
withdrawal may exacerbate symptoms of Fentanyl, Phenothiazine Antipsychotic Agents,
hyperthyroidism or precipitate thyroid storm) Barbiturates e.g. Phenobarbital, Brimonidine (Topical),
Abrupt withdrawal (may cause acute tachycardia, Calcium Channel Blockers, Non-Dihydropyridine [except
hypertension, and/or ischemia; severe exacerbation of Bepridil], Diazoxide, MAO Inhibitors [except Linezolid,
angina, ventricular arrhythmias, and myocardial Tedizolid], Molsidomine, Nicardipine, Nicorandil,
infarction have been reported; chronic beta­blocker Nifedipine (also inotropic effects), Other
therapy should not be routinely withdrawn prior to major Antihypertensive Agents , Pentoxifylline,
surgery) Phosphodiesterase-5 Inhibitors e.g. Sidenafil,
Elderly (bradycardia may be observed more frequently). Prostacyclin Analogues e.g. Epoporestenol, Reserpine;
Pregnancy (increased risk of cardiovascular defects was Propafenone (possesses independent beta blocking
observed); lactation (not known if excreted in breastmilk; activity)
may cause serious adverse reactions in the nursing
infant). Enhances therapeutic effect of the following drugs:
Bradycardic effect: Fingolimod, Ivabradine, Midodrine
Adverse Drug Reactions: Hypoglycemic effect: Insulin, Sulfonylureas e.g.,
Common: Hypotension, bradycardia, syncope, peripheral Gliclazide
edema, generalized edema, angina, dependent edema, Disopyramide (negative inotropic effect)
AV block, cerebrovascular accident, hypertension, Lacosamide (AV blocking effect)
hypervolemia or hypovolemia, orthostatic hypotension,
palpitation, dizziness, fatigue, headache, depression, Increases risk of adverse or toxic effects of Carvedilol:
fever, hypoesthesia, hypotonia, insomnia, malaise, Amiodarone (cardiac arrest), Calcium Channel Blockers,
somnolence, vertigo, hyperglycemia, Non-Dihydropyridine [except Bepridil] (bradycardia; signs
hypercholesterolemia, hypertriglyceridemia, diabetes of heart failure), MAO Inhibitors [except Linezolid,
mellitus, gout, hyperkalemia, hyperuricemia, Tedizolid] (orthostatic hypotension), Nicardipine (may
hypoglycemia, hyponatremia, weight gain, diarrhea, precipitate signs of heart failure), Other Antihypertensive
nausea, vomiting, abdominal pain, melena, periodontitis, Agent
weight loss, impotence, anemia, decreased prothrombin,
purpura, thrombocytopenia, weakness, back pain, Increases risk of adverse or toxic effects of the following
arthralgia, arthritis, muscle cramps, paresthesia, blurred drugs:
vision, glycosuria, hematuria, renal insufficiency, cough, Cholinergic Agonists e.g., Betanechol (cardiac
nasopharyngitis, rales, dyspnea, pulmonary edema, conduction abnormalities; bronchoconstriction),
rhinitis, nasal congestion, sinus congestion, injury, Duloxetine (orthostatic hypotension), Levodopa
allergy, flu­like syndrome, sudden death (orthostatic hypotension), Risperidone (hypotensive
Less Common: Anaphylactoid reaction, alopecia, effect)
angioedema, aplastic anemia, amnesia, asthma,
bronchospasm, bundle branch block, cholestatic Reduces therapeutic effect of Carvedilol:
jaundice, concentration decreased, diaphoresis, Antihypertensive effect: Methylphenidate, Nonsteroidal
erythema multiforme, exfoliative dermatitis, GI Anti-Inflammatory Agents
hemorrhage, decreased hearing, hypersensitivity
reaction, hypokalemia, hypokinesia, interstitial Avoid concomitant use with:
pneumonitis, leukopenia, libido decreased, migraine, Decreases metabolism of Carvedilol:
myocardial ischemia, nervousness, neuralgia, CYP2D6 Inhibitors
nightmares, pancytopenia, paresis, peripheral ischemia, Enhances therapeutic effect of Carvedilol:
photosensitivity, pruritus, rash, respiratory alkalosis, Bradycardic effect: Dronedarone, Rivastigmine
seizure, Stevens-Johnson syndrome, tachycardia,
tinnitus, toxic epidermal necrolysis, urinary incontinence, Enhances therapeutic effect of the following drugs:
urticaria, xerostomia

125
 CARDIOVASCULAR SYSTEM

Alpha / Beta Agonists, Direct-Acting [except Dipivefrin] Indications: Antianginal; Management of acute coronary
(vasopressor effect), Ceritinib (bradycardic effect), Ergot syndrome; post-myocardial infarction (MI) maintenance;
Derivatives e.g., Ergotamine (vasoconstricting effect) antihypertensive

Increases risk of adverse or toxic effects of Carvedilol: Dose:

Alpha2 Agonists e.g., Clonidine (AV-blocking and sinus Hypertension, by mouth, ADULT, 40 mg twice daily; increase
node dysfunction effects; rebound hypertension), dosage every 3–7 days; usual dosage range, 40–160 mg
Floctafenine twice daily; usual dose, 120 to 240 mg divided in 2–3
doses daily (maximum daily dose, 640 mg);
C

Increases risk of adverse or toxic effects of the following ADOLESCENT and CHILD, initially 1–2 mg/kg daily
drugs: divided in 2–3 doses daily; titrate dose to effect
Alpha1 Blockers e.g. Tamsulosin (orthostatic (maximum dose, 4 mg/kg daily up to 640 mg daily).
hypotension), Amifostine (hypotensive effect), Grass Obstructive hypertrophic cardiomyopathy, by mouth, ADULT,
Pollen Allergen Extract / 5 Grass Extract (inhibits the 20–40 mg 3–4 times daily.
ability to effectively treat severe allergic reactions with Post-MI mortality reduction, by mouth, ADULT, initially 40
Epinephrine), Methacholine, Obinutuzumab mg 3 times daily; usual dosage range, 180 to 240 mg
(hypotensive effect), Rituximab (hypotensive effect) daily in 3–4 divided doses.
Stable angina, by mouth, ADULT, 80–320 mg daily in
Increases serum concentration of Carvedilol: divided doses 2–4 times daily.
Abiraterone Acetate, Dronedarone, Panobinostat
Dose Adjustment:
Increases serum concentration of the following drugs: Geriatric:
Afatinib [reduce Afatinib by 10 mg], Bosutinib, Colchicine For use in hypertension, consider lower initial doses and
(increase distribution into certain tissues, e.g., brain), titrate to response.
Cyclosporine (Systemic), Dabigatran Etexilate,
Doxorubicin (Conventional), Edoxaban, Everolimus. Renal and Hepatic Impairment:
Pazopanib, Silodosin, Topotecan, Vincristine (Liposomal) Use with caution. Renal and/or hepatic impairment
increases systemic exposure to propranolol.
Reduces therapeutic effect of the following drugs:
Alpha / Beta Agonists, Direct-Acting [except Dipivefrin] Administration: To be taken on an empty stomach.
(beta-adrenoceptor-mediated effects, including anti-
anaphylactic effects of epinephrine), Beta2 Agonists See Propranolol under Cardiac Therapy – Antiarrhythmics
(bronchodilatory effect), Theophylline Derivatives (Class II Antiarrhythmics) in Chapter 3: Cardiovascular
(bronchodilatory effect) System for other information.

Administration: Administer with food to minimize the risk of Pregnancy Category: C

orthostatic hypotension.
ATC Code: C07AA05
Initiate only in stable patients or hospitalized patients
after volume status has been optimized and IV diuretics,
vasodilators, and inotropic agents have all been BETA-BLOCKING AGENTS, SELECTIVE
successfully discontinued. Stabilize other heart failure
medications and minimize fluid retention prior to GENERAL INFORMATION
initiating therapy.
Selective beta-blockers (cardio-selective) exhibit a
Pregnancy Category: C competitive inhibitory effect on beta1­adrenergic
receptors, with little or no effect on beta2­receptors,
ATC Code: C07AG02 except at high doses.

Mode of Action: Competitively inhibits beta1­adrenergic

BETA-BLOCKING AGENTS, receptors, preventing the action of norepinephrine and
NON-SELECTIVE epinephrine on these receptors. Beta1-adrenergic
receptors are primarily located in the heart. Their activity
causes a reduction in sympathetic influences, including
Rx PROPRANOLOL chronotropy (heart rate), inotropy (contractility),
dromotropy (electrical conduction), and lusitropy
Oral: 10 mg and 40 mg tablet (as hydrochloride) (relaxation).

A non-selective beta-adrenergic blocker that competitively Contraindications: Reversible airway diseases; second- or
blocks responses to beta1­ and beta2­adrenergic third-degree heart block (except in patients with
stimulation, which results in decreases in heart rate, functioning artificial pacemaker); shock (cardiogenic and
myocardial contractility, blood pressure, and myocardial hypovolemic); bradycardia (45 to 50 beats/minute); sick
oxygen demand. Propranolol exhibits no intrinsic sinus syndrome (except in the presence of a pacemaker);
sympathomimetic activity (ISA). severe hypotension; uncontrolled heart failure;
concomitant IV administration of calcium channel
blockers; pulmonary hypertension

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CARDIOVASCULAR SYSTEM

Precautions: Adverse Drug Reactions:

Common: Alteration of glucose and lipid metabolism,
WARNING: Do NOT withdraw beta blocker therapy bradycardia, bronchospasm, cold extremities,
abruptly. Gradually taper over 1–2 weeks to avoid depression, diarrhea, dizziness, dyspepsia, dyspnea,
acute tachycardia, hypertension, and/or ischemia. exacerbation of Raynaud’s phenomenon, fatigue,
Abrupt withdrawal may exacerbate angina and, in hallucinations, first-degree heart block (P-R interval
some cases, cause myocardial infarction, ventricular ≥0.26 seconds), heart failure, hypotension, nausea,
arrhythmias, and rebound hypertension. Temporary pruritus, second- and third-degree heart block, shortness
but prompt resumption of beta-blocker therapy may of breath, tiredness, syncope, vomiting, wheezing

C
be indicated with worsening of angina or acute Less Common: Acute urinary retention, anxiety, cardiogenic
coronary insufficiency. shock, chest pain, claudication, confusion, constipation,
flatulence, gastric pain, headache, heartburn,
hyperhidrosis, impaired concentration, impotence,
Major surgery: Do NOT withdraw chronic beta blocker
insomnia, muscle cramps, nasal congestion,
therapy prior to major surgery.
nervousness, nightmares, palpitations, peripheral
edema, Peyronie’s disease, rash, reduced libido, sleep
Atrial fibrillation; Atrioventricular block (commonly produces disturbances, somnolence, taste disturbance, urticaria,
mild first-degree heart block; may also produce severe visual disturbances, vertigo, xerostomia
first- (P-R interval ≥0.26 sec), second-, or third-degree Rare: Agranulocytosis, alopecia, arthritis, blurred vision,
heart block; patients with acute myocardial infarction cardiac arrest, catatonia, emotional lability, exacerbation
have a high risk of developing heart block of varying of psoriasis, gangrene, hepatitis, hypersensitivity
degrees) reaction, jaundice, laryngospasm, liver function
Hypotension (symptomatic hypotension may occur with use) abnormality, respiratory distress, retroperitoneal fibrosis,
Anaphylactic reactions (may become more sensitive to thrombocytopenia, thrombocytopenic purpura, tinnitus
repeated challenges; treatment of anaphylaxis, e.g.,
epinephrine, may be ineffective or even promote Drug Interactions:
undesirable effects) Monitor closely with:
Extravasation (can lead to skin necrosis and sloughing) Decreases metabolism of Beta Blockers:
Hyperkalemia (associated with elevations in serum Aminoquinolines e.g., Antimalarial drugs
potassium and development of hyperkalemia; monitor
serum potassium during therapy); hepatic impairment. Enhances therapeutic effect of Beta Blockers:
Bronchospastic disease (may be exacerbated) Bradycardic effect: Acetylcholinesterase Inhibitors e.g.,
Conduction abnormality (can cause bradycardia, including Neostigmine, Amiodarone; Anilidopiperidine Opioids e.g.,
sinus pause, heart block, severe bradycardia, and Fentanyl (bradycardic and antihypertensive effects),
cardiac arrest) Bretylium (also AV blockade), Dipyridamole,
Diabetes (may potentiate and/or mask signs and symptoms Disopyramide (also negative inotropic effect),
of hypoglycemia) Regorafenib, Tofacitinib, Other Bradycardia-causing
Heart failure (monitor for worsening of condition). Agents
Myasthenia gravis Antihypertensive effect: Barbiturates e.g., Phenobarbital,
Peripheral vascular disease and Raynaud’s disease (can Brimonidine (Topical), Calcium Channel Blockers, Non-
precipitate or aggravate symptoms or arterial Dihydropyridine [except Bepridil] e.g., Verapamil,
insufficiency) Diazoxide, Molsidomine, Nicorandil, Nifedipine (also
Pheochromocytoma (may aggravate hypertension; requires negative inotropic effect), Other Antihypertensives,
adequate alpha blockade prior to use of beta-blockers) Pentoxifylline, Phosphodiesterase-5 Inhibitors e.g.,
Prinzmetal variant angina (requires concomitant alpha1- Sildenafil, Prostacyclin Analogues e.g., Epoprostenol,
adrenergic receptor blockage, unopposed alpha1- Reserpine; Propafenone (possesses independent beta
adrenergic receptors mediate coronary vasoconstriction blocking activity)
and can worsen angina symptoms).
Psoriasis (associated with induction or exacerbation of Enhances therapeutic effect of the following drugs:
psoriasis) Bradycardic effect: Fingolimod, Ivabradine, Midodrine
Psychiatric disease (may cause or exacerbate CNS Hypoglycemic effect: Insulin, Sulfonylureas e.g.,
depression) Gliclazide
Renal impairment (active metabolite is retained); thyroid Lacosamide (AV blocking effect)
disease (may mask signs of hyperthyroidism, e.g.,
tachycardia; abrupt withdrawal may exacerbate Increases risk of adverse or toxic effects of Beta Blockers:
symptoms of hyperthyroidism and precipitate thyroid Amiodarone (cardiac arrest), Calcium Channel Blockers,
storm; may alter thyroid function tests). Non-Dihydropyridine [except Bepridil] (bradycardia; signs
Elderly (bradycardia may be observed more frequently in of heart failure), MAO Inhibitors [except Linezolid,
patients >65 years). Tedizolid] (orthostatic hypotension), Other
Pregnancy (crosses the placenta; may cause intrauterine Antihypertensive Agents
growth restriction, small placenta, fetal or neonatal
bradycardia, hypoglycemia, respiratory depression); Increases risk of adverse or toxic effects of the following
lactation (excreted in breast milk and detected in the drugs:
serum and urine of nursing infants; use with caution). Cardiac Glycosides (bradycardic effect); Cholinergic
Agonists (cardiac conduction abnormalities;

127
 CARDIOVASCULAR SYSTEM

bronchoconstriction); Duloxetine (orthostatic Dose:

hypotension) Hypertension, by mouth, ADULT, initially 25–50 mg once
Levodopa (orthostatic hypotension); MAO Inhibitors daily, may increase to 100 mg once daily after 1–2
[except Linezolid, Tedizolid] (orthostatic hypotension) weeks (usual dose, 100 mg once daily; target dose, 100
Risperidone (hypotensive effect) mg once daily); CHILD, 0.5–1 mg/kg per dose daily;
usual dosage range, 0.5 to 1.5 mg/kg daily (maximum
Reduces therapeutic effect of Beta Blockers: dose, 2 mg/kg daily for up to 100 mg daily).
Methylphenidate (antihypertensive effect); Nonsteroidal Angina pectoris, by mouth, ADULT, 50 mg once daily; may
Anti-Inflammatory Agents (antihypertensive effect) increase to 100 mg daily; some patients may require 200
C

mg daily.
Reduces therapeutic effect of the following drugs: Post-myocardial infarction, by mouth, ADULT, 100 mg daily
Beta2 Agonists (bronchodilatory effect); Theophylline or 50 mg twice daily for 6–9 days post-myocardial
Derivatives (bronchodilatory effect) infarction.

Avoid concomitant use with: Dose Adjustment:

Enhances therapeutic effect of Beta Blockers: Geriatric:
Alpha2 Agonists (AV blocking effect), In the management of hypertension, consider lower initial
Bradycardic effect: Dronedarone, Rivastigmine, doses and titrate to response.
Ruxolitinib
Renal Impairment:
Enhances therapeutic effect of the following drugs: If CrCl is 15–35 mL/minute per 1.73m2, maximum dose is
Alpha / Beta Agonists, Direct-Acting [except Dipivefrin] 50 mg daily.
(vasopressor effect); Ceritinib (bradycardic effect); Ergot If CrCl is <15 mL/minute per 1.73m2, maximum dose is 25
Derivatives (vasoconstricting effect) mg daily.
For patients on hemodialysis, administer dose post-dialysis
Increases risk of adverse or toxic effects of Beta Blockers: or administer 25–50 mg supplemental dose. Atenolol is
CYP2D6 Inhibitors (heart block) moderately dialyzable (20% to 50%) via hemodialysis.

Increases risk of adverse or toxic effects of the following Administration: May be taken without regard to meals.
drugs:
Alpha1 Blockers (orthostatic hypotension), Alpha2 NOTE: When administered acutely, monitor ECG and blood
Agonists (rebound hypertension; sinus node pressure.
dysfunction), Amifostine (hypotensive effect),
Floctafenine, Grass Pollen Allergen Extract / 5 Grass See General Information on Beta Blocking Agents, Selective
Extract (inhibits the ability to effectively treat severe listed above for other information.
allergic reactions with Epinephrine)
Methacholine, Obinutuzumab (hypotensive effect), Pregnancy Category: D
Rituximab (hypotensive effect)
ATC Code: C07AB03
Increases serum concentration of Beta Blockers:
CYP2D6 Inhibitors, Dronedarone

Reduces therapeutic effect of the following drugs: Rx BISOPROLOL

Alpha / Beta Agonists, Direct-Acting [except Dipivefrin]
(beta-adrenoceptor mediated effects, including anti- Oral: 2.5 mg and 5 mg tablet (as fumarate)
anaphylactic effects of Epinephrine)
A beta1-selective antagonist that competitively blocks beta1
adrenergic stimulation, with little or no effect on beta2-
receptors at doses ≤20 mg.
Rx ATENOLOL
Indication: Management of coronary heart failure
Oral: 50 mg and 100 mg tablet
Dose:
A beta1-selective antagonist that competitively blocks beta1- Hypertension, by mouth, ADULT, initially 2.5–5 mg once
adrenergic stimulation, with little or no effect on beta2- daily; may be increased to 10 mg and then up to 20 mg
receptors except at high doses. It exhibits no intrinsic once daily, if necessary; usual dose range 5–10 mg once
sympathomimetic activity (ISA). daily.
Heart failure, by mouth, ADULT, initially 1.25 mg once daily
Indications: Treatment of hypertension, alone or in (maximum dose, 10 mg once daily); increase dose
combination with other agents; management of angina gradually and monitor for congestive signs and
pectoris; secondary prevention post-myocardial symptoms of HF making every effort to achieve target
infarction; for acute coronary syndrome dose shown to be effective.

NOTE: Initiate only in stable patients or hospitalized patients

after volume status has been optimized and IV diuretics,
vasodilators, and inotropic agents have all been

128
CARDIOVASCULAR SYSTEM

successfully discontinued. Caution should be used when In the management of hypertension, consider lower initial
initiating in patients who require inotropes during their doses and titrate to response.
hospital course.
Renal Impairment:
Dose Adjustment: For mild-to-moderate impairment, no dose adjustment is
Renal Impairment: necessary.
For use in hypertension, if CrCl <40 mL/minute, initiate at For severe impairment, refer patient to a specialist.
2.5 mg daily; increase cautiously.
Hepatic Impairment:

C
Hepatic Impairment: For mild-to-moderate impairment, dose reduction may be
For patients with hepatitis or cirrhosis, initiate at 2.5 mg warranted
daily; increase cautiously. For severe impairment, refer patient to a specialist.

Administration: May be taken without regard to meals. Administration: To be taken with or immediately following
food.
See General Information on Beta Blocking Agents, Selective
listed above for other information. See General Information on Beta Blocking Agents, Selective
listed above for other information.
Pregnancy Category: C
Pregnancy Category: C
ATC Code: C07AB07
ATC Code: C07AB02

Rx METOPROLOL
CALCIUM CHANNEL BLOCKERS
Oral: 50 mg and 100 mg tablet (as tartrate)

A beta1-adrenoceptor (cardio-selective) antagonist without

SELECTIVE CALCIUM CHANNEL BLOCKERS WITH
intrinsic sympathomimetic activity (ISA), which may be MAINLY VASCULAR EFFECTS
advantageous in treating hypertensive patients who also
suffer from asthma, diabetes, or peripheral vascular
disease. Rx AMLODIPINE

Indications: Management of hypertension; angina pectoris; Oral: 5 mg and 10 mg tablet (as besilate / camsylate)
acute coronary syndrome; post-myocardial infarction
maintenance A long-acting dihydropyridine, calcium channel blocker,
which is useful for hypertension and coronary artery
Dose: disease.
Angina, by mouth, ADULT, initially 50 mg twice daily; usual
dosage range is 50–200 mg twice daily (maximum dose, Indication: Management of hypertension
400 mg daily); increase dose gradually at weekly
intervals to achieve desired effect. Contraindications: unstable angina; cardiogenic shock;
Hypertension, by mouth, ADULT, initially 50 mg twice daily; hypotension; significant aortic stenosis; in instances of
effective dosage range is 100–450 mg daily in 2–3 MI with heart failure or poor LV function
divided doses; increase dose at weekly intervals to
desired effect (maximum total daily dose, 450 mg; usual Dose:
dosage range, 50–100 mg twice daily; target dose, 100– Hypertension, by mouth, ADULT, initially 2.5 mg once daily,
200 mg daily); CHILD 1–17 years, initially 1–2 mg/kg increased if necessary (maximum dose, 10 mg once
daily (maximum dose, 6 mg/kg daily (≤200 mg daily) ; daily); CHILD, refer to a specialist.
administer in 2 divided doses.
Myocardial infarction, early treatment, by mouth, ADULT, Dose Adjustment:
25–50 mg every 6–12 hours; transition over the next 2– Hepatic Impairment:
3 days to twice daily dosing and increase as tolerated to In patients with hepatic insufficiency, consider dose
a maximum daily dose of 200 mg. [NOTE: The ACCF/AHA reduction, initiating with 2.5 mg daily.
guidelines for the management of STEMI recommend initiation In patients with severe impairment, titrate slowly.
within the first 24 hours. Do not initiate this regimen in those with
signs of heart failure, a low output state, increased risk of
Precautions:
cardiogenic shock, or other contraindications.]
Hypotension (poor cardiac function if given with other
Myocardial infarction, secondary prevention, by mouth,
cardiodepressant drugs); congestive heart failure; aortic
ADULT, 25–100 mg twice daily; optimize dose based on
stenosis; pre-existing abnormalities in the sinoatrial
heart rate and blood pressure; continue indefinitely.
and/or atrioventricular node (increased angina or MI can
develop after starting or increasing the dose, particularly
Dose Adjustment:
in patients with severe obstructive coronary artery
Geriaric:
disease).
Hepatic impairment (half-life prolonged); Acute porphyria

129
 CARDIOVASCULAR SYSTEM

Increased intracranial pressure; Glaucoma ≥6 years, initially 2.5 mg once daily; may increase as
Pregnancy (limited information on use in humans; risk to needed at no less than 2-week intervals (maximum dose,
fetus should be balanced against the risk of uncontrolled 10 mg once daily).
maternal hypertension); lactation (presence in milk is
possible; monitor infant). Dose Adjustment:
Geriatric:
Adverse Drug Reactions: Consider lower initial doses and titrate at no less than 2-
Common: Abdominal pain, dizziness, fatigue, flushing, week intervals to response.
gingival hyperplasia, headache, nausea, palpitation,
C

peripheral edema, pulmonary edema, rash, sleep Hepatic Impairment:

disturbances Initially administer 2.5 mg once daily. Monitor blood
Less Common: Arthralgia, dryness of mouth, chest pain, pressure closely during titration.
constipation, dyspepsia, dyspnea, GI disturbances,
gynecomastia, hypotension, impotence, myalgia, Precautions:
paresthesia, polyuria, mood changes, pruritus, Angina or myocardial infarction (reflex tachycardia may
pulmonary edema, sweating, syncope, tachycardia, taste occur)
disturbances, tinnitus, tremor, urinary disturbances, Hypotension or syncope (symptomatic hypotension with or
weight changes without syncope rarely occur)
Rare: Agitation, alopecia, amnesia, angioedema, Peripheral edema (dose-dependent)
arrhythmias, ataxia, cardiac failure, cholestasis, Aortic stenosis (may reduce coronary perfusion resulting in
coughing, dermatitis, erythema multiforme, gastritis, ischemia); Heart failure (avoid use)
hepatitis, hyperglycemia, myocardial infarction, Hepatic impairment (may require lower starting dose)
pancreatitis, Parkinsonism, parosmia, jaundice, Hypertrophic cardiomyopathy (reduction in afterload may
peripheral neuropathy, purpura, thrombocytopenia, worsen symptoms associated with this condition)
twitching, vasculitis, abnormal visual accommodation, Elderly (may experience a greater hypotensive response;
xerophthalmia constipation may be more of a problem)
Pregnancy (untreated chronic maternal hypertension is
Drug Interactions: associated with adverse events in the fetus, infant, and
Monitor closely with: mother); lactation (not known if excreted in breastmilk)
Enhances therapeutic effect of Amlodipine:
Drugs that reduce blood pressure (enhanced Adverse Drug Reactions:
hypotensive effects) Common: Headache, peripheral edema, flushing,
tachycardia
Avoid concomitant use with: Less Common: Abdominal pain, acid regurgitation, anemia,
Reduces therapeutic effect of Amlodipine: angioedema, angina pectoris, anxiety disorders, arm
Calcium Salts pain, arrhythmia, arthralgia, back pain, bronchitis, chest
pain, CHF, constipation, contusion, CVA, decreased
Increases serum concentration of the following drugs, libido, depression, diarrhea, dizziness, dry mouth,
increasing its risk of adverse or toxic effects: dyspnea, dysuria, epistaxis, erythema, facial edema,
Simvastatin [limit Simvastatin dose to 20 mg daily] flatulence, flu­like illness, flushing, foot pain, gingival
(myopathy) hyperplasia, gynecomastia, hip pain, hypotension,
impotence, influenza, insomnia, irritability, knee pain, leg
Administration: May be taken with or without food. pain, leukocytoclastic vasculitis, MI, muscle cramps,
myalgia, nausea, nervousness, palpitation, paresthesia,
Pregnancy Category: C pharyngitis, polyuria, premature beats, respiratory
infection, sinusitis, somnolence, syncope, urinary
ATC Code: C08CA01 frequency, urinary urgency, urticaria, visual
disturbances, vomiting

NOTE: Doses >10 mg daily are associated with greater

Rx FELODIPINE antihypertensive effects but also with a large increase in
the incidence of peripheral edema and other
Oral: 5 mg and 10 mg MR tablet vasodilatory adverse effects.

A dihydropyridine calcium channel blocker that inhibits Drug Interactions:

calcium ions from entering select voltage-sensitive areas Monitor closely with:
of vascular smooth muscle and myocardium during Decreases metabolism of Felodipine:
depolarization, producing a relaxation of coronary Cyclosporine (Systemic), CYP2C8 Substrates, CYP3A4
vascular smooth muscle and coronary vasodilation. Inhibitors (Moderate)

Indication: Management of hypertension Enhances antihypertensive effect of Felodipine:

Alfuzosin, Alpha1 Blockers, Barbiturates e.g.,
Dose: Phenobarbital, Brimonidine (Topical); Non-
Hypertension, by mouth, ADULT, 5 mg once daily; adjust Dihydropyridine Calcium Channel Blockers e.g.,
dose as needed at no less than 2-week intervals; usual Verapamil, Diazoxide, Magnesium Salts, MAO Inhibitors
dose range, 5–10 once daily; ADOLESCENT and CHILD [except Linezolid, Tedizolid], Molsidomine, Nicorandil,

130
CARDIOVASCULAR SYSTEM

Other Antihypertensive Agents; Pentoxifylline, Phenytoin

Phosphodiesterase-5 Inhibitors e.g., Sildenafil,
Prostacyclin Analogues e.g., Epoprostenol Administration: May be administered without food or with a
small meal that is low in fat and carbohydrates. Avoid
Enhances therapeutic effect of the following drugs: grapefruit juice during therapy.
Nondepolarizing neuromuscular-blocking Agents e.g.,
Vecuronium (neuromuscular-blocking effect), Swallow tablet whole. Do NOT divide, crush, or chew.
Nitroprusside (hypotensive effect)
NOTE: Felodipine peak plasma concentrations are

C
Increases absorption of Felodipine: increased up to two-fold when taken after a meal high in
Ethyl Alcohol fat or carbohydrates. Grapefruit juice similarly increases
felodipine Cmax by two-fold. Increased therapeutic and
Increases metabolism of Felodipine: vasodilator side effects, including severe hypotension
Barbiturates e.g., Phenobarbital and myocardial ischemia, may occur.

Increases risk of adverse or toxic effects of Felodipine: Pregnancy Category: C

Dapoxetine (orthostatic hypotension), MAO Inhibitors
[except Linezolid, Tedizolid] (orthostatic hypotension), ATC Code: C08CA02
Other Antihypertensive Agents

Increases risk of adverse or toxic effects of the following

drugs:
Rx NICARDIPINE
Atosiban (pulmonary edema and/or dyspnea),
Duloxetine (orthostatic hypotension), Levodopa Inj.: 1 mg/mL (as hydrochloride), 2 mL and 10 mL ampule
(orthostatic hypotension), Magnesium Salts, Risperidone (IV)
(hypotensive effect)
A calcium channel blocker that inhibits calcium ions from
Reduces antihypertensive effect of Felodipine: entering select voltage-sensitive areas of vascular
Calcium Salts, Methylphenidate smooth muscle and myocardium. It produces a
relaxation of coronary vascular smooth muscle and
Reduces therapeutic effect of Clopidogrel coronary vasodilation, thus increasing myocardial oxygen
delivery in patients with vasospastic angina.
Avoid concomitant use with:
Decreases metabolism of Felodipine: Indication: Management of acute hypertension
Antifungal Agents, Azole Derivatives, (Systemic) [except
Fluconazole, Isavuconazonium Sulfate], CYP3A4 Contraindications: Advanced aortic stenosis
Inhibitors (Strong), Macrolide Antibiotics [except
Azithromycin, Fidaxomicin, Spiramycin] Dose:
Acute hypertension, by IV infusion, ADULT, 5 mg/ hour
Decreases serum concentration of Felodipine: initially, may increase by 2.5 mg/hour every 5 minutes
Dabrafenib, Mitotane, Phenytoin, Rifamycin Derivatives for rapid titration, to every 15 minutes for gradual
titration (maximum dose, 15 mg/hour); in rapidly titrated
Increases metabolism of Felodipine: patients, consider reduction to 3 mg/hour after response
Carbamazepine, CYP3A4 Inducers (Strong), Nafcillin is achieved

Increases risk of adverse or toxic effects of Felodipine: Dose Adjustment:

Antifungal Agents, Azole Derivatives, Systemic [except Geriatric:
Fluconazole] (negative inotropic effects), Mifepristone, Initiate at the low end of the dosage range. Monitor closely.
Stiripentol
Renal and Hepatic Impairment:
Increases risk of adverse or toxic effects of the following Dose adjustment may be necessary. Titrate slowly with
drugs: careful monitoring. Consider lower starting dose and
Amifostine (hypotensive effect), Obinutuzumab [withhold closely monitor response.
Felodipine 12 hours prior to Obinutuzumab infusion until
1 hour after the end of the infusion] (hypotensive effect), Precautions:
Phenytoin, Rituximab (hypotensive effect)
WARNING: Significant differences exist between oral
and IV dosing. Use caution when converting from
Increases serum concentration of Felodipine:
one route of administration to another.
Cimetidine, Fosphenytoin, Fusidic Acid (Systemic),
Grapefruit Juice, Idelalisib, Itraconazole, Ketoconazole
(Systemic), Mifepristone, Stiripentol Angina, myocardial infarction (increased frequency,
duration, or severity of angina and/or MI has occurred
Increases serum concentration of the following drugs: with initiation or dosage titration; reflex tachycardia may
Amodiaquine, Phenytoin occur);
Hypotension; Syncope (rarely occurs); Peripheral edema
Reduces therapeutic effect of Felodipine: (dose-dependent); Tachycardia (may occur).

131
 CARDIOVASCULAR SYSTEM

Aortic stenosis (may reduce coronary perfusion resulting in Aripiprazole, Carvedilol (hypotensive effect),
ischemia) Nondepolarizing Neuromuscular-blocking Agents e.g.
Heart failure (may worsen symptoms of HF due to mild Pancuronium (neuromuscular-blocking effect),
negative inotropic effects of nicardipine, particularly with Nitroprusside (hypotensive effect)
concomitant beta blockade)
Hypertrophic cardiomyopathy with outflow tract obstruction Increases metabolism of Nicardipine:
(reduction in afterload may worsen symptoms Barbiturates e.g. Phenobarbital
associated with this condition)
Hepatic impairment; Renal impairment Increases risk of adverse or toxic effects of Nicardipine:
C

Abrupt withdrawal may cause rebound angina in patients Dapoxetine (orthostatic hypotension), MAO Inhibitors
with CAD [except Linezolid, Tedizolid] (orthostatic hypotension),
Elderly (constipation may be more of a problem; may Other Antihypertensive Agents
experience greater hypotensive response)
Pregnancy (adverse events have been observed in some Increases risk of adverse or toxic effects of the following
animal reproduction studies; crosses the placenta; drugs:
changes in fetal heart rate, neonatal hypotension and Atosiban (pulmonary edema and/or dyspnea), Carvedilol
neonatal acidosis have been observed following (may precipitate signs of heart failure), Duloxetine
maternal use); lactation (minimally excreted in (orthostatic hypotension), Levodopa (orthostatic
breastmilk; breast­feeding is not recommended). hypotension), Magnesium Salts, Risperidone
(hypotensive effect)
Adverse Drug Reactions:
Common: Flushing, pedal edema, exacerbation of angina Reduces therapeutic effect of Nicardipine:
pectoris, hypotension, palpitations, tachycardia, chest Barbiturates e.g Phenobarbital, Calcium Salts,
pain, extrasystoles, hemopericardium, supraventricular Methylphenidate
tachycardia, hypertension, edema, headache, dizziness,
hypoesthesia, intracranial hemorrhage, pain, Reduces therapeutic effect of the following drugs:
somnolence, diaphoresis, skin rash, hypokalemia, Codeine (prevents metabolic conversion to its active
nausea, vomiting, dyspepsia, abdominal pain, metabolite, morphine); Tramadol (prevents metabolic
xerostomia, hematuria, injection site reaction, pain at conversion to its active metabolite)
injection site, weakness, myalgia, paresthesia
Less Common: Abnormal dreams, abnormal vision, angina Avoid concomitant use with:
pectoris, anxiety, atrial fibrillation, atrioventricular block, Decreases metabolism of Nicardipine:
arthralgia, atypical chest pain, blurred vision, cerebral Antifungal Agents, Azole Derivatives, Systemic [except
ischemia, confusion, conjunctivitis, constipation, deep Fluconazole], CYP2C9 Substrates, CYP3A4 Inhibitors;
vein thrombophlebitis, depression, ST segment Macrolide Antibiotics [except Azithromycin, Spiramycin]
depression, dyspnea, ear disease, fever, gingival
hyperplasia, heart block, hot flash, hyperkinesia, Decreases serum concentration of Nicardipine:
hypersensitivity reaction, hypophosphatemia, Dabrafenib, Efavirenz, Mitotane, Phenytoin, Rifamycin
hypertonia, impotence, infection, insomnia, inversion T Derivatives, Siltuximab
wave on ECG, malaise, myocardial infarction, neck pain,
nervousness, nocturia, orthostatic hypotension, Decreases serum concentration of the following drugs:
parotitis, pericarditis, peripheral vascular disease, Clopidogrel, Tamoxifen
respiratory tract disease, rhinitis, sinus node
dysfunction, sinusitis, sore throat, sustained tachycardia, Enhances therapeutic effect of the following drugs:
syncope, thrombocytopenia, tinnitus, tremor, urinary Highest Risk QTc-prolonging Agents, Indeterminate Risk
frequency, ventricular extrasystoles, ventricular and Risk Modifying (QTc-prolonging effect)
tachycardia, vertigo, vomiting
Enhances therapeutic effect of Nicardipine:
Drug Interactions: Mifepristone (QTc-prolonging effect)
Monitor closely with:
Decreases metabolism of Nicardipine: Increases metabolism of Nicardipine:
Cyclosporine (Systemic), CYP2C19 Substrates, CYP2D6 Carbamazepine, CYP3A4 Inducers, Nafcillin
Substrates
Increases risk of adverse or toxic effects of Nicardipine:
Enhances therapeutic effects of Nicardipine: Azole Antifungal Agents (Systemic) [except Fluconazole,]
Antihypertensive effect: Alpha1 Blockers e.g. Alfuzosin, (negative inotropic effects), Grapefruit Juice,
Barbiturates e.g. Phenobarbital, Brimonidine (Topical), Mifepristone, Stiripentol
Non-Dihydropyridine Calcium Channel Blockers,
Diazoxide, Magnesium Salts, Molsidomine, Nicorandil, Increases risk of adverse or toxic effects of the following
Pentoxifylline, Phosphodiesterase-5 Inhibitors e.g. drugs:
Sildenafil, Prostacyclin Analogues e.g. Epoporestenol, Amifostine [withhold Nicardipine 24 hours prior to
Other Antihypertensive Agents Amifostine administration] (hypotensive effect),
Moderate Risk QTc-prolonging Agents, Indeterminate Citalopram (serotonin syndrome; QT prolongation),
Risk and Risk Modifying (QTc-prolonging agents) Fosphenytoin, Highest Risk QTc-prolonging Agents,
Indeterminate Risk and Risk Modifying (alterations of
Enhances therapeutic effect of the following drugs: cardiac rhythm), Obinutuzumab [withhold Nicardipine 12

132
CARDIOVASCULAR SYSTEM

hours prior to Obinutuzumab infusion until 1 hour after Contraindications: Concomitant use with strong CYP3A4
the end of the infusion] (hypotensive effect), Phenytoin, inducers (e.g., rifampin); cardiogenic shock; STEMI;
Rituximab (hypotensive effect) Heart failure

Increases serum concentration of Nicardipine: Dose:

Fosphenytoin, Fusidic Acid (Systemic), Grapefruit Juice, Hypertension, by mouth, ADULT, initially 30–60 mg once
Idelalisib, Mifepristone, Simeprevir, Stiripentol daily, titrate to 30–90 mg daily (maximum, 90–120 mg
daily).
Increases serum concentration of the following drugs:

C
Afatinib [reduce Afatinib dose by 10mg], Bosutinib, NOTE: Adjust dose at 7– to 14–day intervals to allow for
Cilostazol [reduce Cilostazol dose to 50 mg twice daily], adequate assessment of new dose. If clinically indicated,
Citalopram [limit Citalopram dose to a maximum of 20 titration may be done more rapidly with appropriate
mg daily], Colchicine (increases distribution into certain monitoring.
tissues, e.g., brain), Dabigatran Etexilate, Diclofenac
(Systemic), Doxorubicin (Conventional), Edoxaban, Use same total daily dose when switching from
Eliglustat [reduce Eliglustat dose to 84 mg daily], immediate-release
Everolimus, Lacosamide, Lomitapide [limit maximum to sustained-release formulation.
Lomitapide dose to 30 mg daily], Metoprolol, Pazopanib,
Phenytoin, Pimozide, Silodosin, Thioridazine, Topotecan, Dose Adjustment:
Vincristine (Liposomal) Geriatric:
Consider lower initial doses and titrate to response. Half-life
Reduces therapeutic effect of Nicardipine: is extended in elderly patients (6.7 hours) as compared
Phenytoin to younger subjects (3.8 hours).

Reduces therapeutic effect of the following drugs: Hepatic Impairment:

Clopidogrel, Fosphenytoin Use with caution. Clearance is reduced in cirrhotic patients,
which may lead to increased systemic exposure. Monitor
Administration: Administer by slow continuous IV infusion closely for adverse effects or toxicity and consider dose
via a central line or through a large peripheral vein. Avoid adjustments.
use of small peripheral veins to minimize infusion site
reactions. Precautions:
WARNING: Use with extreme caution due to rapid and
Do NOT combine or run in the same line as other prolonged fall in blood pressure.
medications.
Use is restricted for acute hypertensive emergencies in
patients less than 18 years old.
Monitor infusion site closely to prevent extravasation.
Peripheral venous irritation may be minimized by
changing the site of infusion every 12 hours. Abrupt withdrawal (may cause rebound angina in patients
with CAD).
Evaluate cardiac status and blood pressure and monitor Angina or MI (increased angina and/or MI have occurred;
for rash, hypotension, bradycardia, confusion, and reflex tachycardia may occur resulting in angina and/or
nausea when starting, adjusting dose, or discontinuing. MI in patients with obstructive coronary disease)
Hypotension or syncope (rarely occurs; blood pressure must
NOTE: Parenteral administration is indicated only for short-term use. be lowered at a rate appropriate for the patient's clinical
condition; death, cerebrovascular ischemia, syncope,
Teach patient orthostatic precautions. stroke, acute myocardial infarction, and fetal distress,
have been reported)
Pregnancy Category: C Peripheral edema (most common side effect).
Aortic stenosis (may reduce coronary perfusion resulting in
ATC Code: C08CA04 myocardial ischemia); Heart failure (avoid use)
Hypertrophic cardiomyopathy with outflow tract obstruction
(reduction in afterload may worsen symptoms
Rx NIFEDIPINE associated with this condition).
Gastrointestinal strictures (alterations in GI anatomy, e.g.,
severe GI narrowing, history of GI cancer, obstruction,
Oral: 10 mg capsule bowel resection, gastric bypass, vertical banded
30 mg MR tablet gastroplasty, and underlying hypomotility disorders have
led to bezoar formation with extended release forms);
A calcium channel blocker that inhibits calcium ion from hepatic impairment.
entering select voltage-sensitive areas of vascular Immediate-release formulations should not be used to
smooth muscle and myocardium during depolarization. manage primary hypertension (adequate studies have
It produces coronary vasodilation and reduces peripheral not been conducted)
vascular resistance and ultimately, arterial blood May contain lactose (do not administer in patients with
pressure. galactose intolerance, Lapp lactase deficiency, or
glucose-galactose malabsorption syndromes).
Indication: Treatment of hypertension

133
 CARDIOVASCULAR SYSTEM

Surgery (cardiopulmonary bypass, intraoperative blood loss Barbiturates e.g. Phenobarbital

or vasodilating anesthesia may result in severe
hypotension and/or increased fluid requirements; Increases risk of adverse or toxic effects of Nifedipine:
consider withdrawing nifedipine >36 hours before Dapoxetine (orthostatic hypotension), MAO Inhibitors
surgery). [except Linezolid, Tedizolid] (orthostatic hypotension),
Elderly (immediate-release tablets may cause hypotension Other Antihypertensive Agents
and risk of precipitating myocardial ischemia; may
experience a greater hypotensive response; constipation Increases risk of adverse or toxic effects of the following
may be more of a problem). drugs:
C

Pregnancy (crosses the placenta and small amounts can be Atosiban (pulmonary edema and/or dyspnea),
detected in the urine of newborn infants; an increase in Duloxetine (orthostatic hypotension), Fluoxetine,
perinatal asphyxia, cesarean delivery, prematurity, and Levodopa (orthostatic hypotension), Magnesium Salts,
intrauterine growth retardation have been reported); Risperidone (hypotensive effect)
lactation (excreted in breast milk; breast­feeding is not
recommended). Reduces therapeutic effect of Nifedipine:
Calcium Salts, Melatonin (antihypertensive effect),
Adverse Drug Reactions: Methylphenidate (antihypertensive effect)
Common: Flushing, peripheral edema (dose-related),
palpitation, transient hypotension (dose-related), Reduces therapeutic effect of Clopidogrel
coronary heart failure, lightheadedness, dizziness,
giddiness, nervousness, headache, mood changes, Avoid concomitant use with:
fatigue, shakiness, jitteriness, sleep disturbances, Decreases metabolism of Nifedipine:
difficulties in balance, fever, chills, dermatitis, pruritus, CYP3A4 Inhibitors, Macrolide Antibiotics [except
urticaria, sexual difficulties, nausea, heartburn, Azithromycin, Spiramycin]
constipation, diarrhea, cramps, flatulence, muscle Decreases serum concentration of Nifedipine:
cramps or tremor, weakness, inflammation, joint Dabrafenib, Phenytoin
stiffness, gingival hyperplasia, blurred vision, coughing,
wheezing, nasal congestion, sore throat, chest Enhances therapeutic effect of Nifedipine:
congestion, dyspnea, diaphoresis Cimetidine, Grapefruit Juice
Less Common: Agranulocytosis, allergic hepatitis, alopecia,
anemia, aplastic anemia, angina, angioedema, Enhances therapeutic effect of Tizanidine
arrhythmia, arthritis with positive ANA, bezoars, cerebral
ischemia, depression, dysosmia, epistaxis, EPS, erectile Increases metabolism of Nifedipine:
dysfunction, erythromelalgia, exanthematous pustulosis, CYP3A4 Inducers (Strong), Nafcillin
erythema multiforme, exfoliative dermatitis, facial
edema, gastroesophageal reflux, gastrointestinal Increases risk of adverse or toxic effects of Nifedipine:
obstruction, gastrointestinal ulceration, gynecomastia, Azole Derivatives (Systemic) [except Fluconazole,
hematuria, ischemia, leukopenia, lip cancer, memory Isavuconazonium Sulfate], Grapefruit Juice (severe
dysfunction, migraine, myalgia, myoclonus, nocturia, hypotension; myocardial ischemia), Mifepristone,
paranoid syndrome, parotitis, periorbital edema, Stiripentol
photosensitivity, polyuria, purpura, Stevens-Johnson
syndrome, syncope, tachycardia, taste perversion, Increases risk of adverse or toxic effects of the following
thrombocytopenia, tinnitus, toxic epidermal necrolysis, drugs:
transient blindness, ventricular arrhythm Amifostine [withhold Nifedipine 24 hours prior to
Amifostine administration] (hypotensive effect),
Drug Interactions: Obinutuzumab [withhold Nifedipine 12 hours prior to
Monitor closely with: Obinutuzumab infusion until 1 hour after the end of the
Decreases metabolism of Nifedipine: infusion] (hypotensive effect), Rituximab (hypotensive
Cyclosporine (Systemic) effect), Tizanidine

Enhances antihypertensive effect of Nifedipine: Increases serum concentration of Nifedipine:

Alpha1 Blockers e.g. Alfuzosin, Barbiturates e.g. Cimetidine, Conivaptan, Fusidic Acid (Systemic),
Phenobarbital, Brimonidine (Topical), Non- Idelalisib, Mifepristone, Stiripentol
dihydropyridine Calcium Channel Blockers, Diazoxide,
Magnesium Salts, Molsidomine, Nicorandil, Other Increases serum concentration of the following drugs:
Antihypertensive Agents, Pentoxifylline, Phenytoin, Tizanidine [initiate Tizanidine at 2 mg and
Phosphodiesterase-5 Inhibitors e.g. Sildenafil, increase in 2–4 mg increments based on patient
Prostacyclin Analogues e.g. Epoprostenol response]

Enhances therapeutic effect of the following drugs: Reduces therapeutic effect of Nifedipine:
Aripiprazole, Beta Blockers (hypotensive effect; negative Dabrafenib
inotropic effect), Nondepolarizing Neuromuscular-
blocking Agents e.g. Pancuronium (neuromuscular- Administration: May be taken with or without food. Capsules
blocking effect), Nitroprusside (hypotensive effect) are rapidly absorbed orally if administered without food
but may result in vasodilator side effects. If flushing is
Increases metabolism of Nifedipine:

134
CARDIOVASCULAR SYSTEM

problematic, administer low-fat meals to decrease Hypotension or syncope (symptomatic hypotension with or
flushing. without syncope can occur; monitor blood pressure
Swallow tablets whole. Do NOT crush, split, or chew. closely during treatment); Peripheral edema.
Gastrointestinal events (intestinal pseudo-obstruction and
Teach patient orthostatic precautions. ileus)
Hepatic impairment (monitor blood pressure and heart rate
NOTE: For Adalat CC, Afeditab CR, Nifediac CC, administer closely)
on an empty stomach (as per manufacturer labelling). Hypertrophic cardiomyopathy with outflow tract obstruction
Other extended-release products may not have this Elderly (may experience a greater hypotensive response;

C
recommendation; consult product labeling. constipation may be more of a problem)
Pregnancy (crosses the placenta; adverse events have been
Nifedipine serum levels may be decreased if taken with observed in animal reproduction studies); lactation
food. Food may decrease the rate but not the extent of (excreted into breastmilk; breast-feeding is not
absorption of Procardia XL®. recommended).

Pregnancy Category: C Adverse Drug Reactions:

Common: Decreased blood pressure, bradycardia,
ATC Code: C08CA05 headache, nausea
Less Common: Anemia, decreased platelet count,
diaphoresis, edema, disseminated intravascular
coagulation, dizziness, flushing, gastrointestinal
Rx NIMODIPINE hemorrhage, GI pseudo-obstruction, hematoma,
hepatitis, hypertension, intestinal obstruction, jaundice,
Oral: 30 mg tablet muscle cramps, palpitations, pruritus, rebound
vasospasm, thrombocytopenia, vomiting, wheezing
A calcium channel blocker that inhibits calcium ion from
entering select voltage-sensitive areas of vascular Drug Interactions:
smooth muscle and myocardium during depolarization. Monitor closely with:
Nimodipine has a greater effect on cerebral arterials Decreases metabolism of Nimodipine:
than other arterials due to the drug's increased Cyclosporine (Systemic)
lipophilicity and cerebral distribution.
Enhances antihypertensive effect of Nimodipine:
Indication: Prophylaxis and treatment of ischemic Alpha1 Blockers e.g. Alfuzosin, Barbiturates e.g.
neurologic deficits caused by cerebral vasospasms Phenobarbital, Brimonidine (Topical), Non-
following subarachnoid hemorrhage of aneurysmal origin Dihydropyridine Calcium Channel Blockers e.g.
Verapamil, Diazoxide, Magnesium Salts, MAO Inhibitors
Contraindications: Concomitant use with phenobarbital, [except Linezolid, Tedizolid], Molsidomine, Nicorandil,
phenytoin, carbamazepine, or rifampin; concomitant use Other Antihypertensive Agents, Pentoxifylline,
with strong CYP3A4 inhibitors (e.g., clarithromycin, Phosphodiesterase-5 Inhibitors e.g. Sildenafil,
telithromycin, delaviridine, indinavir, nelfinavir, ritonavir, Prostacyclin Analogues e.g. Epoprostenol
saquinavir, ketoconazole, itraconazole, voriconazole,
and nefazodone) Enhances therapeutic effect of the following drugs:
Nondepolarizing Neuromuscular-blocking Agents e.g.
Dose: Pancuronium (neuromuscular-blocking effect),
Subarachnoid hemorrhage: oral: 60 mg every 4 hours for 21 Nitroprusside (hypotensive effect)
consecutive days (maximum total duration of therapy), or
until transitioning IV therapy is needed. Increases metabolism of Nimodipine:
Barbiturates e.g. Phenobarbital, Nafcillin
Dose Adjustment:
Renal Impairment: Increases risk of adverse or toxic effects of Nimodipine:
Nimodipine undergoes minimal renal elimination. Dose Dapoxetine (orthostatic hypotension)
adjustment may not be necessary. MAO Inhibitors [except Linezolid, Tedizolid] (orthostatic
Not removed by hemodialysis or peritoneal dialysis. hypotension)
Supplemental dose is not necessary. Other Antihypertensive Agents
Increases risk of adverse or toxic effects of the following
Hepatic Impairment: drugs:
Use with caution in patients with cirrhosis. Reduce dose to Atosiban (pulmonary edema and/or dyspnea),
30 mg every 4 hours. Duloxetine (orthostatic hypotension), Levodopa
(orthostatic hypotension), Magnesium Salts, Risperidone
Precautions: (hypotensive effect)
Angina or MI (increased angina and/or MI have occurred
with initiation or dosage titration CCBs; reflex Reduces antihypertensive effect of Nimodipine:
tachycardia may occur resulting in angina and/or MI in Methylphenidate
patients with obstructive coronary disease)
Reduces therapeutic effect of Clopidogrel

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 CARDIOVASCULAR SYSTEM

Avoid concomitant use with: SELECTIVE CALCIUM CHANNEL

Decreases metabolism of Nimodipine: BLOCKERS WITH DIRECT
Macrolide Antibiotics [except Azithromycin, Fidaxomicin, CARDIAC EFFECTS
Spiramycin]

Decreases serum concentration of Nimodipine: GENERAL INFORMATION

CYP3A4 Inducers (Strong), Dabrafenib
Selective calcium-channel blockers (CCBs) exhibit an
Enhances therapeutic effect of Nimodipine: inhibitory effect on L-type calcium channels. It is used for
C

Cimetidine the treatment of hypertension, angina, and arrhythmias.

Increases risk of adverse or toxic effects of Nimodipine: Mode of Action: Binds to L-type calcium channels located on
Mifepristone, Stiripentol the vascular smooth muscle, cardiac myocytes, and
cardiac nodal tissue, blocking entry of calcium into the
Increases risk of adverse or toxic effects of the following cell. This causes vascular smooth muscle relaxation,
drugs: decreased myocardial force generation, decreased heart
Amifostine [withhold Nimodipine 24 hours prior to rate, and decreased conduction velocity within the heart.
Amifostine administration] (hypotensive effect);
Obinutuzumab [withhold Nifedipine 12 hours prior to Precautions:
Obinutuzumab infusion until 1 hour after the end of the WARNING: All CCBs have some degree of negative
infusion] (hypotensive effect); Rituximab (hypotensive inotropic effect and may, in excessive doses or in
effect) combination with other drugs, produce myocardial
depression especially after MI.
Increases serum concentration of Nimodipine:
Cimetidine, Conivaptan, CYP3A4 Inhibitors (Strong),
Fusidic Acid (Systemic), Idelalisib, Mifepristone, Abrupt withdrawal and long-term use (has been associated
Stiripentol with severe angina).
Conduction abnormalities (may worsen first-degree AV
Reduces therapeutic effect of Nimodipine: block and exacerbate bradycardia); arrhythmia (severe
Dabrafenib hypotension likely to occur upon administration); heart
failure (can exacerbate condition); impaired left
Administration: Administer consistently with or without ventricular function; hypotension or syncope
meals. (symptomatic hypotension with or without syncope rarely
occur);
Swallow tablet whole with an adequate amount of fluid, Hypertrophic cardiomyopathy [HCM] with outflow tract
e.g., glass of water. Do NOT crush tablet. obstruction.
Hepatic and renal impairment (in severe impairment,
Avoid alkaline mixtures for 2 hours before or after monitor hemodynamics and ECG); Increased hepatic
administration. Patient should not be lying down during enzymes (rarely observed)
administration. Diabetes mellitus (affects insulin secretion and its
peripheral action).
Do NOT administer parenterally. Life-threatening Attenuated neuromuscular transmission (decreased
adverse events have occurred when contents of oral neuromuscular transmission has been reported).
formulation were administered parenterally. Patients taking beta-blockers or digitalis (at risk of AV block,
bradycardia, asystole, or sinus arrest);
Pregnancy Category: C Patients at risk to develop intestinal obstruction (diltiazem
has an inhibitory effect on intestinal motility; may be
ATC Code: C08CA06 associated with mood changes).
Children (severe apnea, bradycardia, hypotensive
reactions, and cardiac arrest may occur).
Elderly (greater hypotensive response; constipation may be
more of a problem)
Pregnancy (crosses the placenta; adverse events were
observed in some animal reproduction studies); lactation
(excreted into breast milk; not recommended).

136
CARDIOVASCULAR SYSTEM

Carbamazepine, Digoxin, Midazolam (sedative and

Rx DILTIAZEM respiratory depressant effects; due to decreased
metabolism), Phenytoin, Ritonavir (due to increased
Oral: 60 mg tablet (as hydrochloride) serum concentration)
60 mg, 120 mg, 180 mg, and 240 mg MR capsule (as
hydrochloride) Reduces therapeutic effect of Rifampicin (due to increased
120 mg and 180 mg MR tablet (as hydrochloride) metabolism)

A non-dihydropyridine calcium channel blocker, which has a Avoid concomitant use with:

C
negative chronotropic effect, thus decreasing the Increases risk of adverse or toxic effects of the following
workload of the heart, and consequently reducing its drugs due to increased serum concentration:
oxygen requirements. Colchicine, HMG-CoA Reductase Inhibitors, e.g.,
Atorvastatin, Simvastatin (rhabdomyolysis; myopathy)
Indication: Prophylaxis and treatment of angina
Administration: Normal release preparations may be taken
Contraindications: Marked bradycardia (<40 with or without food. Administer immediate-release
beats/minute); sick sinus syndrome (without preparations before meals and at bedtime. For long-
pacemaker); severe hypotension (<90 mmHg systolic); acting dosage forms, swallow whole. Do NOT open, chew,
CHF; acute porphyria; second- or third-degree AV block or crush.
(without pacemaker); Wolff-Parkinson-White syndrome;
acute MI and pulmonary congestion; pregnancy NOTE: Serum levels may be elevated if taken with food.

Dose: See General Information on Calcium Channel Blockers –

Angina, by mouth, ADULT, initially 30 mg 3 or 4 times daily; Selective Calcium Channel Blockers with Direct Cardiac
increase as required or at 1- to 2-day interval until Effects in Chapter 3: Cardiovascular System for other
optimum response is obtained (maximum dose, 360 mg information.
daily in 3–4 divided doses); doses of up to 360 mg/day
may be needed in unstable angina; Pregnancy Category: C
controlled-release products, initially 180 mg once daily;
increase as required up to 360 mg once daily. ATC Code: C08DB01

NOTE: Dose should not be increased if heart rate drops to

50 beats/minute.
Rx VERAPAMIL
Dose Adjustment:
Geriatric: Oral: 80 mg tablet (as hydrochloride)
Start treatment at a lower dose. 240 mg MR tablet (as hydrochloride)
Inj.: 2.5 mg/mL (as hydrochloride), 2 mL ampule (IV)
Renal Impairment:
Start treatment at a lower dose. Use with caution. A calcium channel blocker that inhibits calcium ion from
entering the “slow channels” or select voltage-sensitive
Hepatic Impairment: areas of vascular smooth muscle and myocardium
For mild-to-moderate hepatic impairment, dose reduction during depolarization, producing relaxation of coronary
may be warranted. vascular smooth muscle and coronary vasodilation.
For severe impairment, refer patient to a specialist.
Indication: Treatment of angina pectoris (vasospastic,
Adverse Drug Reactions: chronic stable, unstable), supraventricular arrhythmia,
Common: Abdominal pain, bradycardia, dizziness, dyspnea, and hypertension.
congestion, flushing, headache, fatigue, nausea,
nervousness, pain, palpitations, peripheral edema, Contraindications: Severe left ventricular dysfunction;
vasodilation, vomiting hypotension (systolic pressure <90 mm Hg) or
Less Common: AV block, gout cardiogenic shock; sick sinus syndrome (except in
Rare: Depression, EPS, gum hyperplasia, gynecomastia, patients with a functioning pacemaker) ; second- or third-
hepatitis, hypersensitivity reactions, photosensitivity degree AV block (except in patients with a functioning
reactions, rash pacemaker) ; atrial flutter or fibrillation and an accessory
bypass tract (Wolff-Parkinson-White [WPW] syndrome,
Drug Interactions: Lown-Ganong-Levine syndrome)
Monitor closely with:
Increases risk of adverse or toxic effects of Diltiazem: Dose:
Drugs causing hypotension, bradycardia, or slow cardiac Angina, by mouth, ADULT, immediate-release tablets,
conduction, e.g., Amlodipine, Diazepam, Methyldopa; initially 80-120 mg 3 times daily; usual dose range, 80-
Hydrochlorothiazide (bradycardia; hypotension) 160 mg 3 times daily;
modified-release tablets, initially 180 mg once daily at
Increases risk of adverse or toxic effects of the following bedtime; if inadequate response, may increase dose at
drugs: weekly intervals to 240 mg once daily, then 360 mg once

137
 CARDIOVASCULAR SYSTEM

daily, then 480 mg once daily (maximum dose, 480 mg Enhances therapeutic effect of the following drugs:
daily). Aripiprazole, Beta Blockers [except Levobunolol,
Metipranolol] (hypotensive effect), Cardiac Glycosides
Hypertension, by mouth, ADULT, immediate-release tablets, (AV blocking effect), Ethyl Alcohol, Fingolimod
initially 80-120 mg 3 times daily; usual dose range, 80- (bradycardic effect), Lacosamide (AV blocking effect),
160 mg 3 times daily; Midodrine (bradycardic effect), Non-depolarizing
sustained-release tablets, initially 180-240 mg once Neuromuscular-blocking Agents e.g. Atracurium
daily at bedtime. (neuromuscular-blocking effect), Nitroprusside
(hypotensive effect), Salicylates (anticoagulant effect)
C

Dose Adjustment:
Renal Impairment: Increases risk of adverse or toxic effects of Verapamil:
Use with caution. Monitor ECG. MAO Inhibitors [except Linezolid, Tedizolid] (orthostatic
Hepatic Impairment: hypotension); Other Antihypertensive Agents
Dose reduction may be required.
In patients with cirrhosis, reduce dose to 20% of normal Avoid concomitant use with:
dose. Monitor ECG. Decreases metabolism of Verapamil:
Azole Derivatives (Systemic) e.g. Ketoconazole,
Adverse Drug Reactions: Carbamazepine, Cyclosporine (Systemic), CYP3A4
Common: Peripheral edema, hypotension, CHF, pulmonary Inhibitors (Strong), Macrolide Antibiotics [except
edema, AV block, bradycardia, flushing, headache, Azithromycin, Fidaxomicin, Spiramycin], Protease
fatigue, dizziness, lethargy, pain, sleep disturbance, Inhibitors e.g. Indinavir [reduce Verapamil dose by 50%]
rash, gingival hyperplasia, constipation, dyspepsia,
nausea, diarrhea, myalgia, paresthesia, dyspnea, flu­like Enhances therapeutic effect of Verapamil:
syndrome Cimetidine, Ivabradine (QTc-prolonging effect),
Less Common: Abdominal discomfort, alopecia, angina, Telithromycin (bradycardic effect; antihypertensive
arthralgia, atrioventricular dissociation, blurred vision, effect)
bruising, cerebrovascular accident, chest pain,
claudication, confusion, diaphoresis, ECG abnormal, Enhances therapeutic effect of the following drugs:
equilibrium disorders, erythema multiforme, exanthema, Amiodarone (bradycardic effect) Ceritinib (bradycardic
extrapyramidal symptoms, galactorrhea or effect), Dantrolene (negative inotropic effect),
hyperprolactinemia, gastrointestinal distress, Dronedarone (AV-blocking effect and other
gynecomastia, hyperkeratosis, impotence, insomnia, electrophysiologic effects), Ivabradine (bradycardic
macules, MI, muscle cramps, palpitation, psychosis, effect), Tizanidine
purpura (vasculitis), shakiness, somnolence, spotty
menstruation, SJS, syncope, tinnitus, urination Increases metabolism of Verapamil:
increased, urticaria, weakness, xerostomia, asystole, CYP3A4 Inducers, Nafcillin
eosinophilia, EPS, exfoliative dermatitis, GI obstruction,
hair color change, paralytic ileus, Parkinsonian Increases risk of adverse or toxic effects of Verapamil:
syndrome, pulseless electrical activity, shock, ventricular Azole Derivatives e.g., Ketoconazole (Systemic) (negative
fibrillation inotropic effects); Calcium Channel Blockers,
Dihydropyridine e.g. Amlodipine (hypotensive effect),
Drug Interactions: Dantrolene (hyperkalemic effect), Mifepristone,
NOTE: Verapamil is a substrate of CYP1A2 (minor), CYP2B6 Protease Inhibitors (AV nodal blockade), Stiripentol
(minor), CYP2C9 (minor), CYP2E1 (minor), CYP3A4
(major), and P-glycoprotein. Increases risk of adverse or toxic effects of the following
drugs:
Monitor closely with: Amifostine [withhold Verapamil 24 hours prior to
Decreases metabolism of the following drugs: Amifostine administration], Amiodarone (sinus arrest),
Pimecrolimus, Tacrolimus Avanafil, Budesonide (corticosteroid excess),
Carbamazepine, Ceritinib (symptomatic bradycardia),
Enhances antihypertensive effect of Verapamil: Colchicine (Colchicine toxicity), Disopyramide (profound
Alfuzosin; Alpha1 Blockers e.g. Clonidine; depression of myocardial contractility), Fosphenytoin
Anilidopiperidine Opioids e.g. Fentanyl; Barbiturates e.g. (Phenytoin toxicity), Ibrutinib; Lovastatin [initiate
Phenobarbital, Brimonidine (Topical); Diazoxide; Lovastatin at 10 mg daily; do not exceed 20 mg daily]
Magnesium Salts; MAO Inhibitors [except Linezolid, (myositis; rhabdomyolysis), Obinutuzumab [withhold
Tedizolid]; Molsidomine; Nicorandil; Pentoxifylline; Nicardipine 12 hours prior to Obinutuzumab infusion
Phosphodiesterase-5 Inhibitors e.g. Sildenafil; until 1 hour after the end of the infusion] (hypotensive
Prostacyclin Analogues e.g. Epoprostenol; Quinidine, effect), Oxycodone, Phenytoin, Rituximab (hypotensive
Other Antihypertensive Agents effect), Sonidegib (musculoskeletal adverse reactions),
Tizanidine, Ulipristal, Zopiclone
Enhances therapeutic effects of Verapamil:
Bradycardic effect: Anilidopiperidine Opioids, Bretylium Increases serum concentration of Verapamil:
(AV blockade), Other Bradycardia-causing Agents, Atorvastatin, Cimetidine, Conivaptan, Fusidic Acid
Regorafenib, Ruxolitinib, Tofacitinib (Systemic), Grapefruit Juice, Mifepristone, Protease
AV blocking effect: Clonidine, Bretylium Inhibitors e.g. Indinavir [reduce Verapamil dose by 50%]
Stiripentol

138
CARDIOVASCULAR SYSTEM

Increases serum concentration of the following drugs: Precautions:

Vincristine (Liposomal); Zopiclone [initial Zopiclone dose
should not exceed 3.75 mg] WARNING: Severe withdrawal syndrome (rebound
HTN) may occur after abrupt discontinuation.
Reduces therapeutic effect of Verapamil: Sudden cessation of treatment has, in some cases,
Carbamazepine, Phenytoin resulted in nervousness, agitation, headache, and
tremor accompanied or followed by a rapid rise in
TEST INTERACTION. May produce a false-positive result in the urine BP and elevated catecholamine concentration in
detection of Methadone. the plasma.

C
Administration: May be administered without regard to
Withdrawal syndrome (may be worsened by concomitant
meals. Do NOT crush or chew MR products.
administration of beta blockers; taper dose over 5–7
days before stopping the drug; excessive rise in BP
For Calan SR, Isoptin SR, administer with food or milk.
following discontinuation can be reversed by oral
administration).
Pregnancy Category: C
Mild-to-moderate bradyarrhythmia, constipation, or
polyneuropathy (avoid use in patients with depression or
ATC Code: C08DA01
a history of it); coronary heart disease, severe coronary
insufficiency, conduction disturbances, recent MI,
See Verapamil under Cardiac Therapy – Antiarrhythmics
cerebrovascular disease, Raynaud’s phenomenon or
(Class IV Antiarrhythmics) in Chapter 3: Cardiovascular
other vasospastic peripheral vascular disease (may be
System for other information.
exacerbated).
CNS effects (may cause drowsiness; may increase effects
of alcohol); diabetes mellitus (may cause transient rise
CENTRALLY ACTING in blood glucose); renal impairment (may worsen chronic
ANTIADRENERGIC AGENTS renal failure).
Surgery (stopping abruptly may precipitate a severe
withdrawal syndrome).
Rx CLONIDINE Elderly (can cause drowsiness); children (may be
particularly susceptible to hypertensive episodes
resulting from abrupt inability to take medication).
Oral: 75 micrograms and 150 micrograms tablet (as
Pregnancy (may lower fetal heart rate; risk should be
hydrochloride)
balanced against the risk of uncontrolled maternal
Inj.: 150 micrograms/mL (as hydrochloride), 1 mL ampule
hypertension; avoid IV injection); lactation (avoid use if
(IV)
possible; limited data available; present in breastmilk;
may decrease prolactin secretion).
An imidazoline-derived, centrally-acting agonist at alpha2-
adrenoceptors and imidazoline receptors, which acts by SKILLED TASKS. May impair ability to drive or operate machinery due
reducing sympathetic tone resulting in BP lowering. to drowsiness.

Indication: Hypertension (alone or used concomitantly with Adverse Drug Reactions:

other antihypertensive agents) Common: Constipation, depression, dizziness, drowsiness,
dry mouth, fatigue, headache, malaise, nausea,
Contraindications: Bradyarrhythmia secondary to second- or orthostatic hypotension, salivary gland pain, sedation,
third-degree AV block or sick sinus syndrome. sexual dysfunction, sleep disturbances, vomiting.
Less Common: Bradycardia, confusion, delusion, disturbed
Dose: mental state, hallucination, itching, nightmare,
NOTE: Individualize dose based on patient’s BP response. paresthesia, pruritus, rash, urticaria.
Rare: Alopecia, AV block, colonic pseudoobstruction,
Hypertension, by mouth, ADULT, initially 75 micrograms 2– decreased lacrimation, dry eyes, gynecomastia,
3 times daily, increased by 75 micrograms daily every 2– hepatitis, impaired visual accommodation, nasal
3 days (maximum dose, 1.2 mg daily; maintenance dose, dryness, Raynaud’s phenomenon, urinary retention.
150–300 micrograms twice daily).
Hypertensive urgencies, by mouth, ADULT, 75 micrograms. Drug Interactions:
Monitor closely with:
Dose Adjustment: Enhances therapeutic effect of Clonidine:
Renal Impairment: CNS Depressants [e.g., Alcohol, Barbiturates, Other
Adjust dose according to the degree of impairment. Patients Sedating Drugs], Drugs that affect sinus node function or
may benefit from a lower initial dose. AV nodal conduction [e.g., Digitalis, CCB (AV block;
For mild-to-moderate impairment, use with caution. bradycardia)]
For severe impairment, refer to a specialist.
Increases risk of adverse or toxic effects of Clonidine:
CNS Depressants [e.g., Alcohol, Barbiturates, Other
Sedating Drugs (sedation; bradycardia; hypotension)],
Drugs that reduce blood pressure and slow heart rate
(bradycardia; hypotension)

139
 CARDIOVASCULAR SYSTEM

Avoid concomitant use with: Common: Diarrhea, dizziness, dryness of mouth, fatigue,
Increases risk of adverse or toxic effects of Clonidine: fever, headache, light-headedness, positive Coombs’
Beta Blockers e.g., Propranolol (bradycardia; test, sedation, tiredness, weakness.
hypotension; paradoxical increase in BP), Drugs that Less Common: Angina, bradycardia, constipation,
reduce blood pressure and slow heart rate (bradycardia; depression, edema, sodium and water or fluid retention,
hypotension) hemolytic anemia, impaired concentration and memory,
decreased libido and impotence in men, nasal
Reduces therapeutic effect of Clonidine: congestion, orthostatic hypotension, psychosis, rash,
Tricyclic Antidepressants e.g. Amitryptilline sleep disturbance, sore or “black” tongue.
C

(antihypertensive effect) Rare: Arthralgia, bone marrow depression, hepatotoxicity

with acute or chronic active hepatitis or hepatic necrosis,
Administration: If further increments are needed to produce hyperprolactinemia, hypersensitivity reactions, jaundice,
the desired response, take larger portion of the oral daily leukopenia, myocarditis, nausea, pancreatitis,
dose at bedtime to minimize drowsiness and dry mouth. Parkinsonism, pericarditis, sialadenitis, stomatitis,
Advise the patient to get up gradually from sitting or lying thrombocytopenia, toxic epidermal necrolysis, urine
to minimize this effect, and to sit or lie down if the patient darkens on standing, vomiting.
becomes dizzy or light-headed.
Drug Interactions:
Pregnancy Category: C Monitor closely with:
Enhances therapeutic effect of Methyldopa:
ATC Code: C02AC01 Antihypertensive effect: Chlorpromazine, Drugs that
reduce blood pressure

Increases risk of adverse or toxic effects of Methyldopa:

Rx METHYLDOPA Chlorpromazine (extrapyramidal effects), Salbutamol
(acute hypotension)
Oral: 250 mg tablet
Avoid concomitant use with:
A centrally-acting, alpha2-adrenoceptor agonist that is Reduces therapeutic effect of Methyldopa:
useful in the management of hypertension in pregnancy. Ibuprofen (antagonizes antihypertensive effect), Iron
Preparations {e.g., Ferrous Sulfate, Ferrous Gluconate
Indication: For gestational hypertension and chronic [due to reduced bioavailability] (antihypertensive
hypertension in pregnant women. effect)}, Oral Contraceptives (Estrogen antagonizes
antihypertensive effect)
Contraindications: Pheochromocytoma; active liver disease;
depression, porphyria; patients in whom previous TEST INTERACTION. Produces a positive direct Coombs’
methyldopa treatment resulted in liver abnormalities, or Test, interfering with blood cross-matching.
direct Coombs’ positive hemolytic anemia
Administration: May be taken with or without food.
Dose:
Hypertension in pregnancy, by mouth, ADULT, initially 250 Advise the patient to get up gradually from sitting or lying
mg 2–3 times daily; gradually increase at intervals of 2 to minimize this effect, and to sit or lie down if the patient
or more days, if necessary; (maximum dose, 3 g daily). becomes dizzy or light-headed.

Dose Adjustment: Pregnancy Category: B

Renal Impairment:
Start with a small dose or adjust dosage frequency. May ATC Code: C02AB01 (levorotatory)
require only usual initial dose. C02AB02 (racemic)
For severe impairment, refer patient to a specialist.

Precautions:
Avoid abrupt withdrawal; monitor blood count and liver
DIURETICS
function before treatment and at intervals during first 6–
12 weeks, or if unexplained fever occurs. LOW-CEILING DIURETICS
History of depression (may be exacerbated).
Renal impairment (increased sensitivity to hypotensive and
sedative effects); Hepatic impairment (caution in history Rx HYDROCHLOROTHIAZIDE
of liver disease; avoid use if possible).
Lactation (amount in breastmilk is too small to be harmful).
Oral: 12.5 mg and 25 mg tablet
SKILLED TASKS. May impair ability to perform skilled or
hazardous tasks, e.g., operating machinery or driving. A moderately-potent, thiazide diuretic whose maximal
antihypertensive effect is usually observed at doses
Adverse Drug Reactions: lower than those that produce maximal diuretic effect. It
acts by blocking the reabsorption of sodium in the distal
convoluted tubules of the nephrons.

140
CARDIOVASCULAR SYSTEM

Indications: Management of mild hypertension (alone), or in Avoid concomitant use with:

moderate or severe hypertension (in combination with Increases risk of adverse or toxic effects of
other drugs); edema. Hydrochlorothiazide:
ACE Inhibitors (severe hypotension with the first ACEi
Contraindications: Severe renal impairment or anuria; dose), Angiotensin II Receptor Blockers (excessive
severe hepatic impairment; hyponatremia; hypotension with the first ARB dose due to volume
hypercalcemia; refractory hypokalemia; symptomatic depletion), Hydrocortisone (hypokalemia), Ibuprofen
hyperuricemia; Addison disease. (nephrotoxicity), NSAIDs including Selective COX-2
Inhibitors (nephrotoxicity)

C
Dose:
Hypertension, by mouth, ADULT, 12.5–25 mg daily, Reduces therapeutic effect of Hydrochlorothiazide:
increase to 25–100 mg daily if necessary; CHILD, refer Hydrocortisone (antagonism of diuretic effect), Ibuprofen
to a specialist. (antagonism of diuretic effect), NSAIDs including
Selective COX-2 Inhibitors (renal function; diuretic and
Dose Adjustment: antihypertensive effect), Lidocaine, Metformin
Renal Impairment: (antagonism of hypoglycemic effect), Oral
Avoid use if creatinine clearance <10 mL/minute. Contraceptives (antagonism of antihypertensive effect)

Precautions: Administration: Usually taken once daily in the morning. If

High doses (may cause hypokalemia; avoid use if there is the patient is to take it twice a day, take the first dose in
history of kidney stones). the morning and the second dose before 6 in the
Hypokalemia (may precipitate coma). evening.
Gout (diuretic-induced rise in serum uric acid
concentration). Pregnancy Category: B
Heart failure with significant edema (hyponatremia may
occur). ATC Code: C03AA03
Hepatic impairment (may precipitate hepatic coma or
encephalopathy).
Alcoholic cirrhosis (increased risk of hypomagnesemia).
Renal impairment (may aggravate diabetes mellitus, gout, Rx INDAPAMIDE
and systemic lupus erythematosus); porphyria.
Elderly (more susceptible to electrolyte imbalance and Oral: 1.5 mg MR tablet
orthostatic hypotension).
Pregnancy (avoid use; may cause electrolyte disturbances A thiazide-related diuretic that exerts its diuretic effect at
and thrombocytopenia in neonates if used during third the proximal segment of the distal tubule of the nephron
trimester; reduction of maternal blood volume may by enhancing sodium, chloride, and water excretion, thus
diminish uteroplacental perfusion); Lactation (may interfering with the transport of sodium ions across the
inhibit lactation). renal tubular epithelium. It does not appear to have
significant effect on glomerular filtration rate or renal
Adverse Drug Reactions: blood flow.
Common: Dizziness, headache, hyperuricemia,
hypochloremic alkalosis, hypokalemia, Indication: Management of mild-to-moderate hypertension
hypomagnesemia, hyponatremia, lethargy, muscle in combination with other anti-hypertensive agents.
cramps, orthostatic hypotension, polyuria, weakness
Less Common: Blurred vision, dyslipidemia, hypercalcemia, Contraindication: Anuria
hyperglycemia, impotence, rash
Rare: Agranulocytosis, aplastic anemia, cardiac Dose:
arrhythmias, cholecystitis, constipation, dermatitis, Hypertension, by mouth, ADULT, 1.5 mg once daily; doses
diarrhea, hemolytic anemia, hypersensitivity reactions, >1.5 mg daily may increase saluretic effect.
impotence, intrahepatic cholestatic jaundice,
leukopenia, nausea, necrotizing vasculitis, pancreatitis, Dose Adjustment:
purpura, thrombocytopenia, toxic epidermal necrolysis, Renal Impairment:
visual disturbances, vomiting Do not use in patients with CrCl <30 mL/minute.

Drug Interactions: Hepatic Impairment:

Monitor closely with: Do not use in patients with severe hepatic impairment or
Enhances therapeutic effect of Hydrochlorothiazide: hepatic encephalopathy.
Drugs that reduce blood pressure (additive hypotensive
effects), Loop Diuretics (synergistic effect; profound Precautions:
diuresis and serious electrolyte disturbance)
WARNING: Prolongs QT interval and is accepted as
Increases risk of adverse or toxic effects of having a risk of causing torsade de pointes. The
Hydrochlorothiazide: risk of drug-induced torsade de pointes is
Digoxin (cardiac toxicity due to hypokalemia), Potassium- extremely low with one QT interval prolonging drug.
lowering Drugs (hypokalemia), Salbutamol (hypokalemia
with high doses)

141
 CARDIOVASCULAR SYSTEM

Electrolyte disturbances (severe hyponatremia with Barbiturates e.g. Phenobarbital (orthostatic

hypokalemia has been reported; dose-dependent; hypotension), Beta2 Agonists (hypokalemia), Calcium
hypochloremic alkalosis, hypomagnesemia, or Salts (metabolic alkalosis due to decreased excretion of
hypercalcemia may occur); photosensitivity; sulfonamide Calcium Salts), Corticosteroids (hypokalemia),
(potential for T-cell-mediated type IV reactions). Dexketoprofen, Ethyl Alcohol (orthostatic hypotension),
Diabetes (may alter glucose control); gout (can be Opioid Analgesics, Other Antihypertensive Agents,
precipitated). Licorice (hypokalemia), Multivitamins / Fluoride with ADE
Hypercholesterolemia (may increase cholesterol (hypercalcemic effect), Multivitamins / Minerals [with
concentration). ADEK, Folate, Iron (hypercalcemic effect)], Multivitamins
C

Hypokalemia (use with caution; correct before initiating / Minerals [with AE, no Iron
therapy).
Hepatic impairment (use with caution; undergoes extensive Increases risk of adverse or toxic effects of the following
hepatic metabolism; electrolyte and acid / base drugs:
imbalance in cirrhosis might lead to hepatic ACE Inhibitors (nephrotoxicity), Allopurinol (allergic or
encephalopathy). hypersensitivity reactions), Carbamazepine
Renal impairment (use with caution; approximately 70% is (hyponatremia), Cardiac Glycosides (toxicity due to
excreted in the urine). hypokalemic and hypomagnesemic effects of
Systemic lupus erythematosus (can cause exacerbation or Indapamide), Cyclophosphamide (granulocytopenia),
activation). Diazoxide, Duloxetine (orthostatic hypotension),
Elderly (increased risk for severe hyponatremia with Levodopa (orthostatic hypotension), MAO Inhibitors
hypokalemia in elderly women). [except Linezolid, Tedizolid] (orthostatic hypotension),
Pregnancy (crosses the placenta; found in cord blood; may Oxcarbazepine (hyponatremia), Porfimer
cause fetal or neonatal jaundice, thrombocytopenia, or (photosensitizing effect)
other adverse events); lactation (not known if excreted in
breast milk). Reduces therapeutic effect of Indapamide:
Herbs with hypertensive properties, NSAIDS
Adverse Drug Reactions:
Common: Agitation, anxiety, dizziness, fatigue, headache, Reduces therapeutic effect of Antidiabetic Agents
irritability, lethargy, malaise, nervousness, pain, tension,
tiredness, hypokalemia, back pain, muscle cramps or Avoid concomitant use with:
spasm, paresthesia, weakness, rhinitis, infection, Decreases absorption of Indapamide:
arrhythmia, chest pain, flushing, orthostatic hypotension, Bile Acid Sequestrants e.g. Cholestyramine
palpitation, peripheral edema, PVC, vasculitis,
depression, drowsiness, insomnia, lightheadedness, Decreases excretion of Lithium
vertigo, hives, pruritus, rash, hyperglycemia,
hyperuricemia, hypochloremia, hyponatremia, Enhances therapeutic effect of the following drugs:
decreased libido, abdominal pain, anorexia, Dofetilide (QTc-prolonging effect), QTc-prolonging Agents
constipation, cramping, diarrhea, dyspepsia, gastric
irritation, nausea, vomiting, weight loss, xerostomia, Increases risk of adverse or toxic effects of Indapamide:
nocturia, polyuria, hypertonia, blurred vision, Mifepristone (QTc-prolonging effect), SSRIs e.g.
conjunctivitis, glycosuria, cough, pharyngitis, rhinorrhea, Fluoxetine (hyponatremic effect)
sinusitis, flu­like syndrome
Less Common: Agranulocytosis, anaphylactic reaction, Increases risk of adverse or toxic effects of the following
aplastic anemia, bullous eruptions, erythema drugs:
multiforme, fever, hepatitis, hypercalcemia, cholestatic Amifostine (hypotensive effect), Levosulpiride, Rituximab
jaundice, leukopenia, pancreatitis, photosensitivity, (hypotensive effect), Sodium Phosphates (nephrotoxic
pneumonitis, purpura, Stevens-Johnson syndrome, effect, specifically the risk of acute phosphate
thrombocytopenia, torsade de pointes nephropathy), Topiramate (hypokalemic effect),
Risperidone (hypotensive effect), Verteporfin
Drug Interactions: (photosensitizing effect), Vitamin D Analogues
Monitor closely with: (hypercalcemic effect)
Enhances therapeutic effect of Indapamide:
Antihypertensive effects: ACE Inhibitors, Alfuzosin, Increases serum concentration of the following drugs:
Brimonidine [Topical], Diazoxide, Ethyl Alcohol, Herbs Dofetilide, Topiramate
with hypotensive properties, MAO Inhibitors [except
Linezolid, Tedizolid], Methylphenidate, Molsidomine, Reduces therapeutic effect of Indapamide:
Nicorandil, Other Antihypertensives, Pentoxifylline, Bile Acid Sequestrants e.g. cholestyramine (diuretic
Phosphodiesterase-5 Inhibitors e.g. Sildenafil, response)
Prostacyclin Analogues e.g. Epoprostenol
Administration: May be administered without regard to
Enhances therapeutic effect of the following drugs: meals. Administer with food or milk to decrease GI
QTc-prolonging Agents, Ivabradine (arrhythmogenic adverse effects.
effect)
Administer early in the day to avoid nocturia.
Increases risk of adverse or toxic effects of Indapamide:
Swallow whole. Do NOT crush or chew.

142
CARDIOVASCULAR SYSTEM

Pregnancy Category: B Ototoxicity (may occur with rapid IV administration, renal

impairment, excessive doses, and concurrent use of
ATC Code: C03BA11 other ototoxins),
Sulfonamide allergy (may stimulate T-cell-mediated type IV
reactions),
HIGH-CEILING DIURETICS Cirrhosis and ascites (sudden changes in fluid and
electrolyte balance and acid / base status may lead to
hepatic encephalopathy; increased risk of precipitating
Rx BUMETANIDE hepatic coma),

C
Renal impairment (may exhibit diminished effects;
increased risk of adverse effects).
Oral: 1 mg tablet Diuretic resistance (can be overcome by IV administration,
Inj.: 500 micrograms/mL, 4 mL ampule (IM, IV) use of two diuretics together, or the use of a diuretic with
a positive inotropic agent; monitor serum electrolytes
A loop diuretic that inhibits reabsorption of sodium and very closely).
chloride in the ascending loop of Henle and proximal Surgical patients (may render the patient volume depleted
renal tubule, interfering with the chloride-binding and blood pressure may be labile during general
cotransport system, thus causing increased excretion of anesthesia if given the morning of surgery),
water, sodium, chloride, magnesium, phosphate, and Elderly (excess amounts can lead to profound diuresis with
calcium. fluid and electrolyte loss; severe loss of sodium and/or
increase in BUN can cause confusion); neonates (potent
Indications: Management of congestive heart failure; displacer of bilirubin in critically ill patients),
management of edema secondary to heart failure or Pregnancy (adverse events have been observed in animal
hepatic or renal disease, including nephrotic syndrome reproduction studies); lactation (not known if excreted in
breastmilk; can decrease milk volume and suppress
Contraindications: Anuria; hepatic coma or states of severe lactation; breast­feeding is not recommended),
electrolyte depletion until the condition improves or is
corrected Adverse Drug Reactions:
Common: Dizziness, hyperuricemia, hypochloremia,
Dose: hypokalemia, hyponatremia, hyperglycemia, phosphorus
Heart failure, by mouth, ADULT, 0.5–2 mg 1–2 times daily; change, variations in bicarbonate and CO2 content,
may repeat in 4–5 hours for up to 2 doses (maximum abnormal serum calcium, abnormal lactate
dose, 10 mg daily); dehydrogenase, azotemia, and muscle cramps.
by IM or IV injection, 0.5–1 mg per dose; may repeat in Less Common: Abdominal pain, arthritic pain, asterixis,
2–3 hours for up to 2 doses (maximum dose, 10 mg auditory impairment, brain disease (preexisting liver
daily). disease), chest pain, dehydration, diaphoresis, diarrhea,
Edema, by mouth, ADULT, 0.5–2 mg 1–2 times daily; may dyspepsia, ECG changes, erectile dysfunction, fatigue,
repeat in 4–5 hours for up to 2 doses (maximum dose, glycosuria, headache, hyperventilation, hypotension,
10 mg daily); musculoskeletal pain, nausea, nipple tenderness,
by IM or IV injection, 0.5–1 mg per dose; may repeat in orthostatic hypotension, otalgia, ototoxicity, premature
2–3 hours for up to 2 doses (maximum dose, 10 mg ejaculation, proteinuria, pruritus, renal failure, skin rash,
daily; Stevens-Johnson syndrome, thrombocytopenia, toxic
by mouth, IM or IV injection, CHILD and INFANT, 0.015– epidermal necrolysis, urticaria, vertigo, vomiting,
0.1 mg/kg per dose every 6–24 hours (maximum dose, weakness, xerostomia
10 mg daily).
Drug Interactions:
NOTE: Adjust doses based on individual patient’s needs. Monitor closely with:
Dose equivalency for patients with normal renal function Enhances therapeutic effect of Bumetanide:
(approximate): Furosemide 40 mg = Bumetanide 1 mg = Antihypertensive effect: Alfuzosin, Barbiturates e.g.
Torsemide 20 mg = Ethacrynic Acid 50 mg Phenobarbital, Brimonidine [Topical], Diazoxide, Herbs
with hypotensive properties, MAO Inhibitors [except
Precautions: Linezolid, Tedizolid], Molsidomine, Nicorandil, Other
WARNING: Bumetanide is a potent diuretic. If given in Antihypertensive Agents, Pentoxifylline,
excess, can lead to a profound diuresis with water Phosphodiesterase-5 Inhibitors e.g. Sildenafil,
and electrolyte depletion. Careful medical Prostacyclin Analogues e.g., Epoprostenol
supervision is required. Diuretic effect: Fosphenytoin

Enhances therapeutic effect of the following drugs:

Fluid or electrolyte loss (can lower serum calcium
Dofetilide (QTc-prolonging effect), Ivabradine
concentrations; can predispose a patient to serious
(arrhythmogenic effect), Neuromuscular-blocking Agents
cardiac arrhythmias), (neuromuscular-blocking effect)
Hyperuricemia; Nephrotoxicity (monitor fluid status and
renal function to prevent oliguria, azotemia, and
Increases risk of adverse or toxic effects of Bumetanide:
reversible increases in BUN and creatinine),
Beta2 Agonists (hypokalemic effect), Corticosteroids
(hypokalemic effect), Cyclosporine, Licorice

143
 CARDIOVASCULAR SYSTEM

(hypokalemic effect), Opioid Analgesics, Other

Antihypertensive Agents, Probenecid Rx FUROSEMIDE

Increases risk of adverse or toxic effects of the following Oral: 20 mg and 40 mg tablet
drugs: Inj.: 10 mg/mL, 2 mL ampule (IM, IV)
ACE Inhibitors (hypotensive and nephrotoxic effects), 10 mg/mL, 25 mL ampule (IV infusion)
Allopurinol, Aminoglycosides (nephrotoxicity; ototoxicity),
Cardiac Glycosides (hypokalemia; hypomagnesemia), A potent, high-ceiling, sulfonamide loop diuretic, which
Cisplatin (nephrotoxicity; ototoxicity), Duloxetine produces dose dependent diuresis of relatively short
C

(orthostatic hypotension), Levodopa (orthostatic duration.

hypotension), MAO Inhibitors [except Linezolid, Tedizolid]
(orthostatic hypotension), Topiramate (hypokalemic Indications: Management of edema; pulmonary edema;
effect) cerebral edema; hepatic cirrhosis; nephrotic syndrome;
oliguria due to renal failure; congestive heart failure
Reduces therapeutic effect of Bumetanide:
Methylphenidate (antihypertensive effect), Phenytoin Contraindication: Severe fluid and sodium depletion
(diuretic effect), Probenecid, Salicylates (diuretic effect),
Dose:
Reduces therapeutic effect of the following drugs: Edema, by mouth, ADULT, 40 mg daily in divided doses, may
Antidiabetic Agents, Neuromuscular-blocking Agents be increased gradually to 120 mg in resistant edema;
(neuromuscular-blocking effect) CHILD, 1–3 mg/kg daily (maximum, 40 mg daily);
INFANT, 1–6 mg/kg daily given in divided doses every 6–
Avoid concomitant use with: 12 hours; NEONATES or PREMATURE INFANTS, 1–4
Decreases absorption of Bumetamide: mg/kg per dose once or twice daily due to poor
Bile Acid Sequestrants e.g. Cholestryamine bioavailability;
by IV injection, NEONATES or PREMATURE INFANTS, 1–2
Enhances therapeutic effect of Bumetanide: mg/kg per dose every 12–24 hours;
Canagliflozin (antihypertensive effect) by continuous IV infusion, NEONATES or PREMATURE
INFANTS, 0.05 mg/kg per hour (maximum, 0.4 mg/kg
Increases risk of adverse or toxic effects of the following per hour).
drugs: Heart failure, by mouth, ADULT, initially 20–40 mg; may
Hypotensive effect: Amifostine, Levosulpiride, repeat the same dose or increase dose in increments of
Obinutuzumab, Risperidone, Rituximab 20–40 mg per dose at intervals of 6–8 hours (maximum
Sodium Phosphates (nephrotoxic effect, specifically, total daily dose, 600 mg); usual maintenance dose
acute phosphate nephropathy) interval is once or twice daily; adjust dosing frequency
based on patient-specific needs; CHILD and INFANT,
Increases serum concentration of Bumetanide: initially 2 mg/kg per dose, increased in increments of 1–
Methotrexate 2 mg/kg per dose at intervals of 6–8 hours until a
satisfactory response is achieved (maximum dose, 6
Increases serum concentration of the following drugs: mg/kg per dose);
Foscarnet, Methotrexate by IM or IV injection, ADULT, initially 20–40 mg per dose,
may repeat the same dose or increase dose in
Reduces therapeutic effect of Bumetanide: increments of 20 mg per dose and administer 1–2 hours
Methotrexate, NSAIDS (diuretic effect) after previous dose (maximum dose, 200 mg per dose);
given once or twice daily; CHILD and INFANT, initially 1
Administration: mg/kg per dose, may increase dose in increments of 1
For oral administration, take without food. Administering mg/kg per dose and administer not sooner than 2 hours
with food slows the rate of absorption and reduces the after previous dose, until a satisfactory response is
extent of absorption and may reduce diuretic efficacy. achieved; may administer maintenance dose at intervals
May require increased intake of potassium-rich foods. of every 6–12 hours (maximum dose, 6 mg/kg per dose);
by continuous IV infusion, ADULT, initially administer an
Administer an alternate-day schedule or a 3–4 daily IV bolus dose 40–100 mg over 1 to 2 minutes, followed
dosing regimen with rest periods of 1–2 days in between. by continuous IV infusion rate of 10–40 mg/hour; repeat
loading dose before increasing infusion rate.
For IV administration, administer slowly, over 1–2 Acute pulmonary edema, by slow IV injection, ADULT, 40 mg
minutes. initially, dose may be doubled every hour until a ceiling
dose of 160 mg; CHILD 1 mg/kg daily (maximum,
Pregnancy Category: C 6mg/kg daily);
by slow IV drip or infusion, ADULT, 40 mg/hour.
ATC Code: C03CA02 Oliguria with glomerular filtration rate <20 mL/minute, by
slow IV infusion at a rate not exceeding 4 mg/minute,
ADULT, initially 250 mg over 1 hour; if urine output is not
satisfactory during the hour after the first dose, infuse
500 mg over 2 hours then, if there is no satisfactory
response during the hour after the second dose, infuse
1 g over 4 hours; if there still is no response after the

144
CARDIOVASCULAR SYSTEM

third dose, dialysis is probably necessary; may repeat photosensitivity, Stevens-Johnson syndrome,
effective dose, up to 1 g, every 24 hours. thrombocytopenia, tinnitus, vertigo

Dose Adjustment: Drug Interactions:

Geriatric: Monitor closely with:
Reduce dose. Enhances therapeutic effect of Furosemide:
Alcohol (antihypertensive effect), Thiazide Diuretics [e.g.,
Renal Impairment: Hydrochlorothiazide (profound diuresis; serious
In acute renal failure, higher doses may be required to electrolyte disturbance)]

C
initiate desired response. Avoid use in oliguric states.
Not removed by hemodialysis or peritoneal dialysis. Increases risk of adverse or toxic effects of Furosemide:
Supplemental dose is not necessary. Salbutamol (hypokalemia)
In CrCl <25 mL/minute, use upper end of the initial infusion
dosage range. If urine output is <1 mL/kg per hour, Increases risk of adverse or toxic effects of the following
double as necessary to a maximum of 80–160 mg/hour. drugs:
Monitor effects, particularly with high doses. ACE Inhibitors [e.g., Enalapril (severe hypotension with
the first ACEi dose; ACEi-induced renal impairment)],
NOTE: Dose equivalency for patients with normal renal function ARBs (excessive hypotension with the first ARB dose due
(approximate): Furosemide 40 mg = Bumetanide 1 mg = to volume depletion), Drugs causing hypotension [e.g.,
Torsemide 20 mg = Ethacrynic Acid 50 mg
Amlodipine, Diazepam, Hydrochlorothiazide, Methyldopa
(hypotension)], Digoxin (cardiac toxicity due to
Precautions: hypokalemia), NSAIDs including COX-2 Inhibitors
(nephrotoxicity), Ototoxic Drugs [e.g., Gentamicin,
WARNING: Cases of tinnitus, hearing impairment,
Streptomycin (ototoxicity)]
and deafness have been reported. Ototoxicity is
related to rapid injection, severe renal impairment,
Reduces therapeutic effect of Furosemide:
use of higher than recommended doses,
Selective and non-selective NSAIDs
hyponatremia, or concomitant therapy with
aminoglycoside antibiotics or other ototoxic drugs.
If high doses are necessary, parenteral therapy
Avoid concomitant use with:
Increases risk of adverse or toxic effects of Furosemide:
with controlled IV infusion is advisable.
Hydrocortisone (hypokalemia)

Prostatic enlargement and/or obstruction (may precipitate Increases risk of adverse or toxic of Ibuprofen
acute urinary retention). (nephrotoxicity)
Gout (may be aggravated by diuretic-induced
hyperuricemia). Reduces therapeutic effect of Furosemide:
Hypotension. Hydrocortisone (antagonism of diuretic effect), Ibuprofen
Diabetes (may see changes in glucose control); SLE (may (antagonism of diuretic effect), Oral Contraceptives
cause SLE exacerbation or activation). (Estrogen antagonizes diuretic effect)
Oliguria (correct hypovolemia before administration).
Renal impairment (monitor electrolytes particularly Reduces therapeutic effect of the following drugs:
potassium and sodium, as well as creatinine). Lidocaine (antagonized by hypokalemia), Metformin
Hepatic impairment (hypokalemia may precipitate coma); (antagonism of hypoglycemic effect)
cirrhosis (diminished natriuretic effect with increased
sensitivity to hypokalemia and volume depletion); Administration:
alcoholic cirrhosis (increased risk of hypomagnesemia). For oral administration, take tablet once daily, in the
Severe urinary retention. morning. If to be taken twice daily, take the first dose in
Patients at high risk for radiocontrast nephropathy (can lead the morning and the second dose at lunchtime.
to higher incidence of deterioration in renal function).
Elderly (more susceptible to electrolyte imbalance and Advise the patient to get up gradually from sitting or lying
orthostatic hypotension). to minimize dizziness upon standing when taking the
Pregnancy (avoid use; may cause electrolyte disturbance in medicine. The patient should sit or lie down if dizziness
fetus; possible neonatal thrombocytopenia; monitor fetal occurs
growth because of potential for higher fetal birth
weights); lactation (enters breastmilk; use with caution). For IV administration, administer no faster than 4
mg/minute to avoid ototoxicity. Dilute dose in a suitable
Adverse Drug Reactions: amount of infusion fluid, according to the hydration of
Common: Dehydration, dizziness, gout, hyperuricemia, the patient.
hypokalemia, hypomagnesemia, hyponatremia,
orthostatic hypotension, syncope Pregnancy Category: C
Less Common: Dyslipidemia, hyperglycemia, hypocalcemia,
concentration, rash ATC Code: C03CA01
Rare: Acute pancreatitis, agranulocytosis, bone marrow
depression, bullous eruptions, exfoliative dermatitis,
hemolytic anemia, interstitial nephritis, jaundice,

145
 CARDIOVASCULAR SYSTEM

POTASSIUM-SPARING AGENTS weeks of treatment with potassium ≤5 mEq/L); if eGFR

<30 mL/minute/1.73 m2, use is not recommended.
Discontinue therapy if potassium >5 mEq/L or serum
Rx SPIRONOLACTONE creatinine >4 mg/dL. Withhold treatment if potassium
>5.5 mEq/L or renal function worsens. Hold doses until
potassium is <5 mEq/L and consider restarting with a
Oral: 25 mg, 50 mg, and 100 mg tablet
reduced dose after confirming resolution of
hyperkalemia or renal insufficiency for at least 72 hours.
A mineralocorticoid (aldosterone) receptor antagonist that
competes with aldosterone for receptor sites in the distal
C

SKILLED TASKS. May cause drowsiness or blurred vision.

renal tubules, increasing sodium chloride and water
Avoid performing tasks, which require mental alertness,
excretion while conserving potassium and hydrogen ions.
e.g., operating machinery or driving.
Indications: Management of edema associated with
Precautions:
excessive aldosterone excretion or congestive heart
failure alone or in combination with other diuretics; WARNING: Hazardous agent. Use appropriate
hypertension; primary hyperaldosteronism (establishing precautions for handling and disposal.
diagnosis, short-term preoperative treatment, and long-
term maintenance therapy) ; hypokalemia; severe heart
failure (NYHA class III­IV) Spironolactone has been shown to be tumorigenic
in chronic toxicity studies in rats. Avoid
Contraindications: Anuria; acute renal insufficiency; unnecessary use of this drug.
significant impairment of renal excretory function;
hyperkalemia; Addison disease; concomitant use with CNS effects (somnolence and dizziness have been
eplerenone. reported); gynecomastia (dose-related).
Fluid or electrolyte loss (excess amounts can lead to
Dose: profound diuresis); hyperkalemia (dose-related; rates of
Edema, by mouth, ADULT, 25–200 mg daily in 1–2 divided hyperkalemia increase with declining renal function;
doses; CHILD 1–17 years, 1 mg/kg daily, divided every concurrent use of large doses of ACE inhibitors increases
12–24 hours (maximum dose: 3.3 mg/kg daily, up to the risk of hyperkalemia).
100 mg daily). Adrenal vein catheterization; cirrhosis (avoid electrolyte and
Hypokalemia, by mouth, ADULT, 25–100 mg once daily. acid / base imbalances that may lead to hepatic
Hypertension, by mouth, ADULT, 50–100 mg in 1–2 divided encephalopathy); heart failure (eGFR should be >30
doses; may adjust dose after 2 weeks (usual dosage mL/minute/1.73 m2 or creatinine should be ≤2.5 mg/dL
range, 25–50 mg daily); CHILD 1 to 17 years, 1 mg/kg (men) or ≤2 mg/dL (women) with no recent worsening,
daily, divided every 12–24 hours (maximum dose: 3.3 and potassium should be <5 mEq/L with no history of
mg/kg daily, up to 100 mg daily). severe hyperkalemia; renal impairment (increased risk of
Diagnosis of primary aldosteronism, by mouth, ADULT, hyperkalemia).
long test, 400 mg once daily for 3–4 weeks; short test, Ethanol use (may increase risk of orthostasis).
400 mg once daily for 4 days (maintenance until surgical Elderly (monitor patient for increased risk of hyperkalemia).
correction: 100–400 mg once daily). Pregnancy (crosses the placenta; have been shown to
Severe heart failure, NYHA class III–IV, by mouth, ADULT, cause feminization of the male fetus in animal studies;
initially 12.5–25 mg once daily (maximum daily dose, 50 avoid use during first trimester; avoid use in women of
mg); if 25 mg once daily is not tolerated, reduce to 25 mg reproductive potential); lactation (active metabolite,
every other day. canrenone, has been found in breastmilk; may decrease
milk volume and suppress lactation).
NOTE: To reduce delay in onset of effect, a loading dose of
2 or 3 times the daily dose may be administered on the Adverse Drug Reactions:
first day of therapy. Common: Vasculitis, ataxia, confusion, drowsiness,
headache, erythematous maculopapular rash, lethargy,
Dose Adjustment: Stevens-Johnson syndrome, toxic epidermal necrolysis,
Geriatric: urticaria, amenorrhea, gynecomastia, hyperkalemia,
Use with caution and monitor potassium closely. Avoid using abdominal cramps, diarrhea, gastritis, gastrointestinal
doses >25 mg daily in heart failure or reduced renal hemorrhage, gastrointestinal ulcer, nausea, vomiting,
function. impotence, irregular menses, postmenopausal bleeding,
agranulocytosis, malignant neoplasm of breast,
Renal Impairment: hepatotoxicity, anaphylaxis, DRESS syndrome, increased
In patients with heart failure: blood urea nitrogen, renal failure, renal insufficiency,
If eGFR ≥50 mL/minute/1.73 m2, administer an initial fever.
dose of 12.5–25 mg once daily (maintenance dose, 25
mg once daily; after 4 weeks of treatment with potassium Drug Interactions:
≤5 mEq/L). Monitor closely with:
If eGFR 30–49 mL/minute/1.73 m2, administer an initial Enhances antihypertensive effect of Spironolactone:
dose of 12.5 mg once daily or every other day Alfuzosin, Barbiturates, Brimonidine (Topical), Diazoxide,
(maintenance dose, 12.5–25 mg once daily; after 4 Herbs with hypotensive properties, MAO Inhibitors
[except Linezolid, Tedizolid], Methylphenidate,

146
CARDIOVASCULAR SYSTEM

Molsidomine, Nicorandil, Other Antihypertensive Agents, OTHER DIURETICS

Pentoxifylline, Phosphodiesterase-5 Inhibitors,
Prostacyclin Analogues, Yohimbine
Enhances therapeutic effect of the following drugs: Rx MANNITOL
ACE Inhibitors (hyperkalemic effect), Neuromuscular-
blocking Agents [Non-Depolarizing (neuromuscular-
Inj.: 20%, 250 mL and 500 mL bottle (IV)
blocking effect)], Quinidine
A hexahydric alcohol related to mannose that acts as an
Increases risk of adverse or toxic effects of Spironolactone:
osmotic agent with little energy value. It is eliminated

C
Angiotensin II Receptor Blockers (hyperkalemia),
from the body before any metabolism can take place.
Atorvastatin (enhanced effects on reducing endogenous
When given parenterally, mannitol raises the osmotic
steroid activity), Canagliflozin (hyperkalemia;
pressure of the plasma, thus drawing water out of body
hypotension), Cholestyramine Resin (metabolic acidosis;
tissues and producing an osmotic diuresis.
hyperkalemia), Digoxin, Drospirenone (hyperkalemia),
Heparin (hyperkalemia), MAO Inhibitors [except
Indications: To reduce cerebral edema; to reduce increased
Linezolid, Tedizolid] (orthostatic hypotension), Nicorandil
intraocular pressure
(hyperkalemia), Nitrofurantoin (hyperkalemia),
Nonsteroidal Anti-Inflammatory Agents (hyperkalemia),
NOTE: NOT recommended for the prevention of acute renal
Opioid Analgesics, Other Antihypertensive Agents,
failure and/or promotion of diuresis.
Tolvaptan (hyperkalemia), Trimethoprim (hyperkalemia)
Dose:
Increases risk of adverse or toxic effects of the following
Increased intracranial pressure, cerebral edema, by IV
drugs:
injection, ADULT, 0.25–1 g/kg per dose; may repeat
Ciprofloxacin [Systemic (arrhythmogenic effect)],
every 6–8 hours, as needed; maintain serum osmolality
Duloxetine (orthostatic hypotension), Levodopa
<300–320 mOsm/kg; CHILD, 0.25–1 g/kg per dose;
(orthostatic hypotension), Risperidone (hypotensive
repeat as needed to maintain serum osmolality <300–
effect)
320 mOsm/kg; administer over 30–60 minutes.
Reduction of intraocular pressure, by IV injection, ADULT,
Reduces antihypertensive effect of Spironolactone:
0.25–2 g/kg administered over 30–60 minutes 1–1.5
Nonsteroidal Anti-Inflammatory Agents
hours prior to surgery; CHILD, 1 to 2 g/kg or 30–60 g/m2
administered over 30–60 minutes 1–1.5 hours prior to
Reduces therapeutic effect of the following drugs:
surgery.
Abiraterone acetate, Alpha / Beta Agonists
Reduction of intraocular pressure, traumatic hyphema, by IV
(vasoconstricting effect), Cardiac Glycosides (inotropic
injection, ADULT, 1.5 g/kg administered over 45 minutes
effects)
twice daily for IOP >35 mm Hg; may administer every 8
hours; CHILD, 1.5 g/kg administered over 45 minutes
Avoid concomitant use with:
twice daily for IOP >35 mm Hg; may administer every 8
Enhances therapeutic effect of the following drugs:
hours in patients with extremely high pressure.
Mitotane
Administration: Administer by intravenous route.
Increases risk of adverse or toxic effects of Spironolactone:
Concentration and rate of administration depends on
Hyperkalemia: Amiloride, Eplerenone, Potassium Salts,
indication, severity, or adjusted to urine flow.
Triamterene
Inspect for crystals prior to administration. If crystals are
Ammonium Chloride (systemic acidosis)
present, warm solution to re-dissolve crystals. Use filter
type administration set for infusion solutions greater
Increases risk of adverse or toxic effects of the following
than or equal to 20%.
drugs:
Amifostine (hypotensive effect), Cyclosporine [Systemic
Do NOT administer until adequacy of renal function and
(hyperkalemia)], Obinutuzumab (hypotensive effect),
urine flow is established. Use 1–2 test doses to assess
Rituximab (hypotensive effect), Sodium Phosphates
renal response.
(nephrotoxic effect, specifically, acute phosphate
nephropathy), Tacrolimus [Systemic (hyperkalemia)]
NEVER add to whole blood for transfusion or administer
through the same set by which blood is being infused to
TEST INTERACTIONS. Produces a false increase in assays
prevent crenation and agglutination of red blood cells.
used to determine digoxin concentrations.
See Mannitol under Blood Substitutes and Perfusion
Administration: Administer with food to increase absorption
Solutions – I.V. Solutions producing Osmotic Diuresis in
and decrease GI upset.
Chapter 2: Blood and Blood Forming Organs for other
information.
Pregnancy Category: C
Pregnancy Category: C
ATC Code: C03DA01
ATC Code: Not available

147
 CARDIOVASCULAR SYSTEM

been observed in animal studies); stroke or TIA (may

LIPID MODIFYING AGENTS occur).
Elderly (use with caution; age ≥65 years is a predisposing
factor for myopathy); children (use of doses >20 mg has
HMG CoA REDUCTASE INHIBITORS not been studied).
Pregnancy (crosses the placenta; use with caution;
insufficient studies on use during pregnancy); lactation
Rx ATORVASTATIN (not known if excreted in breastmilk; use with caution).
C

Oral: 10 mg, 20 mg, 40 mg, and 80 mg tablet (as calcium) Adverse Drug Reactions:
Common: Nasopharyngitis, arthralgia, diarrhea, pain in
A selective, competitive inhibitor of 3-hydroxy-3- extremity, urinary tract infection, dyspepsia, nausea,
methylglutaryl coenzyme A (HMG-CoA) reductase, which musculoskeletal pain, muscle spasms, myalgia,
prevents the conversion of HMG-CoA to mevalonate, an insomnia, pharyngolaryngeal pain
early and rate-limiting step in cholesterol biosynthesis. Less Common and Rare: Rhabdomyolysis, myopathy, liver
enzyme abnormalities, malaise, pyrexia, abdominal
Indication: Adjunct to diet for the reduction of elevated total discomfort, eructation, flatulence, hepatitis, cholestasis,
cholesterol, LDL cholesterol, apolipoprotein B, and muscle fatigue, neck pain, joint swelling, hyperglycemia,
triglycerides, and elevation HDL cholesterol in patients nightmare, epistaxis, urticaria, vision blurred, tinnitus,
with primary hypercholesterolemia and combined positive WBC in urine, anaphylaxis, angioneurotic
hyperlipidemia edema, bullous rashes, fatigue, tendon rupture, fatal and
non-fatal hepatic failure, dizziness, depression,
NOTE: Atorvastatin has not been studied in conditions peripheral neuropathy, pancreatitis
where the major lipoprotein abnormality is elevation of
chylomicrons (Fredrickson Types I and V). Drug Interactions:
Monitor closely with:
Contraindications: Active liver disease, including Increases distribution of the following drugs:
unexplained persistent elevations in hepatic Oral Contraceptives [norethindrone; ethinyl estradiol]
transaminase levels; pregnancy; breastfeeding
Avoid concomitant use with:
Dose: Increases distribution of Atorvastatin:
NOTE: Individualize starting and maintenance doses Cyclosporine
according to patient characteristics, such as goal of
therapy and response. Increases risk of adverse or toxic effects (myopathy) of
Atorvastatin:
Hyperlipidemia, by mouth, ADULT, initially 10 or 20 mg once Colchicine (including rhabdomyolysis), Cyclosporine,
daily; usual range, 10–80 mg once daily; CYP3A4 Inhibitors, i.e., Clarithromycin, HIV Protease
patients who require an LDL-C reduction of more than Inhibitors, Itraconazole, Fibric Acid Derivatives, Niacin
45% may be started at 40 mg once daily.
Heterozygous Familial Hypercholesterolemia, by mouth, Increases serum concentration of Atorvastatin:
CHILD 10–17 years, initially 10 mg daily (maximum CYP3A4 Inhibitors (Strong) i.e., Clarithromycin, HIV
dose, 20 mg daily); adjust doses at intervals of 4 weeks Protease Inhibitors, Itraconazole, Grapefruit Juice [avoid
or more. excessive consumption, i.e., >1.2 L/day]
Homozygous Familial Hypercholesterolemia, by mouth,
ADULT, 10–80 mg daily. Administration: Administer as a single dose at any time of
the day, with or without food.
Dose Adjustment:
Renal Impairment: Pregnancy Category: X
Hemodialysis does not have any significant effect on
atorvastatin clearance. ATC Code: C10AA05

Hepatic Impairment:
In patients with active liver disease, use is contraindicated.
Rx ROSUVASTATIN
Precautions:
Skeletal muscle effects (rare cases of rhabdomyolysis with Oral: 10 mg and 20 mg tablet (as calcium salt)
acute renal failure secondary to myoglobinuria have
been reported; immune-mediated necrotizing myopathy, An active HMG-CoA reductase inhibitor, which is effective in
IMNM, rarely occurs). reducing LDL-cholesterol concentration and has been
Liver dysfunction (jaundice has been reported; reversible efficacious in severe hypercholesterolemia.
increases in liver function tests may occur); hepatic
impairment; endocrine function (increased HbA1c and Indications: Prevention of cardiovascular events in patients
fasting serum glucose levels have been reported). at high risk of a first cardiovascular event; mixed
CNS toxicity (brain hemorrhage and CNS vascular lesions, dyslipidemia, or homozygous familial
characterized by perivascular hemorrhages, edema, and hypercholesterolemia in patients who have not
mononuclear cell infiltration of perivascular spaces have responded adequately to diet and other appropriate

148
CARDIOVASCULAR SYSTEM

measures; (adults) treatment of primary Elderly (risk of myopathy is higher); children (safety and
hypercholesterolemia, e.g., heterozygous familial and efficacy have not been established in children <10 years;
non-familial hypercholesterolemia; (children and establish a healthy lifestyle to reduce cardiovascular
adolescents) treatment of heterozygous familial risk)
hypercholesterolemia Pregnancy (use during first trimester has been associated
with fetal malformation; decreased synthesis of
Contraindications: Pregnancy; breastfeeding; women who cholesterol may possibly affect fetal development);
are planning to conceive or those using inadequate lactation
contraception; severe renal impairment; active liver

C
disease; unexplained persistent elevation in serum Adverse Drug Reactions:
transaminases Common: Abdominal pain, arthralgia, constipation, diabetes
mellitus, dizziness, headache, flu-like illness, insomnia,
Dose: mild GI symptoms, myalgia, nausea, UTI, weakness
NOTE: Individualize doses based on baseline LDL- Less Common: Pruritus, rash, urticaria
cholesterol levels, recommended goal of therapy, and Rare: Myopathy (including myositis), angioedema, alopecia,
patient response. Adjust doses at 4-week intervals or amnesia, anaphylaxis, gynecomastia, hematuria,
more. hepatitis, hypersensitivity (rash, pruritus, urticaria),
impotence, interstitial lung disease, jaundice, liver
Reserve highest dose (40 mg) only for patients who fail failure, pancreatitis, paresthesia, peripheral neuropathy,
to achieve desired cholesterol level at 20 mg daily. proteinuria, rhabdomyolysis, renal failure, toxic
epidermal necrolysis
High cardiovascular risk, by mouth, ADULT MEN >50 years
and WOMEN >60 years, 20 mg once daily. Drug Interactions:
Hypercholesterolemia, by mouth, ADULT, initially 5 or 10 mg Monitor closely with:
once daily, may increase dose to 20 mg if necessary at Enhances therapeutic effect of Rosuvastatin:
intervals of at least 4 weeks; usual range, 5–20 mg once Fibrates e.g. Fenofibrate (myopathy; rhabdomyolysis)
daily (maximum dose, 40 mg once daily); CHILD 10–18
years, initially 5 mg once daily (maximum dose, 20 mg Avoid concomitant use with:
once daily). Enhances therapeutic effect of the following drugs:
Warfarin (increases INR)
Dose Adjustment:
Geriatric: Increases risk of adverse or toxic effects of Rosuvastatin:
Start at low dose. Initiate dose at 5 mg once daily. Niacin (rhabdomyolysis; increased toxicity due to
pharmacodynamic synergism)
Renal Impairment:
For mild-to-moderate impairment, initiate dose at 5 mg once Increases risk of adverse or toxic effects of Warfarin
daily with a maximum dose of 10 mg once daily. (bleeding)

Asian Ancestry: Reduces absorption of Rosuvastatin:

Patients may build up higher drug levels and be at higher Bile Acid Binding Resins [administer statin at least 1 hour
risk to develop myopathy. Initiate dose at 5 mg. Do not before, or 4 hours after, the resin]
administer 40 mg dose.
Administration: May be taken with or without food. May be
Patients at Risk for Myopathy: taken at any time of the day.
Consider lower initial dose, e.g., 5 mg daily in adults.
Pregnancy Category: X
Precautions:
Renal impairment (may reduce elimination of rosuvastatin; ATC Code: C10AA07
increases risk of myopathy); Hepatic effects (hepatic
impairment may impair elimination of rosuvastatin).
Myopathy (may occur with lipid lowering agent; monitor
creatine kinase (CK) levels and discontinue if these are Rx SIMVASTATIN
markedly elevated; increased risk for rhabdomyolysis);
immune-mediated necrotizing myopathy (have been Oral: 20 mg and 40 mg tablet
rarely reported)
Severe intercurrent illness, e.g., infection, trauma, An HMG-CoA reductase inhibitor, which is effective in
metabolic disorder, endocrine and electrolyte reducing LDL cholesterol concentration, and has been
disturbances, uncontrolled seizures (increases risk of reported to reduce the incidence of fatal and non-fatal
myopathy, rhabdomyolysis, and renal failure). MI, stroke and mortality, and the need for coronary and
Diabetes mellitus (small increases in HbA1c and fasting non-coronary revascularization procedures.
blood glucose have been reported); hematuria and
proteinuria; hypothyroidism (should be managed Indications: For prevention of cardiovascular events in
adequately before starting treatment with a statin) patients with high cardiovascular risk due to
Treatment with systemic Sodium Fusidate (may increase atherosclerotic cardiovascular disease or DM; primary
the risk of rhabdomyolysis) hypercholesterolemia; homozygous familial
hypercholesterolemia, or combined hyperlipidemia in

149
 CARDIOVASCULAR SYSTEM

patients who have not yet responded adequately to diet (rarely occurs; risk may be increased in renal impairment
or other appropriate measures; (children and and hypothyroidism).
adolescents) heterozygous familial Severe intercurrent illness, e.g., infection, trauma, or
hypercholesterolemia metabolic disorder (increased risk of myopathy,
rhabdomyolysis, and renal failure;); hypothyroidism
Contraindications: Known hypersensitivity to simvastatin or (should be managed before starting treatment with a
any component of the formulation; active liver disease, statin); surgery (increased risk of acute renal
or persistently abnormal liver function tests; porphyria; impairment, which increases the likelihood of myopathy
pregnancy (congenital anomalies reported; decreased and rhabdomyolysis).
C

synthesis of cholesterol possibly affects fetal History of liver disease, or high alcohol intake (monitor liver
development); breastfeeding function at initiation of treatment, after 4 to 12 weeks
and periodically thereafter, e.g., at 6-month intervals or
Dose: when clinically indicated; discontinue if serum
Homozygous familial hypercholesterolemia, by mouth, transaminase concentration rises to, and persists at, 3
ADULT, initially 40 mg daily at night, adjusted at intervals times the upper limit of the reference range); renal
of at least 4 weeks (see restricted dosing with 80 mg impairment).
once daily at night). Elderly (increased risk of myopathy); Children (safety and
Prevention of cardiovascular events, by mouth, ADULT, efficacy have not been established in children <10
initially 10–40 mg once daily at night, adjusted at years).
intervals of at least 4 weeks with recommended starting Adverse Drug Reactions:
dose of 40 mg for those at high risk of cardiovascular Common: Abdominal pain, atrial fibrillation, constipation,
events. diabetes mellitus, dizziness, eczema, edema, elevated
Primary hypercholesterolemia or combined hyperlipidemia, CK and serum transaminase level, flatulence, gastritis,
by mouth, ADULT, 10–20 mg daily at night, adjusted at headache, insomnia, myalgia, nausea, upper respiratory
intervals of at least 4 weeks (see restricted dosing with infection, urinary tract infection, vertigo, vomiting
80 mg once daily at night). Less Common: Mild GI symptoms
Heterozygous familial hypercholesterolemia, by mouth, Rare: Anaphylaxis, anemia, angioedema, gynecomastia,
ADOLESCENT 10–18 years, initially 10 mg at night, may hepatitis, hypersensitivity, impotence, interstitial lung
increase if necessary, at intervals of at least 4 weeks to disease, jaundice, liver failure, myopathy, pancreatitis,
a maximum of 40 mg at night. peripheral neuropathy, pruritus, rash, renal failure,
rhabdomyolysis, toxic epidermal necrolysis
NOTE: Maximum simvastatin dose:
with concomitant and diltiazem, 10 mg daily; Drug Interactions:
with concomitant amiodarone or amlodipine, 20 mg Monitor closely with:
daily. Contraindicated with erythromycin, clarithromycin, Reduces therapeutic effect of Simvastatin:
ketoconazole, HIV protease inhibitors, and gemfibrozil. Carbamazepine

Dose Adjustment: Avoid concomitant use with:

Geriatric: Increases risk of adverse or toxic effects of simvastatin:
Use with caution. Start at low dose. Clotrimazole (myopathy), CYP3A4 Inhibitors, e.g.,
Clarithromycin, Erythromycin, Ketoconazole, Diltiazem
Renal Impairment: (myopathy; rhabdomyolysis)
For mild-to-moderate renal impairment, dose reduction is
warranted. Increases serum concentration of the following drugs:
For severe impairment, refer patient to a specialist. CYP3A4 Inhibitors, e.g., Clarithromycin, Erythromycin,
Ketoconazole, Diltiazem
Hepatic Impairment:
Use with caution. Start at low dose. Contraindicated in Reduces absorption of simvastatin:
active liver disease or persistent abnormal liver function Bile Acid Binding Resins [administer statin at least 1 hour
tests. before, or 4 hours after, the resin]

Restricted Dosing for 80 mg: Administration: May be taken with or without food.
Restrict use of 80-mg dose to patients who have been
taking Simvastatin 80 mg chronically, e.g., for 12 months Avoid excessive consumption, i.e., >1 L daily of grapefruit
or more, without evidence of muscle toxicity, to minimize juice.
the risk of myopathy, including rhabdomyolysis,
particularly during the first year of treatment. Pregnancy Category: X

Precautions: ATC Code: C10AA01

Muscle effects (do not start simvastatin if creatine kinase
[CK] is elevated in patients at high risk of muscle effects;
risk of myopathy is increased if simvastatin is given at
high doses or with a fibrate, with lipid-lowering doses of
nicotinic acid, or with immunosuppressants; monitor
liver function and creatine kinase). Rhabdomyolysis

150
CARDIOVASCULAR SYSTEM

FIBRATES Elderly (higher incident of renal impairment)

Pregnancy (embryotoxicity in animal studies); lactation.

Rx FENOFIBRATE Adverse Drug Reactions:

Common: Arthralgia, bronchitis, cough, dizziness, fatigue,
headache, insomnia, GI disturbances (e.g., dyspepsia,
Oral: 200 mg capsule
abdominal pain); hypertension, nausea, rhinitis,
160 mg tablet
infections (e.g., urinary tract, respiratory tract)
Less Common: Pancreatitis, photosensitivity, pulmonary
A peroxisome proliferator receptor alpha (PPARα) activator,

C
embolism, VTE
which modulates lipoprotein synthesis and catabolism. It
Rare: Agranulocytosis, anemia, arrhythmias, hepatitis,
reduces plasma triglyceride, moderately increases high-
cholestatic jaundice, gallstones, hypersensitivity
density lipoprotein (HDL) and has a variable effect on
reactions (e.g., angioedema, anaphylaxis, exfoliative
LDL concentrations.
dermatitis), hypokalemia, leukopenia, myopathy,
rhabdomyolysis, thrombocytopenia
Indications: Hypertriglyceridemia; dyslipidemia associated
with type 2 diabetes; second-line treatment in
Drug Interactions:
hypercholesterolemia
Monitor closely with:
Enhances therapeutic effect of the following drugs:
Contraindications: Photosensitivity to ketoprofen;
Insulins, Sulfonylureas e.g. Gliclazide (hypoglycemic
pancreatitis, unless due to hypertriglyceridemia; severe
effect)
renal impairment, including patients receiving dialysis;
hepatic impairment; primary biliary cirrhosis; gallstones;
Increases risk of adverse or toxic effects of Statins e.g.
gall bladder disease; unexplained, persistent liver
Atorvastatin (myopathy; rhabdomyolysis)
function abnormality; pregnancy; lactation
Avoid concomitant use with:
Dose:
Enhances therapeutic effect of Anticoagulants, e.g.,
NOTE: At least 2-3 months of therapy is required to
Warfarin (anticoagulant effect)
determine efficacy.
Increases risk of adverse or toxic effects of Anticoagulants,
Hyperlipidemias, by mouth, ADULT, 200–300 mg once daily
e.g., Warfarin (bleeding)
in divided doses; usual range, 200–400 mg daily; CHILD
>10 years old, up to maximum of 5 mg/kg daily.
Reduces absorption of Fenofibrate:
Bile Acid Sequestrants
Dose Adjustment:
Geriatric:
Administration: Best taken with food as food increases the
Use with caution. May need dose adjustment.
bioavailability of fenofibrate.
Renal Impairment:
Pregnancy Category: C
For mild-to-moderate impairment, dose reduction is
warranted. Initiate dose at 40–50 mg once daily in
ATC Code: C10AB05
adults. Refer child to pediatrician.
For severe impairment, fenofibrate is contraindicated.

Precautions:
NOTE: Fenofibrate has a uricosuric effect, which may reduce
uric acid concentrations by about 25%.

Hyperlipidemia; myopathy, myositis, and rhabdomyolysis

(have been reported; concomitant HMG-CoA reductase
inhibitor may potentiate rhabdomyolysis and lead to
acute renal failure).
Increase in hepatic transaminases (monitor regularly and
discontinue if enzyme levels persist 3 times above the
upper limit of normal); increase in serum creatinine (may
occur; monitor renal function).
Avoid exposure of skin to sun, wear protective clothing and
use sunscreen
Lack of optimal response (withdraw therapy if an adequate
response is not obtained after 2–3 months of therapy at
the maximal daily dose).
Women and obese individuals (at high risk for biliary tract
disease; modest increase in the risk of cholesterol
gallstones, reflecting an increase in the cholesterol
content of bile; may cause cholelithiasis)
Patients at risk for venous thromboembolism (associated
with pulmonary embolism and deep venous thrombosis).

151
 DERMATOLOGICALS

Administration: For topical application, gently massage

DERMATOLOGICALS sufficient amount into the affected and surrounding skin
areas twice daily, in the morning and evening.
If the feet are infected, wash and dry feet, especially
between the toes, before applying the cream.
ANTIFUNGALS FOR
DERMATOLOGICAL USE Pregnancy Category: B

ATC Code: D01AC01

ANTIFUNGALS FOR TOPICAL USE

IMIDAZOLE AND TRIAZOLE DERIVATIVES

D

Rx KETOCONAZOLE
Rx CLOTRIMAZOLE Topical: 2% (20mg/g) cream 3.5 g and 15 g
2% (20mg/g) shampoo 6 mL, 10 mL, 60 mL,
Topical: 1% (10 mg/g) cream, 3 g, 10 g, and 20 g 100 mL
2% (20 mg/g) cream, 30 g
Vaginal: 1% 10 g (vaginal cream) Imidazole derivate that exerts its antifungal effects by
altering the permeability of the cell wall by blocking
A broad-spectrum imidazole active against fungi, (both fungal cytochrome P450. This inhibits the biosynthesis
dermatophytes and yeasts) and gram-positive cocci of triglycerides and phospholipids in the fungal cell,
(Staphylococcus and Streptococcus spp.) inhibiting several fungal enzymes that results in a build-
up of toxic concentrations of hydrogen peroxide.
Indications: Management of anogenital and vulvovaginal
candidiasis; ringworm; skin infections, including Indications: Treatment of tinea corporis, tinea cruris, tinea
pityriasis versicolor and dermatophytosis (e.g., tinea pedis, tinea versicolor, cutaneous candidiasis,
corporis, tinea pedis, tinea cruris); protozoal infections seborrheic dermatitis, pityriasis capitis; treatment and
(e.g. trichomoniasis) prophylaxis of pityriasis versicolor

Contraindication: Severe liver impairment Dose:

Tinea corporis and tinea cruris, by topical application, rub
Dose: gently onto the affected area once daily for 2 weeks.
Anogenital candidiasis, by topical use, ADULT, apply 1% Tinea versicolor and cutaneous candidiasis, by topical
cream to anogenital area 2–3 times daily. application, apply once daily to cover affected and
Skin infections, including pityriasis versicolor and immediate surrounding area for 2 weeks.
dermatophytosis, by topical use, ADULT, apply cream 2– Tinea pedis, by topical application, rub gently onto the
3 times daily for 1–2 weeks. affected area once daily for 6 weeks.
Vulvovaginal candidiasis, by vaginal administration, ADULT, As shampoo, massage onto scalp. Leave on for 3-5 minutes
apply 5 g of 10% vaginal cream as a single dose at night, then rinse.
repeated once if necessary 1% is to 6 doses; 2% is to 3 Seborrheic dermatitis and pityriasis capitis, treatment,
doses). apply shampoo twice weekly for 2-4 weeks
Seborrheic dermatitis and pityriasis capitis, prophylaxis,
Dose Adjustment: apply shampoo once every 1 or 2 weeks
Vulvovaginal candidiasis in pregnancy: Pityriasis versicolor, treatment, apply once daily for 5 days.
Requires a longer duration of treatment, about 7 days, to Pityriasis versicolor, prophylaxis, once daily for 3 days during
clear the infection. Avoid oral antifungals. a single treatment course.

Precautions: Dose Adjustment: No information found

Discontinue if irritation or sensitivity occurs; Damages latex
condoms and diaphragms; Pregnancy (safety in the first Precautions:
trimester has not been established) Hypersensitivity reactions; Irritation; Lactation (do not apply
to breast area of breastfeeding mothers).
Adverse Drug Reactions:
Common: Local pain or discomfort Adverse Drug Reactions:
Less Common: Blistering, burning, edema, erythema, Common: Stinging, local burning, acne, allergic reaction,
general skin irritation, itch, peeling, pruritus, stinging contact dermatitis, discharge, dizziness, dryness,
Rare: Allergic reactions erythema, facial swelling, headache, impetigo,
keratoconjunctivitis sicca, nail discoloration, ocular
Drug Interactions: irritation or swelling, pain, paresthesia, pruritus,
Monitor closely with: pustules, pyogenic granuloma, severe irritation
Increases risk of adverse or toxic effect of Simvastatin
(myopathy) Drug Interactions: No known significant interactions

Administration: For external use only. Do NOT administer

intravaginally.

152
DERMATOLOGICALS

Do NOT apply directly to hands. Do NOT apply to the eyes. professional. Prolong treatment for 10 days after all
If contact with eyes, mouth, or vagina occurs, rinse the lesions have disappeared to prevent relapse.
exposed areas thoroughly with water.
Avoid contact with the eyes. If contact with eyes occurs,
Pregnancy Category: C rinse the exposed areas thoroughly with water.

ATC Code: D01AC08 NOTE: For tinea pedis, instruct patients to wear well-fitting
ventilated shoes, and to change socks at least once
daily.
Rx MICONAZOLE Do NOT use on children under 2 years of age unless
directed by a healthcare professional.

D
Topical: 2% cream, 5 g
Oral gel: 20 mg, 3.5 g Pregnancy Category: C

A synthetic imidazole derivative that inhibits 14-α- ATC Code: D01AC02

demethylase, a microsomal cytochrome P450-
dependent enzyme system critical to sterol synthesis,
causing membrane defects, reducing growth rate of the OTHER ANTIFUNGALS FOR TOPICAL USE
fungal cell.

Indications: Treatment of tinea pedis, tinea cruris, tinea Rx SALICYLIC ACID

capitis, oropharyngeal candidiasis, and GIT candidiasis
Topical: 5% solution, 30 mL and 60 mL bottle
Contraindication: Self-administration of intravaginal
miconazole for longer than 7 days 2-hydroxy derivative of benzoic acid that produces
desquamation of the horny layer of skin while not
Dose: effecting qualitative or quantitative changes in the
Tinea pedis, by topical application, ADULT, apply to the structure of the viable epidermis.
cleansed, dry infected area twice daily for 4 weeks; pay
special attention to the areas between the toes. Indications: Keratolytic; management of keratosis in arsenic
Tinea capitis, by topical application, ADULT, apply to the poisoning; removal of excessive keratin in hyperkeratotic
cleansed, dry infected area twice daily for 4 weeks. skin disorders; acne
Tinea cruris, by topical application, ADULT, apply to the
cleansed, dry infected area twice daily for 2 weeks. Contraindications: Prolonged use or application to large
Oropharyngeal candidiasis, oral gel, ADULT and CHILD ≥2 yr, areas; impaired circulation; warts with hair growth or on
2.5 mL (½ measuring spoon) four times daily; INFANT 6- face; birthmarks; moles
24 months, 1.25 mL (¼ measuring spoon) four times
daily Dose:
GIT candidiasis, oral gel, CHILD ≥6 months, 20 mg/kg body Plantar warts, calluses, corns, by topical application, ADULT,
weight per day in 4 divided doses. (Maximum dose, 250 apply to affected area; repeat until condition clears;
mg four times daily. occasional use will maintain remission.
Acne, by topical application, ADULT, as 0.5 to 2%
Precautions: preparation, apply thinly to the affected area 1–3 times
WARNING: Keep out of reach of children. If swallowed, get medical daily, reduce to once daily or every other day if dryness
help or contact a Poison Control Center immediately. or peeling occurs.

Avoid continuous and long-term use particularly on large NOTE: Safety and efficacy in children is not yet established.
skin area; Avoid contact with eyes and moist membranes
lining the inside of mouth and nasal passages; Children; Precautions:
Lactation. Renal or hepatic impairment (monitor for signs of salicylate
toxicity, i.e., nausea, vomiting, dizziness, loss of hearing,
Adverse Drug Reactions: Local sensitization or irritation tinnitus, lethargy, hyperpnea, diarrhea, psychic
disturbances); Impaired peripheral circulation; Diabetes;
Drug Interactions: No known significant interactions Significant peripheral neuropathy; Children (monitor for
signs of salicylate toxicity, listed above; avoid use in
Administration: For external use only. Supervise children in children with varicella or influenza due to potential risk
the use of this product. of developing Reye’s Syndrome); Lactation.

Do NOT use if the safety-sealed tube is punctured or Adverse Drug Reactions:

damaged. Common: Dermatitis, skin peeling, discomfort, irritation,
dryness, ulceration, erosion, salicylate toxicity (systemic),
Clean the affected area and dry thoroughly. Apply a thin toxic inner ear damage, excessive erythema and scaling
layer of the product over the affected area twice daily (when used on open skin lesions)
(morning and night) or as directed by a healthcare Rare: Hypersensitivity reactions (potentially fatal e.g.
anaphylactic reaction)

153
 DERMATOLOGICALS

Drug Interactions: Drug Interactions: No known significant interactions

Increases risk of adverse or toxic effects of the following
drugs: Administration: For external use only. Protect from heat.
Oral Anticoagulants (bleeding); Pyrazinamide
(pyrazinamide-induced uricemia); Sulfonylureas Shake well before use. Keep tightly capped. Keep out of
(hypoglycemia) reach of children.

Increases serum concentration of Salicylic Acid: Avoid getting shampoo in eyes or in contact with genital
Aspirin, Other salicylate-containing Medications area as it may cause irritation and burning.

Reduces therapeutic effect of Heparin (interferes with Avoid use within 48 hours of applying hair dye,
heparin hemostasis due to decreased platelet straightening, or waving preparations.
D

adhesiveness)
Pregnancy Category: C
Administration: For external use only. Avoid contact with
eyes or mucous membrane. ATC Code: D01AE13

NOTE. Excessive application of the product other than is

needed to cover the affected area will not result in more
therapeutic benefit. OTC TERBINAFINE

Pregnancy Category: C Topical: 1% cream (as hydrochloride), 3 g, 5 g, 10 g, and

15 g tube
ATC Code: D01AE12
An allylamine derivative with a wide spectrum of antifungal
activity against pathogens of the skin, hair, and nails. It
inhibits squalene epoxidase, preventing fungal sterol
Rx SELENIUM SULFIDE synthesis, resulting in ergosterol deficiency. This causes
membrane disruption and cell death.
Topical: 2.5% lotion, 100 mL bottle
Indications: Dermatophytosis (tinea corporis, tinea cruris,
An anti-seborrheic and antifungal preparation for topical tinea pedis, cutaneous candidiasis, and pityriasis)
application. It has a cytostatic effect on cells of the
epidermis and follicular epithelium, reducing corneocyte Dose:
production. Tinea corporis and tinea cruris, by topical application,
ADULT, apply once daily for 1 week or as directed by a
Indications: For treatment of tinea versicolor; seborrheic doctor.
dermatitis or dandruff Tinea pedis, by topical application, ADULT, apply 1–2 times
for 1 week; apply twice daily between the toes for 1 week
Contraindications: Broken or severely inflamed skin or as directed by a doctor; apply twice daily on the bottom
or sides of the foot for 2 weeks or as directed by a doctor
Dose: (wear well-fitting, ventilated shoes; change shoes and
Tinea versicolor, by topical application, ADULT, apply to socks at least once daily).
affected areas and lather with a small amount of water; Cutaneous candidiasis and pityriasis, by topical application,
leave on skin for 10 minutes; rinse body thoroughly; ADULT, apply 1–2 times daily to affected area(s) for 2
repeat once daily for 7 days. weeks.
Seborrheic dermatitis, by topical application, ADULT,
massage 1 or 2 teaspoonfuls of shampoo into wet scalp; NOTE: NOT for vaginal yeast infections.
leave on scalp for 2–3 minutes; rinse thoroughly; repeat
application and rinse thoroughly; apply 1 to 2 times Precautions:
weekly; may repeat at less frequent intervals Do not use on nails or scalp, in or near the mouth or the
subsequently. eyes; Presence of lesions.

NOTE: After treatment, wash hands well. Do NOT apply more NOTE: Stop use and ask a doctor if too much irritation
frequently than required to maintain control. occurs or gets worse.

Precautions: Adverse Drug Reactions:

WARNING: Do NOT use on broken skin or inflamed areas. If Common: Psoriasis exacerbation, rash, pruritus, urticaria,
allergic reactions occur, discontinue use. skin exfoliation, application site reaction
Rare: Serious skin reaction (potentially fatal)
Do not use when acute inflammation or exudation is present
as increased absorption may occur; Children. Drug Interactions: No known significant interactions

Adverse Drug Reactions: Skin irritation, hair loss, hair Administration: For external use only. Do NOT use if seal on
discoloration, oiliness and dryness of scalp tube is broken or is not visible.

154
DERMATOLOGICALS

Wash hands after each use. ANTIFUNGALS FOR SYSTEMIC USE

Avoid contact with eyes. If contact with eyes occur, rinse
thoroughly with water. Rx TERBINAFINE

Pregnancy Category: B/C Oral: 250 mg tablet

ATC Code: D01AE15 An allylamine derivative with a wide spectrum of antifungal
activity against pathogens of the skin, hair, and nails. It
inhibits squalene epoxidase, preventing fungal sterol
OTC SODIUM THIOSULFATE synthesis, resulting in ergosterol deficiency and causes

D
membrane disruption and cell death.

Topical: 2.5% and 5% solution Indications: Treatment of oncychomycosis of the toenail or

fingernail due to dermatophytes; dermatophytosis (tinea
A solution containing sodium thiosulfate, used topically for corporis, tinea cruris, tinea pedis)
fungal infections of the skin.
Contraindications: Chronic or active hepatic disease;
Indication: Treatment of pityriasis versicolor caused by Lactation
Malassezia furfur
Dose:
Dose: Fingernail onychomycosis, by mouth, ADULT, 250 mg once
Fungal infections, by topical application, ADULT, thoroughly daily for 6 weeks.
clean affected area and dry well, apply a thin layer on the Toenail onychomycosis, by mouth, ADULT, 250 mg once
affected and other susceptible areas and rub in gently; daily for 12 weeks.
apply twice daily; treatment usually lasts several weeks Tinea cruris, by mouth, ADULT, 250 mg once daily for 2–4
to months. weeks.
Tinea corporis, by mouth, ADULT, 250 mg once daily for 4
NOTE: Evidence of infection may disappear within a few weeks.
days. Continue treatment as directed by physician Tinea pedis, by mouth, ADULT, 250 mg once daily for 2–6
despite lack of signs or symptoms. weeks.

Precautions: Dose Adjustment:

Do not put on irritated skin or healthy skin; Use only as Geriatric:
directed; Children; Lactation. Start at the low end of dosing range, increasing frequency
for decreased hepatic, renal, or cardiac function, and of
Adverse Drug Reactions: concomitant disease or other drug therapy.
Common: Skin irritation
Rare: Allergic reactions (e.g., rash, hives, itching, red, Renal Impairment:
swollen, blistered, or peeling skin with or without fever, For patients with CrCl <50 mL/minute, reduce dose to 50%
wheezing, tightness in the chest or throat, trouble of usual dose.
breathing or talking, unusual hoarseness, swelling of the
mouth, face, lips, tongue, or throat) Precautions:
Immunosuppression; Psoriasis; Autoimmune disease;
Drug Interactions: No known significant interactions Renal impairment; Hepatotoxicity; Hematologic effects;
Thrombotic microangiopathy; Elderly; Children;
Administration: For external use only. Shake well before use. Lactation.
Keep out of mouth, nose, and eyes. Contact may cause
a burning sensation. Adverse Drug Reactions:
Common: Headache, diarrhea, dyspepsia, abdominal pain,
Do NOT use coverings, e.g., bandages, dressings, unless nausea, flatulence, rash, pruritus, urticaria, liver enzyme
told to do so by the doctor. abnormalities, decreased appetite, feeling of fullness,
visual disturbance, application site reactions (redness,
Wash your hands before and after use. Do NOT wash itching, stinging)
your hands after use if putting this on your hand. Less Common: Pancytopenia, agranulocytosis, severe
neutropenia, anemia, thrombotic microangiopathy,
Pregnancy Category: C hemolytic uremic syndrome, anxiety, depression, weight
loss, smell disturbances, paresthesia, hypoesthesia,
ATC Code: Not available ocular lens and retina changes, vision color changes,
color confusion, decreased visual acuity, hearing
impairment, vertigo, tinnitus, vasculitis, psoriasis
exacerbation, photosensitivity, hair loss, rhabdomyolysis,
arthralgia, myalgia, malaise, fatigue, influenza-like
illness, pyrexia
Rare: Systemic lupus erythematosus, serious skin and
hypersensitivity reaction (potentially fatal), taste

155
 DERMATOLOGICALS

disturbance, hepatic failure (potentially fatal), Indications: Symptomatic treatment of mild pruritus and
hepatobiliary dysfunction insect stings

Drug Interactions: Contraindication: Avoid application prior to x-ray (zinc oxide

Monitor closely with: may affect outcomes)
Increases risk of adverse or toxic effects of Oral
Contraceptives (menstrual disturbances) Dose:
Mild pruritus, ADULT and CHILD, apply liberally to the entire
Avoid concomitant use with: affected area 3–4 times daily, or as often as needed.
Increases risk of adverse or toxic effects of Warfarin
(increases blood creatine phosphokinase)
Precautions:
D

Administration: May be taken with or without food. If condition worsens or if rash develops, stop the medication
immediately.
Pregnancy Category: B
Adverse Drug Reactions:
ATC Code: D01AE15 Rare: Irritation, rash

Drug Interactions: No known significant interactions

EMOLLIENTS AND PROTECTIVES Administration: Shake well prior to use. Apply gently with a
pad of cotton wool to the affected parts as required.

OTC PETROLATUM (PETROLEUM) Do NOT use on open wounds or burns. Avoid contact with
the eyes and the mucous membranes of the mouth,
nose, and anogenital area.
Topical: USP grade jelly, 25 g, 100 g, and 200 g jar
Pregnancy Category: No information found
An emollient used to soothe, smooth, and hydrate the skin.
ATC Code: Not available
Indications: Skin emollient; protectant

Contraindication: No information found

ANTIPSORIATICS
Dose:
Apply topically to affected area(s) as needed.
ANTIPSORIATICS FOR TOPICAL USE
Precautions:
Do not use in eyes, on puncture wounds, animal bites, or
serious burns or for more than one week unless directed Rx CALCIPOTRIOL
by a doctor; Do not use in nose to avoid lipid aspiration;
Breastfeeding. Topical: 50 micrograms per g ointment, 30 g tube or
bottle
Adverse Drug Reaction: Hypersensitivity
A synthetic vitamin D3 derivative that binds to vitamin D
Drug Interactions: No known significant interactions receptors to induce differentiation and suppress
proliferation of keratocytes.
Administration: For external use only.
Indication: Management of mild-to-moderate plaque
Pregnancy Category: A psoriasis
ATC Code: D02AX Contraindications: Severe renal or hepatic impairment;
Hypercalcemia; Calcium metabolism disorder; Acute
psoriatic eruptions
ANTIPRURITICS, INCLUDING
ANTIHISTAMINES, ANESTHETICS, ETC. Dose:
Mild-to-moderate plaque psoriasis, by topical application,
ADULT, apply a thin layer and rub in gently and
OTC CALAMINE, PLAIN completely to the affected area 1–2 times daily
(maximum, 100 g per week); CHILD >12 years, apply
2 times daily (maximum, 75 g per week); CHILD 6-12
Topical: 8% lotion, 60 mL and 120 mL bottle years, apply 2 times daily (maximum, 50 g per week).

A topical antipruritic substance, which contains basic zinc Precautions:

oxide with about 0.5% colored ferric oxide. Erythrodermic exfoliative psoriasis; Generalized pustular
psoriasis; Lactation.

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DERMATOLOGICALS

Adverse Drug Reactions: hypothalamic-pituitary-adrenal (HPA) axis suppression,

Common and Less Common: Skin irritation, burning, itching, manifestations of Cushing’s syndrome, hyperglycemia,
erythema, dryness, eczema, contact dermatitis, glucosuria
aggravated psoriasis, hypercalcemia, hypercalciuria Rare: Hypercalcemia, hypercalciuria, angioedema, facial
Rare: Skin atrophy, hyperpigmentation, photosensitivity edema

Drug Interactions: Administration: For external use only.

Avoid concomitant use with:
Reduces therapeutic effect of Calcipotriol: Avoid exposure to natural or artificial sunlight. Avoid
Salicylic Acid (Topical) (inactivates Calcipotriol) application under occlusive dressings.

Administration: For external use only. Pregnancy Category: C

D
Avoid application to the face, eyes, or mucous ATC Code: D05AX52
membranes. Avoid exposure to natural or artificial
sunlight.
Rx SALICYLIC ACID
Pregnancy Category: C
Topical: 5% solution, 30 mL and 60 mL bottle
ATC Code: D05AX02
2-hydroxy derivative of benzoic acid that has been shown to
produce desquamation of the horny layer of skin while
CALCIPOTRIOL + not effecting qualitative or quantitative changes in the
Rx
BETAMETHASONE structure of the viable epidermis.

Topical: 50 micrograms calcipotriol (as hydrate) + 500 Indications: Management of hyperkeratotic and scaling skin
micrograms betamethasone (as dipropionate) conditions
per gram ointment, 30 g tube
Dose:
Calcipotriol is a synthetic vitamin D3 derivative that binds to Hyperkeratotic and scaling skin conditions, by topical
vitamin D receptors to induce differentiation and application, ADULT, apply as 1.8 to 3% preparation to
suppress proliferation of keratocytes. Betamethasone is affected area of the skin and/or scalp 1–4 times daily.
a topical corticosteroid with anti-inflammatory,
antipruritic, and vasoconstrictive properties. It depresses NOTE: Safety and efficacy in children is not yet established.
the formation, release, and activity of endogenous
chemical mediators of inflammation through the Administration: For external use only. Avoid contact with
induction of phospholipase A2 inhibitory proteins eyes or mucous membrane.
(lipocortins) and subsequent inhibition of the release of
arachidonic acid. NOTE. Excessive application of the product other than is
needed to cover the affected area will not result in more
Indication: Psoriasis vulgaris therapeutic benefit.

Contraindications: Known or suspected disorder of calcium See Salicylic Acid under Antifungals for Dermatological Use
metabolism; erythrodermic, exfoliative and pustular – Other Antifungals for Topical Use in Chapter 4:
psoriasis; viral lesions of the skin, fungal or bacterial skin Dermatologicals for other information.
infections, parasitic infections, skin manifestations in
relation to TB, perioral dermatitis, atrophic skin, striae Pregnancy Category: C
atrophicae, fragility of skin veins, ichthyosis, acne
vulgaris, rosacea, ulcers and wounds ATC Code: Not available

Dose:
Psoriasis vulgaris, by topical application, ADULT, apply to
affected area once daily for up to 4 weeks for scalp
areas, or 8 weeks for non-scalp areas (maximum, 15 g
daily or 30% of body surface).

Dose Adjustment: No information found

Precautions:
Diabetes mellitus; Lactation.

Adverse Drug Reactions:

Common and Less Common: Allergic contact dermatitis,
pruritus, headache, nasopharyngitis, psoriasis, rash,
influenza, erythema, pain, burning sensation, eye
irritation, dry skin, skin atrophy, folliculitis, reversible

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 DERMATOLOGICALS

Dose:
ANTIBIOTICS AND CHEMOTHERAPEUTICS FOR Secondary skin infection, by topical application, ADULT and
DERMATOLOGICAL USE CHILD ≥3 months, as cream, apply to affected area 3
times daily for up to 10 days; re-evaluate within 7 days if
no clinical response.
ANTIBIOTICS FOR TOPICAL USE Impetigo, by topical application, ADULT and CHILD ≥2
months, as ointment, apply to affected area 3 times daily
for up to 5–10 days; re-evaluate after 3–5 days if no
FUSIDATE SODIUM clinical response.
OTC
(FUSIDIC ACID)
Dose Adjustment:
Topical: 2% cream, 5 g tube Renal Impairment:
D

2% ointment, 15 g tube Use with caution. Some products contain polyethylene

glycol, which may be absorbed from open wounds and
An antibiotic derived from Fusidium coccineum, which is damaged skin and secreted by the kidneys.
active against several gram-positive organisms and can
penetrate intact skin. It acts by disrupting translocation Precautions:
of peptide subunits and elongating the peptide chain of WARNING: Prolonged use may result in overgrowth of non-
susceptible bacteria, inhibiting protein synthesis. susceptible microorganisms, including fungi.

Indications: Treatment of skin infections caused by

staphylococci, streptococci and Corynebacterium Extensive burns and wounds; Renal impairment; Local
minutissimum; impetigo; infected wounds; folliculitis; irritation (discontinue use when sensitization or severe
boils; sycosis barbae; carbuncles; hidradenitis; local irritation occurs); Lactation (not known if present in
paronychia; erythrasma breastmilk, has effects on breastfed child and milk
production).
Dose:
Skin infection, by topical application, ADULT, apply to the Adverse Drug Reactions:
affected area 2–3 times daily for 7 days; may be used Common and Less Common: Burning, stinging, pruritus,
with or without covering dressing. pain, rash, erythema, dry skin, tenderness, cellulitis, pain
or bleeding secondary to eczema, secondary wound
Precautions: infection, urticaria, swelling, increased exudates, contact
Hepatic disease (monitor liver function); Neonates; dermatitis, furunculosis, exfoliative dermatitis
Lactation. Rare: Systemic reactions (e.g., nausea, headache,
dizziness, abdominal pain, ulcerative stomatitis,
Adverse Drug Reactions: systemic allergic reactions)
Common: Rashes, irritation
Less Common: Hypersensitivity reactions Drug Interaction:
Avoid concomitant use with:
Drug Interaction: Reduces therapeutic effect of Mupirocin:
Avoid concomitant use with: Chloramphenicol (interferes with antibacterial action of
Ciprofloxacin (antagonistic activity) Mupirocin in RNA synthesis)

Administration: For external use only. Observe caution when Administration: For external use only. NOT for intranasal,
applying in the eye region; may cause eye irritation. ophthalmic, or other mucosal use.

Pregnancy Category: Not available Avoid contact with eyes. In case of accidental contact,
rinse well with water.
ATC Code: D06AX01
Apply a small amount to the affected area using a cotton
swab or gauze pad. If desired, cover the treated area with
gauze dressing.
Rx MUPIROCIN
Do NOT apply concurrently with any other lotions,
creams, or ointments.
Topical: 2% cream, 5 g sachet and 15 g tube
2% ointment, 5 g and 15 g tube Pregnancy Category: C
A bacteriostatic that inhibits protein synthesis of the ATC Code: D06AX09
bacteria by binding to isoleucyl transfer RNA synthetase

Indications: Management of impetigo; secondary skin

infections (up to 10 cm in length or 100 cm2 in area) due
to susceptible Staphylococcus aureus and
Streptococcus pyogenes.

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DERMATOLOGICALS

CHEMOTHERAPEUTICS FOR TOPICAL USE

Rx SILVER SULFADIAZINE
Rx IMIQUIMOD Topical: 1% cream, 15 g and 25 g tube
1% cream, 500 g jar (micronized)
Cream: 5%, aluminum foil sachet
A bactericidal agent with a broad spectrum of activity
Imiquimod, an immune response modifier, is a Toll-like against gram-negative and gram-positive bacterial, as
receptor 7 agonist that activates immune cells. Topical well as yeast.
application to the skin is associated with increases in
markers for cytokines and immune cells. Indications: Adjunct for the prevention and treatment of
wound sepsis in patients with second- and third-degree

D
Indications: Treatment of external genital and perianal burns
warts.
Contraindications: Pregnancy approaching or at term;
Dose: Lactation; Premature infants; Newborns ≤2 months;
External genital warts, by topical use, ADULT and CHILD, Porphyria
apply 3 times a week on alternate days until total
clearance of warts or for a maximum of 16 weeks. Dose:
Condition, by topical administration, ADULT, apply 1 to 2
Dose Adjustment: times daily to a thickness of approximately one-sixteenth
Renal and Hepatic impairment: of an inch; reapply as needed.
No dosage adjustments provided in the manufacturer’s
labeling. Dose Adjustment:
Renal Impairment:
Precautions: Use with caution. Some products contain polyethylene
Avoid or minimize exposure to sunlight; glycol, which may be absorbed from open wounds and
Local inflammatory reactions, flu-like symptoms, and vulvar damaged skin and secreted by the kidneys.
swelling;
Patients with actinic keratosis, autoimmune disorders, and Precautions:
basal cell carcinoma; Maintain adequate fluid intake; Prolonged application over
Not recommended for oral, ophthalmic, urethral, a large area may result in argyria; Sulfonamides; G6PD
intravaginal, cervical, rectal, or intra-anal human deficiency; Renal and hepatic impairment; Children;
papilloma viral disease. Lactation (use with caution).

Adverse Drug Reactions: Adverse Drug Reactions:

Common: Application site reaction, URTI, erythema, erosion, Common: Leukopenia, nausea, vomiting, diarrhea,
excoriation, edema, and itching. hypersensitivity, skin reactions, hematuria, crystalluria,
Less Common: Sinusitis, burning sensation, headache, thrombocytopenia, leucopenia, eosinophilia, Stevens-
squamous carcinoma, diarrhea, bleeding, stinging, pain, Johnson syndrome (potentially fatal), agranulocytosis
eczema, induration, tenderness, irritation, back pain, (potentially fatal), jaundice (potentially fatal), hepatitis
fatigue, atrial fibrillation, viral infection, dizziness, (potentially fatal)
vomiting, UTI, fever, rigor, and alopecia. Less Common: Skin necrosis, erythema multiforme, skin
Rare: Headache, flu-like symptoms, and myalgia. discoloration, burning sensation, rashes, and interstitial
nephritis
Drug Interactions: Rare: Skin rash
Monitor closely with:
Increases levels or effects of Imiquimod: Trastuzumab Drug Interaction: No known significant interactions

Avoid concomitant use with: Administration: For external use only. Dressings may or may
Decreases levels or effects of imiquimod: BCG not be used.
Increases levels or effects of imiquimod: Tacrolimus
Clean and debride burn wounds, then apply to affected
Administration: Wash hands prior to and following area under sterile conditions. Burn areas should always
application. For topical use only. Apply a thin layer prior be well covered by the cream.
to normal sleeping hours and leave on skin for
approximately 6-10 hours, then remove with mild soap Reapply immediately after hydrotherapy. Continue
and water. Non-occlusive dressings may be used in the treatment until satisfactory healing has occurred or until
management of skin reactions. the burn site is ready for grafting.

Pregnancy Category: C Do NOT withdraw from the therapeutic regimen while

there remains the possibility of infection except if a
ATC Code: D06BB10 significant adverse reaction occurs.

Pregnancy Category: B

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 DERMATOLOGICALS

ATC Code: D06BA01 Drug Interactions:

Monitor closely with:
Enhances therapeutic effect of Ceritinib (hyperglycemic
effect)
CORTICOSTEROIDS,
DERMATOLOGICAL PREPARATIONS Increases risk of adverse or toxic effects of Deferasirox (GI
ulceration, irritation, or bleeding)
CORTICOSTEROIDS
Reduces therapeutic effect of Corticorelin (plasma ACTH
GENERAL INFORMATION response)

Avoid concomitant use with:

D

Corticosteroids are group of natural and synthetic

analogues of the hormones secreted by the Reduces therapeutic effect of the following drugs:
hypothalamic-anterior pituitary-adrenocortical (HPA) Aldesleukin (antineoplastic effect)
axis. Corticosteroids are classified as glucocorticoids, Hyaluronidase
mineralocorticoids, and corticotropins.
Fingertip units (FTU) for Topical Steroids:
Glucocorticoids are potent anti-inflammatory agents that One FTU is the amount of topical steroid that is squeezed
affect glucose utilization, fat metabolism, and bone out from a standard tube (5 mm nozzle) along an adult's
development. fingertip, from the very end of the finger to the first
Mineralocorticoids control the retention of sodium and crease in the finger. Two FTUs are about the same as 1
water in the kidneys. g of topical steroid. One FTU is enough to treat an area
Corticotropins, also known as adrenocorticotropic hormone of skin twice the size of the flat of an adult's hand with
(ACTH), control the secretion of hormones by the pituitary the fingers together.
gland. Area of skin to be
FTU per dose
treated (average adult)
Precautions:
Hand and fingers (front
1 FTU
WARNING: NOT for use in children under 2 years of and back)
age.
Front of chest and
7 FTU
abdomen
NOT for diaper dermatitis, ocular herpes simplex,
cerebral malaria, fungal infections, or viral Back and buttocks 7 FTU
hepatitis.
Face and neck 2.5 FTU
Application under occlusion may result to increased
incidence of adverse effects. Entire arm and hand 4 FTU
Entire leg and foot 8 FTU
Adrenal suppression; Anaphylactoid reactions; contact
dermatitis; Eczema; Irritation (discontinue immediately); NOTE: Above measurements are approximated on an
Skin infections (use appropriate antifungal or average adult. Values may differ based on patient
antibacterial agent; discontinue use until the infection size.
has been adequately controlled); Fungal or bacterial
dermatologic infection (institute appropriate antifungal
or antibacterial therapy; if the infection does not resolve
promptly, discontinue use until the infection has been Rx BETAMETHASONE
adequately controlled); Immunosuppression (observe
closely patients with latent tuberculosis and/or Topical: 0.05% cream / ointment (as dipropionate), 5 g
tuberculosis reactivity); Kaposi sarcoma; Myopathy; and 10 g tube
Myasthenia gravis; Psychiatric disturbances; 0.1% cream / ointment (as valerate), 5 g tube
Sensitization; Skin reactions (discontinue if skin irritation
or contact dermatitis occurs; do not use in patients with A topical corticosteroid with intermediate to very high range
decreased skin circulation); Systemic effects; Diabetes potency. It exerts its anti-inflammatory, antipruritic, and
mellitus; Gastrointestinal disease; Ulcerative colitis; vasoconstrictive properties by depressing the formation,
Osteoporosis; Hepatic impairment; Renal impairment; release, and activity of endogenous chemical mediators
Cardiovascular disease; Myocardial infarction; Ocular of inflammation through the induction of phospholipase
disease; Thyroid disease (dose adjustment may be A2.
required); Stress due to trauma, surgery, or severe
infection (may require higher doses); Some dosage forms Indications: Relief of inflammatory and pruritic
may contain benzyl alcohol and/or sodium benzoate or manifestations of corticosteroid-responsive dermatoses
benzoic acid; Elderly; Children; Lactation

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DERMATOLOGICALS

Dose: psoriasis; (ointment / cream) children <1 year;

NOTE: Base dosage on severity of disease and patient (shampoo) children <2 years
response. Therapy should be discontinued when control
is achieved. Reassess if no improvement after 2 weeks Dose:
of treatment. NOTE: Use should be limited to small areas at any one time.
Do NOT use for more than 2 weeks at a time.
Corticosteroid-responsive dermatoses, by topical Discontinue use once control has been achieved.
application, ADULT, as 0.05% dipropionate salt, apply 1–
2 times daily (maximum, 50 g weekly); as 0.1% valerate Dermatoses, by topical application,
salt, apply 1–3 times daily. as ointment, ADULT, apply to affected area 1–2 times
daily, reduce if necessary (maximum, 50 g weekly for 2
Dose Adjustment: weeks); CHILD >1 year, apply to affected area 1–2 times

D
Geriatric and Pediatric: daily, reduce if necessary (maximum, 50 g weekly for 5
Use lowest effective dose for the shortest possible duration. days);
as shampoo, ADULT, apply directly to scalp once daily,
Adverse Drug Reactions: Acneiform eruptions, allergic leave for 15 minutes; do not cover with shower cap
dermatitis, burning, dry skin, erythema, folliculitis, (maximum duration, 4 weeks).
hypertrichosis, irritation, miliaria, pruritus, skin atrophy,
striae, vesiculation Dose Adjustment: No information found

Administration: For external use only. NOT for oral, Adverse Drug Reactions:
ophthalmic, or intravaginal use. Common and Less Common: Hypothalamic-pituitary-
adrenal (HPA) axis suppression or hypercorticism,
Apply sparingly to affected areas. Cushing’s syndrome (prolonged use), contact dermatitis,
skin irritation, numbness of fingers, intracranial
Do NOT use with occlusive dressings or on weeping or hypertension, burning and stinging sensation, tingling,
exudative lesions. cracking, irritation, itching, dryness, hypopigmentation,
Do NOT use on broken skin or in areas of infection. maceration, erythema, folliculitis, perioral dermatitis,
Do NOT apply to wet skin unless directed. skin atrophy, hypertrichosis, tenderness, telangiectasia,
Do NOT apply very high potency agents to face, groin, striae, miliaria, alopecia, pustules, tightening of the
axillae, or diaper area. scalp, acneiform eruptions, allergic contact dermatitis,
secondary infection
Do NOT apply on breasts when breastfeeding.
Administration: For external use only. NOT for oral,
NOTE: Withdraw therapy with gradual tapering of dose by ophthalmic, or intravaginal use.
reducing the frequency of application or substitution of a
less potent steroid. Apply thinly and rub gently and completely to the affected
area.
See General Information on Corticosteroids under
Corticosteroids, Dermatological Preparations in Chapter Do NOT use on the face, groin, or axillae.
4: Dermatologicals for other information. Do NOT cover with occlusive dressing.

Pregnancy Category: C NOTE: Withdraw therapy with gradual tapering of dose by reducing the
frequency of application or substitution of a less potent steroid.
ATC Code: D07AC01
See General Information on Corticosteroids under
Corticosteroids, Dermatological Preparations in Chapter
4: Dermatologicals for other information.
Rx CLOBETASOL
Pregnancy Category: C
Topical: 0.05% cream / ointment (as propionate), 5 g
ATC Code: D07AD01
and 15 g tube
0.05% shampoo (as propionate), 25 mL bottle

An analogue of prednisolone with a high degree of Rx FLUOCINONIDE

glucocorticoid activity and a slight degree of
mineralocorticoid activity. It has anti-inflammatory,
antipruritic, and vasoconstrictive properties by the Topical: 0.05% cream / ointment, 5 g and 15 g tube
induction of phospholipase A2.
A topical corticosteroid with anti-inflammatory, antipruritic,
Indication: For the relief of inflammatory and pruritic and vasoconstrictive properties. It has glucocorticoid
manifestations of corticosteroid-responsive dermatoses activity, used in the treatment of various skin disorders.

Contraindications: Untreated bacteria, fungal, or viral skin Indications: For the relief of inflammatory and pruritic
lesions; rosacea; perioral dermatitis; acne; plaque manifestations of corticosteroid-responsive dermatoses

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 DERMATOLOGICALS

Contraindications: Infection at treatment site; drug irritation, itching, maceration of skin, miliaria, perioral
intolerance; preexisting skin atrophy dermatitis, secondary infection, skin atrophy, striae

Dose: Administration: For external use only. Shake lotion well

Dermatoses, by topical application, ADULT, apply on before use.
affected area(s) 1–4 times daily; reduce dose as
condition improves. Apply a thin film to clean, dry skin and rub in gently.

Dose Adjustment: No information found Do NOT use with occlusive dressings or on weeping or
exudative lesions.
Adverse Drug Reactions: Do NOT apply on breasts when breastfeeding.
Common: Burning, itching, irritation, dryness, folliculitis,
D

hypertrichosis, acneiform eruptions, hypopigmentation, NOTE: After long-term use, withdraw therapy with gradual
perioral dermatitis, allergic contact dermatitis, tapering of dose.
maceration of the skin, secondary infection, skin
atrophy, striae, miliaria See General Information on Corticosteroids under
Corticosteroids, Dermatological Preparations in Chapter
Administration: For external use only. 4: Dermatologicals for other information.

Avoid contact with eyes and prolonged facial application. Pregnancy Category: C
Do NOT cover with occlusive dressing. Do NOT use more
than instructed. ATC Code: D07AA02

Do NOT apply on breasts when breastfeeding.

See General Information on Corticosteroids under ANTISEPTICS AND DISINFECTANTS

Corticosteroids, Dermatological Preparations in Chapter
4: Dermatologicals for other information. BIGUANIDES AND AMIDINES
Pregnancy Category: C
Rx (0.12% preparation)
OTC (4% preparation)
CHLORHEXIDINE
ATC Code: D07AC08

Topical: 0.12% and 4% solution (as gluconate), 50 mL,

120 mL, 380 mL, 500 mL, 4 L, and 5 L
OTC HYDROCORTISONE
A very potent cationic chemoprophylactic agent with broad-
Topical: 1% cream / ointment, 5 g and 10 g tube spectrum of activity against gram-positive and gram-
1% and 2.5% lotion, 25 mL bottle negative bacteria. It is bactericidal at high
concentrations by altering the bacterial cell osmotic
A topical corticosteroid with anti-inflammatory, antipruritic, equilibrium and leakage of potassium and phosphorus.
and vasoconstrictive properties by depressing the
formation, release, and activity of endogenous chemical Indications: Treatment of gingivitis; surgical hand scrub;
mediators of inflammation through the induction of health care personnel hand wash; preoperative skin
phospholipase A2. preparation; skin wound and general cleansing

Indications: Dermatosis; anal and genital itching (external) Dose:

Gingivitis, by mouth, ADULT, as 0.12% preparation, swish 1
Dose: tablespoon (15 mL) in mouth undiluted for 30 seconds,
Dermatosis, by topical application, ADULT and CHILD, apply then spit out; rinse twice daily, morning and evening,
a thin film to the affected area 2–4 times daily. after tooth brushing
Anal and external genital itching, by topical application, Surgical hand scrub, by topical application, ADULT, as 4%
ADULT and CHILD, apply to the affected area 3–4 times preparation, wet hands and forearms under running
daily. water for 30 seconds; scrub hands and forearms with 5
Atopic dermatitis, by topical application, ADOLESCENT, mL of product with or without wet brush for 3 minutes;
CHILD, and INFANT ≥3 months, apply thin film to affected pay close attention to the nails, cuticles, and interdigital
area twice daily. spaces; rinse thoroughly under running water for 30
seconds; dry thoroughly.
Dose Adjustment: Health care personnel hand wash, by topical application,
Geriatric: ADULT, as 4% preparation, wet hands with water; wash
Use in the smallest possible effective dose for the shortest hands with 5 mL of product in a vigorous manner for 15
duration. Limit use due to age-related changes in the seconds; rinse and dry thoroughly.
skin. Preoperative skin preparation, by topical application,
ADULT, as 4% preparation, apply liberally to surgical site
Adverse Drug Reactions: Acneiform eruptions, burning, and swab for at least 2 minutes; dry with a sterile towel;
dryness, folliculitis, hypertrichosis, hypopigmentation,

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DERMATOLOGICALS

repeat cleansing for an additional 2 minutes and dry with Contraindication: Hypersensitivity to iodine or any
a sterile towel. component in the formulation
Skin wound and general cleansing, by topical application,
ADULT, as 4% preparation, thoroughly rinse with water Dose:
the area to be cleansed; apply the minimum amount of Clean the affected area; apply a small amount 1–3 times
product necessary to cover the skin or wound area and daily; if to be bandaged, allow sufficient time for the
wash gently; rinse thoroughly. iodine to dry completely.

Precautions: Precautions:
Gingivitis and periodontitis; Staining of oral surfaces; Stains skin and clothing.
Alteration in taste perception; Children; Lactation.
Adverse Drug Reaction:

D
Adverse Drug Reactions: Common: Skin irritation
Common: Reversible brown staining of teeth and other oral
surfaces, increased calculus formation, transient taste Drug Interactions: No information found.
disturbance, skin sensitivity, irritation of conjunctiva,
mucosal irritation, burning sensation of tongue, Administration: For external use only. Apply topically to the
anaphylaxis affected areas as necessary.
Less Common: Aphthous ulcer, grossly obvious gingivitis,
trauma, ulceration, erythema, desquamation, coated Do NOT cover iodine-treated wounds to avoid irritation.
tongue, keratinization, geographic tongue, mucocele, Do NOT apply over large areas of the body.
short frenum, stomatitis, glossitis, dry mouth,
hypesthesia, glossal edema, paresthesia, parotid gland Avoid contact with eyes. If contact occurs, flush with large
swelling, sialadenitis amounts of water while lifting upper and lower lids.

Drug Interactions: No known significant interactions Pregnancy Category: Not available

Administration: Avoid contact w/ brain, meninges, middle ATC Code: D08AG03

ear or sensitive tissues and eyes. Do NOT inject or use in
body cavities.

For 0.12% preparation: NOT intended for ingestion. OTC POVIDONE-IODINE

Should be expectorated after rinsing. Do NOT rinse with
water, or other mouthwashes, brush teeth, or eat Topical: 10% ointment, 5 g, 15 g, and 30 g tube
immediately after. Initiate oral rinse therapy directly 10% paint, 10 mL bottle
following a dental prophylaxis. Reevaluate patients and 10% solution, 15 mL, 30 mL, 60 mL, 120 mL, 1
give a thorough prophylaxis at intervals no longer than 6 L, and 1-gallon bottle
months. 7.5% surgical cleanser, 60 mL, 120 mL, 480
mL, 1 L, and 1-gallon bottle
For 4% preparation: For external use only. Do NOT use in
the genital area. Do NOT use as a preoperative skin An antiseptic preparation of a soluble form of iodine used
preparation on the head or face. for the disinfection of minor skin infections.

Keep out of reach of children. If swallowed, get medical Indications: Skin disinfection; antiseptic; treatment of
help or contact a poison control center immediately common skin infections; prevention of infection in minor
burns, lacerations, cuts, and abrasions; infection control
Pregnancy Category: B (0.12%; mouth or throat); during insertion and care of urinary catheters,
C (periodontal) circumcision, suture removal, and dressing changes;
degerming care of stasis ulcers and umbilical area;
ATC Code: D08AC02 degerming during use of IV devices in blood transfusions,
hyperalimentation, cutdowns, central venous pressure
(CVP) catheterization, and in other procedures;
IODINE PRODUCTS treatment of mouth sores (aphthous ulcers), herpes
simplex, herpes zoster (shingles), herpes labialis (cold
sores), grazes abrasions, cuts and wounds, or any break
OTC IODINE in the skin which requires protection from infection;
maximum degerming of skin as preoperative preparation
Topical: 1% and 2% tincture
2% and 5% solution Contraindications: Postmenstrual age of 32 weeks; regular
or prolonged use in patients with thyroid disorders, or
A nonmetallic element with germicidal activity. those taking lithium; regular use in neonates; in very low-
birthweight infants (e.g., <1.5 kg); hyperthyroidism
Indications: First aid to prevent infection in minor cuts,
scrapes, and burns Dose:
Prevention and treatment of infections, by topical
application, ADULT and CHILD, as 10% ointment, clean

163
 DERMATOLOGICALS

and dry affected area; apply liberally and cover with a Indications: Disinfection of skin prior to injection,
dressing or bandage; may be used as often as required; venipuncture, or surgical procedures
use only as prescribed.
Mouth sores, herpes simplex, herpes zoster, herpes labialis, Contraindications: Management of broken skin; patients
grazes abrasions, cuts and wounds, by topical who have suffered severe burns when diathermy has
application, ADULT and CHILD, as 10% paint, apply been preceded by application of alcoholic skin
undiluted to affected area and allow to dry; use twice disinfectants
daily and cover with a dressing if desired.
Pre-operative and post-operative skin disinfection, by Dose:
topical application, ADULT and CHILD, as 10% solution, Disinfection of skin, by topical application, ADULT and
apply an appropriate volume of solution directly to the CHILD, apply an appropriate volume of solution directly
skin area. to the skin area.
D

Antiseptic (minor wounds and burns), by topical application,

ADULT and CHILD, as 10% solution, apply an appropriate Precautions:
volume of solution to the affected area, twice daily (see Avoid heat, sparks and open flame and temperatures above
Precautions below). 30°C; Emission of toxic fumes of carbon monoxide and
Degerming of skin on patients, by topical application, carbon dioxide, if exposed to fire.
ADULT, as 7.5% surgical cleanser, apply necessary
quantity on area to wash, thoroughly distribute while Adverse Drug Reaction: Skin dryness and irritation with
rubbing for at least 5 minutes; rinse off with a sterile frequent application of the aqueous solution
gauze saturated with water.
Degerming of skin on health care personnel, by topical Drug Interactions: No information found
application, ADULT, as 7.5% surgical cleanser, apply
necessary quantity on area to wash, thoroughly distribute Administration: For external use only. Apply locally as
while rubbing for at least 5 minutes; clean under needed.
fingernails using a brush if desired; rinse under running
water. Pregnancy Category: No information found

Precautions: ATC Code: D08AX08

WARNING: Do NOT use 10% paint preparation in
children <3 years.
OTC HYDROGEN PEROXIDE
Broken skin; Renal impairment (avoid regular application to
inflamed or broken mucosa); Pregnancy (second and Topical: 3% solution, 60 mL and 120 mL bottle
third trimesters: sufficient iodine may be absorbed to
affect the fetal thyroid). A clear, colorless solution of hydrogen peroxide, which is a
powerful oxidizing agent, and is used as a disinfectant.
Adverse Drug Reactions:
Rare: local irritation of the skin and mucous membranes Indications: Mild disinfectant for minor cuts, skin ulcers, and
wounds
Drug Interactions: No information found.
Contraindication: Injection or instillation into closed body
TEST INTERACTION. May interfere with thyroid function tests cavities for which the released oxygen has no free exit
due to systemic effects.
Dose:
Administration: For external use only. Apply locally as Disinfection, by topical application, ADULT and CHILD, dress
needed. the wound with cotton wool soaked in an appropriate
volume of hydrogen peroxide.
Pregnancy Category: D
Precautions:
ATC Code: D08AG02 Use with caution in large or deep wounds; Avoid contact with
healthy skin, eyes and clothes.

OTHER ANTISEPTICS AND DISINFECTANTS Adverse Drug Reactions:

Rare: Hypersensitivity reactions, irritating burns on the skin
and mucous membranes with a white eschar (strong
OTC ALCOHOL, ETHYL solution)

Topical: 95% solution, for dilution to 70% Drug Interactions:

(with BIR seal) Avoid concomitant use with:
Incompatible with the following products:
A clear, aqueous solution of ethyl alcohol which is used as a Preparations containing Iodine,
disinfectant and skin antiseptic. Preparations containing Potassium Permanganate

164
DERMATOLOGICALS

Administration: For external use only. Apply locally as

needed. SODIUM DICHLOROISOCYANURATE

Pregnancy Category: No information found Solution: 3.5 mg tablet (2 mg free available chlorine)
8.68 mg tablet (5 mg free available chlorine)
ATC Code: D08AX01 12.5 mg tablet (8 mg free available chlorine)
17 mg tablet (10 mg free available chlorine)
67 mg tablet (40 mg free available chlorine)
OTC SODIUM HYPOCHLORITE The sodium salt of a chlorinated hydroxytriazine used as a
source of free available chlorine, in the form of
Solution: 1.25% available chlorine hypochlorous acid, for the disinfection of water.

D
A strong oxidizing agent that can be used for water Indication: For water purification used in cleaning hospital
purification by producing chlorine when dissolved in facilities, washing of hands, gloves, and other daily use
water. articles, and sterilizing of items used in hospitals;
disinfection of water in the prevention of water-borne
Indications: To prevent and treat infections of the skin diseases
tissue; pre- and post-surgery antiseptic; for cuts,
abrasions, and skin ulcers; for water purification

Contraindication: Sensitivity to chlorine compounds Appropriate use:

Approximate
Dose: Approximate
Tablet Volume of
Available
Management of lightly or moderately exudative wounds, by Strength Water to be
Chlorine
topical application, ADULT and CHILD, pour on or apply Treated
to affected area once daily; protect intact skin with a 8.68 mg 5 mg 1L
moisture barrier ointment or skin sealant as needed. 17 mg 10 mg 4L
Management of highly exudative or highly contaminated 75 mg 45 mg 10–20 L
wounds, by topical application, ADULT and CHILD, pour
on or apply to affected area twice daily; protect intact Precautions:
skin with a moisture barrier ointment or skin sealant as
WARNING: Not for consumption. Do NOT ingest
needed.
tablet.
Water purification
Approximate Volume of Approximate Volume of Ensure that use of tablets, especially for large volume
Sodium Hypochlorite Water to be Treated waters, is conducted in a well-ventilated area.
2.5 mL (½ teaspoon) 22.5 L (5 gallons)
Adverse Drug Reactions:
5 mL (1 teaspoon) 45 L (10 gallons) Rare: Cough, sore throat, redness, skin burns, pain
25 mL (5 teaspoons) 227 L (50 gallons) Pregnancy Category: Not applicable
ATC Code: Not applicable
Precautions:
WARNING: Not for consumption. Do NOT ingest tablet.

Ensure that use of tablets, especially for large volume ANTI-ACNE PREPARATIONS
waters, is conducted in a well-ventilated area; Stop use
and ask a doctor if redness, irritation, swelling or pain
persists or increases. OTC BENZOYL PEROXIDE
Adverse Drug Reactions: Cough, sore throat
Topical: 5% gel, 20 g tube
Administration: For external use only.
A topical peroxide preparation used in the treatment of
Keep out of reach of children. If swallowed, get medical help acne.
or contact a Poison Control Center immediately.
Indication: Treatment of acne vulgaris
Keep container closed when not using.
Contraindication: Sensitive skin
Pregnancy Category: C
Dose:
ATC Code: D10AE01 Acne vulgaris, by topical application, ADULT, initially, cover
the entire affected area with a thin layer once daily;
gradually increase to 2–3 times daily if needed or as
directed by a doctor

165
 DERMATOLOGICALS

Precautions:
Skin irritation and dryness; On initial application, a mild
burning sensation may be felt, and redness and peeling
may occur (reversible when drug is discontinued).

Adverse Drug Reactions: Allergic contact dermatitis, dryness

Drug Interactions: No information found

Administration: For external use only. Apply as directed after

thoroughly cleaning the affected area with a mild
cleanser and water.
D

Avoid contact with the eyes, lips, mouth, and mucous

membranes. Avoid unnecessary sun exposure and use
sunscreen. Avoid contact with hair and dyed fabrics
which may be bleached by this product.
Keep out of reach of children. If swallowed, get medical
help or contact a Poison Control Center right away.

Pregnancy Category: C

ATC Code: D10AE01

166
GENITO URINARY SYSTEM AND SEX HORMONES

Pregnancy Category: A
GENITO URINARY SYSTEM
AND SEX HORMONES ATC Code: G01AA01

ANTIINFECTIVES AND ANTISEPTICS, OTHER GYNECOLOGICALS

EXCLUDING COMBINATIONS WITH
CORTICOSTEROIDS
UTEROTONICS

Rx NYSTATIN ERGOT ALKALOIDS

Vaginal: 100,000 units per tablet METHYLERGOMETRINE

Rx

G
(METHYLERGONOVINE)
A polyene antifungal obtained from Streptomyces noursei
that interfere with the permeability of cell membrane of Inj.: 200 micrograms/mL (as hydrogen maleate or
fungi, particularly Candida. maleate), 1 mL ampule (IM, IV)

Indications: Used in the prophylaxis and treatment of Methylergometrine is an amine ergot alkaloid that increases
infections caused by Candida, including vulvovaginal tone, rate, and amplitude of contractions on the smooth
candidiasis muscles of the uterus.

NOTE: Diagnosis should be confirmed by KOH smears Indications: For management of third stage labor; routine
and/or cultures prior to treatment. Some pathogens that management after delivery of the placenta;
are also commonly associated with vulvovaginitis like management of postpartum hemorrhage, uterine
Trichomonas and Haemophilus vaginalis should be ruled subinvolution, and postpartum atony
out through adequate laboratory procedures.
Contraindications: Hypertension; toxemia; pregnancy or
Dose: patients with threatened spontaneous abortion
Vaginal candidiasis, by vaginal insertion, ADULT, 100,000–
200,000 units daily for 14 days or longer. Dose:
Management of postpartum hemorrhage, by IM or IV
NOTE: For cutaneous lesions, ointment, gel, cream, or injection, ADULT, 0.2 mg after delivery of anterior
dusting powder having 100,000 units per gram can be shoulder, after delivery of placenta, or during
applied 2 to 4 times daily. puerperium, may be repeated every 24 hours as needed.
Management of postpartum hemorrhage, severe
Precautions: hemorrhage, by IM or IV injection, ADULT, 0.2 mg after
Intravaginal preparations may damage latex contraceptives delivery of anterior shoulder, after delivery of placenta,
(an additional contraceptive method is recommended or during puerperium, may be repeated as required at 2-
during treatment); to 4-hour intervals.
Pregnancy (check first with a health care professional if
pregnant or trying to get pregnant). NOTE: IV administration must only be considered during life-
threatening situations due to the possibility of inducing
Adverse Drug Reactions: sudden hypertension and cerebrovascular incident.
Contact dermatitis, ashes, including urticaria, irritation,
sensitization, generalized pustular eruptions Dose Adjustment:
Renal and Hepatic Impairment:
Drug Interactions: Use with caution.
Monitor closely with:
Increases risk of adverse or toxic effects: Precautions:
Other vaginal products [consult health care professional]
WARNING: Do NOT exceed dosing guidelines and
Avoid concomitant use with: avoid prolonged administration. Ergot alkaloids
Increases risk of adverse or toxic effects of Progesterone use may result in ergotism or intense
(Intravaginal gel) (alters progesterone release) vasoconstriction resulting in peripheral vascular
ischemia and possible gangrene, usually
Administration: For use in the vagina only. Do NOT take by associated with overdose or prolonged chronic use.
mouth.
Wash hands first before and after use. Insert 1 tablet in the Coronary heart disease; Hypertension; Heart disease;
applicator tip. Lie on the back then gently insert Venoatrial shunts;
applicator high in the vagina and push plunger to release Mitral valve stenosis;
the tablet. Gently remove the applicator. Wash it well with Sepsis;
warm water and soap. Obliterative vascular disease;
Follow course of medication. Do NOT use in amounts other Ergotism;
than what is directed.

167
 GENITO URINARY SYSTEM AND SEX HORMONES

Pleural and/or retroperitoneal fibrosis; clinicians recommend diluting the IV dose to a volume of
Hepatic and renal impairment; 5 mL with 0.9% sodium chloride injection before
Pregnancy (use with caution in women in second stage of administration. Monitor blood pressure, CNS status, and
labor). vaginal bleeding regularly.
Adverse Drug Reactions: Acute MI, angina pectoris, arterial
spasm, atrioventricular block, bradycardia, Pregnancy Category: C
cerebrovascular accident, chest pain,
hyper/hypotension, palpitation, tachycardia, vasospasm, ATC Code: G02AB01
ventricular fibrillation, dizziness, hallucinations,
headache, seizure, rash, water intoxication, abdominal
pain, diarrhea, foul taste, nausea, vomiting, PROSTAGLANDINS
thrombophlebitis, leg cramps, paresthesia, tinnitus,
hematuria, dyspnea, nasal congestion, anaphylaxis, and
diaphoresis Rx CARBOPROST
G

Drug Interactions:
Inj.: 125 micrograms/0.5 mL, 250 micrograms/mL
Monitor closely with:
solution and 1 mL ampule/vial
Enhances therapeutic effect of Methylergometrine:
Metoclopramide, Tedizolid (serotonergic effects)
Carboprost is a synthetic derivative of prostaglandin that
stimulates uterine smooth muscle, increasing uterine
Enhances therapeutic effect of Anti-emetics e.g., 5-HT3
tone.
Antagonists, Anti-psychotic Agents (dopamine blockade)
Indication: For the treatment of post-partum hemorrhage
Increases risk of adverse or toxic effects of
after failure of treatment with oxytocin therapy or if the
Methylergometrine:
use of methylergometrine is contraindicated (pre-
Anti-psychotic Agents, Tedizolid (serotonin syndrome),
eclampsia, hypertension, cardiovascular disease)
CYP3A4 Inhibitors (ergotism), Metoclopramide
(serotonin syndrome; neuroleptic malignant syndrome)
Contraindications: Acute pelvic inflammatory disease;
active cardiac, pulmonary, renal or hepatic disease
Increases risk of adverse or toxic effects of the following
drugs:
Dose:
Anti-emetics, e.g., 5-HT3 Antagonists (serotonin
NOTE: Ask clinician regarding the need for additional doses
syndrome), Anti-psychotic Agents (neuroleptic malignant
and adequate dosing interval based on clinical events of
syndrome)
the patient.
Avoid concomitant use with: Post-partum hemorrhage, by deep IM injection, ADULT, 250
Enhances therapeutic effect of Methylergometrine: micrograms/mL, then repeat every 15–90 minutes, if
Beta Blockers, Serotonin 5-HT1 Receptor Agonists needed (maximum total dose, 2 mg or 8 doses).
(vasoconstricting effects).
Dose Adjustment:
Enhances therapeutic effect of the following drugs: Renal and Hepatic Impairment:
Alpha / Beta Agonists, Alpha1 Agonists (hypertensive Use with caution.
effects), Serotonin 5-HT1 Receptor Agonists
(vasoconstricting effects) Precautions:
Increases risk of adverse or toxic effects of WARNING: A potent oxytocic agent. Strictly adhere to
Methylergometrine: recommended dosing. Use should only be under
Azole Antifungals, CYP3A4 Inhibitors, Dapoxetine, the direct supervision of medically trained
Protease Inhibitors (ergotism), Serotonin Modulators personnel in a hospital that can immediately
[except Tedizolid] (serotonin syndrome) provide intensive care unit and surgical facilities.

Increases serum concentration of Methylergometrine:

Anti-hepaciviral Combination Products, Boceprevir, Glaucoma or raised intraocular pressure;
Fusidic Acid, Macrolide Antibiotics [except Azithromycin], Asthma;
Mifepristone, Nitroglycerin Hypertension, Hypotension, or any cardiovascular disease;
Anemia;
Reduces therapeutic effect of Nitroglycerin (vasodilatory Jaundice;
effect) Hepatic and renal impairment;
Diabetes;
Administration: May be administered by IM or IV injection. Epilepsy

Limit IV use to patients with severe uterine bleeding or other Adverse Drug Reactions:
life-threatening emergency situations with doses given Common: Diarrhea, nausea, vomiting, increase in body
over a period of not less than 1 minute. NOT for routine temperature, flushing/hot flashes, chills, endometritis,
IV administration due to risk of inducing sudden uterine hemorrhage, retained placenta or membranes,
hypertensive and cerebrovascular accidents. Some headaches, cough

168
GENITO URINARY SYSTEM AND SEX HORMONES

Less Common / Rare: Nervousness, epistaxis, sleep Precautions:

disorder, asthma, wheezing, chest pain, hypertension, WARNING: Extreme caution is required for risk of maternal
syncope, palpation, tachycardia, chest tightness, anxiety, pulmonary edema or respiratory distress syndrome.
dizziness, drowsiness, dystonia, faintness, lethargy, light-
headedness, nervousness, sleep disturbance, vasovagal Elderly (avoid use due to its lack of reported efficacy in this
syndrome, vertigo, rash, breast tenderness, age group); Pregnancy (monitor maternal blood pressure
dysmenorrhea-like pain, thyroid storm, gagging/retching, and hydration, as well as maternal and fetal heart rates
drowsiness, dry throat, choking sensation, thirst, taste all throughout infusion).
alterations, perforated uterus, posterior cervical
perforation, urinary tract infection, excessive uterine Adverse Drug Reactions: Chest pain, hypotension,
bleeding, uterine rupture, uterine sacculation, pain at the tachycardia, dizziness, rash, abdominal distress,
injection site, backache, leg cramps, muscular pain, nausea, vomiting, transient flushing, maternal
parethesia, torticollis, weakness, blurred vision, eye pulmonary edema, fetal tachycardia, trembling,
pain, eyelid twitching, tinnitus, coughing, bronchospasm, nervousness, weakness, transient palpitation

G
hyperventilation, pulmonary edema, respiratory distress,
upper respiratory tract infection, wheezing, diaphoresis, Drug Interactions:
hiccups, retained placental fragment, septic shock Monitor closely with:
Enhances therapeutic effect of Isoxsuprine:
Drug Interactions: Barbiturates, Nicorandil (hypotensive effect)
Avoid concomitant use with:
Enhances therapeutic effect of Carboprost: Enhances therapeutic effect of Risperidone (hypotensive
Oxytocic agents effect)

Administration: Administer by deep IM injection directly to Increases risk of adverse or toxic effects of Isoxsuprine:
the uterine corpus. Do NOT administer intravenously. Hypotensive Agents (orthostatic hypotension)

Consider administration of anti-emetic and anti-diarrheal Increases risk of adverse or toxic effects of the following
drugs prior to therapy to decrease incidence of GI effects. drugs:
Duloxetine, Levodopa (orthostatic hypotension)
Pregnancy Category: C
Administration:
ATC Code: G02AD04 For parenteral administration, may be administered by
syringe pump. Limit therapy to a maximum of 48 hours.

For oral administration, may be taken with meals, milk, or

Rx ISOXSUPRINE antacids to minimize GI discomfort.

Oral: 10 mg and 40 mg tablet (as hydrochloride) Pregnancy Category: C

Inj.: 5 mg/mL (as hydrochloride), 2 mL ampule (IM, IV
infusion) ATC Code: Not available

A beta-adrenergic agonist that stimulates the beta2

receptors, causing direct relaxation of vascular and
uterine smooth muscle. Rx MAGNESIUM SULFATE

Indications: For management of uncomplicated premature Inj.: 250 mg/mL (as heptahydrate), 2 mL and 10 mL
labor; uterine hypermotility disorder; threatened ampule (IM, IV)
abortion; dysmenorrhea 250 mg/mL, 10 mL, 20 mL and 50 mL vial (IV)
500 mg/mL (as heptahydrate), 2 mL and 10 mL
Contraindications: Recent arterial hemorrhage or bleeding; ampule (IM, IV)
immediately postpartum; infection
A sterile preparation that contains magnesium salt as
Dose: heptahydrate.
Premature labor, treatment, IV infusion, ADULT, 200 to 500
micrograms/minute, adjusted according to the response Indications: Drug of choice for the prevention of seizures in
of the patient until control is achieved; once labor has women with severe preeclampsia; control of seizures or
been arrested, by IM injection, ADULT, 10 mg every 3–8 prevention of recurrence among eclamptic patients
hours.
Premature labor, prophylaxis, by mouth, ADULT, 30 to 90 Contraindications: Heart block; myocardial infarction;
mg daily after parental therapy. hypermagnesemia; deranged renal function; myasthenia
gravis
NOTE: Oral therapy is no longer recommended because of
lack of reported evidence of benefit from this route. Dose:
Prevention of recurrent seizures, by IV injection, ADULT, 4 g
as loading dose over 5–15 minutes followed by IV
infusion of maintenance dose of 1 g/hour for at least 24

169
 GENITO URINARY SYSTEM AND SEX HORMONES

hours after the last seizure or delivery, whichever occurs Administration: For IV administration, do not exceed the rate
later; of 150 mg/minute. See manufacturer’s directions for
by deep IM injection (used when IV lines are not instructions on dilution and administration.
available), ADULT, 5 g into each buttock, then 5 g every
4 hours into alternate buttocks for at least 24 hours after NOTE: Should NOT be used via IV route for pre-eclampsia or
the last seizure or delivery; treat recurrent seizure by eclampsia during 2 hours prior to delivery.
further IV bolus of 2 g or 4 g if body weight is over 70 kg. Do NOT freeze since it may result in precipitation or
crystallization.
Dose Adjustment:
Renal Impairment:
Dose should not exceed 20 g in 48 hours. Use with caution
and monitor for hypermagnesemia. Route Preparation
Concentration should NOT exceed 20% (200
Precautions:
mg/mL). Dilute 1 part magnesium sulfate,
G

IV
WARNING: Magnesium toxicity can cause loss of deep 50%, with at least 1.5 parts of water for
tendon reflexes, followed by respiratory depression injection)
and ultimately respiratory arrest. If deep tendon
reflexes are absent, withhold further doses of Adult: Concentrations of 25% (250 mg/mL)
magnesium sulfate until reflexes return. If or 50% (500 mg/mL). Mix magnesium
repeated seizures occur despite magnesium, other IM sulfate, 50%, with 1 mL lidocaine injection,
pre-hospital options include administering 2%
diazepam. Child: Should not exceed 20% (200 mg/mL)

Magnesium toxicity can be reversed with Pregnancy Category: D

administration of calcium gluconate, administered
as a 10–20 mL IV of 10% solution, as an antidote ATC Code: Not available
for problematic signs associated with
hypermagnesemia.

Magnesium is excreted by the kidney. Monitor SEX HORMONES AND MODULATORS OF

serum levels regularly in women with oliguria (urine THE GENITAL SYSTEM
output <100 mL/4 hours).

Myasthenia gravis;
HORMONAL CONTRACEPTIVES
Hepatic impairment (avoid in hepatic coma if there is a risk FOR SYSTEMIC USE
of renal failure);
Renal impairment; PROGESTINS AND ESTROGENS,
Magnesium toxicity can lead to fatal cardiovascular arrest FIXED COMBINATIONS
and/or respiratory failure or paralysis;
Pregnancy. General Information
Adverse Drug Reactions: Combination of hormonal contraceptives that inhibit
Common: Flushing, nausea, vomiting ovulation via a negative feedback mechanism involving
Less Common: Dizziness, drowsiness, headache, thirst the hypothalamus. These modify the normal pattern of
Rare: Arrhythmias, cardiac arrest, coma, confusion, loss of gonadotropin secretion of the follicle stimulating
tendon reflexes, muscle weakness, respiratory hormone (FSH) and luteinizing hormone by the anterior
depression pituitary. Thus, inhibiting the follicular phase FSH and
midcycle surge of gonadotropins. These contraceptives
Drug Interactions: also produce alterations in the genital tract, including
Monitor closely when used with drugs that: changes in the cervical mucus, making it unfavorable for
Enhance the therapeutic effect of Mg Sulfate: sperm penetration.
Aminoglycosides e.g. Streptomycin (additive
neuromuscular blocking effect), CNS Depressants, e.g., Indication: Contraception
Barbiturates, Opiates, General Anesthetics, Gabapentin
(additive central depressant effects), Neuromuscular Contraindications: Breast cancer (current or recent); risk
Blockers e.g., Tubocurarine, Succinylcholine, factors for venous thromboembolism and arterial
Vecuronium (potentiates neuromuscular blockade), disease; heart disease associated with pulmonary
Nifedipine (Parenteral) hypertension or risk of embolism; migraine; history of
subacute bacterial endocarditis; ischemic
Increases risk of adverse or toxic effects of Magnesium cerebrovascular disease; liver disease, including
Sulfate: disorders of hepatic secretion; porphyria; systemic lupus
Nifedipine (hypotension) erythematosus (SLE); history of hemolytic uremic
syndrome; liver adenoma; gallstones; estrogen-
dependent neoplasm; neoplasm of genital tract;

170
GENITO URINARY SYSTEM AND SEX HORMONES

undiagnosed vaginal bleeding; history of pruritus during precautions should be used during, and for 7 days after,
pregnancy, chorea, deteriorating otosclerosis, recovery. If vomiting and diarrhea occur during the last 7
cholestatic jaundice, or pemphigoid gestationis; after pills, omit inactive pills or next pill-free period.
evacuation of hydatidiform mole; smokers >35 years
Dose Adjustment:
Dose: Renal Impairment
ADMINISTRATION. Each tablet (“pill”) should be taken at In mild-to-moderate impairment, use with caution.
approximately the same time each day. If one or more In severe impairment, refer patient to a specialist.
tablets are forgotten for more than 12 hours,
contraceptive protection will be reduced. Precautions:
WARNING: Increased risk of cardiovascular side
For Schedule 1: effects in women who smoke cigarettes
Begins dose on first Sunday after onset of (especially heavy smokers with ≥15 cigarettes
menstruation. If the menstrual period per day). Strongly advise women who use

G
starts on a Sunday, take first tablet that combination hormonal contraceptives to stop
Sunday
very same day. With a Sunday start, an use of oral contraceptives or not to smoke.
Starter
additional method of contraception should
be used until after the first 7 days of Unexplained vaginal bleeding (investigate cause before
consecutive administration. starting contraceptive);
Take 1 tablet daily for 21 consecutive Risk factors for venous thromboembolism and arterial
21- days, followed by 7 days off the disease;
tablet medication. Migraine without focal aura or controlled with 5HT1 agonist;
package Start new course on the 8th day after the Hyperprolactinemia;
last tablet is taken. Gallbladder disease;
28- Some types of hyperlipidemia;
tablet Take 1 tablet daily without interruption. History of severe depression especially if induced by
package hormonal contraception;
Long-term immobilization [see Travel below];
For Schedule 2: Sickle-cell disease;
Day 1 Take 1 tablet daily starting on the first day Inflammatory bowel disease, including Crohn’s disease;
Starter of the menstrual cycle. Diabetes;
Take 1 tablet daily for 21 consecutive Smoking;
days, followed by 7 days off the BMI >30;
21- Malabsorption syndromes;
medication (during which withdrawal
tablet Surgery;
bleeding occurs).
package Systemic Lupus Erythematosus (SLE);
Start new course on the 8th day after the
last tablet is taken. Pregnancy (epidemiological evidence suggests no harmful
effects on fetus; use within 3 weeks of birth);
28- Take 1 tablet daily without interruption Breastfeeding (combined oral contraceptives may inhibit
tablet (withdrawal bleeding occurs when inactive lactation; use alternative method of contraception until
package tablets are being taken). weaning or for 6 months after birth).

NOTE: If all doses have not been taken on schedule and one MIGRAINE. Report any increase in headache frequency or
menstrual period is missed, the possibility of pregnancy onset of focal symptoms. Discontinue immediately and
should be considered. If 2 consecutive menstrual refer urgently to a neurologist if focal neurological
periods are missed, pregnancy test is required before symptoms not typical of aura persist for more than 1
starting a new dosing cycle. hour.

MISSED PILL. The critical time for loss of contraception TRAVEL. Women may be at an increased risk of deep-vein
protection is when a pill is omitted either at the beginning thrombosis during travel involving long periods of
or at the end of a cycle (as this lengthens the pill free immobility (over 5 hours). The risk may be reduced by
interval). If a woman forgets to take a pill, she should appropriate exercise during the journey, and possibly by
take it as soon as she remembers, and take the next one wearing elastic hosiery.
at the normal time. If the delay with any pill is 24 hours
or longer, the pill may not work. Continue taking the pill Adverse Drug Reactions:
normally but be aware that contraception may not work Common: Acne, breakthrough bleeding, breast enlargement
for the next 7 days. If these 7 days run beyond the end and tenderness, changes in libido, chloasma, fluid
of the packet, the next packet should be started at once, retention, headache, hypertension, mood changes (e.g.,
omitting the 7 inactive tablets or the pill-free interval. depression), nausea, thrush, vomiting
Emergency contraception is recommended if more than Less Common: Alopecia, amenorrhea, contact lens
2 combined oral contraceptive tablets are missed from intolerance, hirsutism, hyperinsulinemia, insulin
the first 7 tablets in a packet. resistance, rash
Rare: Allergy, breast cancer, cervical cancer, hypertension,
DIARRHEA AND VOMITING. Vomiting within 2 hours of taking jaundice, liver cancer, pancreatitis, photosensitivity,
an oral contraceptive or very severe diarrhea can stroke, VTE
interfere with the absorption of the drug. Additional

171
 GENITO URINARY SYSTEM AND SEX HORMONES

Drug Interactions: ETHINYLESTRADIOL +

NOTE: Combined oral contraceptives are metabolized by Rx
DESOGESTREL
CYP3A4.
Oral: 30 micrograms ethinylestradiol + 150 micrograms
Monitor closely with:
desogestrel per tablet as 21 active tablets or 28-day
Enhances therapeutic effect of Fixed Combinations of
tablet with 21 active and 7 inactive pills
Progestins and Estrogens:
NSAIDs including COX-2 Inhibitors (thrombogenic effect)
A combined oral contraceptive, which contains estrogen as
ethinylestradiol, and progesterone as desogestrel. It
Enhances therapeutic effect of Immune Globulin
inhibits ovulation, reduces receptivity of the
(thrombogenic effect)
endometrium for implantation, and thickens cervical
mucus that serves as a barrier to sperm.
Reduces contraceptive effect of Fixed Combinations of
Progestins and Estrogens:
Indication: Contraception
G

Cephalosporins e.g. Ceftriaxone, Macrolide Antibiotics

e.g., Azithromycin, Erythromycin, Metronidazole,
Dose:
Penicillins e.g., Benzylpenicillin, Amoxicillin,
Contraception, by mouth, ADULT (female), 1 tablet (30
Phenoxymethylpenicillin, Ampicillin, Quinolones e.g.,
micrograms ethinylestradiol + 150 micrograms
Ciprofloxacin, Levofloxacin, Tetracyclines e.g.
desogestrel) daily for 21 days, followed by 7 days of
Doxycycline
inactive pills.
Reduces therapeutic effect of the following drugs:
Administration: Administer at the same time each day at
Anti-diabetic Agents, Thyroid Products
intervals not more than 24 hours. If 1 or more tablets are
forgotten for more than 12 hours, contraceptive
Avoid concomitant use with:
protection will be reduced.
Decreases serum concentration of Fixed Combinations of
Progestins and Estrogens:
Take 1 tab daily starting the 1st pack on the 1st day of
Bile Acid Sequestrants [administer oral contraceptives at
menstruation, without interruption for 22 days, followed
least 1-4 hours prior to or 4-6 hours after a Bile Acid
by 6 tab-free days. Start with the blue tablets and follow
Sequestrant], Dabrafenib, Efavirenz, Exemestane,
the directional arrows on the pack. For missed doses,
Griseofulvin, Lamotrigine, Topiramate
take as soon as remembered. If remembered >12 hours
than intended, risk of becoming pregnant increases.
Enhances therapeutic effect of Tranexamic Acid
(thrombogenic effect)
See General Information on Progestins and Estrogens,
Fixed Combinations listed above for further information.
Increases metabolism of Fixed Combinations of Progestins
and Estrogens:
Pregnancy Category: X
Carbamazepine, CYP2C19 Inducers, CYP3A4 Inducers,
Phenobarbital, Rifampicin
ATC Code: G03AA09
Increases risk of adverse or toxic effects of the following
drugs:
Anti-hepaciviral Combination Products (hepatotoxic ETHINYLESTRADIOL +
Rx
effect), Vitamin K Antagonists, e.g., Warfarin LEVONORGESTREL
(thromboembolic disorders)
Oral: 30 micrograms ethinylestradiol + 150 micrograms
Reduces therapeutic effect of Fixed Combinations of levonorgestrel per tablet as 21 active tablets or 28-
Progestins and Estrogens, leading to contraceptive day tablet with 21 active and 7 inactive pills
failure:
Artemether, Barbiturates e.g. Phenobarbital, A combined, oral contraceptive, which contains estrogen as
Carbamazepine, CYP2C19 Inducers, CYP3A4 Inducers, ethinylestradiol and progesterone as levonorgestrel. It
Fosphenytoin, Mifepristone, Mycophenolate, inhibits ovulation, reduces receptivity of the
Phenobarbital, Phenytoin, Protease Inhibitor [except endometrium for implantation, and thickens cervical
Indinavir], Retinoic Acid Derivatives [except Adapalene, mucus that serves as a barrier to sperm.
Tretinoin (topical)], Rifamycin Derivatives, Rifampicin
Indication: Contraception
Reduces therapeutic effect of the following drugs:
Amlodipine, Enalapril, Isosorbide Dinitrate, Methyldopa Dose:
(antagonizes hypotensive effect), Anastrozole, Anti- Contraception, by mouth, 1 tablet daily for 21 days starting
coagulants e.g. Warfarin, Heparin (counteracts on day 1 of the menstrual cycle; repeat subsequent
anticoagulant effects), Furosemide, Hyaluronidase, courses after a 7-day tablet-free interval (during which
Hydrochlorothiazide (antagonizes diuretic effect), withdrawal bleeding occurs); or
Metformin (antagonizes hypoglycemic effect) 28 tablets of everyday (ED) preparations, take 1 active
tablet daily starting on D1 of the cycle up to D21; repeat
subsequent courses without interval (withdrawal
bleeding occurs when inactive tablets are being taken).

172
GENITO URINARY SYSTEM AND SEX HORMONES

Administration: Take each pill at approximately the same ETHINYLESTRADIOL +

time each day. If delayed by longer than 24 hours, Rx
NORGESTREL
contraceptive protection may be lost.
Oral: 30 micrograms ethinylestradiol + 300 micrograms
See General Information on Progestins and Estrogens,
norgestrel per tablet as 21 active tablets or 28-day
Fixed Combinations listed above for further information.
tablet with 21 active and 7 inactive pills
Pregnancy Category: X
A combined oral contraceptive, which contains estrogen as
ethinylestradiol and progesterone as norgestrel. It
ATC Code: G03AA07
inhibits ovulation, reduces receptivity of the
endometrium for implantation, and thickens cervical
mucus that serves as a barrier to sperm.
ETHINYLESTRADIOL +
Rx
NORETHISTERONE Indication: Contraception

G
Oral: 35 micrograms ethinylestradiol + 400 micrograms Dose:
norethisterone acetate per tablet as 21 active tablets Contraception, by mouth, ADULT (female), 1 tablet (30
or 28-day tablet with 21 active and 7 inactive pills micrograms ethinylestradiol + 300 micrograms
norgestrel) daily.
A combined oral contraceptive, which contains estrogen as
ethinylestradiol and progesterone as norethisterone. It Administration: Administer at the same time each day at
inhibits ovulation, reduces the receptivity of the intervals for not more than 24 hours. If one or more
endometrium for implantation, and thickens cervical tablets are forgotten for more than 12 hours,
mucus that serves as a barrier to sperm. contraceptive protection will be reduced.

Indication: Contraception See General Information on Progestins and Estrogens,

Fixed Combinations listed above for further information.
Dose:
Contraception, by mouth, ADULT (female), 1 tablet (35 Pregnancy Category: X
micrograms ethinylestradiol + 400 micrograms
norethisterone acetate) daily beginning on the 5th day of ATC Code: G03AA06
menstrual cycle for 21 days, followed by 7 tab-free days.

Precautions: PROGESTINS
WARNING: NOT for use as prophylaxis of dementia. An increased
incidence of dementia was observed in women ≥65 years of Rx ETONOGESTREL
age taking conjugated estrogens alone or in combination with
medroxyprogesterone acetate.
Subdermal: 68 mg subdermal implant
NOT for use in the prevention of cardiovascular disease. An
increased risk of deep vein thrombosis (DVT), stroke, Etonogestrel is a hormone that prevents ovulation by
pulmonary emboli (PE), and myocardial infarction (MI) was reducing reception of endometrium to implantation and
observed in postmenopausal women. thickening of the cervical mucus that serves as a barrier
to sperm.
The use of unopposed estrogen in women with an intact uterus
is associated with an increased risk of endometrial cancer. Indication: Contraception
Combination or inclusion of a progestin to estrogen treatment
may decrease the risk of endometrial hyperplasia, a precursor Contraindications: Breast cancer or other estrogen-
to endometrial cancer. dependent or progestin-dependent neoplasms (current
or a history of); hepatic impairment; hepatic tumors or
disease; pregnancy; thrombosis or thromboembolic
Administration: Administer at the same time each day at
disorders (current or history of); undiagnosed abnormal
intervals for not more than 24 hours. If one or more
genital bleeding
tablets are forgotten for more than 12 hours,
contraceptive protection will be reduced.
Dose:
Contraception, by subdermal implant, ADULT, 68 mg
Use for the shortest duration possible at the lowest
implant under the skin at the inner side of the non-
effective dose in accordance with treatment goals.
dominant upper arm (therapy can be started at any time
in the menstrual cycle once it is determined that the
See General Information on Progestins and Estrogens,
woman is not pregnant); back-up contraception is not
Fixed Combinations listed above for further information.
needed if started within 5 days of onset of menstruation;
Pregnancy Category: X if started >5 days after the onset of menstruation or at
any time in a woman experiencing amenorrhea (not
ATC Code: G03AA05 postpartum), back-up contraception should be used for
7 days.

173
 GENITO URINARY SYSTEM AND SEX HORMONES

Remove no later than the end of the third year. This can be Adverse Drug Reactions:
replaced with a new implant at time of removal if Common: Headache, acne vulgaris, menstrual disease (<3
continued contraception is needed, after ruling out episodes or 90 days; prolonged menstrual bleeding
possibility of pregnancy. Insertion can be done as lasting >14 days: >5 episodes in 90 days) amenorrhea
follows: (no bleeding in 90 days); weight gain, abdominal pain,
vaginitis, mastalgia, pharyngitis
Less Common: Dizziness, emotional lability, depression,
No hormonal nervousness, pain, localized erythema, dysmenorrhea,
Insert between days 1 through 5 of
contraceptives
within past month
menstruation, even if still bleeding nausea, leukorrhea, hypersensitivity, application site
reaction, local pain, hematoma at injection site, bruising
at injection site, back pain, flu-like symptoms
Transdermal system or vaginal ring
Switching from
Insert on the day of the removal of the Rare: Alopecia, angioedema (including exacerbation of
combination hereditary angioedema), cerebrovascular accident,
transdermal system or vaginal ring or on
hormonal
the day following the transdermal-free or anaphylaxis, convulsions, migraine, hypertension,
contraceptive
G

ring-free interval myocardial infarction, ovarian cyst, pulmonary embolism,

seizure
Implant or intrauterine device (IUD)
Insert on same day as removal of implant
Switching from a Drug Interactions:
or IUD
progestin-only Monitor closely with:
contraceptive
Injection Enhances therapeutic effect of C1 Inhibitors (thrombogenic
Insert on day next injection is due effect)
First trimester
Insert within first 5 days following first Reduces therapeutic effect of Antidiabetic Agents
abortion or
trimester abortion or miscarriage.
miscarriage
Avoid concomitant use with drugs that
Second trimester Decrease serum concentration of Etonogestrel:
Insert between 21 and 28 days following
abortion or
miscarriage
second trimester abortion or miscarriage. Acitretin, Aprepitant, Artemether, Bile Acid Sequestrants
[administer Etonogestrel at least 1–4 hours prior to or
If not breast-feeding, insert between 21 to 4–6 hours after Bile Acid Sequestrants], Bosentan,
28 days postpartum. Carbamazepine, Dabrafenib, Exenatide, Lixisenatide
[administer Etonogestrel 1 hour before or 11 hours after
Postpartum If breast-feeding, insert after the fourth Lixisenatide], Lumacaftor, Mycophenolate, Nelfinavir,
post-partum week and use a second non- Nevirapine, Oxcarbazepine, Perampanel, Prucalopride,
hormonal form of contraception for the Rifamycin Derivatives, Saquinavir, Sugammadex,
first 7 days of insertion.
Telaprevir, Topiramate

Precautions: Enhance therapeutic effect of Etonogestrel:

Breast cancer; Tranexamic Acid (thrombogenic effect)
Carbohydrate intolerance and diabetes;
Ovarian cysts; Increase risk of adverse or toxic effects of Vitamin K
Retinal vascular thrombosis (discontinue if there is loss of Antagonists e.g. Warfarin (thromboembolic disorders)
vision, proptosis, diplopia, papilledema, or retinal
vascular lesions); Increases serum concentration of Etonogestrel:
Thromboembolism and other vascular events (e.g., deep Atazanavir
vein thrombosis, myocardial infarction, pulmonary
embolism); Reduces therapeutic effect of Etonogestrel, leading to
Changes in vaginal bleeding; contraceptive failure:
Cardiovascular diseases; Barbiturates, Efavirenz, Fosphenytoin, Griseofulvin,
Depression; Mifepristone, Phenytoin, Retinoic Acid Derivatives
Disease that may be exacerbated by fluid retention; [except Adapalene, Tretinoin (topical)], Ulipristal [for
Gallbladder disease; uterine fibroids, avoid Etonogestrel within 12 days of
Hepatic adenomas or carcinomas; stopping Ulipristal; for emergency contraceptive, avoid
Hepatic impairment; Etonogestrel within 5 days of stopping Ulipristal]
Hyperlipidemia;
Hypertension; Reduces therapeutic effect of Anticoagulants, Vitamin K
Renal impairment; Antagonists e.g. Warfarin (anticoagulant effect)
Overweight women;
Wearers of contact lens; Administration: Insert implant subdermally at the inner side
Increased risk of cervical or ovarian cancer; of the non-dominant upper arm approximately 8–10 cm
May change results of some laboratory tests (e.g., (3–4 inches) above the medial epicondyle of the
coagulation factors, lipids, glucose tolerance, binding humerus just under the skin. Implant must be palpable
proteins); after insertion.
Does not protect against HIV infection or other sexually
transmitted disease X-ray, CT scan, ultrasound scanning, or MRI can be used to
confirm the location of the implant if it is not palpable.

174
GENITO URINARY SYSTEM AND SEX HORMONES

Use of a non-hormonal contraceptive is required until the Smoking;

verification of the presence of the implant. Systemic Lupus Erythematosus (SLE);
Hypertension;
Confirm first that the entire implant has been removed by Renal disease;
measuring its length (4 cm), when removing. Get rid of all Gall bladder disease;
pieces if implant has broken. A new implant may be Severe arterial disease (multiple risk factors for venous
inserted in the same arm through the same incision. thromboembolism and arterial disease);
History of breast cancer (may be used after 5 years if no
Pregnancy Category: X evidence of current disease);
Elderly; (increased risk of coronary heart disease, stroke,
ATC Code: G03AC08 VTE and breast cancer);
Pregnancy (genital malformations and cardiac defects have
been reported in male and female fetuses; inadvertent
use of depot contraceptive injection unlikely to harm
Rx MEDROXYPROGESTERONE

G
fetus; avoid use if there is history of pruritus during
pregnancy);
Inj.: 50 mg/mL (as acetate), 3 mL vial + syringe (IM) Lactation (present in breastmilk; no adverse effects
150 mg/mL (as enanthate), 1 mL vial (IM) reported; preferably start injectable contraceptive 6
weeks after birth or later)
NOTE: Use one (1) inch long needle
Adverse Drug Reactions:
A long-acting, progestin injectable contraceptive indicated Common: Breast enlargement and tenderness, change in
for the prevention of pregnancy. libido, depression, endometrial hyperplasia, headache,
irregular or breakthrough bleeding, leg cramps, spotting
Indication: Parenteral progestin-only contraception (short- Less Common: Acne, benign proliferative breast disease,
or long-term) breast cancer, cardiovascular events, dementia, edema,
exacerbation or recurrence of endometriosis, fluid
Contraindications: Pregnancy; undiagnosed vaginal retention, gall stones, itch, migraine, nausea,
bleeding; history of pruritus during pregnancy; active liver premenstrual-like syndrome
disease and history of pruritus during pregnancy; severe Rare: Chloasma, cholestatic jaundice, endometrial cancer,
arterial disease; porphyria enlargement of hepatic hemangiomas, enlargement of
uterine fibroids, galactorrhea, glucose intolerance,
Dose: hypersensitivity reactions, ovarian cancer, pancreatitis,
Contraception, by deep IM injection, ADULT (female), visual changes
short-term, 150 mg within the first 7 days of cycle or
within the first 5 days after parturition, delay until 6 Drug Interactions:
weeks after parturition if breastfeeding; Avoid concomitant use with:
long-term, by deep IM injection, ADULT (female), as for Reduces therapeutic effect of Metformin (antagonizes
short-term, repeated every 3 months. hypoglycemic effect)

NOTE: If the interval between injections is >3 months and Administration: If the interval between injections is >3
14 days, exclude pregnancy before administering the months and 14 days, exclude pregnancy before
next injection and advise patient to use additional administering the next injection and advise patient to
contraceptive measures (e.g., a condom) for 7 days after use additional contraceptive measures (e.g. condom) for
the injection. 7 days after the injection.

PATIENT ADVICE. Women should receive full counseling on Pregnancy Category: X

the likelihood of menstrual irregularities and the
potential for a delay in return to full fertility with long-term ATC Code: G03AC06
use before treatment.

Dose Adjustment: ANDROGENS

Hepatic Impairment:
Use with caution. Avoid use in active or severe liver disease.
Rx TESTOSTERONE
Precautions:
Unexplained vaginal bleeding (investigate cause before Inj.: 250 mg/mL solution (as undecanoate), 4 mL
starting treatment);
History of endometriosis; The principal endogenous androgen responsible for
Uterine fibroids; promoting growth and development of the male sex
Migraine; organs and maintaining secondary sex characteristics in
Liver disease (avoid use in active liver disease); androgen-deficient males.
Thromboembolic or coronary vascular disease;
Diabetes Mellitus (monitor and adjust dose of antidiabetic Indication: For use in men who lack or have low testosterone
drug if necessary); levels in conjunction with an associated medical
Epilepsy; condition

175
 GENITO URINARY SYSTEM AND SEX HORMONES

Contraindication: Known or suspected prostate cancer necrosis, hepatocellular neoplasms, peliosis hepatis,
malignant neoplasm of prostate, clotting factors
Dose: suppression, hemorrhage, carcinoma, anaphylactoid
Hypogonadism, by IM injection, ADULT, 750 mg followed by reaction, hypersensitivity reaction (including pulmonary
750 mg administered 4 weeks later, then 750 mg oil microembolism), pain at injection site, erythema at
administered every 10 weeks thereafter. injection site, inflammation at injection site, arthralgia,
back pain, abnormal bone growth (accelerated),
Dose Adjustment: hemarthrosis, hyperkinesia, increased lacrimation,
Renal and Hepatic Impairment: polyuria, bronchitis, nasopharyngitis, sinusitis, upper
May enhance edema formation. Contraindicated in serious respiratory tract infection, dyspnea
renal and hepatic disease.
Drug Interactions:
Precautions: Monitor closely with:
Enhances therapeutic effect of the following drugs:
WARNING: Serious pulmonary oil microembolism
G

Blood Glucose Lowering Agents (hypoglycemic effect),

(POME) reactions, involving urge to cough, C1 Inhibitors (thrombogenic effect)
dyspnea, throat tightening, chest pain, dizziness,
syncope, and episodes of anaphylaxis, including Increases risk of adverse effects of Testosterone:
life-threatening reactions, have been observed Corticosteroids (fluid-retaining effect)
during or immediately after administration of
testosterone. Observe patients for 30 minutes Avoid concomitant use with:
following each injection to provide adequate Enhances therapeutic effect of Vitamin K Antagonists e.g.
medical treatment in the event of serious POME Warfarin (anticoagulant effect)
reactions or anaphylaxis.
Increases risk of adverse or toxic effects of Cyclosporine
(hepatotoxic effect)
Caution must be performed for possible risk of developing
major adverse cardiovascular events such as MI, stroke, Increases serum concentration of Cyclosporine
or cardiovascular death;
Gynecomastia; Administration: Inject 3 mL of air through the gray rubber
Hypercalcemia in patients with prolonged immobilization or stopper into the vial to create positive pressure, then
cancer; withdraw 3 mL of solution (750 mg) from the vial. Expel
Oligospermia; air bubbles from the syringe and change the syringe
Polycythemia priapism; needle to a new IM needle. Discard unused portion.
Venous thromboembolism;
Prostate cancer; Benign prostatic hyperplasia; Pregnancy Category: X
Diseases that may be exacerbated by fluid retention
including cardiac, hepatic, or renal dysfunction; ATC Code: G03BA03
Sleep apnea.

Adverse Drug Reactions: Hypertension, hypotension, deep

vein thrombosis, edema, vasodilatation, headache, ESTROGENS
fatigue, irritability, insomnia, mood swings, aggressive
behavior, taste disorder, altered sense of smell,
abnormal dreams, amnesia, anxiety, chills, depression,
Rx CONJUGATED ESTROGEN
dizziness, emotional lability, excitement, hostility,
malaise, nervousness, outbursts of anger, paresthesia, Oral: 625 micrograms and 1.25 mg tablet
seizure, sleep apnea, suicidal ideation, acne vulgaris,
hyperhidrosis, alopecia, contact dermatitis, diaphoresis, Conjugated estrogen is a mixture of estrogens that are
erythema, folliculitis, hair discoloration, pruritus, available either as preparations that meet current official
seborrhea, skin rash, xeroderma, increased plasma USP standards or as nonofficial preparations, which are
estradiol concentration, weight gain, gynecomastia, hot prepared synthetically from plant sources (e.g., synthetic
flash, change in libido, fluid retention, hirsutism conjugated estrogens A, synthetic conjugated estrogens
(increase in pubic hair growth), hypercalcemia, B).
hyperchloremia, hyperglycemia, hyperkalemia,
hypernatremia, hypoglycemia, hypokalemia, inorganic Estrogens modulate the pituitary secretion of
phosphate retention, menstrual disease (including gonadotropins, luteinizing hormone, and follicle-
amenorrhea), diarrhea, gastroesophageal reflux disease, stimulating hormone through a negative feedback
gastrointestinal hemorrhage, gastrointestinal irritation, system reducing elevated levels of these hormones
increased appetite, nausea, vomiting, prostatitis, possible for symptoms experienced by postmenopausal
ejaculatory disorder, prostate induration, spontaneous women.
erections, benign prostatic hypertrophy, difficulty in
micturition, hematuria, impotence, irritable bladder, Indications: For estrogen replacement therapy; prevention
mastalgia, oligospermia, priapism, testicular atrophy, of progression of osteoporosis associated with estrogen
urinary tract infection, virilization, cholestatic hepatitis, deficiency in postmenopausal women; management of
cholestatic jaundice, hepatic insufficiency, hepatic moderate to severe vasomotor symptoms associated

176
GENITO URINARY SYSTEM AND SEX HORMONES

with menopause; management of vulvar and vaginal malignancy in postmenopausal women with
atrophy (atrophic vaginitis); management of female undiagnosed abnormal vaginal bleeding.
hypoestrogenism secondary to hypogonadism,
castration, or primary ovarian failure; palliative treatment
of advanced, inoperable, metastatic carcinoma of the An increased risk of invasive breast cancer was
breast in postmenopausal women and in men; palliative observed in postmenopausal women using
treatment of advanced carcinoma of the prostate in men conjugated estrogens in combination with
medroxyprogesterone acetate. An increase in
Contraindications: Angioedema or anaphylactic reaction to abnormal mammogram findings has also been
estrogen or any component of the formulation; reported with estrogen alone or in combination
undiagnosed abnormal genital bleeding; DVT or PE with progestin therapy. Treatment may also lead to
(current or history of); active or history of arterial severe hypercalcemia in patients with breast
thromboembolic disease (e.g., stroke, MI); breast cancer cancer and bone metastases. Stop treatment of
(known, suspected or history of); estrogen-dependent estrogen if this occurs. Use is contraindicated in
patients with known or suspected breast cancer.

G
tumor (known or suspected); hepatic impairment or
disease; protein C, protein S, antithrombin deficiency, or
other known thrombophilic disorders; pregnancy Endometriosis (consider adding a progestin with residual
endometriosis post-hysterectomy);
Dose: Venous thromboembolism in women with inherited
Treatment of moderate to severe vasomotor symptoms due thrombophilias;
to menopause, by mouth, ADULT, 300 micrograms once Ovarian cancer;
daily then maintain using 450 micrograms to 1.25 mg Retinal vascular thrombosis (discontinue if migraine, loss of
daily, continuous or in cyclical regimens (e.g., 25 days on vision, proptosis, diplopia, or other visual disturbances
therapy then 5 days off). occur);
Treatment of moderate to severe vaginal dryness and pain Asthma;
with intercourse, symptoms of vulvar and vaginal atrophy Diabetes;
due to intercourse, by mouth, ADULT, 300 micrograms Cardiovascular diseases (avoid use);
once daily, continuous or in cyclical regimens (e.g., 25 Diseases exacerbated by fluid retention;
days on therapy then 5 days off). Epilepsy;
Female hypoestrogenism due to hypogonadism, by mouth, Gallbladder disease requiring surgery;
ADULT, 300–625 micrograms once daily administered History of cholestatic jaundice associated with prior
cyclically (e.g., 3 weeks on therapy then 1 week off). estrogen use or pregnancy (discontinue if jaundice
Palliative treatment of advanced androgen-dependent develops or acute or chronic hepatic disturbances
carcinoma of prostate, by mouth, ADULT, 1.25 to 2.5 mg occur);
3 times daily. Hepatic hemangiomas;
Female castration or primary ovarian failure, by mouth, Hereditary angioedema;
ADULT, 1.25 mg once daily administered cyclically (e.g., Hypoparathyroidism;
3 weeks on therapy then 1 week off). Migraine;
Palliative treatment of breast cancer in appropriately Porphyria;
selected women and men with metastatic disease, by Renal impairment;
mouth, ADULT, 10 mg 3 times daily for at least 3 months. Systemic lupus erythematosus;
Estrogens should also be stopped at least 4-6 weeks prior
Precautions: to elective surgery or be subjected to prolonged
Warning: Do NOT use for prophylaxis of dementia. An immobilization due to increased risk of
increased incidence of dementia was observed in thromboembolism. The use of estrogens may also modify
women ≥65 years of age taking conjugated results of some laboratory tests (e.g., coagulation
estrogens alone or in combination with factors, lipids, glucose tolerance, binding proteins)
medroxyprogesterone acetate. Elderly (higher incidence of stroke and breast cancer was
seen in women >75 years old).
Do NOT use in the prevention of cardiovascular Adverse Drug Reactions:
disease. An increased risk of deep vein thrombosis Common: Headache, paresthesia, dizziness, pain,
(DVT), stroke, pulmonary emboli (PE), and abdominal pain, nausea, mastalgia, endometrial
myocardial infarction (MI) was observed with hyperplasia, uterine hemorrhage, infection, back pain,
conjugated estrogens with medroxyprogesterone upper respiratory tract infection
acetate in postmenopausal women. Less Common: Anxiety, hypertonia, weight gain, dyspepsia,
Use of unopposed estrogen in women with an vomiting, constipation, diarrhea, vaginitis, leg cramps,
intact uterus is associated with an increased risk cough, rhinitis, fever
of endometrial cancer. Combination therapy of a
progestin to estrogen treatment may decrease the Drug Interactions:
risk of endometrial hyperplasia, a precursor to Monitor closely with:
endometrial cancer. Conduct appropriate Enhances thrombogenic effect of Conjugated Estrogen:
monitoring and diagnostic measures, including C1 Inhibitors, NSAIDs including COX-2 Inhibitors
endometrial sampling if indicated, to rule out
Enhances thrombogenic effect of the following drugs:
Anthrax Immune Globulin (Human), Immune Globulin

177
 GENITO URINARY SYSTEM AND SEX HORMONES

Do NOT use in the prevention of cardiovascular

Increases risk of adverse or toxic effects of Dantrolene
disease. An increased risk of deep vein
(hepatotoxic effect)
thrombosis, stroke, pulmonary emboli, and
myocardial infarction was observed in conjugated
Reduces therapeutic effect of Conjugated Estrogen:
estrogens with medroxyprogesterone acetate in
Tocilizumab
postmenopausal women.
Reduces therapeutic effect of the following drugs: An increased risk of invasive breast cancer was
Antidiabetic Agents, Thyroid Products observed in postmenopausal women using
conjugated estrogens in combination with
Avoid concomitant use with: medroxyprogesterone acetate. An increase in
Decreases serum concentration of Conjugated Estrogen: abnormal mammogram findings has also been
Dabrafenib, Enzalutamide observed with estrogen alone or in combination
with progestin therapy. Treatment may also lead to
G

Increases metabolism of Conjugated Estrogen: severe hypercalcemia in patients with breast

CYP1A2 Inducers, CYP3A4 Inducers cancer and bone metastases. Use is
contraindicated in patients with known or
Increases serum concentration of Tizanidine suspected breast cancer.
Reduces therapeutic effect of the following drugs:
Anastrozole, Anticoagulants, Exemestane, Breast, cervical or ovarian cancer; Ovarian cysts;
Hyaluronidase, Somatropin Retinal vascular thrombosis (discontinue if there is loss of
vision, proptosis, diplopia, papilledema, or retinal
Administration: May be taken without regard to meals. Use vascular lesions);
alone or in combination with progestin with the lowest Transient dizziness or drowsiness;
effective dose and for the shortest duration possible. Cardiovascular diseases;
Depression;
Consider adding progestin when prescribing estrogen for a Disease that may be exacerbated by fluid retention;
postmenopausal woman with a uterus to reduce the risk Thromboembolism and other vascular events, e.g., DVT, MI,
of endometrial cancer. PE;
Hypertension;
NOTE: Women without uterus do not need progestin, Changes in vaginal bleeding;
however, hysterectomized women with a history of Carbohydrate intolerance and diabetes;
endometriosis may need progestin. Gallbladder disease;
Hepatic tumor;
Pregnancy Category: X Hepatic impairment;
Hyperlipidemia;
ATC Code: G03CA57 Renal impairment;
Porphyria;
Does not protect against HIV infection or other sexually
PROGESTINS transmitted disease;
Laboratory tests (may alter results, e.g., coagulation factors,
lipids, glucose tolerance, binding proteins);
General Information Overweight women;
Progestins are synthetic forms of progesterone that Wearers of contact lens
suppresses ovulation, thickens cervical mucus, alters
follicle stimulating hormone (FSH) and luteinizing Drug Interactions:
hormone (LH) concentrations, slows the movement of Monitor closely with:
ovum through the fallopian tubes, and alters the Enhances therapeutic effect of C1 Inhibitors (thrombogenic
endometrium. effect)
Contraindications: Breast cancer or other estrogen- or Reduces therapeutic effect of Antidiabetic Agents
progestin-dependent neoplasms (current or a history of);
hepatic tumors or disease; thrombosis or Avoid concomitant use with:
thromboembolic disorders (current or history of); Decreases serum concentration of Progestins:
undiagnosed abnormal genital bleeding Acitretin, Aprepitant, Artemether, Bile Acid Sequestrants
[administer oral progestin-containing contraceptives at
Precautions: least 1-4 hours prior to or 4-6 hours after Bile Acid
Warning: Do NOT use for prophylaxis of dementia. An Sequestrants], Bosentan, Carbamazepine, Clobazam,
increased incidence of dementia was observed in Dabrafenib, Darunavir, Exenatide, Felbamate,
women ≥65 years of age taking conjugated Fosaprepitant, Lixisenatide [administer oral
estrogens alone or in combination with contraceptives 1 hour before or at least 11 hours after
medroxyprogesterone acetate. Lixisenatide], Lumacaftor, Mycophenolate, Nelfinavir,
Nevirapine, Oxcarbazepine, Prucalopride, Rifamycin
Derivatives, Saquinavir, Sugammadex, Telaprevir,
Topiramate

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GENITO URINARY SYSTEM AND SEX HORMONES

Enhances therapeutic effect of Progestins: administration can be reduced if improvement or

Tranexamic Acid (thrombogenic effect) stabilization occurs.

Increases risk of adverse or toxic effects of Vitamin K Administration: Shake injectable suspension immediately
Antagonists e.g. Warfarin (thromboembolic disorders) prior to use. Administer IM injection deeply into gluteal,
deltoid or anterior thigh muscle.
Reduces therapeutic effect of Progestins, leading to
contraceptive failure: See Medroxyprogesterone under Hormonal Contraceptives
Barbiturates, Fosphenytoin, Griseofulvin, Mifepristone, for Systemic Use for other information.
Phenytoin, Retinoic Acid Derivatives [except Adapalene,
Topical Bexarotene, Tretinoin (Topical)], Ulipristal [avoid Pregnancy Category: X
Progestins within 5 days of stopping Ulipristal]
ATC Code: G03DA02
Reduces therapeutic effect of the following drugs:

G
Anticoagulants, Vitamin K Antagonists e.g. Warfarin
(anticoagulant effect) PREGNADIEN DERIVATIVES
Administration: Use for the shortest duration possible at the
lowest effective dose in accordance with treatment Rx DYDROGESTERONE
goals.
Oral: 10 mg tablet
PREGNEN (4) DERIVATIVES A synthetic retroisomer of progesterone that lacks
androgenic, estrogenic, thermogenic, corticoid, and
anabolic properties. It induces secretory changes in the
Rx MEDROXYPROGESTERONE endometrium.

Oral: 5 mg and 10 mg tablet (as acetate) Indications: Abnormal uterine bleeding; secondary
Inj.: 50 mg/mL (as acetate), 3 mL vial + syringe (IM) amenorrhea; dysmenorrhea; endometriosis; infertility;
150 mg/mL (as acetate or enanthate), 1 mL vial (IM) irregular menstrual cycle; menopause; recurrent and
threated pregnancy loss; premenstrual syndrome;
NOTE: Use one (1) inch long needle severe hepatic impairment

Medroxyprogesterone transforms the endometrium from a Dose:

proliferative to a secretory state. If given parenterally, it Abnormal uterine bleeding, by mouth, ADULT, 10 mg twice
can inhibit gonadotropin production, preventing follicular daily for 5-7 days to stop bleeding. Then continue to 10
maturation and ovulation. mg twice daily on days 11–25 of cycle for prevention.
Amenorrhea, secondary, by mouth, ADULT, 10 mg twice
Indications: Prophylaxis for endometrial hyperplasia; daily on days 11–25 of cycle. [NOTE: Prime endometrium with
Management of abnormal uterine bleeding, adequate estrogen, exogenous or endogenous, prior to
amenorrhea, renal cell carcinoma andendometrial administration. A dose of 10 mg once daily for 14 consecutive days
of each 28-day cycle has shown efficacy in premenopausal women
carcinoma; hormonal replacement therapy
with normal estrogen levels.]
Contraindications: Suspected or known pregnancy; hepatic Dysmenorrhea, by mouth, ADULT, 10 mg twice daily on days
impairment or disease 5–25 of cycle.
Endometriosis, by mouth, ADULT, 10 mg 2 or 3 times daily
Dose: on days 5–25 of cycle, or continuously.
Prophylaxis for endometrial hyperplasia, by mouth, ADULT, Infertility due to luteal insufficiency, by mouth, ADULT, 10
5–10 mg once a day, in combination with estrogen mg once daily on days 14–25 of cycle for ≥6 consecutive
replacement therapy beginning on day 1 or day 16 of cycles.
each cycle, continuing for 12 to 14 consecutive days per Irregular menstrual cycle, by mouth, ADULT, 10 mg twice
month; or 2.5 mg once a day continuously with estrogen daily on days 11–25 of cycle.
replacement therapy. Menopause, by mouth, ADULT, in combination with cyclic
Abnormal uterine bleeding, by IM injection, ADULT and estrogen therapy, 10 mg once daily for the last 12–14
ADOLESCENT, 5–10 mg once a day starting on the 16th days of cycle, may increase to 10 mg twice daily if
day of the cycle and continue for 10 days; or begin on the evidence of lack of response or withdrawal bleeding
21st day of the cycle and continue for 5 days (withdrawal occurs; in combination with continuous estrogen
bleeding usually occurs within 3–7 days after the therapy, 10 mg once daily for 14 consecutive days of a
discontinuation).
28-day cycle.
Amenorrhea, by IM injection, ADULT and ADOLESCENT, 5–
Pregnancy loss, recurrent, by mouth, ADULT, 10 mg twice
10 mg once a day starting at any time and continuing for daily; may be taken through week 20 of pregnancy.
5–10 days (withdrawal bleeding usually occurs within 3– Pregnancy loss, threatened, by mouth, ADULT, 40 mg
7 days after the discontinuation). loading dose, followed by 10 mg every 8 hours until
Renal cell carcinoma and endometrial carcinoma, by IM symptoms resolve; or 10 mg twice daily, with or without
injection, ADULT, 400–1,000 mg once a week; can be 40 mg loading dose.
reduced to 400 mg once a month; frequency of

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 GENITO URINARY SYSTEM AND SEX HORMONES

Premenstrual syndrome, by mouth, ADULT, 10 mg twice Adverse Drug Reactions:

daily on days 11 to 25 of cycle. Common: Gastrointestinal disturbances, changes in
appetite or weight, fluid retention, edema, chloasma,
Adverse Drug Reactions: allergic skin rashes, urticarial, mental depression, breast
Less Common: Headache, migraine, amenorrhea, changes including discomfort or occasionally
hypermenorrhea, oligomenorrhea, nausea, breast gynecomastia, changes in libido, hair loss, hirsutism,
tenderness, dysmenorrhea, mastalgia fatigue, drowsiness, insomnia, fever, headache,
Rare: Abdominal pain, allergic dermatitis, angioedema, premenstrual syndrome-like symptoms and altered
breast swelling, depressed mood, dizziness, drowsiness, menstrual cycles or irregular menstrual bleeding.
edema, exacerbation of porphyria, hemolytic anemia, Rare: Anaphylaxis or anaphylactoid reactions, serum lipid
hypersensitivity, jaundice, malaise, pruritus, rash, tumor profile and liver function test alterations, and jaundice.
growth (meningioma), urticaria, vomiting, weakness,
weight gain Drug Interactions:
Decreases effects of Lynestrenol:
G

Administration: May split tablet to facilitate swallowing. Carbamazepine, Nevirapine, Oxcarbazepine, Phenytoin,
Missed dose can be administered as soon as possible if Phenobarbital, Topiramate, Rifabutin, Rifampicin
<12 hours have elapsed; otherwise, skip missed dose
and resume with next scheduled dose. Increases side effects of the following drugs:
Atorvastatin, Tacrolimus
NOTE: May contain lactose. Use with caution in patients with
galactose intolerance. May enhance or reduce anticoagulant effect of Coumarins
e.g. Warfarin
See General Information on Progestins listed under Chapter
5: Genito Urinary System and Sex Hormones for further Antagonizes the effect of Antidiabetics (hypoglycemic
information. effect)

Pregnancy Category: B Administration: Take one pill daily beginning on the first day
of menstrual bleeding or any other day as long as not
ATC Code: G03DB01 pregnant. Breastfeeding women can start six weeks after
giving birth. The interval between two pills should be 24
hours. If a pill is missed, take within three hours after the
ESTREN DERIVATIVES 24-hour lapse to sustain its efficacy.

Pregnancy Category: D
Rx LYNESTRENOL
ATC Code: G03DC03
Oral: 500 mcg tablet

A progestin-only pill that contains very low doses of a Rx NORETHISTERONE

progestin similar to the natural hormone, progesterone,
in a woman’s body.
Oral: 5 mg tablet (as acetate and as base)
Indication: For contraception in cases of intolerance to
estrogen-progestogen combined pills or when estrogen Progestin-only contraception that acts by inhibiting
is contraindicated. ovulation through thickening of cervical mucus, inhibiting
sperm penetration; altering FSH and LH concentrations;
Contraindications: Pregnancy, possible pregnancy, slowing the movement of ovum through the fallopian
porphyria, severe arterial disease, undiagnosed vaginal tubes, and modifying the endometrium.
bleeding, hormone-dependent neoplasms, severe liver
disease such as hepatic adenoma, and after recent Indications: Management of abnormal uterine bleeding,
evacuation of a hydatidiform mole. amenorrhea, and endometriosis; contraception;

Dose: Contraindications: Current or history of deep vein

Contraceptive, by mouth, ADULT, one tablet daily. thrombosis, active or recent history of arterial
thromboembolic disease (e.g., stroke, MI); as a
Dose Adjustment: diagnostic test for pregnancy; suspected or known
No dosage adjustments provided in the manufacturer’s pregnancy; hepatic impairment or tumors
labeling.
Dose:
Precautions: Abnormal uterine bleeding and amenorrhea, by mouth,
Use in caution in patients with asthma, diabetes mellitus, ADULT, 2.5–10 mg once a day for 5–10 days; withdrawal
epilepsy, heart disease, hypertension, thromboembolic bleeding usually occurs within 3–7 days after the last
disorders, history of depression, past ectopic pregnancy, dose.
functional ovarian cysts, malabsorption syndromes, Endometriosis, by mouth, ADULT, 5 mg once a day for 14
migraine, renal impairment, liver dysfunction, and other days; increase dose at increments of 2.5 mg per day
conditions which may be aggravated by fluid retention.

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GENITO URINARY SYSTEM AND SEX HORMONES

every 2 weeks until reaching 15 mg daily, continue for 6– Contraindications: Hepatic disease or history of hepatic
9 months or until presence of breakthrough bleeding. impairment; abnormal uterine bleeding; enlargement or
Contraception, by mouth, ADULT, 350 micrograms once development of ovarian cyst not due to polycystic ovarian
daily; start on the first day of menstruation or after syndrome; uncontrolled thyroid or adrenal dysfunction;
miscarriage or abortion; if switching from a combined presence of an organic intracranial lesion such as
oral contraceptive, begin on the day after finishing the pituitary tumor; pregnancy
last active pill if the patient is not pregnant; if switching
from an UID, continue this or abstain or use an Dose:
alternative emergency contraceptive for at least 2 days NOTE: Schedule intercourse to coincide with the expected
after contraceptive is initiated; in case of missed dose, time of ovulation, usually 5–10 days after taking
take as soon as remembered; if ≥3 hours late, use a Clomifene.
backup method of contraception for 48 hours. [NOTE:
Back up contraception is needed if therapy is initiated within 5 Ovulation induction, by mouth, ADULT (female), 50 mg once
days of onset of menstruation. If started >5 days or at any time a day for 5 days. Begin on or about the fifth day of cycle
women experienced amenorrhea, back up contraception should if progestin-induced bleeding is expected or

G
be used for 2 days.]
spontaneous uterine bleeding occurs before starting
therapy. Therapy can be started anytime if there is no
Adverse Drug Reactions: Cerebral embolism, cerebral recent uterine bleeding. Subsequent doses may be
thrombosis, deep vein thrombosis, edema, pulmonary increased to 100 mg once daily for 5 days only if
embolism, retinal thrombosis, depression, dizziness, ovulation does not occur at the initial dose. Maximum
fatigue, headache, insomnia, migraine, emotional dose is 100 mg once a day for 5 days for 6 cycles (150
lability, nervousness, acne vulgaris, alopecia, chloasma, mg for women with PCOS). Long-term therapy of >6
pruritus, skin rash, urticarial, amenorrhea, hirsutism, cycles is not recommended; lower doses (12.5 to 25 mg
hypermenorrhea, menstrual disease, weight gain, daily) can be used in women sensitive to clomiphene or
abdominal pain, nausea, vomiting, breakthrough who consistently develop large ovarian cysts.
bleeding, breast hypertrophy, breast tenderness, cervical
erosion, change in cervical secretions, decreased NOTE: May repeat 5-day cycle if needed as early as 30 days
lactation, genital discharge, mastalgia, spotting, vaginal after the previous therapy, ruling out the possibility of
hemorrhage, hypersensitivity, cholestatic jaundice, pregnancy and using the lowest effective dose.
hepatitis, arm pain, leg pain, optic neuritis (with or Discontinue treatment if ovulation does not occur after 3
without vision loss) courses of treatment; or if 3 ovulatory responses already
occurred but pregnancy is still not achieved.
Drug Interactions: No information found
Precautions:
Administration: Administer tablets at the same time each Ovarian enlargement (generally regresses after stopping
day. NOT used for emergency contraception. treatment);
Visual disturbances;
Pregnancy Category: X Ovarian hyperstimulation syndrome;
Ascitic, pleural or pericardial fluids can be removed if
ATC Code: G03DC02 necessary to lessen symptoms (women with OHSS
should avoid pelvic examination and/or intercourse);
Borderline or invasive ovarian cancer;
GONADOTROPINS AND OTHER Polycystic ovarian syndrome;
OVULATION STIMULANTS Patients unusually sensitive to pituitary gonadotropins;
Uterine fibroids
OVULATION STIMULANTS, SYNTHETIC
Adverse Drug Reactions:
Common: Ovarian enlargement
Rx CLOMIFENE Less Common: Headache, hot flashes, breast discomfort,
abnormal uterine bleeding, distention,
bloating/discomfort, nausea, vomiting, visual symptoms
Oral: 50 mg tablet (as citrate)
including blurred vision, diplopia, floaters, lights,
phosphenes, photophobia, scotomata, waves
A racemic mixture that acts at the level of the hypothalamus,
Rare: Acute abdomen, alopecia, appetite increased,
occupying the cell surface and intracellular estrogen
constipation, depression, dermatitis, diarrhea, dizziness,
receptors (ERs) for longer durations than estrogen. It
dry hair, fatigue, insomnia, lightheadedness,
inhibits receptor recycling, depletes hypothalamic ERs,
nervousness, rash, urinary frequency/volume increased,
and prevents normal estrogenic negative feedback.
vaginal dryness, vertigo, weight gain or loss
Inhibition of the feedback signal results in increased
pulsatile secretion of GnRH from the hypothalamus and
Administration: Total daily dose should only be taken one at
release of pituitary gonadotropins (FSH, LH) causing
a time to maximize effectiveness.
growth of the ovarian follicle, followed by follicular
rupture.
Pregnancy Category: X
Indications: Treatment of anovulatory infertility and male
ATC Code: G03GB02
infertility due to oligospermia

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 GENITO URINARY SYSTEM AND SEX HORMONES

ANTI-ANDROGENS Diseases aggravated by fluid retention or cardiovascular

disease;
History of depression (contraindicated in severe chronic
Rx CYPROTERONE depression);
Diabetes or impaired glucose tolerance;
Fertility effects;
Oral: 50 mg tablet (as acetate)
Pregnancy.
Inj.: 100 mg/mL (as acetate), 3 mL ampule, depot (IM)
SKILLED TASKS. May cause drowsiness or blurred vision.
A steroid possessing anti-androgenic, anti-gonadotropic, Avoid performing tasks, which require mental alertness,
and progestin-like activity. It blocks binding of e.g., operating machinery or driving.
dihydrotestosterone (DHT) to prostatic cancer cells and
utilizes negative feedback on hypothalamic-pituitary axis Adverse Drug Reactions: Edema, heart failure, hypotension,
by inhibiting luteinizing hormone (LH) secretion, leading myocardial infarction, phlebitis, shock, stroke, syncope,
to decreased testosterone production. tachycardia, thrombosis (DVT, embolus, superficial
G

venous thrombosis), aphasia, chills, coma, depression,

Indication: Palliative treatment for advanced prostate dizziness, encephalopathy, fatigue, headache,
cancer hemiplegia, lassitude, personality disorder, meningioma
(chronic therapy), psychotic depression, restlessness,
Contraindications: Hepatic disease or dysfunction; Dubin- vascular headache, vasovagal reactions, dry skin (sebum
Johnson syndrome; Rotor syndrome; previous or existing reduction), malaise, eczema, erythema nodosum,
hepatic tumors (if not due to metastases from prostate exfoliative dermatitis, hirsutism, maculopapular rash,
cancer); presence or history of meningioma; wasting patchy loss of body hair, pruritus, rash, photosensitivity,
diseases (except inoperable prostate cancer); severe scleroderma, skin discoloration, urticaria, adrenal
chronic depression; existing thromboembolic processes suppression (dose-related), benign nodular breast
hyperplasia, diabetes mellitus, galactorrhea,
Dose: gynecomastia, decreased libido, hypercalcemia, hot
Palliative treatment of advanced prostate cancer, by mouth, flashes, hypernatremia, impotence, inhibition of
ADULT (males), 200–300 mg once daily in 2–3 divided spermatogenesis, negative nitrogen balance, anorexia,
doses; if following orchiectomy, reduce to 100–200 mg constipation, diarrhea, dyspepsia, glossitis, nausea,
once daily (maximum dose, 300 mg daily); pancreatitis, vomiting, weight gain/loss, bladder
by IM injection, ADULT, 300 mg equivalent to 3 mL once carcinoma, urinary frequency, uterine fibroids enlarged,
a week; if following orchiectomy, reduce to 300 mg every uterine hemorrhage, anemia crystalluria, ascites,
2 weeks. cholestatic jaundice, cirrhosis, hepatic coma, hepatic
carcinoma, hepatic dysfunction (dose related), hepatic
NOTE: Oral and IM administration may be interchanged but failure, hepatitis, hepatoma, hepatic necrosis,
must remain in the usual ranges (100–300 mg once hepatomegaly, injection site reaction, abnormal gait,
daily for oral route and 300 mg every 1 or 2 weeks for IM myasthenia, abnormal accommodation, osteoporosis,
route). weakness, blindness, abnormal vision, optic neuritis,
optic atrophy, retinal vascular disorder, retinal vein
thrombosis, asthma, hematuria, renal failure, pulmonary
Precautions: embolism, cough, dyspnea, hyperventilation, pulmonary
WARNING: Use is associated with dose-dependent fibrosis, pulmonary oil microembolism, allergic reaction,
hepatotoxicity (jaundice, hepatitis, acute hepatic diaphoresis
failure) including fatal case reports with doses
≥100 mg daily. Hepatotoxicity typically develops NOTE: Reduces sperm count and volume of ejaculate at oral
after a few weeks to several months of treatment doses of 30–50 mg daily. Infertility may be noted after
initiation. Use caution with concurrent use of other approximately 2 months of treatment. Changes are
hepatotoxic drugs. Monitor hepatic function and reversible upon discontinuation of therapy, usually within
discontinue in patients with evidence of hepatic 3–5 months, up to 20 months.
injury.
Drug Interactions:
Monitor closely with:
Adrenal cortical function suppression may occur; Decreases metabolism of Cyproterone:
Hypochromic anemia (monitor CBC regularly); CYP3A4 Inhibitors
Metastatic prostate cancer;
Benign and malignant hepatic tumors (rule out the presence Enhances therapeutic effect of C1 Inhibitors (thrombogenic
of tumor in patients presenting with severe upper effect)
abdominal discomfort, hepatic enlargement, or signs of
intraabdominal hemorrhage); Reduces therapeutic effect of Cyproterone:
CNS depression Ethyl Alcohol (androgenic effect)
Lassitude, weakness, and fatigue;
Gynecomastia; Reduces therapeutic effect of the following drugs:
Thromboembolism; Antidiabetic Agents, Choline C11
Existing pulmonary dysfunction;
Familial defects of lipoprotein metabolism;

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GENITO URINARY SYSTEM AND SEX HORMONES

Avoid concomitant use with: may be eliminated in 2–3 months; elimination of

Decreases metabolism of Cyproterone: nodularity may require therapy for 4–6 months.
CYP3A4 Inhibitors Hereditary angioedema, by mouth, ADULT, 200 mg 2 to 3
times daily; after favorable response, decrease the
Decreases serum concentration of Cyproterone: dosage to ≤100 mg at 1–3 months interval or longer if
CYP3A4 Inducers, Dabrafenib needed; if an attack occurs, increase dose by up to 200
mg daily.
Increases serum concentration of Cyproterone:
Mifepristone Precautions:
WARNING: Thromboembolism, thrombotic, and
Increases serum concentration of the following drugs: thrombophlebitic events, including sagittal sinus
Amodiaquine, HMG-CoA Reductase Inhibitors [except thrombosis and life-threatening or fatal strokes,
Pitavastatin, Pravastatin, Rosuvastatin] have been reported.

G
Reduces therapeutic effect of Cyproterone: Peliosis hepatis and benign hepatic adenoma have
Ulipristal [for uterine fibroids, avoid progestins within 12 been reported with long-term use of the drug.
days of stopping ulipristal; for emergency contraception,
avoid progestins within 5 days of stopping ulipristal] Has been associated with pseudomotor cerebri, a
case of benign intracranial hypertension.
Reduces therapeutic effect of Anticoagulants

Administration: Androgenic effects;

For oral administration, take tablets at the same time each Blood lipid changes;
day, after meals and with liquids. May be divided into Diabetes;
equal halves to facilitate swallowing. Edematous condition;
Fibrocystic disease;
For IM injection, administer slowly. Avoid IV injection to Porphyria;
prevent pulmonary microembolism. Pregnancy (if patient becomes pregnant during treatment,
discontinue the drug, and appraise patient on the
Pregnancy Category: X potential risk to the fetus).

ATC Code: G03HA01 Adverse Drug Reactions:

Common and Less Common: Edema, flushing,
hypertension, MI, palpitation, tachycardia, depression,
OTHER SEX HORMONES AND MODULATORS OF THE dizziness, emotional lability, fainting, fatigue, headache,
nervousness, sleep disorders, Acne, alopecia, mild
GENITAL SYSTEM hirsutism, maculopapular rash, papular rash, petechial
rash, pruritus, purpuric rash, seborrhea, urticaria,
Rx DANAZOL vesicular rash, amenorrhea (may continue post therapy),
breast size reduction, glucose intolerance or glucagon
changes, libido changes, menstrual disturbances
Oral: 200 mg capsule (spotting, altered timing of cycle), semen abnormalities
(changes in volume, viscosity, sperm count or motility),
A synthetic derivative of ethisterone with weak androgenic sex hormone and thyroid binding globulin changes,
and anabolic properties. It suppresses pituitary output of constipation, gastroenteritis, nausea, vomiting,
FSH and LH resulting to the regression and atrophy of spermatogenesis reduction, weight gain, vaginal
normal and ectopic endometrial tissues. dryness, vaginal irritation, cholestatic jaundice, hepatic
adenoma, jaundice, malignant tumors (prolonged use),
Indications: Treatment of endometriosis, fibrocystic breast peliosis, hepatis, back pain, extremity pain, joint lockup,
diseases, and hereditary angioedema joint pain, joint swelling, muscle cramps, paresthesia,
spasms, neck pain, tremor, visual disturbances,
Contraindications: Undiagnosed genital bleeding; weakness, hematuria, Interstitial pneumonitis,
pregnancy; breastfeeding; porphyria; markedly impaired diaphoresis, voice change (hoarseness, sore throat,
hepatic, renal, or cardiac function; androgen-dependent instability, deepening of pitch), hepatotoxicity
tumor; thrombosis or thromboembolic disease (active or (idiosyncratic)
history) Rare: Benign intracranial hypertension, anxiety, chills,
convulsions, Guillain Barré syndrome, erythema
Dose: multiforme, fever, Stevens-Johnson syndrome,
Endometriosis, by mouth, ADULT (female), photosensitivity, clitoris hypertrophy, nipple discharge,
mild disease, 200–400 mg daily; appetite changes, bleeding gums, pancreatitis, splenic
moderate-to-severe, 800 mg daily in 2 divided doses; peliosis, pelvic pain, carpal tunnel syndrome, cataracts,
continue therapy uninterrupted for 3–6 months up to 9 nasal congestion
months.
Fibrocystic breast disease, by mouth, ADULT (female), 100–
400 mg daily in 2 divided doses; pain and tenderness

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 GENITO URINARY SYSTEM AND SEX HORMONES

Drug Interactions: Drug Interactions:

Monitor closely with: Monitor closely with:
Enhances therapeutic effect of C1 Inhibitors (thrombogenic Enhances therapeutic effect of Alpha-adrenoceptor
effect) Antagonists:
Anti-hypertensives, Aprepitant, Calcium Channel
Increases risk of adverse or toxic effects of Vitamin D Blockers (hypotensive effect), Cimetidine, Dasatinib,
Analogues [except Calcipotriene] (hypercalcemic effect) Fosaprepitant, Ivacaftor, Luliconazole, Netupitant

Increases risk of adverse or toxic effects of Danazol: Enhances therapeutic effect of Alpha-adrenoceptor
Corticosteroids (Dofetilide) Antagonists:
Nitroglycerin (hypotensive effect), Palbociclib,
Reduces therapeutic effect of Antidiabetic Agents Phosphodiesterase Inhibitors (hypotensive effect),
Simeprevir
Avoid concomitant use with:
G

Decreases metabolism of Carbamazepine Increases risk of adverse or toxic effects of Alpha-

adrenoceptor Antagonists:
Enhances therapeutic effect of Vitamin K Antagonists e.g. Beta Blockers (orthostatic hypotension), CYP3A4
Warfarin (anticoagulant effect) Inhibitors, e.g., Ketoconazole, Itraconazole, Ritonavir,
Dapoxetine (orthostatic hypotension), MAO Inhibitors
Increases risk of adverse or toxic effects of Cyclosporine [except Linezolid, Tedizolid] (orthostatic hypotension)
(hepatotoxic effect)
Reduces therapeutic effect of Alpha-adrenoceptor
Increases serum concentration of the following drugs: Antagonists:
Cyclosporine, HMG-CoA Reductase Inhibitors [except Alpha / Beta Agonists (vasoconstricting effect),
Fluvastatin, Pravastatin, Rosuvastatin], Bosentan, CYP3A4 Inducers, Deferasirox, Siltuximab,
Toclizumab
Increases serum concentration of the following drugs:
Pimozide, Simvastatin Avoid concomitant use with:
Decreases serum concentration of Alpha-adrenoceptor
Pregnancy Category: X Antagonists:
CYP3A4 Inducers, Dabrafenib
ATC Code: G03XA01
Enhances therapeutic effect of Alpha-adrenoceptor
Antagonists:
Alpha1 Blockers (antihypertensive effect),
UROLOGICALS Phosphodiesterase-5 Inhibitors e.g. Sildenafil
(antihypertensive effect), Protease Inhibitors e.g.,
Indinavir, Telaprevir
DRUGS USED IN BENIGN PROSTATIC
HYPERTROPHY (BPH) Enhances therapeutic effect of QTc-prolonging Agents
(Highest Risk)
ALPHA-ADRENOCEPTOR ANTAGONISTS
General Information Increases risk of adverse or toxic effects of Alpha-
adrenoceptor Antagonists:
Beta Blockers [except Levobunolol, Metipranolol],
Alpha–adrenoceptor blockers act preferentially on the
Stiripentol (orthostatic hypotension), CYP3A4 Inhibitors,
receptors in the lower urinary tract resulting to relaxation
Fusidic Acid, Mifepristone (orthostatic hypotension),
in the muscles of bladder and prostate.
Increases serum concentration of Alpha-adrenoceptor
Indications: Treatment of signs and symptoms of benign
Antagonists:
prostatic hypertrophy and relief of symptoms of urinary
CYP3A4 Inhibitors, Fusidic Acid, Telaprevir
obstruction
Reduces therapeutic effect of Alpha-adrenoceptor
Precautions:
Antagonists:
Hypotension;
Dabrafenib
Volume depletion;
Renal impairment;
Hepatic impairment;
Patients who are receiving an antihypertensive treatment Rx ALFUZOSIN
may require dose reduction and supervision;
Monitor for an improved urine flow and for “first dose”
orthostatic hypotension, headache, or GI disturbances, Oral: 10 mg tablet (as hydrochloride)
e.g., nausea, vomiting, at the beginning of therapy and
on a regular basis; An alpha1-selective adrenoceptor antagonist used in Benign
Elderly and patients undergoing cataract surgery (risk of Prostatic Hypertrophy (BPH) to relieve symptoms of
intraoperative floppy iris syndrome) urinary obstruction, including acute urinary retention.

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GENITO URINARY SYSTEM AND SEX HORMONES

Indication: Treatment of functional symptoms of benign Dose may be increased after 2-4 weeks to 800
prostatic hypertrophy micrograms once daily in patients who fail to respond. If
therapy is interrupted for several days, restart with 400
Contraindications: Moderate or severe hepatic impairment micrograms once daily.
Dose: Dose Adjustment:
Benign prostatic hypertrophy, by mouth, ADULT, 10 mg once Renal and Hepatic Impairment:
daily. For mild-to-moderate impairment, use with caution.
For severe impairment, refer patient to a specialist.
NOTE: Do NOT use as an antihypertensive.
Adverse Drug Reactions:
Dose Adjustment: Common: Abnormal ejaculation, chest pain, dizziness,
Renal Impairment: drowsiness, fatigue, headache, insomnia, nasal
Use with caution in patients with creatinine clearance <30 congestion, rhinitis, urinary urgency, weakness
mL/minute. Less Common: Blurred vision, dryness of mouth, edema,

G
first-dose hypotension, orthostatic hypotension,
Hepatic Impairment: increased sweating, nausea, palpitations, syncope,
Use with caution in patients with mild impairment. tachycardia, urinary incontinence, vomiting
Rare: Angioedema, depression, dyspnea, hypersensitivity
Adverse Drug Reactions: reactions, itch, mood changes, paresthesia, rash,
Less Common: Dizziness, fatigue, headache, pain, urticaria, vertigo
constipation, dyspepsia, nausea, impotence, upper
respiratory tract infection, bronchitis, pharyngitis, Administration: Administer 30 minutes after the same meal
sinusitis each day. Swallow capsules whole. Do NOT crush, chew,
Rare: Angina pectoris, angioedema, atrial fibrillation, chest or open.
pain, diarrhea, edema, flushing, hepatic injury,
orthostatic hypotension, intraoperative floppy iris NOTE: The extent and rate of absorption are reduced by the
syndrome, jaundice, priapism, pruritus, rhinitis, skin presence of food.
rash, syncope, tachycardia, toxic epidermal necrolysis,
urticaria See General Information on Alpha-Adrenoceptor
Antagonists under Drugs used in Benign Prostatic
Administration: Administer immediately following a meal at Hypertrophy listed above for further information.
the same time each day. Swallow tablets whole. Do NOT
crush or chew. Pregnancy Category: B
NOTE: Food increases extent of absorption.
ATC Code: G04CA02
See General Information on Alpha-Adrenoceptor
Antagonists under Drugs used in Benign Prostatic
Hypertrophy listed above for further information. Rx TERAZOSIN

Pregnancy Category: B Oral: 1 mg, 2 mg, and 5 mg tablet (as hydrochloride)

ATC Code: G04CA01 An alpha1-selective adrenoceptor antagonist used in BPH to
relieve symptoms of urinary obstruction, including acute
urinary retention.
Rx TAMSULOSIN
Indications: For hypertension and lower urinary tract
symptoms (LUTS) associated with BPH; treatment of
Oral: 200 micrograms capsule (as hydrochloride) signs and symptoms of BPH and relief of symptoms of
200 micrograms orally disintegrating tablet urinary obstruction
400 micrograms prolonged-release FC tablet
Dose:
An alpha1-selective adrenoceptor antagonist that is used in Benign prostatic hypertrophy, by mouth, ADULT, 1 mg every
mediating smooth muscle tone in the prostate to relieve bedtime; may gradually increase at 7-day intervals
symptoms of urinary obstruction caused by BPH. according to response; (maintenance dose, 5–10 mg
once every bedtime).
Indications: Treatment of sign and symptoms of BPH; relief
of symptoms of obstruction in BPH Adverse Drug Reactions:
Common: Dizziness, asthenia
Contraindications: History of micturition, syncope, and Less Common: Hypotension, rhinitis, light-headedness,
postural hypotension somnolence, palpitation, nausea, edema, sinusitis,
dyspnea, fatigue, headache, back pain, flu-like
Dose: syndrome, tachycardia, amblyopia, blurred vision,
Benign prostatic hypertrophy, by mouth, ADULT, 400 impotence, syncope
micrograms once daily.

NOTE: Do NOT use as an antihypertensive.

185
 GENITO URINARY SYSTEM AND SEX HORMONES

Administration: Administer with or without food once daily at crushed or broken tablets can be absorbed through the
bedtime. Give first dose and subsequent increase at skin and may negatively impact fetal development).
bedtime to prevent syncope.

See General Information on Alpha-Adrenoceptor

Antagonists under Drugs used in Benign Prostatic Adverse Drug Reactions:
Hypertrophy listed above for further information. Common: Orthostatic hypotension, dizziness, decreased
libido, impotence, neuromuscular and skeletal
Pregnancy Category: C weakness
Less Common: Edema, drowsiness, skin rash,
ATC Code: G04CA03 gynecomastia, decreased ejaculate volume, breast
tenderness, dyspnea, rhinitis
Rare: Altered mental status; change in libido, decreased
TESTOSTERONE-5-ALPHA testicular size, depression, disturbed sleep,
G

REDUCTASE INHIBITORS hypersensitivity (angioedema, facial swelling, pharyngeal

edema, pruritus, skin rash, swelling of the lips, swollen
tongue, urticaria), male infertility (temporary), malignant
Rx FINASTERIDE neoplasm of the male breast, prostate cancer high
grade, prostatitis, reduction in penile curvature,
reduction in penile size, sexual disorder (may not be
Oral: 5 mg tablet reversible with discontinuation), testicular pain
A type II 5-alpha reductase inhibitor with anti-androgenic Drug Interactions: No known significant interactions
properties due to the conversion of testosterone to
dihydrotestosterone. Administration: May be administered with or without meals.
Indications: Management of BPH; reduction of incidence of Pregnancy Category: X
acute urinary retention and need for surgery
ATC Code: G04CB01
NOTE: Although effective in partially relieving lower urinary
tract symptoms, therapy with and alpha1-adrenergic
blocker appears to result in greater improvement in
symptoms.

Contraindications: Pregnant or women of childbearing age

Dose:
Benign prostatic hypertrophy, by mouth, ADULT, initially 1
mg at bedtime, subsequently increase stepwise to 2, 5,
or 10 mg once daily, as single drug or in combination, at
7-day intervals.

NOTE: A minimum of 6 months of treatment may be

necessary to determine if an individual will respond to
finasteride.

Dose Adjustment:
Hepatic Impairment:
Use with caution. Finasteride is metabolized extensively in
the liver.

Precautions:
WARNING: Decreases concentration of serum
markers of prostate cancer such as the Prostate
Specific Antigen (PSA) by up to 50% even if cancer
is present. Adjust reference values accordingly.

Monitor patients carefully with severely diminished urinary

flow;
Hepatic impairment (metabolized extensively in the liver);
Men at risk of obstructive uropathy;
Rule out prostate cancer before initiating treatment;
Pregnancy (women of childbearing age should not touch or
handle crushed or broken tablets; active ingredient of

186
SYSTEMIC HORMONAL PREPARATIONS, EXCLUDING SEX HORMONES AND INSULINS

Dose Adjustment:
SYSTEMIC HORMONAL Renal Impairment:
PREPARATIONS, EXCLUDING SEX In CrCl <50 mL/minute, use is contraindicated.
HORMONES AND INSULINS
Precautions:
Allergic reactions;
Hyponatremia;
PITUITARY AND HYPOTHALAMIC Thrombotic events (use with caution in patients
HORMONES AND ANALOGUES predisposed to thrombus formation);
Von Willebrand disease type 2B; Habitual or psychogenic
polydipsia (use with caution);
POSTERIOR PITUITARY LOBE HORMONES Primary nocturnal enuresis (interrupt treatment if the
patient experiences an acute illness, e.g. fever,
VASOPRESSIN AND ANALOGUES recurrent vomiting, or diarrhea);
Vigorous exercise;
Any condition associated with increase in water
Rx DESMOPRESSIN consumption;

H
Elderly and children.
Oral: 100 micrograms and 200 micrograms tablet (as
Adverse Drug Reactions:
acetate)
Inj.: 15 micrograms/mL (as acetate), 1 mL ampule (IM,
Common: Flushing (facial), headache, skin rash,
hyponatremia, water intoxication, abdominal cramps,
SC)
burning sensation at injection site, sore throat, erythema
or swelling at injection site, cough, nasal congestion,
A synthetic analogue of the antidiuretic hormone arginine
upper respiratory tract infection
vasopressin. It increases cAMP in renal tubular cells in a
dose dependent manner. This increases water
Less Common: Abnormality in thinking, agitation, balanitis,
chest pain, diarrhea, drowsiness, pain, coma, dyspepsia,
permeability, resulting in decreased urine volume and
insomnia, edema, localized warm feeling, palpitations,
increased urine osmolality, as well as increases plasma
photophobia, seizure, eye pruritus, tachycardia,
levels of von Willebrand factor, factor VIII, and tPA
vomiting, vulvar pain
contributing to a shortened activated partial
thromboplastin time (aPTT) and bleeding time.
Rare: Anaphylaxis, hypersensitivity reaction

Indications: For the treatment of central diabetes insipidus Drug Interactions:

and primary nocturnal enuresis in children aged 5 years Monitor closely with:
and above Increases risk of adverse or toxic effects of Desmopressin:
Carbamazepine, Chlorpromazine, Chlorpropramide,
Contraindications: Hyponatremia (current or a history of), Lamotrigine, Nonsteroidal Anti-Inflammatory Agents,
CrCl <50 mL/minute), type 2B or platelet type (pseudo) Opioid Analgesics e.g., morphine, fentanyl, Selective
von Willebrand’s disease; habitual or psychogenic Serotonin Reuptake Inhibitors e.g. Fluoxetine, Sertraline,
polydipsia; cardiac insufficiency; conditions requiring Tricyclic Antidepressants e.g., Amitriptyline Imipramine,
diuretic therapy (sublingual); nephrosis, severe hepatic Urea
dysfunction (sublingual)
Reduces therapeutic effect of Desmopressin:
Dose: Demeclocycline, Epinephrine [large doses], Ethyl Alcohol,
Nocturnal emesis, by mouth, ADULT and CHILD ≥5 years, Heparin, Lithium
initially 0.2 mg at bedtime, may be titrated up to 0.6 mg.
[NOTE: Limit fluid intake 1 hour prior to dose until the Avoid concomitant use with:
next morning, or at least 8 hours after administration]. Reduces therapeutic effect of Desmopressin:
Diabetes insipidus, IM, SC, ADULT, 2–4 micrograms (0.5–1 Tolvaptan
mL) daily in 2 divided doses;
Administration: Restrict fluid intake from 1 hour before to 8
by mouth, ADULT and CHILD ≥4 years, 0.05 mg twice daily;
hours after taking desmopressin tablets to decrease the
total daily dose should be increased or decreased as
possibility of water intoxication and hyponatremia.
needed to obtain adequate anti-diuresis (range: 0.1 to 1.2
mg 2–3 divided doses). [NOTE: Observe fluid restriction].
Pregnancy Category: B
Initial Dose Range ATC Code: H01BA02
Age (years) (micrograms, 2- (micrograms
3 times daily) daily)
Neonate 1–4 None stated
1 month -
10 30 – 150
2 years
2 – 12 50 100 – 800
12 – 18 100 200 – 1,200

187
 SYSTEMIC HORMONAL PREPARATIONS, EXCLUDING SEX HORMONES AND INSULINS

OXYTOCIN AND ANALOGUES

Rx OXYTOCIN (SYNTHETIC)

Rx CARBETOCIN Inj.: 10 IU/mL, 1 mL ampule (IM, IV)

Inj: 100 mcg/mL, 1 mL ampule/vial, solution for injection A synthetic nonapeptide identical with oxytocin, a peptide
(IV) hormone, which participates in labor or delivery and
stimulates uterine contraction.
Carbetocin binds oxytocin receptors located in uterine
smooth muscle producing rhythmic uterine contractions Indications: Prevention and treatment of postpartum and
characteristic to deliver, as well as increasing both the post-abortion hemorrhage; induction and augmentation
frequency of existing contractions and uterine tone. It of labor
enhances uterine involution early in postpartum.
Contraindications: Hypertonic uterine contractions;
Indications: Prevention of uterine atony and postpartum mechanical obstruction to delivery; fetal distress; any
hemorrhage following cesarean section under epidural condition where spontaneous labor or vaginal delivery is
or spinal anesthesia. inadvisable; major cephalopelvic disproportion
H

Contraindications: Hypersensitivity to carbetocin, oxytocin, Dose:

or any component of the formulation; administration Induction of labor, by IV infusion, ADULT and ADOLESCENT,
prior to delivery of infant for any reason (including initially 0.0005–0.001 IU/minute increased in 0.001–
elective or medical induction of labor); serious 0.002 IU/minute increments at intervals of 30 minutes
cardiovascular disorders; use in children. until up to 3–4 contractions occur every 10 minutes
(maximum rate, 0.02 IU/minute).
Dose:
Prevention of uterine atony and postpartum hemorrhage, by NOTE: Careful monitoring of fetal heart rate and uterine
IV injection, ADULT, 100 mcg (single dose only). motility is essential for dose titration. Discontinue
immediately in uterine hyperactivity or fetal distress.
Dose Adjustment:
Renal and Hepatic impairment: Prevention of postpartum hemorrhage, by IM injection,
No dosage adjustments provided in the manufacturer’s ADULT and ADOLESCENT, 10 IU when the anterior
labeling. shoulder is delivered or immediately after birth.
Prevention of postpartum hemorrhage, by slow IM injection,
Precautions: ADULT and ADOLESCENT, 5 IU when the anterior
Antidiuretic effect and bleeding; shoulder is delivered or immediately after birth.
Use in caution in patients with asthma, cardiovascular Treatment of postpartum hemorrhage, by slow IV injection,
disease, epilepsy, and migraines. ADULT, 10-40 IU in 1000 mL of IV fluid at a rate sufficient
to control uterine atony; ADOLESCENT, 5-10 IU;
Adverse Drug Reactions: by IM injection, ADULT and ADOLESCENT, 10 IU, followed
Common: Flushing, hypotension, headache, pruritus, in severe cases by a total of 40 IU, by intravenous
abdominal pain, nausea, vomiting, tremor, and feeling of infusion, at a rate of 0.02-0.04 IU/minute; this should be
warmth. started after the placenta is delivered.
Less Common: Chest pain, tachycardia, anxiety, chills,
dizziness, metallic taste, anemia, back pain, dyspnea, Dose Adjustment:
and diaphoresis. Renal Impairment:
Use with caution (increased risk of water retention and
Drug Interactions: oxytocin accumulation).
Monitor closely with:
Increased levels/effects by Carbetocin: Precautions:
Antipsychotic Agents (Second Generation), Hypotension- Oxytocin-resistant uterine inertia (avoid prolonged
Associated Agents, Levodopa-Containing Products. administration);
Severe pre-eclamptic toxemia;
Increases levels/effects of Carbetocin: Severe cardiovascular disease;
Alfuzosin, Barbiturates, Blood Pressure Lowering Agent, Previous uterine surgery, multiple pregnancy, or >4 previous
Brimonidine, Carboprost. births;
Induction or enhancement of labor in the presence of
Administration: Administer as bolus IV injection over 1 borderline cephalopelvic disproportion (avoid use if
minute only after delivery of infant has been completed significant);
by cesarean section. May administer before or after Mild-to-moderate pregnancy-associated hypertension or
delivery of placenta. cardiovascular disease;
Age >35 years;
Pregnancy Category: C History of low-uterine segment caesarean section;
Caudal block anesthesia;
ATC Code: H01BB03 Avoid tumultuous labor if fetal death or meconium-stained
amniotic fluid

188
SYSTEMIC HORMONAL PREPARATIONS, EXCLUDING SEX HORMONES AND INSULINS

Adverse Drug Reactions: Head injury (high doses should not be used for the
Less Common: Nausea, vomiting management of head injury);
Rare: Anaphylactoid reaction, arrhythmias, ECG changes, Ocular disease;
flushing, prolonged QT interval, rash, reflex tachycardia, Hepatic impairment i.e. cirrhosis and renal impairment;
severe (tetanic) uterine spasm and contraction leading Osteoporosis;
to uterine rupture or fetal distress, hypoxia and death, Thyroid disease;
seizures, transient hypotension, water intoxication Stress (may require higher doses when subject to stress,
i.e., trauma, surgery, severe infection);
Drug Interactions: Elderly;
Monitor closely with: Children;
Increases risk of adverse or toxic effects of the following Pregnancy (use in early pregnancy may slightly increase the
drugs due to enhanced vasopressor effect: risk of orofacial clefts);
Ephedrine, Epinephrine Lactation (allow a 4-hour interval between administration
and breastfeeding).
Administration: For IV bolus injection, administer slowly.
Avoid rapid injection due to risk of cardiovascular effects. Administration: For IM, intraarticular or intralesional use
Avoid bolus IV injection during labor. only. Do NOT administer by IV or epidural injection. Avoid

H
injection into the deltoid muscle due to high incidence of
For IV infusion, monitor fluid balance to prevent water SC atrophy.
intoxication.
Use caution when transferring from systemic to inhaled
Avoid large volume infusions and restrict fluid intake to corticosteroids due to possible adrenal insufficiency or
prevent water intoxication and hyponatremia. withdrawal from steroids, including an increase in
allergic symptoms.
Pregnancy Category: X
NOTE: Withdraw therapy with gradual tapering of dose.
ATC Code: H01BB02 Chronic use may result in hypothalamic-pituitary adrenal
axis suppression, Cushing’s syndrome, and
hyperglycemia

CORTICOSTEROIDS FOR
SYSTEMIC USE
Rx DEXAMETHASONE
GLUCOCORTICOIDS Oral: 500 micrograms, 750 micrograms, 3 mg, and 4 mg
tablet
GENERAL INFORMATION Inj.: 4 mg/mL (as sodium phosphate), 1 mL and 2 mL
ampule / vial (IM, IV)
Glucocorticoids act as an anti-inflammatory agent by 5 mg/mL (as sodium phosphate), 1 mL ampule (IM,
suppressing the release of inflammatory proteins. It also IV)
aids in the biological response to stress, which includes
mobilization of fat and sugar stores in the body. A corticosteroid with mainly glucocorticoid activity, but lacks
mineralocorticoid properties.
Mode of Action: Glucocorticoids mimic the actions of
corticosteroids produced in the adrenal cortex and Indications: Management of a wide variety of inflammation
naturally found in the human body. and allergic disorders responsive to corticosteroid
therapy; management of asthma and related
Dose Adjustment: bronchospastic disorders; treatment of cerebral edema
Geriatric: caused by malignancy in intensive therapy or in
Use in the smallest effective dose for the shortest duration emergencies; prevention of nausea and vomiting
possible. induced by the cancer chemotherapy; treatment of all
conditions for which corticosteroid therapy is indicated
Precautions: except adrenal deficiency states; replacement therapy in
Adrenal suppression; adrenal insufficiency
Anaphylactoid reactions;
Diabetes; Contraindications: Systemic fungal infections; cerebral
Immunosuppression; malaria.
Latent TB;
Kaposi sarcoma; Dose:
Myopathy; Anti-inflammatory, by mouth or by IM or IV injection, ADULT,
Myasthenia gravis; 0.75–9 mg daily in divided doses every 6–12 hours.
Psychiatric disturbances; Anti-inflammatory or immunosuppressant, by mouth or by
Seizure disorders; IM or IV injection, CHILD, 0.08–0.3 mg/kg daily or 2.5–
Cardiovascular disease; Myocardial infarction; 10 mg/m2 daily in divided doses every 6–12 hours.
GI disease (avoid ethanol since this may enhance gastric For extubation or airway edema, by mouth or by IM or IV
mucosal irritation); injection, ADULT and CHILD, 0.5–2 mg/kg daily in

189
 SYSTEMIC HORMONAL PREPARATIONS, EXCLUDING SEX HORMONES AND INSULINS

divided doses every 6 hours beginning 24 hours prior to atrophy, impaired skin test reaction, striae, urticaria,
extubation and continuing for 4–6 doses afterwards impaired wound healing, adrenal suppression,
Antiemetic, by mouth or by IV injection, ADULT, 10 to 20 mg decreased carbohydrate tolerance and glucose
15–30 minutes before treatment on each treatment day; intolerance, Cushing's syndrome, diabetes mellitus,
by IV injection, CHILD, 10 mg/m2 per dose every 12–24 growth suppression (children), hypokalemic alkalosis,
hours on days of chemotherapy for severely emetogenic hyperglycemia, menstrual irregularities, negative
chemotherapy courses. nitrogen balance, protein catabolism, pituitary-adrenal
axis suppression, sodium retention, abdominal
Type of Therapy for distention, increased appetite, GI hemorrhage, GI
Route Dose perforation, pancreatitis, peptic ulcer, ulcerative
Adults
10 mg every 12 esophagitis, weight gain; altered spermatogenesis,
Continuous Oral or hepatomegaly, nausea, arthropathy, aseptic necrosis
hours on each
infusion regimen IV (femoral and humoral heads), fractures, muscle mass
treatment day
loss, myopathy (in conjunction with neuromuscular
Mildly emetogenic Oral, IM, 4 mg every 46
disease or neuromuscular-blocking agents),
therapy or IV hours
thrombophlebitis, neuropathy, osteoporosis,
paresthesia, tendon rupture, weakness, vertebral
H

Delayed nausea and vomiting, by mouth, ADULT, 4 to 10 mg compression fractures, cataracts, exophthalmos,
1–2 times daily for 2–4 days. glaucoma, increased intraocular pressure, glucosuria,
Multiple myeloma, by mouth or by IV injection, ADULT, 40 pulmonary edema, abnormal fat deposition,
mg daily, days 1 to 4, 9 to 12, and 17 to 20, repeated anaphylactoid reaction, anaphylaxis, avascular necrosis,
every 4 weeks, alone or as part of a regimen. diaphoresis, hiccups, hypersensitivity, impaired wound
Multiple sclerosis, by mouth, ADULT, 30 mg daily for 1 week, healing, infections, Kaposi sarcoma, moon face,
followed by 4–12 mg daily for 1 month. secondary malignancy
Treatment of Addisonian crisis or shock, by IV injection,
ADULT, 4–10 mg as a single dose, may be repeated if Drug Interactions:
necessary. Monitor closely with:
Treatment of unresponsive shock, by IV route, ADULT, 1-6 Enhances therapeutic effect of Dexamethasone:
mg/kg as a single dose or up to 40 mg initially followed Trastuzumab (neutropenic effect)
by repeat doses every 2–6 hours while shock persists.
Physiological replacement, by mouth or by IM or IV injection, Enhances therapeutic effect of Warfarin (anticoagulant
ADULT, as sodium phosphate, 0.03–0.15 mg/kg daily or effect)
0.6 to 0.75 mg/m2 daily in divided doses every 6–12
hours; CHILD, 0.03 to 0.15 mg/kg daily or 0.6–0.75 Increases risk of adverse or toxic effects of Dexamethasone:
mg/m2 daily in divided doses every 6-12 hours. Denosumab (serious infections), Salicylates (GI
Croup or laryngotracheobronchitis, by mouth or by IM or IV ulceration and bleeding)
injection, CHILD, 0.6 mg/kg once (usual maximum dose,
16 mg; doses as high as 20 mg have been used), a single Increases risk of adverse or toxic effects of the following
oral dose of 0.15 mg/kg has been shown effective in drugs:
children with mild-to-moderate croup. Acetylcholinesterase Inhibitors e.g. pyridostigmine
Bacterial meningitis, by IV injection, INFANT and CHILD >6 edrophonium (increased muscular weakness),
weeks, 0.15 mg/kg per dose every 6 hours for the first Amphotericin B, Thiazide Diuretics, Loop Diuretics
2–4 days of antibiotic treatment; initiate 10–20 minutes (hypokalemic effect), Androgens (fluid-retaining effect),
before or with the first dose of antibiotic. COX-2 Inhibitors e.g. Celecoxib, Deferasirox (GI
Cushing's syndrome, diagnosis, by mouth, ADULT, 1 mg at ulceration or irritation; GI bleeding), NSAID (Non-
11 PM, draw blood at 8 AM; greater accuracy for selective), Quinolone Antibiotics e.g. Levofloxacin
Cushing's syndrome may be achieved by the following: (tendonitis; tendon rupture)
0.5 mg every 6 hours for 48 hours (with 24­hour urine
collection for 17­hydroxycorticosteroid excretion) Reduces absorption of Dexamethasone:
Differentiation of Cushing's syndrome due to ACTH Bile Acid Sequestrants
excess from Cushing's due to other causes, 2 mg every 6
hours for 48 hours (with 24­hour urine collection for Reduces diagnostic effect of Coccidioides immitis Skin Test
17­hydroxy-corticosteroid excretion).
Reduces therapeutic effect of the following drugs:
Adverse Drug Reactions: Arrhythmia, bradycardia, cardiac Antidiabetic Agents, Calcitriol, Corticorelin (blunts
arrest, cardiomyopathy, CHF, circulatory collapse, plasma ACTH response to corticorelin), Urea Cycle
edema, hypertension, myocardial rupture (post-MI), Disorder Agents (increases protein catabolism and
syncope, thromboembolism, vasculitis, depression, plasma ammonia concentrations, increasing doses of
euphoria, emotional instability, headache, increased Urea Cycle Disorder Agents needed to maintain
intracranial pressure, insomnia, malaise, neuritis, mood concentrations in the target range)
swings, personality changes, pseudotumor cerebri
(following discontinuation), seizure, psychic disorders, Avoid concomitant use with:
vertigo, allergic dermatitis, acne, alopecia, angioedema, Decreases bioavailability of Dexamethasone:
bruising, dry skin, erythema, fragile skin, hypertrichosis, Antacids [separate doses by at least 2 hours]
hirsutism, hyperpigmentation or hypopigmentation, rash,
perianal pruritus (following IV injection), petechiae, skin Decreases serum concentration of Dexamethasone:

190
SYSTEMIC HORMONAL PREPARATIONS, EXCLUDING SEX HORMONES AND INSULINS

Fosphenytoin, Phenytoin
Rx HYDROCORTISONE
Decreases serum concentration of the following drugs:
Dasatinib, Fosphenytoin, Imatinib [increase Imatinib Oral: 5 mg and 20 mg tablet
dose by at least 50%], Nilotinib, Phenytoin, Rilpivirine, Inj.: 100 mg and 250 mg (as sodium succinate), vial (IV)
Ticagrelor [including its active metabolites], Vincristine 50 mg/mL (as sodium succinate), 2 mL vial (IM, IV)
125 mg/mL powder (as sodium succinate), 2 mL vial
Enhances therapeutic effect of Dexamethasone: (IV)
Nondepolarazing Neuromuscular-Blocking Agents e.g.
Pancuronium, Atracurium (neuromuscular effect) A glucocorticoid used for replacement therapy in adrenal
insufficiency, management of autoimmune and
Enhances therapeutic effect of Thalidomide (thrombogenic inflammatory conditions, and as emergency
effect) management of anaphylaxis and severe systemic
allergies.
Increases risk of adverse or toxic effects of Dexamethasone:
Nondepolarizing Neuromuscular-Blocking Agents, Indications: Management of autoimmune or inflammatory
(increased muscle weakness, possibly progressing to conditions; endocrinal disorders; management of all

H
polyneuropathies and myopathies)], Pimecrolimus, conditions requiring corticosteroids; replacement
Tacrolimus (Topical) therapy in cases of adrenocortical insufficiency (usually
in combination with a more potent mineral corticoid);
Increases risk of adverse or toxic effects of the following hypersensitivity reactions, such as anaphylactic shock
drugs: and angioedema; bilateral adrenalectomy
Leflunomide (hematologic toxicity such as pancytopenia,
agranulocytosis, and/or thrombocytopenia), Contraindications: Systemic fungal infections; serious
Thalidomide (dermatologic adverse effect), Tofacitinib infections, except septic shock or tuberculous
(immunosuppressive effect), Vaccines (Live) meningitis; viral, fungal, or tubercular skin lesions;
infective arthritis, skin or soft tissue infections near joints
Increases serum concentration of Dexamethasone: or a prosthetic joint; concurrent administration of live
Mifepristone virus vaccines and immunosuppressive doses of
corticosteroids; IM administration in idiopathic
Increases serum concentration of the following drugs: thrombocytopenia purpura; intrathecal administration
Fosphenytoin, Phenytoin
Dose:
Reduces therapeutic effect of Dexamethasone: Anti-inflammatory, by IV or IM injection, ADULT, 100 to 500
Mifepristone mg 3 or 4 times daily; CHILD, 2–4 mg/kg every 6 hours
for 24 hours, reduce over subsequent 24 hours or
Reduces therapeutic effect of the following drugs: change to oral prednisone
Aldesleukin (antineoplastic effect), BCG, (boosting by mouth, ADULT, 20–240 mg once daily.
effects), Hyaluronidase, Vaccines (Inactivated) Initial control of autoimmune disease, by IV injection,
[complete all age-appropriate vaccinations at least 2 ADULT, 100–500 mg 3 or 4 times daily according to
weeks prior to starting Dexamethasone; if vaccinated severity of condition.
during Dexamethasone therapy, revaccinate at least 3 Status asthmaticus, by IV injection, ADULT and CHILD, 1–2
months after discontinuation], mg/kg per dose every 6 hours for 24 hours, then
maintenance of 0.5–1 mg/kg every 6 hours.
Unknown impact on the therapeutic effect of Budesonide EC Physiologic replacement, by mouth, CHILD, 0.4–0.8 mg/m2
Tablets (could dissolve prematurely if given with drugs daily divided in 2–3 divided doses.
that lower gastric acid) Stress dosing, surgery in patients who are adrenally-
suppressed or on chronic systemic steroids, by IV
Administration: For oral administration, take after meals or injection, ADULT:
with food or milk to decrease GI effects. Increased
dietary intake of pyridoxine, vitamins A, B6, C, D, folate, Level of
calcium, zinc, and phosphorus is also recommended. Conditions Dose
Stress
See General Information on Corticosteroids for Systemic Inguinal
Minor 25 mg for 1 day
Use – Glucocorticoids listed under Chapter 6: Systemic herniorrhaphy
Hormonal Preparations for further information. 50–75 mg daily
Joint replacement, (25 mg every 8–
Moderate
Pregnancy Category: C cholecystectomy 12 hours) for 1–2
days
ATC Code: H02AB02 Pancreatico- 100–150 mg
duodenectomey, daily
Major esophago- (50 mg every 8–
gastrectomy, 12 hours) for 2–3
cardiac surgery days

191
 SYSTEMIC HORMONAL PREPARATIONS, EXCLUDING SEX HORMONES AND INSULINS

Dose Adjustment: Increases risk of adverse or toxic effects of the following

Renal and Hepatic Impairment: drugs:
For mild-to-moderate impairment, dose reduction is Diuretics e.g., Furosemide, Hydrochlorothiazide
warranted. (hypokalemia), Drugs controlling Blood Glucose
For severe impairment, refer patient to a specialist. Concentration (may increase blood glucose
concentration; may alter control of diabetes),
Adverse Drug Reactions: Leflunomide (hematologic toxicity such as pancytopenia,
Common: Acne, adrenal suppression, amenorrhea, agranulocytosis, and/or thrombocytopenia), Tofacitinib
bruising, delayed wound healing, dyslipidemia, (immunosuppressive effect), Vaccines (Live)
dyspepsia, edema, fat redistribution, fractures, growth
retardation, hirsutism, hyperglycemia, hypertension, Increases serum concentration of Hydrocortisone:
hypokalemia, increased appetite, increased Mifepristone
susceptibility to infection, masking of signs of infection,
muscle weakness and wasting, myopathy, osteoporosis, Reduces therapeutic effect of Hydrocortisone:
psychiatric effects, skin atrophy, sodium and water Mifepristone
retention, weight gain
Less Common: Glaucoma, ocular hypertension, Reduces therapeutic effect of the following drugs:
H

osteonecrosis (femoral and humeral heads) Aldesleukin (antineoplastic effect), Amlodipine,

Rare: Anaphylactoid reaction, chorioretinopathy (central), Antihypertensives (e.g., Enalapril, Isosorbide Dinitrate,
euphoria, hypersensitivity reactions, hypomania, peptic Methyldopa), Diuretics (e.g., Furosemide,
ulceration, tendon rupture Hydrochlorothiazide (antagonizes hypotensive effect),
BCG (Intravesical)
Drug Interactions:
Monitor closely with: Reduces therapeutic effect of the following drugs:
Enhances therapeutic effect of Hydrocortisone: Hyaluronidase, Vaccines (Inactivated [complete all age-
Trastuzumab (neutropenic effect) appropriate vaccinations at least 2 weeks prior to
starting Dexamethasone; if vaccinated during
Enhances therapeutic effect of the following drugs: Dexamethasone therapy, revaccinate at least 3 months
Warfarin (anticoagulant effect) after discontinuation]), Vaccines (Live)

Increases risk of adverse or toxic effects of Hydrocortisone: Reduces absorption of Calcium Salts
Denosumab (serious infections), Salicylates (GI
ulceration and bleeding) Unknown impact on the therapeutic effect of Budesonide EC
Tablets (could dissolve prematurely if given with drugs
Increases risk of adverse or toxic effects of the following that lower gastric acid)
drugs:
Acetylcholinesterase Inhibitors (increased muscular Administration: Give directly or dilute in normal saline or
weakness), Amphotericin B, Thiazide Diuretics, Loop D5W. Administer within 24 hours after diluting.
Diuretics (hypokalemic effect), Androgens (fluid-
retaining effect), COX-2 Inhibitors e.g. Celecoxib, See General Information on Corticosteroids for Systemic
Deferasirox (GI ulceration or irritation; GI bleeding), Use – Glucocorticoids listed under Chapter 6: Systemic
NSAID (Non-selective), Quinolone Antibiotics (tendonitis; Hormonal Preparations for further information.
tendon rupture)
Pregnancy Category: C; D in the 1st trimester
Reduces absorption of Hydrocortisone:
Bile Acid Sequestrants ATC Code: H02AB09

Reduces therapeutic effect of the following drugs:

Antidiabetic Agents, Calcitriol, Corticorelin (blunts
plasma ACTH response to Corticorelin), Urea Cycle
Disorder Agents (increases protein catabolism and
plasma ammonia concentrations, increasing doses of
Urea Cycle Disorder Agents needed to maintain
concentrations in target range)

Reduces diagnostic effect of Coccidioides immitis Skin Test

Avoid concomitant use with:

Decreases bioavailability of Hydrocortisone:
Antacids [separate doses by at least 2 hours]

Increases risk of adverse or toxic effects of Hydrocortisone:

Nondepolarazing Neuromuscular-Blocking Agents,
(increased muscle weakness, possibly progressing to
polyneuropathies and myopathies), Pimecrolimus,
Tacrolimus (Topical)

192
SYSTEMIC HORMONAL PREPARATIONS, EXCLUDING SEX HORMONES AND INSULINS

Severe persistent asthma or long-term control, by mouth,

Rx METHYLPREDNISOLONE ADULT and CHILD ≥12 years, 6–48 mg once daily or
every other day as needed for asthma control; CHILD
Oral: 4 mg and 16 mg tablet <12 years, 0.2–1.6 mg/kg once daily or every other day
Inj.: 500 mg lyophilized powder (as sodium succinate), vial as needed for asthma control (maximum dose, 48 mg).
(IM, IV) For acute gout, by IM injection, ADULT, 4–120 mg.
1 g lyophilized powder (as sodium succinate), vial (IM, For dermatomyositis or polymyositis, by IV injection, ADULT,
IV) as sodium succinate, 1 g daily for 3–5 days for severe
125 mg/mL powder (as sodium succinate), 2 mL vial muscle weakness, followed by conversion to oral
+ diluent vial (IM, IV, IV infusion) prednisone.
500 mg/7.7 mL powder (as sodium succinate), vial +
diluent vial (IM, IV, IV infusion) Adverse Drug Reactions:
500 mg/8.0 mL powder (as sodium succinate), vial + Common: Arrhythmias, bradycardia, cardiac arrest,
diluent vial (IM, IV, IV infusion) cardiomegaly, circulatory collapse, congestive heart
1 g/16 mL powder (as sodium succinate), vial + failure, edema, hypertension, hypertrophic
diluent vial (IM, IV, IV infusion) cardiomyopathy (premature infants), myocardial rupture
40 mg solution (as sodium succinate), single-dose vial (post-MI), fat embolism, syncope, tachycardia,

H
(IV, IM) thromboembolism, vasculitis, delirium, depression,
emotional instability, euphoria, hallucinations,
A synthetic glucocorticoid used principally as an anti- headache, increased intracranial pressure, insomnia,
inflammatory or immunosuppressant agent. malaise, mood swings, nervousness, neuritis, personality
changes, psychic disorders, pseudotumor cerebri
Indications: For the suppression of inflammatory and (following discontinuation), seizure, vertigo, acne,
allergic disorders, rheumatic diseases, and various skin allergic dermatitis, alopecia, dry scaly skin, ecchymoses,
disorders; emergency management of acute idiopathic edema, erythema, hyperpigmentation or
thrombocytopenic purpura (ITP); management of the hypopigmentation, rash, hirsutism, hypertrichosis,
chronic form of ITP impaired wound healing, petechiae, skin atrophy, sterile
abscess, impaired skin test reaction, striae, urticaria,
Contraindications: Systemic fungal infection; formulations adrenal suppression, amenorrhea, increased
containing benzyl alcohol preservative are carbohydrate intolerance, Cushing's syndrome, diabetes
contraindicated in premature infants; IM administration mellitus, fluid retention, glucose intolerance, growth
in idiopathic thrombocytopenic purpura; intrathecal suppression (children), hyperglycemia, hyperlipidemia,
administration hypokalemia, hypokalemic alkalosis, menstrual
irregularities, negative nitrogen balance, pituitary-
Dose: adrenal axis suppression, protein catabolism, sodium
Anti-inflammatory or immunosuppressive, and water retention, abdominal distention, increased
by mouth, ADULT, initially mg daily in 1–4 divided doses, appetite, GI hemorrhage, GI perforation, nausea,
followed by a gradual reduction in dose to the lowest pancreatitis, peptic ulcer, perforation of the small and
effective dose; large intestine, ulcerative esophagitis, vomiting, weight
by IM injection, ADULT, as sodium succinate, 10–80 mg gain, leukocytosis (transient); hepatomegaly,
once daily; thrombophlebitis, arthralgia, arthropathy, aseptic
by IM injection, ADULT, as acetate, 10–80 mg every 1–2 necrosis (femoral and humoral heads), fractures, muscle
weeks; mass loss, muscle weakness, myopathy (in conjunction
by IV injection, ADULT, as sodium succinate, 10 to 40 mg with neuromuscular disease or neuromuscular-blocking
over a period of several minutes and repeated IV or IM at agents), neuropathy, osteoporosis, paresthesia, tendon
intervals depending on the clinical response; when high rupture, vertebral compression fractures, weakness,
doses are required, a 30 mg/kg dose over a period of at cataracts, glaucoma, glycosuria, pulmonary edema,
least 30 minutes may be given and may be repeated abnormal fat disposition, anaphylactoid reaction,
every 4–6 hours for 48 hours; angioedema, avascular necrosis, anaphylaxis, increased
by mouth or by IM or IV injection, CHILD, as sodium intraocular pressure, diaphoresis, hiccups,
succinate, 0.5–1.7 mg/kg daily or 5–25 mg/m2 daily in hypersensitivity reactions, infections, exophthalmoses,
divided doses every 6–12 hours (“pulse” therapy may secondary malignancy
also be given at 15–30 mg/kg per dose for at least 30 Rare: Venous thrombosis
minutes given once daily for 3 days).
Allergic condition, by mouth, ADULT Drug Interactions:
Asthma exacerbations, including status asthmaticus, Monitor closely with:
emergency medical care or hospital doses, by mouth or Enhances therapeutic effect of Methylprednisolone:
IV injection, ADULT, 32–64 mg daily in 1–2 divided doses Trastuzumab (neutropenic effect)
until peak expiratory flow is 70% of predicted or personal
best; CHILD ≥12 years, 32–48 mg/kg daily in 2 divided Enhances therapeutic effect of Warfarin (anticoagulant
doses until symptoms resolve and peak expiratory flow is effect)
80% of predicted or personal best; CHILD <12 years,
0.8–1.6 mg/kg daily in 2 divided doses (maximum, 60 Increases risk of adverse or toxic effects of
mg daily), until peak expiratory flow is 80% of predicted Methylprednisolone:
or personal best. Denosumab (serious infections), Salicylates (GI
ulceration and bleeding)

193
 SYSTEMIC HORMONAL PREPARATIONS, EXCLUDING SEX HORMONES AND INSULINS

Increases risk of adverse or toxic effects of the following

drugs: Rx PREDNISOLONE
Acetylcholinesterase Inhibitors (increased muscular
weakness), Amphotericin B (hypokalemic effect), Oral: 15 mg/5 mL syrup (as sodium phosphate), 60 mL
Androgens (fluid-retaining effect), COX-2 Inhibitor,
Deferasirox (GI ulceration or irritation; GI bleeding), Loop A synthetic glucocorticoid, which can decrease
Diuretics (hypokalemic effect), NSAIDs (Non-selective), inflammation by suppressing migration of
Quinolone Antibiotics (tendonitis; tendon rupture), polymorphonuclear leukocytes and by the reversal of
Thiazide Diuretics (hypokalemic effect) increased capillary permeability. It also suppresses the
immune system by reducing activity and volume of the
Reduces absorption of Methylprednisolone: lymphatic system.
Bile Acid Sequestrants
Indications: Relief of severe asthma; suppression of
Reduces diagnostic effect of Coccidioides immitis Skin Test inflammatory and allergic disorder

Reduces therapeutic effect of the following drugs: Contraindications: Acute superficial herpes simplex
Antidiabetic Agents, Calcitriol (Systemic), Corticorelin keratitis; live or attenuated virus vaccines; systemic
H

(blunts plasma ACTH response to Corticorelin), Urea fungal infections; varicella

Cycle Disorder Agents (increases protein catabolism and
plasma ammonia concentrations, increasing doses of Dose:
Urea Cycle Disorder Agents needed to maintain NOTE: Asthma Exacerbations. For the short course
concentrations in target range) outpatient “burst” type, continue burst until symptoms
resolve and the peak expiratory flow is at least 80% of
Avoid concomitant use with: personal best.
Decreases bioavailability of Methylprednisolone:
Antacids [separate doses by at least 2 hours] Asthma exacerbations, by mouth, ADULT and CHILD ≥12
years, dose will depend on the type of treatment:
Increases risk of adverse or toxic effects of
Methylprednisolone: Type of
Neuromuscular-blocking agents [Non-depolarizing Guideline Dose
Treatment
(increased muscle weakness, possibly progressing to Global 1mg/kg daily as a
polyneuropathies and myopathies)], Pimecrolimus, Management
Initiative for single daily dose
Tacrolimus in primary
Asthma usually given for 5–
care or acute
(GINA) 7 days (maximum,
Increases risk of adverse or toxic effects of the following care facility
2015 50 mg daily).
drugs: 40–80 mg daily in
Leflunomide (hematologic toxicity such as pancytopenia, Asthma a single dose or in
agranulocytosis, and/or thrombocytopenia), Tofacitinib exacerbation 2 divided doses
(immunosuppressive effect), Vaccines (Live) (emergency until peak
care or expiratory flow is
Increases serum concentration of Methylprednisolone: hospital 70% of the
Mifepristone National
doses) predicted or
Asthma personal best.
Reduces therapeutic effect of Methylprednisolone: Education
Short course 40–60 mg daily in
Mifepristone and
outpatient a single dose or in
Prevention
“burst” (acute 2 divided doses for
Reduces therapeutic effect of the following drugs: Program
asthma) 5 to 10 days.
Aldesleukin (antineoplastic effect), BCG (Intravesical), (NAEPP)
7.5–60 mg daily
Hyaluronidase, Vaccines (Inactivated [complete all age- 2007
given as a single
appropriate vaccinations at least 2 weeks prior to
dose in the
starting Dexamethasone; if vaccinated during Long-term
morning or every
Dexamethasone therapy, revaccinate at least 3 months treatment
other day as
after discontinuation]), Vaccines (Live)
needed for control
of asthma.
Unknown impact on the therapeutic effect of Budesonide EC
Tablets (could dissolve prematurely if given with drugs
that lower gastric acid) Asthma exacerbations, by mouth, CHILD <12 YEARS, dose
will depend on the age of the child,
See General Information on Corticosteroids for Systemic Based on the Global Initiative for Asthma (GINA)
Use – Glucocorticoids listed under Chapter 6: Systemic 2015:
Hormonal Preparations for further information. Age Maximum Dose
Dose
(Years) (mg daily)
Pregnancy Category: C 1–2 mg/kg daily for up
<3 20
to 5 days
ATC Code: H02AB04 1–2 mg/kg daily for up
3–5 30
to 5 days

194
SYSTEMIC HORMONAL PREPARATIONS, EXCLUDING SEX HORMONES AND INSULINS

1–2 mg/kg daily weakness, cataracts, exophthalmus, eyelid edema,

6–11 usually given for 3–5 40 glaucoma, increased intraocular pressure, epistaxis,
days increased diaphoresis, irritation, impaired wound healing
Rare: Venous thrombosis
Based on the National Asthma Education and
Prevention Program (NAEPP) 2007 Guidelines: Drug Interactions:
Type of Monitor closely with:
Dose Enhances therapeutic effect of Prednisolone:
Treatment
Asthma Trastuzumab (neutropenic effect)
1–2 mg/kg daily in 2 divided
exacerbation
doses (maximum, 60 mg daily) Enhances therapeutic effect of Warfarin (anticoagulant
(emergency
until peak expiratory flow is 70% effect)
care or hospital
of the predicted or personal best.
doses)
Short course 1–2 mg/kg daily as a single dose Increases risk of adverse or toxic effects of Prednisolone:
outpatient or in 2 divided doses for 3–10 Denosumab (serious infections), Salicylates (GI
“burst” (acute days (maximum dose, 60 mg ulceration and bleeding)
asthma) daily).

H
0.25–2 mg/kg daily as a single Increases risk of adverse or toxic effects of the following
dose in the morning or every drugs:
Long-term Acetylcholinesterase Inhibitors e.g. Neostigmine,
other day as needed for control of
treatment Edrophonium (increased muscular weakness),
asthma (maximum dose, 60 mg
daily). Amphotericin B (hypokalemic effect), Androgens e.g.
Testosterone (fluid-retaining effect), COX-2 Inhibitors,
Deferasirox (GI ulceration or irritation; GI bleeding), Loop
Rheumatoid arthritis, by mouth, ADULT, initially 5–7.5 mg
Diuretics, Thiazide Diuretics (hypokalemic effect),
daily, then adjust dose as needed.
Multiple sclerosis, by mouth, ADULT, 200 mg daily for 1 NSAIDs (Non-selective), Quinolone Antibiotics e.g.
week followed by 80 mg every other day for 1 month. Levofloxacin (tendonitis; tendon rupture)
Anti-inflammatory or immunosuppressant, by mouth,
ADULT, 5–60 mg in 2–4 divided doses (maintenance, Reduces absorption of Prednisolone:
2.5–15 mg daily); CHILD, 1–2 mg/kg once daily Bile Acid Sequestrants e.g. Cholestryramine
(maximum, 60 mg daily).
Reduces diagnostic effect of Coccidioides immitis Skin Test
Nephrotic syndrome, by mouth, CHILD, for the first 3
episodes, initially 2 mg/kg daily or 60 mg/m2 daily
(maximum, 80 mg daily) in 3–4 divided doses until urine Reduces therapeutic effect of the following drugs:
is protein-free for 3 consecutive days (maximum of 28 Antidiabetic Agents, Calcitriol (Systemic), Corticorelin
days), followed by 1–1.5 mg/kg per dose or 40 mg/m2 (blunts plasma ACTH response to Corticorelin), Urea
per dose given every other day for 4 weeks; for frequent Cycle Disorder Agents (increases protein catabolism and
relapses, 0.5–1 mg/kg per dose as maintenance every plasma ammonia concentrations, increasing doses of
Urea Cycle Disorder Agents needed to maintain
other day for 3–6 months.
concentrations in target range)
Dose Adjustment:
Renal Impairment: Avoid concomitant use with:
For patients undergoing hemodialysis, administer Decreases bioavailability of Prednisolone:
appropriate dose post-hemodialysis since the drug is Antacids [separate doses by at least 2 hours]
slightly dialyzable.
Increases risk of adverse or toxic effects of Prednisolone:
Precautions: Nondepolarizing Neuromuscular-blocking Agents
Cataracts; Glaucoma (increased muscle weakness, possibly progressing to
polyneuropathies and myopathies), Pimecrolimus,
Adverse Drug Reactions: Tacrolimus (Topical)
Common: Cardiomyopathy, CHF, edema (including facial),
hypertension, headache, insomnia, malaise, Increases risk of adverse or toxic effects of the following
nervousness, pseudotumor cerebri, psychic disorders, drugs:
Leflunomide (hematologic toxicity such as pancytopenia,
seizure, vertigo, bruising, facial erythema, hirsutism,
petechiae, skin test reaction suppression, thin fragile agranulocytosis, and/or thrombocytopenia), Tofacitinib
skin, urticaria, decreased carbohydrate tolerance, (immunosuppressive effect), Vaccines (Live)
Cushing's syndrome, growth suppression,
hyperglycemia, diabetes mellitus, hypernatremia, Increases serum concentration of Prednisolone:
hypokalemia, hypokalemic alkalosis, menstrual Mifepristone, Ritonavir
irregularities, negative nitrogen balance, pituitary-
Reduces therapeutic effect of Prednisolone:
adrenal axis suppression, abdominal distention,
increased appetite, indigestion, nausea, pancreatitis, Mifepristone
peptic ulcer, ulcerative esophagitis, weight gain,
arthralgia, aseptic necrosis (humeral or femoral heads), Reduces therapeutic effect of the following drugs:
fractures, tendon rupture, decreased muscle mass, Aldesleukin (antineoplastic effect), BCG (Intravesical),
muscle weakness, osteoporosis, steroid myopathy, Hyaluronidase, Vaccines (Inactivated [complete all age-

195
 SYSTEMIC HORMONAL PREPARATIONS, EXCLUDING SEX HORMONES AND INSULINS

appropriate vaccinations at least 2 weeks prior to shortest duration of time to minimize the adverse events.
starting Dexamethasone; if vaccinated during Consider alternate day therapy for long-term therapy to
Dexamethasone therapy, revaccinate at least 3 months reduce adverse effects.
after discontinuation]), Vaccines (Live) Dosage for infants and children should be based on severity
of the disease and response of the patient rather than
Unknown impact on the therapeutic effect of Budesonide EC age, weight, or body surface area.
Tablets (could dissolve prematurely if given with drugs Gradually taper dose prior to discontinuing therapy,
that lower gastric acid) especially long-term therapy. Abrupt withdrawal may
precipitate acute adrenal insufficiency.
Administration: Should be taken after meals or with food or Individualize tapering of dose based on the disease and
milk to decrease GI effects. Increased dietary intake of severity of condition. For example, the dose may be
pyridoxine, vitamins A, B6, C, D, folate, calcium, zinc, and tapered off by 10–20% every 3–5 days until a dose of 10
phosphorus is also recommended. mg daily is reached. A slower weekly tapering is
recommended.
See General Information on Corticosteroids for Systemic Autoimmune or inflammatory disease, by mouth, ADULT,
Use – Glucocorticoids listed under Chapter 6: Systemic initially 5–60 mg once daily depending on the disease
Hormonal Preparations for further information. and its severity, adjust dose according to response and
H

recommended guidelines; CHILD, initially 1–2 mg/kg

Pregnancy Category: C or D (product-specific) once daily (usual maximum dose, 60 mg) with dose
adjustments based on guidelines.
ATC Code: H02AB06 Croup, by mouth, CHILD, 1 mg/kg; repeat dose after 12–24
hours if necessary.
Pneumocystis carinii pneumonia, by mouth, ADULT, begin
within 72 hours of PCP therapy: 40 mg twice daily for 5
Rx PREDNISONE days, followed by 20 mg once daily for 11 days or until
antimicrobial regimen is completed; CHILD, 1 mg/kg
Oral: 5 mg, 10 mg, and 20 mg tablet twice daily for 5 days, followed by 0.5–1 mg/kg twice
10 mg/5 mL suspension, 60 mL daily for 5 days, followed by 0.5 mg/kg once daily for 11–
21 days.
A corticosteroid with glucocorticoid and anti-inflammatory Acute asthma, by mouth, ADULT, 40–60 mg daily for 3–10
effects that can suppress adrenal function at high doses. days as a single dose or in 2 divided doses; CHILD <12
It is rapidly converted to the prednisolone in the body. Its years, 1–2 mg/kg daily for 3–10 days, with a maximum
antitumor effects may be related to the inhibition of of 60 mg daily.
glucose transport, phosphorylation, or induction of cell Rheumatoid arthritis, by mouth, ADULT, ≤10 mg daily
death in immature lymphocytes. Its antiemetic effects [NOTE: Once the condition has stabilized, reduce to the
are thought to occur due to blockade of cerebral minimum required to maintain control of disorder.]
innervations of the emetic center by inhibiting Acute gout, by mouth, ADULT, initially at least 0.5 mg/kg for
prostaglandin synthesis. 5–10 days.
Dermatomyositis/polymyositis, by mouth, ADULT, 1 mg/kg
Indications: Management of autoimmune disease; croup; daily (range of 0.5–1.5 mg/kg daily), often in conjunction
short-term suppression of inflammation in allergic with steroid-sparing therapies.
disorders; Pneumocystis carinii pneumonia; atopic Immune thrombocytopenia, by mouth, ADULT, 1–2 mg/kg
dermatitis; dermatomyositis or polymyositis; nephrotic daily.
syndrome (idiopathic or related to lupus erythematosus); Nephrotic syndrome, by mouth, CHILD, initially 2 mg/kg
immune-mediated thrombocytopenia; inflammatory daily or 60 mg/m2 daily in 1–3 divided doses, with a
bowel disease; eye inflammation; rheumatic disease; maximum of 80 mg daily until urine is protein free for 4–
immunosuppression; acute severe asthma (reliever); 6 weeks; followed by a maintenance dose of 2 mg/kgor
severe persistent asthma not responding to high-dose 40 mg/m2every other day in the morning; discontinue
inhaled steroids, long-acting agonists, and after 4–6 weeks by gradual tapering.
methylxanthines (controller); adrenal insufficiency Lupus nephritis, induction, by mouth, ADULT, the following
doses apply:
Contraindications: Untreated systemic fungal infections;
administration of live attenuated virus vaccines with Lupus
immunosuppressive doses of prednisone Nephritis Dose
Class
Dose: 0.5–1 mg/kg daily (after glucocorticoid pulse)
NOTE: No definitive treatment guidelines exist. Dosing is III–IV
tapered, after a few weeks, to the lowest
dependent on institution protocols and individual effective dose, combined with an
response. immunosuppressive agent

0.5 mg/kg daily for 6 months combined with

General dosing range, by mouth, initially 5–60 mg daily: mycophenolate mofetil and, if no improvement is
V seen after 6 months, use 0.5–1 mg/kg daily
RECOMMENDATIONS ON APPROPRIATE USE: (after glucocorticoid pulse) for an additional 6
Prior to use, dose and duration of treatment should be months combined with cyclophosphamide
based on the risk versus benefit for each individual
patient. Generally, use the smallest effective dose for the

196
SYSTEMIC HORMONAL PREPARATIONS, EXCLUDING SEX HORMONES AND INSULINS

Dose Adjustment: Dose:

Renal Impairment: Chronic hypothyroidism, by mouth, CHILD, initially 25
For mild-to-moderate renal impairment, dose reduction is micrograms daily, adjust by 25 micrograms every 2–4
warranted. weeks.
For severe impairment, refer patient to a specialist. Congenital hypothyroidism, juvenile myxedema, by mouth,
NEONATE ≤1 month, initially 5–10 micrograms/kg daily,
Adverse Drug Reactions: adjust by 25 micrograms every 2–4 weeks until mild
Common: Acne, adrenal suppression, amenorrhea, toxic symptoms appear, then reduce dose slightly;
bruising, delayed wound healing, dyslipidemia, INFANT and CHILD >1 month, 5 micrograms/kg daily,
dyspepsia, edema, fat redistribution, fractures, growth adjust by 25 micrograms every 2–4 weeks until mild
retardation, hirsutism, hyperglycemia, hiccups, toxic symptoms appear, then reduce dose slightly.
hypertension, hypokalemia, increased appetite, Severe hypothyroidism, by mouth, ADULT, initially 12.5–25
increased susceptibility to infections, malaise, masking micrograms daily, adjust by 25 micrograms every 2–4
of signs of infection, muscle weakness and wasting, weeks, as appropriate; CHILD, initially 25 micrograms
myopathy, nausea, osteoporosis, psychiatric effects, skin daily, adjust by 25 micrograms every 2–4 weeks
atrophy, sodium and water retention, weight gain Subclinical hypothyroidism, if treated, by mouth, ADULT, 1
Less Common: Glaucoma, ocular hypertension, microgram/kg daily.

H
Osteonecrosis or aseptic necrosis (femoral and humeral Hypothyroidism, by mouth, ADULT, usually 1.6–1.7
heads) micrograms/kg daily, may give full dose right away if
Rare: Anaphylactoid reaction, chorioretinopathy (central), without contraindications; for most, initially 50–100
euphoria, hypersensitivity reactions, hypomania, peptic micrograms daily before breakfast (25–50 micrograms
ulceration, tendon rupture for patients >50 years), increase by 25–50 micrograms
every 3 to 4 weeks until normal metabolism is
Drug Interactions: maintained (maintenance dose, 100–200 micrograms
NOTE: Prednisone is a substrate for CYP3A-based daily);
interaction. CHILD, dose would depend on the age:
Age Daily Dose (microgram/kg)
Please see Drug Interactions under Prednisolone
1–3
10–15
months*
Administration: Best taken with food. Taking it early in the
morning reduces possible side effects. 3–6 months 8–10
6–12
6–8
See General Information on Corticosteroids for Systemic months
Use – Glucocorticoids listed under Chapter 6: Systemic 1–5 years 5–6
Hormonal Preparations for further information. 6–12 years 4–5
>12 years 2–3
Pregnancy Category: C; D in the 1st trimester [NOTE: For infants 1-3 months at risk for developing
cardiac failure, administer a lower starting dose of 25
ATC Code: H02AB07 micrograms daily. If the initial serum thyroxine is
below 5 micrograms/dL, begin treatment at a higher
dose of 50 micrograms daily (12–17 micrograms/kg
daily).];
THYROID THERAPY
in cardiac disease, initially 25 micrograms daily or 50
THYROID PREPARATIONS micrograms on alternate days, adjusted by 25
micrograms every 4 weeks);
dosing for specific populations:
Rx LEVOTHYROXINE
Population Dose
Oral: 50, 100, and 150 micrograms tablet (as Adults <50 years;
1.6–1.7
sodium/anhydrous sodium) children in whom
micrograms/kg daily;
growth and puberty
usually ≤200
A synthetic form of thyroxine (T4), a thyroid hormone are complete; adults
micrograms daily;
involved in normal metabolism, growth, and >50 years recently
titrate dose every 6
development. It promotes gluconeogenesis, increase treated for
weeks; may give full
utilization of glycogen stores, stimulate synthesis of hyperthyroidism or
dose right away if
proteins, and increase basal metabolic rate. who have been
without
hypothyroid for only a
contraindications.
Indications: Management of hypothyroidism of any etiology; few months
TSH suppression Initially 25–50
Adults <50 years with micrograms daily,
Contraindications: Hyperthyroidism from any cause; acute or without cardiac adjust by 12.5–25
MI; untreated subclinical (suppressed serum TSH level disease microgram
with normal T3 and T4 levels); overt thyrotoxicosis of any increments at 6– to
etiology; uncorrected adrenal insufficiency

197
 SYSTEMIC HORMONAL PREPARATIONS, EXCLUDING SEX HORMONES AND INSULINS

8-week intervals, as Myasthenic syndrome;

needed. Osteoporosis;
Initially 12.5–25 Benign thyroid nodules (treatment should never be fully
micrograms daily, repressive;
then adjusted by Avoid use in postmenopausal women, men more than 60
Adults >50 years with years of age, patients with cardiovascular disease,
12.5–25 microgram
cardiac disease osteoporosis, or systemic illness, and patients with large
increments at 4- to
6-week intervals, as thyroid nodules or long-standing goiters, or low-normal
needed. TSH levels);
Elderly;
TSH suppression in well-differentiated thyroid cancer, Pregnancy (monitor thyroid function each trimester;
papillary and follicular, by mouth, ADULT, dose is highly reassess thyroxine maintenance dosage 6–8 weeks
individualized; in general, more than 2 micrograms/kg post-partum);
daily may be needed to suppress TSH to <0.1 mIU/L in Lactation (amount is too small to affect tests for neonatal
intermediate- to high-risk tumors; low-risk tumors may be hypothyroidism).
maintained at 0.1–0.5 mIU/L.
TSH suppression in benign nodules and nontoxic Adverse Drug Reactions:
H

multinodular goiter, by mouth, ADULT, initially 1.7–2 Common: Anginal pain, excitability, headache, flushing,
micrograms/kg daily may be used with a target TSH of muscular weakness, restlessness, sweating, vomiting,
0.1–0.3 mIU/L [NOTE: Routine use is not recommended. weight loss
Avoid if TSH is already suppressed]. Less Common: Cramps, diarrhea, nervousness, insomnia,
palpitations, tachycardia
Dose Adjustment: Rare: Arrhythmias, decreased bone density (women),
Geriatric: papilledema, seizures, tremors
Introduce gradually to avoid sudden increase in metabolic
demands. Maintenance replacement dose may be less Drug Interactions:
than in younger people. Monitor closely with:
The initial dose should not exceed 25–50 micrograms daily. Decreases metabolism of Theophylline (hypothyroidism)
Maintain at intervals of at least 4 weeks.
Enhances therapeutic effect of the following drugs:
Cardiovascular disorders (angina, heart failure, myocardial Anticoagulants e.g. Warfarin, Tricyclic Antidepressants
infarction or insufficiency, hypertension): e.g. (stimulatory effect)
Lower initial doses. Smaller increments and longer intervals
between increases could be necessary. Full replacement Increases metabolism of Levothyroxine, increasing its
dose may not be appropriate. Use with caution and requirements in hypothyroidism:
reduce dose as needed. Phenobarbital, Phenytoin, Rifampicin

Long-standing Hypothyroidism: Increases risk of adverse or toxic effects of Levothyroxine:

Introduce gradually to avoid sudden increase in metabolic Piracetam (confusion, irritability, and sleep disorders)
demands. Maintenance replacement dose may be less
than in younger people. Increases risk of adverse or toxic effects of the following
drugs:
Precautions: Tricyclic Antidepressants (arrhythmogenic effect)
WARNING: Use with caution in patients with underlying
Reduces therapeutic effect of Levothyroxine:
coronary artery disease, previous MI, or acute coronary
syndromes and tachyarrhythmias. Selective Serotonin Reuptake Inhibitors

Thyroid supplements are ineffective and potentially toxic Avoid concomitant use with:
when used for the treatment of obesity or for weight Decreases serum concentration of Levothyroxine:
reduction, especially in euthyroid patients. High doses may Aluminum Hydroxide [administer at least 4 hours apart],
produce serious or even life-threatening toxic effects, Bile Acid Sequestrants [administer 4 hours prior to
particularly when used with some anorectic. Colesevelam; administer at least 1 hour before or 4–6
hours after Cholestyramine]
Cardiovascular disorders, including angina, heart failure, Decreases serum concentration of Levothyroxine:
myocardial infarction or insufficiency, and hypertension; Calcium Polystyrene Sulfonate [separate dosing or
Hypopituitarism or predisposition to adrenal insufficiency administer Calcium Polystyrene Sulfonate rectally],
(correct with a corticosteroid prior to treatment with Lanthanum [administer at least 2 hours apart],
levothyroxine to prevent precipitation of an acute adrenal Magnesium Salts [administer at least 4 hours apart],
crisis, e.g., panhypopituitarism); Multivitamins / Minerals (with ADEK, Folate, Iron)
Adrenal insufficiency (in uncorrected adrenal insufficiency, [administer at least 4 hours apart], Sevelamer, Sodium
glucocorticoid treatment should precede use of Polystyrene Sulfonate [separate dosing or administer
levothyroxine); Sodium Polystyrene Sulfonate rectally], Sucroferric
Myxedema; Oxyhydroxide
Diabetes insipidus or diabetes mellitus (may need to
increase dose of insulin or oral antidiabetic drug);

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SYSTEMIC HORMONAL PREPARATIONS, EXCLUDING SEX HORMONES AND INSULINS

Reduces absorption of Levothyroxine, reducing its Hypothyroidism;

therapeutic effect, resulting to hypothyroidism: Lupus-like syndrome;
Calcium Salts [administer at least 4 hours apart], Nephritis;
Ciprofloxacin, Ferrous Salts [administer at least 4 hours Interstitial pneumonitis; Vasculitis
apart], Orlistat, Raloxifene, Simethicone
Adverse Drug Reactions: Allergy, periarteritis, edema,
Reduces therapeutic effect of Sodium Iodide I 131 vasculitis (ANCA-positive, cutaneous, leukocytoclastic),
drowsiness, headache, drug fever, neuritis, paresthesia,
Administration: Should be taken in the morning on an empty vertigo, alopecia, dermal ulcer, erythema nodosum,
stomach, at least 30–90 minutes before food intake. exfoliative dermatitis, pruritus, skin pigmentation, skin
rash, Stevens-Johnson syndrome, toxic epidermal
The tablet may be crushed and suspended in 5 to 10 mL necrolysis, urticaria, ageusia, dysgeusia, nausea, salivary
water, however, this must be used immediately. gland disease, stomach pain, vomiting, agranulocytosis,
aplastic anemia, granulocytopenia,
Pregnancy Category: A hypoprothrombinemia, acute hepatic failure,
hemorrhage, leukopenia, lymphadenopathy,
ATC Code: H03AA01 thrombocytopenia, hepatitis, hepatotoxicity, jaundice,

H
arthralgia, lupus-like syndrome, splenomegaly, myalgia,
acute renal failure, glomerulonephritis, nephritis;
ANTITHYROID PREPARATIONS interstitial pneumonitis, pulmonary alveolar hemorrhage;
fever

Rx PROPYLTHIOURACIL Drug Interactions:

Avoid concomitant use with:
Increases risk of adverse or toxic effects of the following
Oral: 50 mg tablet drugs:
Clozapine (agranulocytosis), Dipyrone (agranulocytosis
An antithyroid agent derived from thiourea. It inhibits the and pancytopenia)
peripheral conversion of thyroxine to triiodothyronine in
the tissues. Reduces therapeutic effect of the following drugs:
BCG, Intravesical, Sodium Iodide I 131 [discontinue
Indication: Treatment of hyperthyroidism antithyroid therapy 3–4 days prior to sodium iodide I 131
administration], Vitamin K Antagonists [e.g. Warfarin
Contraindication: Breastfeeding patients (anticoagulant effect)]
Dose: Pregnancy Category: D
Hyperthyroidism, by mouth, ADULT, initially 300–400 mg
daily in 3 equally divided doses at 8-hour intervals; ATC Code: H03BA02
Severe hyperthyroidism and/or very large goiters, by mouth,
ADULT, 400 mg daily; some may require 600–900 mg
daily; maintenance dose is usually at 100–150 mg daily
SULFUR-CONTAINING IMIDAZOLE
in 3 equally divided doses; ADOLESCENT and CHILD >10
years, initially 150–300 mg daily in 3 equally divided DERIVATIVES
doses, then maintain at 50 mg twice daily when
euthyroid; CHILD 6–10 years, initially 50–150 mg daily
in 3 equally divided doses, then maintain at 50 mg twice
Rx METHIMAZOLE (THIAMAZOLE)
daily when euthyroid.
Oral: 5 mg and 10 mg tablet
Precautions:
WARNING: Severe liver injury and acute liver failure A thioamide used as an antithyroid agent that inhibits the
(sometimes fatal) were reported, requiring liver synthesis of thyroid hormones by blocking iodine
transplantation in some patients, including oxidation in the thyroid gland.
pregnant women. Reserve use of PTU for
patients who cannot tolerate methimazole or in Indications: For hyperthyroidism; for long-term use (1–2
whom radioactive iodine therapy or surgery are years) to induce remission in small goiters;
not appropriate. hyperthyroidism associated with Graves’ disease
Treatment of choice when antithyroid is
indicated during to or just prior to first trimester Contraindications: Previous agranulocytosis to
of pregnancy due to the risk of fetal methimazole; drug-induced nephritis or polyarteritis
abnormalities associated with the use of nodosa; liver disease; blood disorders, such as
methimazole. granulocytopenia and aplastic anemia

Bleeding; Bone marrow suppression (discontinue if Dose:

significant bone marrow suppression occurs, particularly Hyperthyroidism, by mouth, ADULT,
agranulocytosis or aplastic anemia); Mild hyperthyroidism, initially 15 mg daily in 3 divided
Dermatologic toxicity; doses, approximately every 8 hours;

199
 SYSTEMIC HORMONAL PREPARATIONS, EXCLUDING SEX HORMONES AND INSULINS

Moderately severe hyperthyroidism, 30–40 mg daily; Anticoagulants e.g. Warfarin

Severe hyperthyroidism, 60 mg daily;
Maintenance, 5–15 mg daily as a single dose, continue Increases risk of adverse or toxic effects of Methimazole:
for 12–18 months to induce remission, or for 6–12 Macrolide Antibiotics e.g. Azithromycin (QT-prolongation)
months to prepare patients for definitive therapy in the
form of surgery or radioactive iodine therapy; Avoid concomitant use with:
CHILD, initially 0.4 mg/kg daily in 3 divided doses, Increases risk of adverse or toxic effects of the following
maintenance: 0.2 mg/kg daily in 3 divided doses; drugs:
suggested dosing based on the age: Clozapine (agranulocytosis), Dipyrone (agranulocytosis and
pancytopenia)
Population Daily Dose (mg)
Infants 1.25 Increases serum concentration of Tizanidine [initiate
Children 1–5 years 2.5–5 Tizanidine at 2 mg and increase in 24 mg increments
Children 5–10 years 5–10 based on patient response]
Children and Reduces therapeutic effect of the following drugs:
10–20
Adolescents 10–18 years BCG (Intravesical), Sodium Iodide I 131 [discontinue
H

Methimazole 3–4 days before Sodium Iodide I 131

Dose Adjustment: administration], Vitamin K Antagonists e.g. Warfarin
Renal Impairment: (anticoagulant effect)
For mild-to-moderate renal impairment, dose reduction is
warranted Administration: May be taken with food or milk to reduce
For severe impairment, refer patient to a specialist. stomach upset.

Hypothyroidism: Pregnancy Category: D

Adjust dose to maintain euthyroid state. Monitor THS and
free T4 levels. ATC Code: H03BB02

Precautions:
Hypoprothrombinemia; IODINE THERAPY
Bone marrow suppression;
Bleeding;
Aplastic anemia; Rx IODINE
Thrombocytopenia;
Leukopenia;
Leukocytoclastic vasculitis and positive vasculitis Oral: aqueous iodine solution (Lugol's solution)
(discontinuation immediately if vasculitis develops 5% iodine, 10% potassium iodide (total iodine = 130
during therapy); mg/mL), 30 mL
Dermatologic toxicity (discontinue if exfoliative dermatitis
develops); An anti-hyperthyroid agent that acts by reducing of the
Urticaria; thyroid gland through various mechanisms, such as the
Infection (discontinue at signs of infections, e.g., fever, sore reduction of vascularity, a firming of the glandular tissue,
throat, mouth ulcer, and clinical evidence of and shrinkage of the size of individual cells.
neutropenia;
Hepatic necrosis (hepatitis, fever); Indication: Antidote to thyroid block following radiation
Encephalopathy (discontinue in the presence of hepatitis; emergency
transaminase >3 times upper limit of normal);
Lupus-like syndrome; Contraindications: Dermatitis herpetiformis;
Pregnancy (first trimester: can cause fetal harm; high risk of hypocomplementemic vasculitis, nodular thyroid
agranulocytosis if doses >40 mg/day). condition with heart disease

Adverse Drug Reactions: Dose:

Common: Pruritus, rash Antidote, by mouth, ADULT (including pregnant and lactating
Less Common: Abnormal loss of hair, arthralgia, edema, women), 130 mg once daily for 10–14 days or until risk
epigastric distress, headache, loss of taste, of exposure is gone; CHILD, dose should continue for
lymphadenopathy, neuritis, paresthesia, pigmentation, 10–14 days or until risk of exposure has passed; dose
pruritus, sialadenopathy, urticaria, myalgia, nausea, based on age:
vertigo, vomiting Dose (mg
Population
Rare: Agranulocytosis, alopecia, aplastic anemia, drug once daily)
fever, granulocytopenia, hypoprothrombinemia, 1 month and below 16.25
hepatitis, jaundice, myopathy, nephritis, lupus-like >1 month – 3 years 32.5
syndrome, periarteritis, thrombocytopenia >3 years – 12 years 65
Drug Interactions: >12 years and adolescent
65
Monitor closely with: weighing less than 68 kg
Enhances therapeutic effect of Methimazole:

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SYSTEMIC HORMONAL PREPARATIONS, EXCLUDING SEX HORMONES AND INSULINS

>12 years and adolescent

weighing at least 68 kg
130 Rx PROPRANOLOL

Precautions: Oral: 10 mg and 40 mg tablet (as hydrochloride)

Allergy to iodine or potassium iodide;
Skin reactions; A non-selective beta-adrenergic blocker that competitively
Hypothyroidism; blocks response to beta adrenergic stimulation.
Adrenal insufficiency, including Addison disease; Indications for thyroid diseases are considered as off-
Bronchitis; label use.
Cardiac disease;
Myotonia congenital; Indications: Management of thyroid storm, thyrotoxicosis
Renal impairment tuberculosis.
Contraindications: Uncompensated congestive heart failure
Adverse Drug Reactions: Cardiac arrhythmia, confusion, (unless the failure is due to tachyarrhythmias being
fatigue, fever, numbness, tingling sensation, skin rash, treated with propranolol); cardiogenic shock; severe
urticaria, hyperthyroidism (prolonged use), sinus bradycardia; sick sinus syndrome or heart block
hypothyroidism (prolonged use), goiter, myxedema, greater than first degree (except in the presence of a

H
diarrhea, enlargement of salivary glands, gastric functioning artificial pacemaker); bronchial asthma
distress, GI hemorrhage, metallic taste, nausea,
stomach pain, vomiting, lymphedema, thyroid adenoma, Dose:
weakness, dyspnea, hypersensitivity reaction Thyroid storm, by mouth, ADULT, 60–80 mg every 4 hours.
(angioedema, cutaneous and mucosal hemorrhage, Thyrotoxicosis, by mouth, ADULT, 10–40 mg/dose every 6–
serum sickness-like symptoms), wheezing, iodine 8 hours; ADOLESCENT and NEONATE, 10–40 mg per
poisoning (prolonged use, high doses) dose every 6 hours.

Drug Interactions: Administration: To be taken on an empty stomach.

Monitor closely with:
Increases risk of adverse or toxic effects of the following Do NOT withdraw abruptly, particularly in patients with CAD.
drugs: Gradually taper dose to avoid acute tachycardia,
ACE Inhibitors e.g., Enalapril, Aliskiren hypertension, and/or ischemia.
Angiotensin II Receptor Blockers e.g. Losartan, Heparin
(hyperkalemic effect) See individual entry for Propranolol under Cardiac Therapy
– Antiarrhythmics, Class II Antiarrhythmics in Chapter 3:
Increases risk of adverse or toxic effects of the following Cardiovascular System for further information.
drugs:
Lithium (hypothyroid effect), Nicorandil (hyperkalemic Pregnancy Category: C
effect)
ATC Code: Not available
Avoid concomitant use with:
Increases risk of adverse or toxic effects of the following
drugs:
Eplerenone (hyperkalemic effect), Potassium-sparing
Diuretics (hyperkalemic effect)

Reduces therapeutic effect of the following drugs:

Sodium Iodide I 131 [discontinue Iodine 3 to 4 days prior
to Sodium Iodide I 131 administration], Vitamin K
Antagonists e.g. Warfarin (anticoagulant effect)

Administration: Administer with food or milk to decrease

gastric irritation. Dilute in a glassful of water, fruit juice,
or milk.

Pregnancy Category: D

ATC Code: H03CA

201
 ANTI-INFECTIVES FOR SYSTEMIC USE

against P aeruginosa, Enterobacteriaceae, S. aureus,

ANTI-INFECTIVES FOR SYSTEMIC USE and S. pneumoniae. It is highly active against
Haemophilus and Neisseria sp.

ANTIBACTERIALS FOR SYSTEMIC USE Monobactams

They have a narrow and characteristic spectrum of activity
Antibacterial Drug Classes which acts by inhibiting bacterial cell wall synthesis due
to its high affinity for penicillin-binding protein 3 (PBP-3)
BETA- LACTAM, PENICILLINS of gram-negative bacteria. It is also active against most
Enterobacteriaceae (including E. coli, Citrobacter,
Penicillins with extended spectrum Enterobacter, Klebsiella, Proteus, Providencia,
The extended-spectrum penicillins are a group of semi- Salmonella, Serratia, Shigella, Yersinia spp. and
synthetic penicillin antibiotics that have a wider Morganella morganii).
spectrum of activity than natural penicillins,
penicillinase-resistant penicillins, and aminopenicillins. Carbapenems
They are more active against gram-negative bacteria Carbapenems have an extremely broad spectrum of
because they are more resistant to inactivation by antimicrobial activity and are highly resistant to a variety of
extended-spectrum β-lactamases and/or because they β-lactamases. They bind to penicillin-binding proteins and
more readily penetrate the outer membranes of these inhibit bacterial cell wall synthesis.
gram-negative organisms.
J

Tetracyclines
Beta-lactamase sensitive penicillins Tetracycline are broad-spectrum antibiotics that inhibit
This class of antibiotics binds to penicillin binding proteins bacteriostatic action by reversibly binding to the 30S
that catalyzes the synthesis of peptidoglycan and this subunits of the ribosome, thus preventing protein
leads to the interruption of cell wall synthesis, leading to synthesis and arresting cell growth. They are active
bacterial cell growth inhibition and cell lysis against many gram-positive and gram-negative bacteria
Beta-lactamase resistant penicillins including Chlamydiaceae, Mycoplasma spp., Rickettsia
These semisynthetic penicillins are indicated for infection by spp., spirochetes, and some protozoa.
β-lactamase-producing staphylococci, although
penicillin-susceptible strains of streptococci and Aminoglycosides
pneumococci are also susceptible to these agents. Aminoglycosides are used most widely in combination with
Listeria monocytogenes, Enterococci, and methicillin- a β-lactam antibiotic in serious infections with gram-
resistant strains of Staphylococci are resistant. negative bacteria, in combination with vancomycin or a
Beta-lactamase inhibitors β-lactam antibiotic for gram-positive endocarditis, and
Commonly used for empirical therapy against a large for treatment of tuberculosis. They are rapid bactericidal
number of pathogens such as treatments for aerobic and irreversible inhibitors of protein synthesis by binding on
anaerobic infections. These class of drugs are potent the 30S ribosome.
inhibitors of beta-lactamases and protects hydrolysable
penicillins from inactivation. Lincosamides
Beta-lactamase inhibitors in combination Lincosamide is an antibiotic that binds to the 50S ribosomal
The β-lactamase inhibitors bind to β-lactamases and subunit at a site closely related to that at which
inactivate them. The β-lactamase inhibitors lack direct macrolides act resulting in bacteriostatic inhibition of
antimicrobial activity but when combined with an microbial protein synthesis.
antibiotic, they extend the spectrum of activity and
increase stability against β-lactamases. Macrolides
Macrolides are bacteriostatic antibiotics with a broad
OTHER BETA-LACTAM ANTIBACTERIALS spectrum of activity against many gram-positive bacteria.
The antimicrobial activity of macrolides is exhibited by
Cephalosphorins (1st, 2nd, 3rd, 4th) the inhibition of bacterial protein biosynthesis after
1st: First-generation cephalosporins include cefazolin, binding of the macrolide, selectively and reversibly, to
cefadroxil, cephalexin, cephalothin, cephapirin, and the 50S ribosomal subunit.
cephradine. These drugs are very active against gram-
positive cocci. Chloramphenicol
2 : Second-generation cephalosporins include cefaclor,
nd Chloramphenicol is a potent inhibitor of microbial protein
cefamandole, cefonicid, cefuroxime, cefprozil, synthesis by reversibly binding to the 50S subunit of the
loracarbef, and ceforanide; and the structurally related bacterial ribosome, thus preventing peptide bond
cephamycins cefoxitin, cefmetazole, and cefotetan, formation by peptidyl transferase. It has both
which have activity against anaerobes. bacteriostatic and bactericidal action against H.
3 : Third-generation cephaosphorins include cefoperazone,
rd influenzae, N. meningitidis and S. pneumoniae.
cefotaxime, ceftazidime, ceftizoxime, ceftriaxone,
cefixime, cefpodoxime proxetil, cefdinir, cefditoren Quinolones
pivoxil, ceftibuten, and moxalactam. They are active Quinolones are broad-spectrum antibacterial agents. They
against Citrobacter, S marcescens, and Providencia. act by blocking bacterial DNA synthesis by inhibiting
4th: Cefepime belongs to the fourth-generation bacterial topoisomerase II and topoisomerase IV.
cephalosporin. It is more resistant to hydrolysis by Inhibition of topoisomerase II prevents the relaxation of
chromosomal β lactamases. Cefepime has good activity positively supercoiled DNA while inhibition of

202
ANTI-INFECTIVES FOR SYSTEMIC USE

topoisomerase IV interferes with separation of replicated Chlamydia infections, by mouth, ADULT, 100 mg twice daily
chromosomal DNA. for 7 days
Pneumonia due to Burkholderia pseudomallei, by mouth,
Glycopeptide antibiotics ADULT, 100 mg twice daily; CHILD, 4 mg/kg divided twice
It is a narrow-spectrum antibiotic which affects gram- daily with Trimethoprim-Sulfamethoxazole
positive bacteria by interfering with the incorporation of Juvenile periodontitis, by mouth, CHILD ≥8 years, 200 mg
penicillin-binding protein enzymes into the cell wall by daily for 7 days.
binding to precursors of cell wall synthesis. Mycoplasma infections, by mouth, ADULT, 100 mg twice a
day for five to ten days
Polymyxins
Polymyxins are bactericidal drugs that bind to Leptospirosis a
lipopolysaccharides (LPS) and phospholipids in the outer Clinical manifestations that should lead a health
cell membrane of gram-negative bacteria. They practitioner to consider suspected leptospirosis: any
competitively displace divalent cations from the individual with acute febrile illness of at least 2 days
phosphate groups of membrane lipids, which leads to duration and residing in a flooded area or has high-risk
disruption of the outer cell membrane, leakage of exposure (defined as wading in floods and contaminated
intracellular contents, and bacterial death. water, contact with animal fluids, swimming in flood
water or ingestion of contaminated water, with or without
Imidazole derivatives cuts or wounds) and with at least 2 of the following
These drugs inhibit the biosynthesis of ergosterol, the symptoms: myalgia, calf tenderness, conjunctival

J
main sterol in membranes of fungi. These agents also suffusion, chills, abdominal pain, headache, jaundice,
affect the synthesis of triglycerides and phospholipids oliguria.
leading to an intracellular buildup of toxic For mild leptospirosis (defined as acute febrile illness and
concentrations of hydrogen peroxide, contributing to the various manifestations BUT with stable vital signs,
deterioration of subcellular organelles and to cell anicteric sclera, good urine output and no evidence of
necrosis. meningismus or meningeal irritation, sepsis or septic
shock, difficulty of breathing, and jaundice, that is able
Nitrofuran derivatives to take oral medications) as first line agent to be started
Nitrofurans are bacteriostatic and bactericidal for many as soon as the diagnosis is suspected regardless of the
gram-negative and gram-positive organisms but may not phase of the disease or duration of symptoms, by mouth,
affect P. aeruginosa and many strains of proteus. ADULT, 100 mg twice daily for 7 days; CHILD ≥8 years, 2-
4 mg/kg daily twice a day for 7 days (maximum dose,
Folic acid antagonists 200 mg daily).
Antifolate agents act at various steps in the folic acid For moderate to severe leptospirosis, refer immediately to a
cycle. Antifolate agents are most commonly used in higher level of healthcare facility or the hospital.
combination to block sequential steps in the folic acid For pre-exposure and post-exposure prophylaxis: Pre-
metabolic pathway. exposure prophylaxis is not routinely recommended
except for travelers, soldiers, those engaged in water-
related recreational and occupational activities in high
TETRACYCLINES endemic areas, by mouth, ADULT, 4 mg/kg single dose
(maximum dose, 200 mg regardless of age), take 100
mg twice daily if 200 mg daily is not tolerated.
Rx DOXYCYCLINE For post-exposure prophylaxis:
Post-exposure prophylaxis depends on type of risk and
Oral: 100 mg capsule (as hyclate) may be repeated once weekly if with continued exposure
to risk factors.
Indications: Treatment of leptospirosis; juvenile - Low-Risk Exposure (defined as single history of wading
periodontitis; gastroenteritis; acute bacterial in flood or contaminated water and the absence of
exacerbation of chronic bronchitis (ABECB); blepharitis wounds, cuts, or open lesions of the skin), by mouth,
with associated acne rosacea; chlamydia and ADULT, 200 mg within 24-72 hours from exposure.
mycoplasma infections; second-line treatment of acute - Moderate-Risk Exposure (defined as single history of
bacterial rhinosinusitis (ABRS) or for patients with severe wading in flood or contaminated water and the presence
penicillin allergy; pneumonia due to Burkholderia of wounds, cuts, or open lesion in the skin, or the
pseudomallei accidental ingestion of contaminated water), by mouth,
ADULT, 200 mg once daily for 3-5 days to be started
Contraindications: Pregnancy; breastfeeding; porphyria; immediately within 24-72 hours from exposure.
SLE - High-Risk Exposure (defined as continuous exposure –
more than a single exposure or several days exposure –
Dose: of wading in flood or contaminated water with or without
Acute bacterial exacerbation of chronic bronchitis ABECB, the presence of wounds, cuts, or open lesions of the skin;
mild-to-moderate, by mouth, ADULT, 100 mg twice daily. swimming in flooded waters especially in areas infested
Acute bacterial rhinosinusitis, ABRS, by mouth, ADULT, 100 with domestic / sewer rats and ingestion of
mg every 12 hours for 5-7 days. contaminated water), by mouth, ADULT, 200 mg once
Blepharitis with associated acne rosacea, by mouth, ADULT, weekly until the end of the exposure.
100 mg twice daily for 2 weeks, then every 24 hours.

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 ANTI-INFECTIVES FOR SYSTEMIC USE

- For Pediatrics: by mouth, CHILD >8 years, 4 mg/kg as Drug Interactions:

single dose (maximum, 200 mg); if child is exposed for Monitor closely with:
more than 7 days, repeat the dose after one week. Reduces therapeutic effect of Contraceptives (oral)

NOTE: Antibiotic prophylaxis in the prevention of Reduces therapeutic effect of Doxycycline:

leptospirosis is NOT 100% effective. Protective Rifampicin
measures should still be used. The most effective
preventive measure remains to be avoidance of high-risk Avoid concomitant use with:
exposure. If unavoidable, use protective measures such Reduces absorption of Doxycycline:
as boots, goggles, overalls, or rubber gloves. Aluminum, Magnesium or Calcium containing antacids
(separate administration by at least 2 hours), Calcium
salts (separate administration by at least 2 hours), Ferric
WARNING: There is currently NO recommended pre-
salts (separate administration by as long as possible, at
exposure and post-exposute prophylaxis that is
least 2 hours), Magnesium salts (separate
safe for pregnant or lactating women.
administration by at least 2 hours), Zinc salts (separate
a The Philippine Clinical Practice Guidelines on the administration by at least 2 hours)
Diagnosis, Treatment and Prevention of Leptospirosis in
Adults 2010, PSMID, Quezon City. Increases risk of adverse or toxic effects Doxycyline:
Oral retinoids (e.g., isotretinoin, acitretin)
Dose Adjustment:
J

Renal Impairment: Reduces therapeutic effect of Penicillin

Doxycycline can be used without dose adjustment (does
NOT lead to excessive accumulation when used at the Administration: To be taken with food or after a meal.
usual recommended doses). Capsules should be swallowed whole with plenty of fluid
(a full glass of water); remain sitting or standing (for at
Hepatic Impairment: least ½ hour) to prevent esophageal irritation or damage.
Avoid high doses (hepatotoxicity more likely to occur in Do not give with milk.
hepatic impairment).
Pregnancy Category: D
Precautions:
WARNING: Do not administer to pregnant women. ATC Code: J01AA02

Avoid use in children less than 8 years of age.

Tetracyclines may increase muscle weakness in patients Rx TETRACYCLINE

with myasthenia gravis and may exacerbate SLE;
Overgrowth of non-susceptible organisms; Oral: 250 mg and 500 mg capsule
Hepatic impairment;
Photosensitivity (avoid exposure to sunlight or sunlamps); Indications: Treatment of susceptible bacterial infections of
tissue hyperpigmentation (skin, nail, eye, tooth, or gum both gram-positive and gram-negative organisms;
discoloration may occur); infections due to Mycoplasma, Chlamydia, and
Intracranial hypertension; Rickettsia; acute diarrhea (suspected cholera);
Autoimmune; gastroenteritis; second-line treatment of malaria;
Possible interaction if co-administered with statins or second-line treatment of trachoma; second-line
laxatives; treatment of syphilis
Breastfeeding (use alternative drugs if possible);
Probable absorption and discoloration of teeth in infants Dose:
may usually be prevented by chelation with calcium from Bacterial infection, general dosing, by mouth, ADULT, 250-
milk. 500 mg every 6 hours; CHILD >8 years, 25 to 50 mg/kg
daily in divided doses every 6 hours.
Adverse Drug Reactions: Gastroenteritis due to Vibrio cholera, by mouth, ADULT, 500
Common: Abdominal pain, diarrhea, enamel dysplasia, mg 4 times daily for 3 days by mouth, CHILD 2 months to
epigastric burning, headache, nausea, photosensitivity, 5 years, 250 mg 4 times daily for 3 days.
reduced bone growth (in children <8 years), tooth Syphilis, primary, secondary, or latent, by mouth, ADULT,
discoloration, vaginitis, vomiting 500 mg 4 times daily for 14 days.
Less Common: Anorexia, bone deformity, dental hypoplasia, Syphilis, late latent, by mouth, ADULT, 500 mg 4 times daily
flushing, fungal overgrowth, rash, stomatitis for 30 days.
Rare: Allergic reactions including SJS and anaphylaxis; Trachoma due to Chlamydia trachomatis, second-line, by
benign intracranial hypertension, blood disorders, C. mouth, ADULT and CHILD, 250 mg 4 times daily for 14
difficile-associated disease, esophageal ulcers, days.
hepatitis, hepatotoxicity, nail discoloration, pancreatitis,
serum sickness-like reactions, toxic epidermal Dose Adjustment:
necrolysis, visual disturbances, tinnitus Renal Impairment:
For patients with CrCl of 50-80mL/minute, administer every
8-12 hours.

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ANTI-INFECTIVES FOR SYSTEMIC USE

For patients with CrCl of 10-50mL/minute, administer every be avoided, separate administration by several hours),
12-24 hours. Quinapril (separate doses by at least 2 hours; if
For patients with CrCl <10mL/minute, administer every 24 concomitant use cannot be avoided, monitor for reduced
hours efficacy of tetracycline), Strontium ranelate
Tetracycline is slightly dialyzable (5-20%) via hemodialysis, (discontinuation of strontium ranelate treatment during
peritoneal dialysis, and continuous arteriovenous or tetracycline therapy is recommended)
venous hemofiltration. Supplemental dose is not
necessary. Increases risk of adverse or toxic effects of the following
drugs:
Precautions: Retinoic acid derivatives (pseudotumor cerebri) (except:
Do NOT administer to pregnant women. Adapalene), Tretinoin (Topical)
Nephropathy;
Photosensitivity (discontinue if skin erythema occurs);
Superinfection; Increases metabolism of the Tetracycline:
Hepatic and renal impairment; CYP3A4 inducers (strong)
Pediatric (may cause tissue hyperpigmentation, enamel
hypoplasia, or permanent tooth discoloration; avoid use Reduces therapeutic effect of the following drugs:
in children <8 years); BCG (intravesical), Penicillin, Sodium picosulfate,
Pregnancy (may affect fetal tooth development; associated Typhoid vaccine (postpone use of this vaccine until at
with retarded skeletal development and reduced bone least 3 days after cessation of antibacterial agents)

J
growth);
Lactation (excreted in breastmilk; binds to calcium in Administration: Administer on an empty stomach (1 hour
maternal milk). before or 2 hours after meals) to increase total
absorption. Administer around-the-clock to promote less
Adverse Drug Reactions: Pericarditis, bulging fontanels in variation in peak and trough serum levels.
infants, increased intracranial pressure, paresthesia, Administer at least 1-2 hours prior to, or 4 hours after
pseudotumor cerebri, exfoliative dermatitis, antacid because aluminum and magnesium cations may
photosensitivity, pigmentation of nails, pruritus, chelate with tetracycline and reduce its total absorption.
abdominal cramps, anorexia, antibiotic-associated Do NOT administer to pregnant women.
pseudomembranous colitis, diarrhea, discoloration of
teeth (young children), enamel hypoplasia (young Pregnancy Category: D
children), esophagitis, nausea, pancreatitis,
staphylococcal enterocolitis, vomiting, thrombophlebitis, ATC Code: J01AA07
hepatotoxicity, acute renal failure, azotemia, renal
damage, anaphylaxis, hypersensitivity reactions,
superinfection AMPHENICOLS
Drug Interactions:
Monitor closely with: Rx CHLORAMPHENICOL
Enhances therapeutic effect of the following drugs:
Neuromuscular-blocking agents e.g. Pancuronium
Oral: 500 mg capsule
Vitamin K antagonists
125 mg/5 mL suspension (as palmitate), 60 mL
Inj.: 1 g vial (as sodium succinate) (IV, IM if recommended)
Increases serum concentration of Quinine
Indications: Treatment of brain abscess in the presence of
Reduces therapeutic effect of BCG vaccine
dental infection, meningitis, uncomplicated typhoid
fever, salmonella gastroenteritis. It is associated with
Avoid concomitant use with:
serious hematological side-effects when given
Reduces absorption of Tetracycline:
systemically and should therefore be reserved for the
Antacids, Bile acid sequestrants e.g. Colestipol
treatment of life-threatening infections
Magnesium salts, Sucralfate (if concomitant use cannot
be avoided, administer at least 2 hours apart), Zinc salts
Contraindications: Treatment of trivial or viral infections;
(if concomitant use cannot be avoided, separate
bacterial prophylaxis.
administration by at least 2 hours; except: Zinc chloride)
Dose:
Reduces absorption of Iron salts
Brain abscess, in the presence of dental infection, by IV or
IM injection, CHILD, 100 mg/kg in divided doses every 6
Decreases serum concentration of Tetracycline:
hours; ADULT, 1g every 6 hours.
Calcium salts, Dabrafenib, Dairy products, Iron salts
Meningitis, by IV injection, CHILD and INFANT >2 months –
(except: ferric carboxymaltose, ferric gluconate, ferric
18 years old, 100 mg/kg in divided doses every 8 hours;
pyrophosphate citrate, ferumoxytol, iron dextran
maximum daily dose: 4g.
complex, iron sucrose), Lanthanum (separate doses by
Uncomplicated typhoid fever, by IV injection or by mouth
at least 2 hours), Multivitamins / Minerals (with ADEK,
CHILD, 50-75 mg/kg in divided doses every 6 hours;
folate, iron) (if concomitant use cannot be avoided,
maximum daily dose: 500 mg 2 capsules every 6 hours;
separate administration by several hours), Multivitamins
by mouth, ADULT, 1 g every 6 hours for 14 days.
/ Minerals (with AE, no iron) (if concomitant use cannot

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 ANTI-INFECTIVES FOR SYSTEMIC USE

Salmonella gastroenteritis, by IV injection or by mouth, BETA-LACTAM ANTIBACTERIALS,

CHILD, 50-75 mg/kg in divided doses every 6 hours for PENICILLINS
7 days; maximum daily dose: 2-4 g.

Dose Adjustment:
PENICILLINS WITH EXTENDED SPECTRUM
Renal and Hepatic Impairment:
Use with caution; monitor serum concentrations. Rx AMOXICILLIN
WHO anti-biotic category: ACCESS
Precautions:
Oral: 250 mg and 500 mg capsule (as trihydrate)
WARNING: Serious and fatal blood dyscrasias (aplastic
100 mg/mL granules / powder for drops (as
anemia, hypoplastic anemia, thrombocytopenia, and
trihydrate), 15 mL
granulocytopenia) have occurred after both short-term
250 mg/5 mL granules / powder for suspension (as
and prolonged therapy. Monitor CBC frequently in all
trihydrate), 60 mL
patients.
Indications: Treatment of acute bacterial exacerbation of
Characterized by circulatory collapse, cyanosis, acidosis, chronic bronchitis, acute otitis media, community
abdominal distention, myocardial depression, coma, and acquired pneumonia, eradication of H. pylori,
death. Reaction appears to be associated with serum uncomplicated typhoid fever, mild leptospirosis,
levels ≥50mcg/mL. May result from drug accumulation pericoronitis and dental prophylaxis; second line
J

in patients with impaired hepatic or renal function; treatment for exudative tonsilitis
Prolonged use may result in fungal or bacterial
superinfections, including C. difficile-associated diarrhea Contraindications: Hypersensitivity to amoxicillin, penicillin,
(CDAD) and pseudomembranous colitis; other beta-lactams, or any component of the formulation
Use with caution in patients with hepatic impairment
(reduced dosage recommended); Dose:
Use with caution in patients with renal impairment. Acute bacterial exacerbation of chronic bronchitis (ABECB),
mild moderate infections, by mouth, ADULT, 500 mg
Adverse Drug Reactions: thrice a day for 5-10 days.
Confusion, delirium, depression, fever, headache, Acute otitis media, by mouth, CHILD <2 years old, 80-90
angioedema, rash, urticaria, diarrhea, enterocolitis, mg/kg in divided doses every 12 hours for 10 days;
glossitis, nausea, stomatitis, vomiting, aplastic anemia, CHILD 2-5 years old, 80-90 mg/kg in divided doses every
bone marrow suppression, granulocytopenia, 12 hours for 7 days; , CHILD >5 years old, 80-90 mg/kg
hypoplastic anemia, pancytopenia, thrombocytopenia, in divided doses every 12 hours for 5-7 days; ADULT, 1g
optic neuritis, anaphylaxis, hypersensitivity reactions, every 8 hours for 10 days.
Gray baby syndrome. Community Acquired Pneumonia with complete Hib
vaccination, by mouth, INFANT and CHILD up to 5 years
Drug Interactions: old, 80-90 mg/kg every 12 hours for 5 days.
Decreases serum concentration of Chloramphenicol: Community Acquired Pneumonia, without co-morbid illness,
Anticonvulsants e.g. Phenytoin by mouth, ADULT, 1g thrice a day for 5-7 days.
Exudative tonsillitis, by mouth, ADULT and CHILD, 50 mg/kg
Decreases metabolism of the following drugs: ever 8-12 hours for 10 days
Anticonvulsants e.g., Phenytoin, Barbiturates Uncomplicated typhoid fever, by mouth, ADULT, 1g every 6
Sulfonylureas hours for 14 days; CHILD, 75-100 mg/kg in divided
doses every 8 hours; maximum daily dose: 500 mg, 2
Increases serum concentration of Voriconazole capsules every 6 hours)
Leptospirosis, mild, by mouth, CHILD, 50 mg/kg every 8
Increases metabolism of Chloramphenicol: hours for 7 days;
Barbiturates, Rifampin Pre-exposure prophylaxis, by mouth, 50 mg/kg every 8
hours for 3-5 days; maximum daily dose: 500 mg every 8
Reduces therapeutic effect of the following drugs: hours
BCG, Cyanocobalamin, Typhoid Vaccine Dental Prophylaxis, by mouth, ADULT, 2 g per day; CHILD,
50 mg/kg per day.
Enhances therapeutic effect of Vitamin K Antagonists e.g. Pericoronitis, by mouth, ADULT, 500 mg every 8 hours for 7
Warfarin days.

Administration: Dose Adjustment:

Do NOT administer IM; can be administered IV push over at Renal Impairment:
least 1 minute at a concentration of 100 mg/mL, or IV Use of certain dosage forms (i.e. ER 775 mg tablet and IR
intermittent infusion over 15-30 minutes at a final 875 mg tablet) should be avoided in patients with CrCl
concentration for administration of ≤20mg/mL. <30 mL/minute or patients requiring hemodialysis.
CrCl 10-30 mL/minute: 250-500 mg every 12 hours.
Pregnancy Category: C CrCl <10 mL/minute: 250-500 mg every 24 hours.
Moderately dialyzable (20% to 50%) by hemodialysis or
ATC Code: J01BA01 peritoneal dialysis; approximately 50 mg of amoxicillin

206
ANTI-INFECTIVES FOR SYSTEMIC USE

per liter of filtrate is removed by continuous AMPICILLIN

arteriovenous or venovenous hemofiltration. Rx
WHO anti-biotic category: ACCESS

Precautions: Inj.: 250 mg, 500 mg, and 1 g vial (as sodium salt) (IM, IV)
WARNING: Serious and occasionally severe or fatal
hypersensitivity reactions have been reported in Indications: Treatment of potential neonatal sepsis,
patients on penicillin therapy. uncomplicated typhoid fever, chronic carrier, moderate
to severe leptospirosis, prosthetic joint infection, native
Prolonged use may result in fungal or bacterial valve infective endocarditis, community acute bacterial
superinfection, including C. difficile-associated diarrhea meningitis, community-acquired pneumonia, and dental
(CDAD) and pseudomembranous colitis; prophylaxis
A high percentage of patients with infectious mononucleosis
have developed rash during therapy; (ampicillin-class Contraindications: Hypersensitivity to ampicillin, any
antibiotics not recommended in these patients); component of the formulation, or other penicillin.
Use with caution in patients with renal impairment (dosage
adjustment recommended). Dose:
Potential neonatal sepsis, by IM injection or IV infusion,
Adverse Drug Reactions: NEONATE ≤7 days old ≤2kg, 50 mg/kg every 12 hours;
Agitation, anxiety, behavioral changes, confusion, dizziness, NEONATE 8-28 days old ≤2kg, 50 mg/kg every 8 hours;
headache, hyperactivity, insomnia, seizure, acute NEONATE ≤7 days old >2kg, 50 mg/kg every 8 hours;

J
exanthematous pustulosis, erythematous NEONATE 8-28 days old >2kg, 50 mg/kg every 6 hours;
maculopapular rash, erythema multiforme, exfoliative with gentamicin or amikacin
dermatitis, hypersensitivity vasculitis, mucocutaneous Sepsis from intra-abdominal source, by IV infusion, CHILD,
candidiasis, SJS, toxic epidermal necrolysis, urticaria, 200-400 mg/kg in divided doses every 8 hours;
black hairy tongue, diarrhea, hemorrhagic colitis, maximum daily dose: 6-12 g.
nausea, pseudomembranous colitis, tooth discoloration, Uncomplicated typhoid fever, by IV infusion, CHILD, 100-
vomiting, agranulocytosis, anemia, eosinophilia, 200 mg/kg in divided doses every 6 hours for 14 days;
hemolytic anemia, leukopenia, thrombocytopenia, acute maximum daily dose: 12 g.
cytolytic hepatitis, cholestatic jaundice, hepatic Chronic carrier, by IV infusion, CHILD, 100-200 mg/kg in
cholestasis, crystalluria, anaphylaxis, serum sickness- divided doses every 6 hours for 4 weeks; maximum daily
like reaction. dose: 12 g.
Leptospirosis, moderate to severe, by IV infusion, CHILD,
Drug Interactions: 100 mg/kg every 6 hours for 7 days; maximum daily
Increases risk of adverse or toxic effects Amoxicillin: dose: 0.5-1 g every 6 hours.
Allopurinol Prosthetic joint infection, Enterococci (penicillin-
susceptible), by IV infusion, ADULT, 2 g every 4 hours for
Reduces therapeutic effect of Amoxicillin: 4-6 weeks.
Fusidic acid, Tetracycline derivatives Native valve infective endocarditis, S. vidaris or S. bovis with
Penicillin G MIC >0.12 to ≤0.5mcg/mL, by IV infusion,
Reduces therapeutic effect of the following drugs: CHILD, 200-300 mg/kg in divided doses every 4-6 hours
BCG, Typhoid vaccine for 6 weeks; maximum daily dose: 12 g; ADULT, 12 g in
divided doses every 4 hours for 4-6 weeks.
Decreases excretion of Methotrexate Native valve infective endocarditis, S. vidaris or S. bovis with
Penicillin G MIC >0.5 mcg/mL, by IV infusion, CHILD, 12
Decreases serum concentration of Mycophenolate g in divided doses every 4 hours for 4-6 weeks with
gentamicin 1 mg/kg every 8 hours for 4-6 weeks.
Increases serum concentration of Amoxicillin: Native valve infective endocarditis, Enterococci, penicillin-
Probenecid susceptible, aminoglycoside-resistant, streptomycin
susceptible, by IV infusion, CHILD, 200–300 mg/kg IV
Administration: divided q4-6h daily (Max dose 12 g/d) with ceftriaxone
May be taken with or without food. Best taken at the start of 100 mg/kg IV/IM in divided doses every 12 hours or 80
meals for better absorption and reduction of GI mg/kg; maximum daily dose: 2 g every 12 hours for 6
discomfort. Administer around-the-clock to promote less weeks; ADULT, 12 g in divided doses every 4 hours with
variation in peak and trough serum levels. Appropriate ceftriaxone 2 g IV every 12 hours for 6 weeks.
amount of suspension may be mixed with formula, milk, Dental prophylaxis, by IM injection or IV infusion, CHILD, 50
fruit juice, water, ginger ale, or cold drinks; administer mg/kg; ADULT, 2 g.
dose immediately after mixing. Community acute bacterial meningitis, by IM injection or IV
infusion, NEONATE <7 days old and <2kg, 50 mg/kg
Pregnancy Category: B every 12 hours; NEONATE <7 days old and ≥2kg, 50
mg/kg every 8 hours; NEONATE >7 days old and <2kg,
ATC Code: J01CA04 50 mg/kg every 8 hours; NEONATE >7 days old and
≥2kg, 50 mg/kg every 6 hours; with amikacin or
gentamicin; by IV infusion, ADULT >50 years old, 2 g
every 4 hours.
Community-acquired pneumonia, by IV infusion, NEONATE,
100-200 mg/kg in divided doses every 6 hours; INFANT

207
 ANTI-INFECTIVES FOR SYSTEMIC USE

and CHILD up to 5 years old, 200 mg/kg in divided doses

every 6 hours. Reduces therapeutic effect of Ampicillin:
Fusidic acid, Tetracycline derivatives
Dose Adjustment:
Renal Impairment: Reduces therapeutic effect of the following drugs:
CrCl >50 mL/minute: Administer every 6 hours. BCG, Typhoid vaccine (only the live attenuated Ty21a
CrCl 10-50 mL/minute: Administer every 6-12 hours. strain is affected)
CrCl <10 mL/minute: Administer every 12-24 hours.
Intermittent hemodialysis (IHD) (administer after Decreases serum concentration of Ampicillin:
hemodialysis on dialysis days): Dialyzable (20% to 50%): Chloroquine, Lanthanum
IV: 1-2 g every 12-24 hours. Note: Dosing dependent on
the assumption of 3 times/week, complete IHD sessions. Decreases serum concentration of Mycophenolate
Peritoneal dialysis (PD): 250 mg every 12 hours.
Continuous renal replacement therapy (CRRT): Drug Decreases excretion of Methotrexate
clearance is highly dependent on the method of renal
replacement, filter type, and flow rate. Appropriate Increases serum concentration of Ampicillin:
dosing requires close monitoring of pharmacologic Probenecid
response, signs of adverse reactions due to drug
accumulation, as well as drug concentrations in relation Administration:
to target trough (if appropriate). The following are general Administer around-the-clock to promote less variation in
J

recommendations only (based on dialysate peak and trough serum levels.

flow/ultrafiltration rates of 1-2 L/hour and minimal Administer over 3-5 minutes (125-500 mg) or over 10-15
residual renal function) and should not supersede minutes (1-2 g). More rapid infusion may cause seizures.
clinical judgment: Ampicillin and gentamicin should not be mixed in the
CVVH: Loading dose of 2 g followed by 1-2 g every 8-12 same IV tubing.
hours.
CVVHD: Loading dose of 2 g followed by 1-2 g every 8 Pregnancy Category: B
hours.
CVVHDF: Loading dose of 2 g followed by 1-2 g every 6-8 ATC Code: J01CA01
hours.

Precautions: BETA-LACTAMASE SENSITIVE

WARNING: Serious and occasionally severe or fatal PENICILLINS
hypersensitivity reactions have been reported in
patients on penicillin therapy, especially with a PENICILLIN G BENZATHINE
history of beta-lactam hypersensitivity, history of Rx (BENZATHINE BENZYLPENICILLIN)
sensitivity to multiple allergens, or previous IgE- WHO anti-biotic category: ACCESS
mediated reactions. Use with caution in asthmatic
patients. Inj: 1,200,000 units vial (MR) (IM)

Appearance of a rash should be carefully evaluated to Indications: Secondary prevention for acute rheumatic fever
differentiate a non-allergic ampicillin rash from a and treatment for pharyngitis or tonsilitis
hypersensitivity reaction; rash occurs in 5% to 10% of
children and is a generalized dull red, maculopapular Contraindications: Hypersensitivity to penicillin or any
rash, generally appearing 3-14 days after the start of component of the formulation.
therapy. It normally begins on the trunk and spreads over
most of the body. It may be most intense at pressure Dose: Acute rheumatic fever, secondary prevention, by IM
areas, elbows and knees; injection, CHILD ≤27kg, 600,000 units every 3 weeks;
Prolonged use may result in fungal or bacterial CHILD >27kg, 1,200,000 units every 3 weeks.
superinfection, including C. difficile-associated diarrhea Pharyngitis or tonsillitis, by IM injection, ADULT, 1,200,000
(CDAD) and pseudomembranous colitis; units.
Use with caution in patients with renal impairment (dosage
adjustment recommended). Dose Adjustment:
Geriatric:
Adverse Drug Reactions: Refer to adult dosing.
Fever, penicillin encephalopathy, seizure, erythema
multiforme, exfoliative dermatitis, rash, urticaria, black Precautions:
hairy tongue, diarrhea, enterocolitis, glossitis, nausea,
WARNING: Not for intravenous use; cardiopulmonary
pseudomembranous colitis, sore mouth or tongue,
arrest and death have occurred from inadvertent IV
stomatitis, vomiting, oral candidiasis, agranulocytosis,
administration.
anemia, hemolytic anemia, eosinophilia, leukopenia,
thrombocytopenia purpura
Serious and occasionally severe or fatal hypersensitivity
Drug Interactions: reactions have been reported in patients on penicillin
Decreases bioavailability of Atenolol therapy, especially a history of beta-lactam

208
ANTI-INFECTIVES FOR SYSTEMIC USE

hypersensitivity, history of sensitivity to multiple Contraindications: Hypersensitivity to penicillin or any

allergens, or previous IgE-mediated reactions (Use with component of the formulation.
caution in asthmatic patients);
Prolonged use may result in fungal or bacterial Dose:
superinfection, including C. difficile-associated diarrhea Native valve infective endocarditis, S. viridans or S. bovis (S.
(CDAD) and pseudomembranous colitis. gallolyticus) with Penicillin G MIC ≤0.12 mcg/mL, by IV
infusion, CHILD, 200,000-300,000 U/kg in divided
Adverse Drug Reactions: doses every 4 hours for 4 weeks.
Cerebral vascular accident, cyanosis, gangrene, Membranous pharyngitis due to diphtheria, by IV infusion,
hypotension, pallor, palpitations, syncope, tachycardia, CHILD, 100,000-150,000 U/kg every 6 hours; ADULT,
vasodilation, vasospasm, vasovagal reaction, anxiety, 50,000 U/kg every 12 hours.
coma, confusion, dizziness, euphoria, fatigue, headache, Rat-bite fever, for mild- moderate infections, by IV, 100,000-
nervousness, pain, seizure, somnolence, bloody stool, 150,000 U/kg/day in 4 doses, for severe infections, by
intestinal necrosis, nausea, vomiting, impotence, IV, 200,000-300,000 U/kg/day in 6 doses
priapism, arthritis, exacerbation, joint disorder, Severe community acquired pneumonia, with complete Hib
neurovascular damage, numbness, periostitis, vaccination, by IV, 200,000 U/kg every six hours daily
rhabdomyolisis, transverse myelitis, tremor, weakness, Neurosyphilis, by IV, 3-4 MU every four hours or continuous
blindness, blurred vision, hematuria, myoglobinuria, infusion for 10- 14 days
neurogenic bladder, proteinuria, renal failure, Proven or highly probable congenital syphilis, by IV, 50,000
diaphoresis, hypersensitivity reactions, Jarisch- U/kg every 12 hours during the first 7 days of life and

J
Herxheimer reaction, lymphadenopathy, mottling, every 8 hours thereafter for a total of 10- 15 days
warmth Possible congenital syphilis, by IV, 50,000 U/kg every 12
hours during the first 7 days of life and every 8 hours
Drug Interactions: thereafter for a total of 10 days
Reduces therapeutic effect of Penicillin G benzathine:
Fusidic acid, Tetracycline derivatives Dose Adjustment:
Renal Impairment:
Reduces therapeutic effect of the following drugs: Uremic patients with CrCl >10 mL/minute/1.73m2:
BCG, Typhoid vaccine (only the live attenuated Ty21a Administer full loading dose followed by ½ of the loading
strain is affected) dose given every 4-5 hours.

Decreases serum concentration of Mycophenolate CrCl <10 mL/minute/1.73m2: Administer full loading dose
followed by ½ of the loading dose given every 8-10
Decreases excretion of Methotrexate hours.

Increases serum concentration of Penicillin G benzathine: Intermittent hemodialysis (IHD) (administer after
Probenecid hemodialysis on dialysis days): Administer normal
loading dose followed by either 25% to 50% of normal
Administration: Warm to room temperature before dose every 4-6 hours or 50% to 100% of normal dose
administration to lessen the pain associated with every 8-12 hours. For mild-to-moderate infections,
injection. Administer by deep IM injection in the upper administer 0.5-1 MU every 4-6 hours or 1-2 MU every 8-
outer quadrant of the buttock; in children <2 years of 12 hours. For neurosyphilis, endocarditis, or serious
age, IM injections should be made into the mid-lateral infections, administer up to 2 MU every 4-6 hours;
muscle of the thigh, not the gluteal region. Do not inject administer after dialysis on dialysis days or supplement
near an artery or a nerve; permanent neurological with 500,000 units after dialysis. Note: Dosing
damage or gangrene may result. When doses are dependent on the assumption of 3 times/week,
repeated, rotate the injection site. Do NOT administer by complete IHD sessions.
IV, SC, or intra-arterially.
Continuous renal replacement therapy (CRRT): Drug
Pregnancy Category: B clearance is highly dependent on the method of renal
replacement, filter type, and flow rate. Appropriate
ATC Code: J01CE08 dosing requires close monitoring of pharmacologic
response, signs of adverse reactions due to drug relation
to target trough (if appropriate). The following are general
PENICILLIN G CRYSTALLINE recommendations only (based on dialysate
Rx (BENZYLPENICILLIN) flow/ultrafiltration rates of 1-2 L/hour and minimal
WHO anti-biotic category: ACCESS residual renal function) and should not supersede
clinical judgment.
Inj.: 1,000,000 units vial (as sodium salt) (IM, IV) CVVH: Loading dose of 4 MU, followed by 2 MU every 4-6
5,000,000 units vial (as sodium salt) (IM, IV) hours.
CVVHD: Loading dose of 4 MU, followed by 2-3 MU every 4-
Indications: Treatment of native valve infective 6 hours.
endocarditis, membranous pharyngitis due to diphtheria, CVVHDF: Loading dose of 4 MU, followed by 2-4 MU every 4-
streptococcal infections, and rat - bite fever severe 6 hours.
community acquired pneumonia in children with
complete Hib vaccination

209
 ANTI-INFECTIVES FOR SYSTEMIC USE

Precautions: PENICILLIN V
WARNING: Serious and occasionally severe or fatal Rx (PHENOXYMETHYLPENICILLIN)
hypersensitivity reactions have been reported in WHO anti-biotic category: ACCESS
patients on penicillin therapy, especially with a history
of beta-lactam hypersensitivity, history of sensitivity to Oral: 250 mg and 500 mg tablet / capsule (as potassium
multiple allergens, or previous IgE-mediated reactions. salt)
Use with caution in asthmatic patients. 250 mg/5 mL granules / powder for syrup /
suspension (as potassium salt), 60 mL
Avoid intra-arterial administration or injection into or near
major peripheral nerves or blood vessels; Prolonged use Indications: Treatment of acute rheumatic fever, acute
may result in fungal or bacterial superinfection, including gingivitis, acute necrotizing ulcerative gingivitis,
C. difficile-associated diarrhea (CDAD) and pericoronitis, pharyngitis, erisipelas and tonsillitis.
pseudomembranous colitis.
Contraindications: Hypersensitivity to penicillin or any
Adverse Drug Reactions: component of the formulation.
Coma, hyper-reflexia, seizures, contact dermatitis, rash,
pseudomembranous colitis, neutropenia, positive Dose:
hemolytic anemia, phlebitis, thrombophlebitis, Acute rheumatic fever, by mouth, ADULT, 250mg twice daily
myoclonus, acute interstitial nephritis, renal tubular for 3 weeks.
damage, anaphylaxis, hypersensitivity reactions, Jarisch- Acute gingivitis, by mouth, ADULT, 500mg every 4 hours
J

Herxheimer reaction, serum sickness. with metronidazole 500mg every 8 hours.

Acute necrotizing ulcerative gingivitis, by mouth, ADULT,
Drug Interactions: 500mg every 6 hours with metronidazole 500mg every 8
Reduces therapeutic effect of Penicillin G crystalline: hours.
Fusidic acid, Tetracycline derivatives Pericoronitis, by mouth, ADULT, 500mg every 6 hours for 7
days.
Reduces therapeutic effect of the following drugs: Pharyngitis or tonsillitis, by mouth, CHILD, 25-50mg/kg
BCG, Typhoid vaccine (only the live attenuated Ty21a every 6 hours for 10 days; ADULT, 500mg every 12 hours
strain is affected) or 250mg every 6 hours for 10 days.
Recurrent pharyngitis, by mouth, CHILD, 25-50mg/kg in
Decreases serum concentration of Mycophenolate divided doses every 6 hours for 10 days; ADULT, 500mg
every 12 hours or 250mg every 6 hours for 10 days.
Decreases excretion of Methotrexate
Dose Adjustment:
Increases serum concentration of Penicillin G crystalline: Geriatric:
Probenecid Refer to adult dosing.

Administration: Renal Impairment:

For IM: Administer IM by deep injection in the upper outer CrCl 10-50mL/minute: Administer every 8-12 hours.
quadrant of the buttock. CrCl <10mL/minute: Administer every 12-16 hours.
For Intermittent IV: May be dissolved in small amounts of
SQFI, NS, D5W and administered peripherally as a Precautions:
50,000-100,000 units/mL solution. In fluid-restricted WARNING: Serious and occasionally severe or fatal
patients, 146,000 units/mL in SQ results in a maximum hypersensitivity reactions have been reported in
recommended osmolality for peripheral infusion. Infused patients on penicillin therapy, especially with a history
over 15-30 minutes. of beta-lactam hypersensitivity, history of sensitivity to
For Continuous IV infusion: Determine the volume of fluid multiple allergens, or previous IgE-mediated reactions.
and rate of its administration required by the patient in a Use with caution in asthmatic patients.
24-hour period. Add the appropriate daily dosage of
penicillin to this fluid.
Prolonged use may result in fungal or bacterial
Pregnancy Category: B superinfection, including C. difficile-associated diarrhea
(CDAD) and pseudomembranous colitis;
ATC Code: J01CE01 Use with caution in patients with severe renal impairment
(dosage adjustment necessary);
Use with caution in patients with a history of seizure
disorder; high levels, particularly in the presence of renal
impairment, may increase risk of seizures.

Adverse Drug Reactions:

Common: Mild diarrhea, vomiting, nausea, oral candidiasis.
Rare: Acute interstitial nephritis, convulsions, hemolytic
anemia, positive Coombs reaction.

Drug Interactions:
Reduces therapeutic effect of the following drugs:

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ANTI-INFECTIVES FOR SYSTEMIC USE

BCG vaccine, Typhoid vaccine diarrhea, flatulence, nausea, oral candidiasis,

pseudomembranous colitis, stomatitis, vomiting,
Reduces therapeutic effect of Penicillin: agranulocytosis, bone marrow depression, eosinophilia,
Fusidic acid, Tetracycline derivatives granulocytopenia, hemolytic anemia, leukopenia,
neutropenia, thrombocytopenia, hepatotoxicity,
Decreases excretion of Methotrexate thrombophlembitis, arthralgia, myalgia, myoclonus,
hematuria, interstitial nephritis, proteinuria, renal
Decreases serum concentration of Mycophenolate insufficiency, renal tubular damage, bronchospasm,
laryngeal edema, sneezing, wheezing, serum sickness-
Increases serum concentration of Penicillin: like reaction.
Probenecid
Drug Interactions:
Administration: Reduces therapeutic effect of the following drugs:
Administer on an empty stomach to increase oral BCG, Typhoid vaccine (Only the live attenuated Ty21a
absorption. strain is affected.)

Pregnancy Category: B Reduces therapeutic effect of Cloxacillin:

Fusidic acid, Tetracycline derivatives
ATC Code: J01CE02
Decreases excretion of Methotrexate

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BETA-LACTAMASE RESISTANT Decreases serum concentration of Mycophenolate
PENICILLINS
Increases serum concentration of Cloxacillin:
Probenecid
Rx CLOXACILLIN
WHO anti-biotic category: ACCESS Administration:
Administer with water 1 hour before or 2 hours after meals.
Oral: 500 mg capsule (as sodium salt)
250 mg/5 mL powder for solution (as sodium salt), Pregnancy Category: B
60 mL
ATC Code: J01CF02
Indications: Treatment of bacterial infections caused by
susceptible strains of penicillinase-producing
staphylococci.
Rx OXACILLIN
Contraindications: Hypersensitivity to cloxacillin, other
penicillins, cephalosporins, or any component of the
formulation. Inj.: 250 mg and 500 mg vial (as sodium salt) (IM, IV)

Dose: Indications: Treatment of infections caused by susceptible

Internal hordeolum, by mouth, ADULT, for MSSA, 250-500 penicillinase­producing staphylococci.
mg every 6 hours with hot packs; CHILD, 100-150 mg/kg
Contraindications: Hypersensitivity to oxacillin, any penicillin
in divided doses every 6 hours.
or any component of the formulation.
Dose Adjustment:
Geriatric: Dose:
Refer to adult dosing. Acute mastoiditis, by IV push, CHILD, 150-200 mg/kg in
divided doses every 6 hours.
Precautions: Bacterial purulent pericarditis, MSSA, by IV push, CHILD,
200 mg/kg every 6 hours for 3-4 weeks.
WARNING: Serious and occasionally severe or fatal Central-line associated bloodstream infection, MSSA, by IV
hypersensitivity reactions have been reported in push, ADULT, 2 g every 4 hours.
patients on penicillin therapy, especially with a history Dacryocystitis, MSSA, by IV push, ADULT, 2 g every 6 hours
of beta-lactam hypersensitivity, history of sensitivity to for 7-14 days.
multiple allergens, or previous IgE-mediated reactions. Neonatal sepsis, by IM injection or IV push, NEONATE ≤7
Use with caution in asthmatic patients. days old ≤2 kg, 25 mg/kg every 12 hours; NEONATE 8-
28 days old ≤2 kg, 50 mg/kg every 8 hours; NEONATE ≤7
days old >2 kg, 50 mg/kg every 8 hours; NEONATE 8-28
Penicillin use has been associated with hematologic days old >2 kg, 50 mg/kg every 6 hours.
disorders believed to be a hypersensitivity phenomenon. Staphylococcal toxic shock syndrome, by IV push, CHILD,
Reactions are most often reversible upon discontinuing 150-200 mg/kg in divided doses 4-6 hours with
therapy. clindamycin or IVIG for 10-14 days; maximum daily dose:
4-12 g.
Adverse Drug Reactions: Osteomyelitis, contiguous focus, mild to moderate, by IV
Hypotension, confusion, fever, lethargy, seizure, pruritus, push, CHILD, 100-150 mg/kg in 4 doses; maximum daily
rash, urticaria, abdominal pain, black or hairy tongue, dose: 4 g;

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 ANTI-INFECTIVES FOR SYSTEMIC USE

Severe, by IV push, CHILD, 150-200 mg/kg in 4-6 doses; push over 10 minutes. Administer IV piggyback over 30
maximum daily dose: 12 g. minutes.
Osteomyelitis, hematogenous unlikely MRSA, long bones, by
IV push, ADULT, 2 g every 4 hours for 4-6 weeks; Pregnancy Category: B
Vertebral, by IV push, ADULT, 2 g every 4 hours with
ceftriaxone, piperacillin-tazobactam, OR levofloxacin for ATC Code: J01CF04
6-12 weeks.
Septic bursitis, MSSA, by IV push, 2 g every 4 hours for 14-
21 days. COMBINATIONS OF PENICILLINS,
Prosthetic joint infection, MSSA, by IV push, ADULT, 2 g INCLUDING BETA-LACTAMASE
every 4 hours with oral rifampin 300 mg twice daily for 2- INHIBITORS
6 weeks.
Native valve infective endocarditis, MSSA, by IV push,
CHILD, 200 mg/kg in divided 4-6 doses for 6 weeks with PENICILLINS + BETA- LACTAMASE INHIBITORS
or without gentamicin; maximum daily dose: 12 g;
ADULT, 2 g every 4 hours for 4-6 weeks.
Prosthetic valve infective endocarditis, MSSA, by IV push,
Rx AMPICILLIN + SULBACTAM
CHILD, 200 mg/kg in divided 4-6 doses for 6 weeks with
rifampicin AND gentamicin; ADULT, 2 g every 4 hours Inj.: 500 mg ampicillin + 250 mg sulbactam (as sodium
with rifampin and gentamicin. salt) per vial (IM, IV)
J

1000 mg ampicillin + 500 mg sulbactam (as sodium

Dose Adjustment: salt) per vial (IM, IV)
Geriatric: 2000 mg ampicillin + 1000 mg sulbactam (as sodium
Refer to adult dosing. salt) per vial (IM, IV)

Precautions: Indications: Treatment of susceptible bacterial infections

involved with skin and skin structure, intra-abdominal
WARNING: Serious and occasionally severe or fatal
infections, Native valve infective endocarditis,
hypersensitivity reactions have been reported in
dentoalveolar infection or peri-apical abscess, Ludwig’s
patients on penicillin therapy, especially with a
angina, peritonsillar abscess, deep neck abscess/
history of beta-lactam hypersensitivity, history of
retropharyngeal abscess, parapharyngeal space
sensitivity to multiple allergens, or previous IgE-
infection, acute epiglottitis, severe community-acquired
mediated reactions. Use with caution in asthmatic
pneumonia, acute emphysema, lung abscess
patients.
Dose:
Monitor patients for anaphylactic/hypersensitivity Intra-abdominal source, by IM/IV injection, CHILD, 200
reactions, hepatitis, superinfection; mg/kg in divided doses every 6 hours with or without
Use with caution in patients with renal impairment; gentamicin/amikacin for 10-14 days or longer.
Elderly; Native valve infective endocarditis, community-acquired, by
Neonates. IV injection, CHILD, 200-300 mg/kg in 4-6 divided doses
with gentamicin; ADULT, 3 g every 6 hours with
Adverse Drug Reactions: gentamicin;
Fever, rash, diarrhea nausea and vomiting, agranulocytosis, Haemophilus sp, Aggregatibacter sp, Cardiobacterium
eosinophilia, leukopenia, neutropenia, hominis, Eikenella corrodens, and Kingella species
thrombocytopenia, hepatotoxicity, acute interstitial (HACEK), beta-lactamase producing, by IV injection,
nephritis, hematuria, serum sickness­like reactions CHILD, 200-300 mg/kg in 4-6 divided doses every 24
hours for 4 weeks; ADULT, 3 g every 6 hours for 4 weeks.
Drug Interactions: Dentoalveolar infection or peri-apical abscess, by IV
Reduces therapeutic effect of the following drugs: injection, CHILD, 200-400 mg every 6 hours for 7-14
BCG, Typhoid vaccine (Only the live attenuated Ty21a days until local inflammation has resolved completely;
strain is affected.) ADULT, 3 g every 6 hours for 7-14 days until local
inflammation has resolved completely.
Reduces therapeutic effect of Oxacillin: Ludwig’s angina, by IV injection, CHILD, 200-400 mg every
Fusidic acid, Tetracycline derivatives 6 hours with metronidazole or clindamycin for 2-3 weeks;
ADULT, 3 g every 6 hours with metronidazole or
Decreases excretion of Methotrexate clindamycin for 2-3 weeks.
Peritonsillar abscess, Deep neck abscess/ retropharyngeal
Decreases serum concentration of Mycophenolate abscess, by IM/IV injection, CHILD, 100 mg/kg in divided
doses every 6 hours; ADULT, 6-12 g in divided doses
Increases serum concentration of Oxacillin: every 6 hours.
Probenecid Parapharyngeal space infection, by IM/IV injection, CHILD,
100 mg/kg in divided doses every 6 hours; ADULT, 3 g in
Administration: divided doses every 6 hours.
For IM: Administer into muscle; Avoid sciatic nerve injury. Acute epiglottitis, by IV injection, CHILD, 100 mg/kg in
For IV: Administer around-the-clock to promote less divided doses every 6 hours for 10 days.
variation in peak and trough serum levels. Administer IV

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ANTI-INFECTIVES FOR SYSTEMIC USE

Community-acquired pneumonia, severe, with no Hib Adverse Drug Reactions:

vaccination or incomplete or unknown vaccination Common: Pain at injection site.
history, by IV injection, INFANT and CHILD up to 5 years, Less Common: Rash, diarrhea, thrombophlebitis, allergic
100 mg/kg in divided doses every 6 hours; reaction.
Moderate-risk, by IV injection, ADULT, 1.5 g every 6 hours Rare: Abdominal distention, candidiasis, chest pain, chills,
with azithromycin OR clarithromycin OR levofloxacin for dysuria, edema, epistaxis, erythema, facial swelling,
7-28 days. fatigue, flatulence, glossitis, hairy tongue, headache,
Acute emphysema, by IV injection, ADULT, 100 mg/kg in interstitial nephritis, itching, malaise, mucosal bleeding,
divided doses every 6 hours for 2-4 weeks. nausea, pseudomembranous colitis, seizure, substernal
Lung abscess, by IV injection, ADULT, 3 g in divided doses pain, throat tightness, thrombocytopenia, urine
every 6 hours with metronidazole or piperacillin- retention, vomiting.
tazobactam for 4-6 weeks.
Pneumonia, anaerobic or aspiration with or without lung Drug Interactions:
abscess, by IV injection, ADULT, 3 g every 6 hours with Decreases bioavailability of Atenolol
clindamycin for 3-4 weeks or longer.
Pathogen-specific treatment, Acinetobacter species, by IV Reduces therapeutic effect of the following drugs:
injection, ADULT, 3 g every 6 hours with meropenem; BCG, Typhoid vaccine (Live attenuated Ty21a strain)
Carbapenem resistant strains, by IV injection, CHILD,
100-200 mg/kg in divided doses every 6 hours with Reduces therapeutic effect of Ampicillin + Sulbactam:
amikacin OR gentamicin. Fusidic acid, Tetracycline derivatives

J
Dose Adjustment: Decreases excretion of Methotrexate
Geriatric:
Refer to adult dosing. Decreases serum concentration of Mycophenolate

Renal Impairment: Increases serum concentration of Ampicillin + Sulbactam:

CrCl 15-29 mL/minute/1.73m2: 1.5-3 g every 12 hours. Probenecid
CrCl 5-14 mL/minute/1.73m2: 1.5-3 g every 24 hours.
Intermittent hemodialysis (IHD) (administer after Decreases serum concentration of Ampicillin + Sulbactam:
hemodialysis on dialysis days): 1.5-3 g every 12-24 Chloroquine, Lanthanum
hours. Note: Dosing dependent on the assumption of 3
times/week, complete IHD sessions. Administration:
Peritoneal dialysis (PD): 3 g every 24 hours. Administer around-the-clock to promote less variation in
Continuous renal replacement therapy (CRRT): Drug peak and trough serum levels. Administer by slow
clearance is highly dependent on the method of renal injection over 10-15 minutes or IV over 15-30 minutes.
replacement, filter type, and flow rate. Appropriate Ampicillin and gentamicin should NOT be mixed in the same
dosing requires close monitoring of pharmacologic IV tubing.
response, signs of adverse reactions due to drug
accumulation, as well as drug levels in relation to target Pregnancy Category: B
trough (if appropriate). The following are general
recommendations only (based on dialysate ATC Code: J01CR01; J01CA51
flow/ultrafiltration rates of 1-2L/hour and minimal
residual renal function) and should not supersede
clinical judgment: CO-AMOXICLAV
CVVH: Initial: 3 g; maintenance: 1.5-3 g every 8-12 hours. (AMOXICILLIN +
CVVHD: Initial: 3 g; maintenance: 1.5-3 g every 8 hours. Rx
CVVHDF: Initial: 3 g; maintenance: 1.5-3 g every 6-8 hours.
POTASSIUM CLAVULANATE)
WHO anti-biotic category: ACCESS
Precautions:
Oral: 500 mg amoxicillin (as trihydrate) + 125 mg
WARNING: Serious and occasionally severe or fatal potassium clavulanate per tablet
hypersensitivity reactions have been reported in 875 mg amoxicillin (as trihydrate) + 125 mg
patients on penicillin therapy, especially with a history potassium clavulanate per tablet
of beta-lactam hypersensitivity, history of sensitivity to 200 mg amoxicillin (as trihydrate) + 28.5 mg
multiple allergens, or previous IgE-mediated reactions. potassium clavulanate per 5 mL granules / powder
Use with caution in asthmatic patients. for suspension, 70 mL
400 mg amoxicillin (as trihydrate) + 57 mg potassium
Appearance of a rash should be carefully evaluated to clavulanate per 5 mL granules / powder for
differentiate a non-allergic ampicillin rash from a suspension, 70 mL
hypersensitivity reaction; rash occurs in 5% to 10% of 600 mg amoxicillin (as trihydrate) + 42.9 mg
children and is a generalized dull, red maculopapular potassium clavulanate per 5 mL granules / powder
rash, generally appearing 3-14 days after the start of for suspension
therapy;
Prolonged use may result in fungal or bacterial Indications: Upper respiratory tract infection: exudative or
superinfection, including C. difficile-associated diarrhea diffuse erythematous, recurrent pharyngitis, peritonsillar
(CDAD) and pseudomembranous colitis. abscess (Quincy), deep neck abscess/retropharyngeal
abscess, parapharyngeal space infection, acute

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 ANTI-INFECTIVES FOR SYSTEMIC USE

bacterial rhinosinusitis (ABRS), acute otitis media, acute Dose Adjustment:

otitis media (clinical failure after 3 days), second line Renal Impairment:
treatment for buccal cellulitis, severe lower respiratory Note: 875 mg tablet is not recommended for patients with
tract infection, community-acquired pneumonia, febrile renal impairment. The extended-release formulation is
neutropenia contraindicated in patients with a CrCl of 30mL/min.

Contraindications: History of cholestatic jaundice or hepatic Adult and pediatric patients weighing more than 40 kg:
dysfunction with amoxicillin/clavulanate potassium CrCl 30 mL/min or more: No dosage adjustment necessary
therapy CrCl 10-30 mL/min 250 to 500 mg (amoxicillin component)
every 12 hours, depending on the severity of the
Dose: infection
Recurrent pharyngitis, by mouth, ADULT, 500 mg/125 mg CrCl less than 10 mL/min 250-500 mg (amoxicillin
every 12 hours for 10 days; CHILD <40 kg (second line component) every 24 hours, depending on the severity
treatment), 25-45 mg/kg/day divided every 8 hours for of the disease
10 days; CHILD >40 kg (second line), 500 mg divided Pediatric patients: dose adjustments are based on a usual
every 12 hours or 250 mg every 8 hours (or more severe dose of 20-40 mg/kg per day (amoxicillin component)
infections, may increase the dose to 500 mg every 8 divided every 8 hours, 25-45 mg/kg per day (amoxicillin
hours); INFANT >3 months old, 15-45 mg/kg/day divided component) divided every 12 hours
every 12 hours for 10 days. CrCl 10-29 mL/min/1.73 m2: 8-20 mg/kg/dose amoxicillin
Peritonsillar abscess (Quincy), by mouth, ADULT, 750 mg– component (20 mg/kg/dose for high dose) every 12
J

1.5 g per day every 8 hours (amoxicillin component) for hours

ten days; CHILD, 40 mg/kg per day divided every 8 hours CrCl less than 10 ml/min/1.73 m2: 8-20 mg/kg/dose
for 10 days. amoxicillin component (20 mg/kg/dose for high dose)
Parapharyngeal space infection, by mouth, CHILD, 40 every 24 hours
mg/kg per day divided every 8 hours for 10 days.
Acute bacterial rhinosinusitis, by mouth, ADULT (first line), Precautions:
875/125 mg every 12 hours for 5-7 days; INFANT 1-3 Monitor for anaphylactic or hypersensitivity reactions,
months (first line), 30 mg/kg per day divided every 12 diarrhea, hepatic effects;
hours for 10-14 days; INFANT >3 months, 20-40 mg/kg Monitor prolonged use for hepatic, renal and hematopoietic
per day divided every 8 hours or 25-45 mg/ kg per day functions and superinfection if used beyond
divided every 12 hours for 10-14 days; For twice daily recommended duration of treatment;
dosing, use 200/28.5 mg or 400/57 mg, CHILD >3 Use with caution in patients with hepatic impairment
months and greater than 40 kg (second line), 90 mg/kg (monitor liver function tests at regular intervals);
per day every 12 hours using 600/42.9 mg. Patients with infectious mononucleosis may develop rash
Acute otitis media, by mouth, ADULT with no penicillin with this product;
allergy (second line), 875/125 mg every 12 hours for 10 Due to differing content of clavulanic acid, not all products
days. are interchangeable.
Acute otitis media (clinical failure after 3 days), by mouth,
CHILD > 3 months and <40 kg (first line treatment), 90 Adverse Drug Reactions:
mg/kg per day every 12 hours using 600/42.9 mg for 10 Common: Diarrhea
days (<2 years old) and for 5-7 days (> 2 years old). Less Common: Diaper rash, skin rash, urticaria, abdominal
Buccal cellulitis, by mouth, CHILD <5 years old, 45 mg/kg distress, vomiting, candidiasis, nausea, vaginal mycosis,
per day divided every 12 hours for 7-14 days vaginitis, cholestatic jaundice, flatulence, headache,
Bite wounds, by mouth, CHILD and ADOLESCENT ≥40 kg, hepatic insufficiency, vasculitis (hypersensitivity
875 mg every 12 hours. Rare: Reversible leucopenia (including neutropenia),
Lower Respiratory Tract Infection, with severe infection, by erythema multiforme
mouth, ADULT, 875/125 mg twice a day for 5-10 days.
Community-acquired pneumonia, PCAP A or B if with no Hib Drug Interactions:
vaccination or incomplete or unknown vaccination Monitor closely with:
history, by mouth, INFANT and CHILD up to 5 years old, Incompatible with Warfarin (unpredictable effects)
80-90 mg/kg per day (amoxicillin component) divided
every 8 hours (4:1 preparations) or divided every 12 Avoid concomitant use with:
hours (7:1 preparations), CHILD >40 kg, 500/125 mg Increases risk of adverse or toxic effects of Methotrexate
every 8 hours (Max 2 g/day of amoxicillin)
Low-risk CAP with stable co-morbid illness, by mouth, Administration: Dosage depends on age, weight and renal
ADULT, 1 g twice daily. function of the patient and the severity of infection.
Pneumonia, anaerobic or aspiration with or without lung Dosages are expressed in terms of co-amoxiclav content
abscess, by mouth, ADULT (first line or second line), 1 g except when doses are stated in terms of an individual
twice daily. component. Therapy can be started parenterally and
Febrile neutropenia, by mouth, ADULT, 625 mg three times continued with an oral preparation.
a day with ciprofloxacin or levofloxacin.
Two co-amoxiclav 250/125 mg tablets should not be
substituted for one co-amoxiclav 500/125 mg tablet
since they are not equivalent.

Pregnancy Category: B

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ANTI-INFECTIVES FOR SYSTEMIC USE

ATC Code: J01CR02 Vertebral, including disk space infection and other sites, by
IV infusion, ADULT, (first and second line) 4.5 g every 8
hours, optimal duration of treatment is unknown, usually
PIPERACILLIN + TAZOBACTAM 6-12 weeks.
Rx Foot bone (calcaneus), following puncture wound, by IV
WHO anti-biotic category: WATCH
infusion, ADULT, 4.5 g every 8 hours.
Inj.: 2 g piperacillin + 250 mg tazobactam (as sodium salt) Long bone, post-internal fixation of fracture, by IV infusion,
per vial (IV infusion) ADULT, 4.5 g every 8 hours.
4 g piperacillin + 500 mg tazobactam (as sodium salt) Spinal implant, by IV infusion, ADULT, 4.5 g every 8 hours
per vial (IV infusion) (within 30 days).
Acute bacterial arthritis, monoarticular, by IV infusion,
Indications: Blood-borne infections due to urinary source ADULT, (not at risk for STI) 4.5 g every 8 hours for 2-4
(complicated UTI), blood-borne infections due to intra- weeks.
abdominal source, high risk blood-borne infection, health CLABSI, by IV infusion, CHILD, 200-300 mg/kg per day every
care associated sepsis, severe sepsis and associated 8 hours (plus vancomycin and aminoglycoside) 5-7 days
shock, febrile neutropenia in children, non-neutropenic or 10-14 days when catheter is retained or removed.
sepsis, sepsis from suspect urinary tract infection, sepsis Cardiovascular infection (impaired host, neutropenic), by IV
from suspect intra-abdominal source, sepsis from infusion, ADULT, 4.5 g every 6-8 hours (plus
suspect illicit drug IV use source, osteomyelitis vancomycin).
(hematogenous), vertebral including disk space infection Primary spontaneous bacterial peritonitis, by IV infusion,

J
and other sites, foot bone (calcaneus) following puncture ADULT (first line), 4.5 g every 6 hours or 4-hour infusion
wound, long bone post-internal fixation of fracture, spinal of 4.5 g every 8 hours; CHILD, 300 mg/kg per day divided
implant, acute bacterial arthritis, central line-associated 3 doses (piperacillin component).
bloodstream infection (CLABSI) in children, Secondary peritonitis, by IV infusion, CHILD, 300 mg/kg per
cardiovascular infection (impaired host, burn day divided 3 doses (piperacillin component) generally
neutropenic), primary spontaneous bacterial peritonitis, given for 5-10 days but the primary basis for duration of
secondary peritonitis, liver abscess, gallbladder antibiotic treatment is the patient’s clinical course.
infection, biliary complicated intra-abdominal infection, Liver abscess, by IV infusion, ADULT, 4.5 g every 4-6 hours
extra-biliary complicated intra-abdominal infection, (with metronidazole); CHILD, 300 mg/kg per day divided
orbital cellulitis, jugular vein suppurative phlebitis in 3 doses (piperacillin component) (plus metronidazole).
(Lemierre’s syndrome), necrotizing otitis externa, acute Gallbladder infection, by IV infusion, CHILD, 300 mg/kg per
mastoiditis, chronic or recurrent mastoiditis, high-risk day divided by 3 doses (piperacillin component).
CAP, lung abscess, pneumonia (anaerobic or aspiration Biliary complicated intra-abdominal infection (community-
with or without lung abscess) acquired acute cholecystitis), by IV infusion, ADULT, (first
line) 4.5 g every 6 hours.
Contraindications: History of acute, severe allergic reaction Extra-biliary complicated intra-abdominal infection (high
to any other ß-lactam active substances (e.g. risk), by IV infusion, ADULT, (first line) 4.5 g every 6 hours.
cephalosporin, monobactam or carbapenem) Acute Peritonitis, by IV infusion, ADULT, (first line) 4.5 g
every 4-6 hours. (Maximum dose for children is 3000
Dose: mg/ dose)
Blood-borne infection due to intra-abdominal source, by IV Orbital Cellulitis, by IV infusion, ADULT, (if MRSA is not
infusion, ADULT (second line), 300 mg (piperacillin considered) 4.5 g/kg every 8 hours; CHILD, (first line)
component) for 10-14 days or longer depending on 240-300 mg/kg per day in 3-4 doses (piperacillin
established foci of infection; (Max: 9-16 g per day) component) (max: 16 g/day).
Healthcare-associated shock, by IV infusion, ADULT, 300 Jugular vein suppurative phlebitis (Lemierre’s syndrome), by
mg/kg per day every 8 hours (piperacillin component) IV infusion, ADULT/CHILD, (first line) 4.5 g every 8 hours.
(Max: 9-16 g per day) for a period of 10-14 days in the Acute sinusitis in hospitalized patients with intubation, by IV
absence of a complication. infusion, ADULT/CHILD, (first line) 4.5 g every 6-8 hours.
Severe sepsis and aseptic shock, by IV infusion, CHILD, 300 Necrotizing otitis externa, by IV infusion, ADULT, (first line)
mg/kg per day every 8 hours (piperacillin component) 4.5 g every 6 hours, (second line) 4.5 g every 6 hours +/-
(Max: 9-16 g per day) for a period of 10-14 days in the gentamicin or amikacin per day; CHILD, (second line)
absence of a complication. 300 mg/kg per day every 8 hours.
Febrile neutropenia, by IV infusion, ADULT, 4.5 g every 6 Acute mastoiditis, by IV infusion, ADULT, (second line) 4.5 g
hours, duration of treatment should be dictated by every 8 hours (plus vancomycin).
organism or site; CHILD, 300 mg/kg per day divided Chronic or recurrent mastoiditis, by IV infusion, CHILD, 300
every 6 hours. mg/kg per day every 6 hours (plus gentamicin).
Sepsis, Non-neutropenic, by IV infusion, ADULT, (first line) High-risk CAP (Risk for P. aeruginosa), by IV infusion, ADULT,
4.5 g every 6-8 hours. 4.5 g every 6 hours (plus azithromycin and gentamicin or
Sepsis, Intra-abdominal suspect, by IV infusion, ADULT (first levofloxacin or ciprofloxacin).
line), 4.5 g every 6-8 hours. Lung abscess, by IV infusion, ADULT, 4.5 g every 8 hours (for
Sepsis, Urinary tract infection suspect, by IV infusion, ADULT mixed infections with resistant gram-negative aerobes)
(first line), 4.5 g every 6-8 hours. in combination with clindamycin or ampicillin-sulbactam
Sepsis, Illegal drug IV use suspect, by IV infusion, ADULT, or ceftriaxone for 4-6 hours.
4.5 g every 6-8 hours. Pneumonia (anaerobic or aspiration with or without lung
Osteomyelitis (hematogenous, long bone), by IV infusion, abscess), by IV infusion, ADULT, (second line) 4.5 g every
ADULT, 4.5 g every 8 hours for 4-6 weeks. 8 hours.

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(HAP) Hospital-acquired pneumonia and Ventilator- Increases serum concentration of Piperacillin +

associated pneumonia (MDR pathogens), by IV infusion, Tazobactam:
ADULT/CHILD, 300 mg/kg/day every 6 hours. Probenecid
HAP with or without high risk of mortality and with or without
risk factor for MDR, by IV infusion, ADULT and CHILD, 4.5 Reduces therapeutic effect of Piperacillin + Tazobactam:
g every 6 hours. Tetracycline, Typhoid Vaccine (Only the live attenuated
Empiric treatment of Ventilation-acquired pneumonia, by IV Ty21a strain is affected)
infusion, ADULT and CHILD, 4.5 g every 6 hours.
Lower respiratory tract infection due to P. aeruginosa, by IV Administration:
infusion, ADULT, 4.5 g every 6 hours by extended Compatible diluents for reconstitution are 0.9% Sodium
infusion; CHILD (second line), 300 mg/kg/day divided Chloride for Injection, Sterile Water for Injection,
every 6 hours. Bacteriostatic Water for Injection, Bacteriostatic Water
for Injection with benzyl alcohol, Bacteriostatic water for
NOTE: Maximum dose for adults is 18 g daily unless injection with parabens.
specified Reconstitute vial with the right diluent. Shake well until
dissolved.
Dose Adjustment:
Renal Impairment: Pregnancy Category: C
CrCl 20 to 40 mL/min:
Nosocomial pneumonia: 3.375 g IV every 6 hours ATC Code: J01CR05
J

Other indications: 2.25 g IV every 6 hours

Precautions: OTHER BETA-LACTAM ANTIBACTERIALS

WARNING: Serious and occasional fatal hypersensitivity
(anaphylactic) reactions for people with hypersensitivity FIRST-GENERATION CEPHALOSPORINS
to multiple allergens.
Cross sensitivity reactions may happen with other CEFALEXIN (CEPHALEXIN)
lactam antibiotics such as cephalosporins. Rx
WHO anti-biotic category: ACCESS
In case of severe, persistent diarrhea, the possibility of
antibiotic -induced pseudomembranous colitis must be Oral: 500 mg capsule (as monohydrate)
taken into consideration. 100 mg/mL, granules / powder for drops (as
monohydrate), 10 mL
Patient with cystic fibrosis, history of seizure disorder, renal 125 mg/5 mL granules / powder for syrup /
impairment, children, pregnancy and lactation suspension (as monohydrate), 30 mL
250 mg/5 mL granules / powder for syrup /
Adverse Drug Reactions: suspension (as monohydrate), 60 mL
Common: Phlebitis, headache, insomnia, skin rash,
pruritus, electrolyte disturbance, hypokalemia, Indications: Treatment of dacryocystitis, mild methicillin
hyperglycemia, diarrhea, constipation, nausea, sensitive staphylococcus aureus infections, and dental
dyspepsia, vomiting, abdominal pain, eosinophilia, prophylaxis
positive direct Coombs test, leukopenia, neutropenia,
prolonged bleeding time, thrombocythemia, Dose:
thrombocytopenia, candidiasis, local irritation, fever Dental prophylaxis, allergic to penicillins or ampicillin, by
Less Common: Flushing, hypotension, rigors, mouth, CHILD, 50 mg/kg; ADULT, 2 g.
thrombophlebitis, purpura, pseudomembranous colitis, Dacryocystitis, by mouth, ADULT, 500 mg four times a day
hypoglycemia, anaphylaxis, injection site reaction, for 7-14 days.
arthralgia, myalgia, epistaxis Methicillin sensitive staphylococcus aureus, mild to
moderate infections, by mouth, 25- 50 mg/kg/day
Drug Interactions: divided in 3-4 doses, severe infections, by mouth, 75-
Monitor closely with: 100 mg/kg/day divided in 3- 4 doses
Reduces therapeutic effect of BCG Vaccine
Dose Adjustment:
Increases risk of adverse or toxic effects of Vancomycin Renal Impairment:
Adults: CrCl 10-50mL/min, 500 mg every 8-12 hours; CrCl
Enhances absorption of Vecuronium < 10 mL/min, 250-500 mg every 12-24 hours
Hemodialysis patients, 250 mg every 12-24 hours;
Enhances therapeutic effect of Vitamin K Antagonists e.g. moderately dialyzable (20-50%); give dose after dialysis
Warfarin session.

Avoid concomitant use with: Precautions:

Decreases serum concentration of Aminoglycosides e.g. Elevated INR especially with nutritionally-deficient patients,
Streptomycin prolonged treatment, hepatic or renal disease;
Penicillin allergy. Use with caution in patients with history of
Reduces therapeutic effect of the following drugs: penicillin allergy, especially IgE-mediated reactions (eg.
BCG (Intravesical), Sodium Picosulfate anaphylaxis, angioedema, urticaria);

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ANTI-INFECTIVES FOR SYSTEMIC USE

Prolonged use may result in bacterial or fungal Severe, by IV injection/ infusion, CHILD, 100-150 mg/kg
superinfection including C. difficile-associated diarrhea in 3 doses; maximum daily dose: 6 g.
(CDAD) and pseudomembranous colitis, CDAD has been Septic bursitis, MSSA, by IV injection/ infusion, ADULT, 2 g
observed >2 months post-antibiotic treatment. every 8 hours for 14-21 days.
Prosthetic joint infection, MSSA, by IV injection/ infusion,
Adverse Drug Reactions: ADULT, 2 g every 8 hours with rifampin for 2-6 weeks.
Common and Less Common: Agitation, confusion, Native valve infective endocarditis, MSSA, by IV injection/
dizziness, fatigue, hallucination, headache, genital infusion, ADULT, 2 g every 8 hours for 6 weeks.
pruritus, skin rash, urticaria, abdominal pain, diarrhea, Dental prophylaxis, by deep IM injection or IV injection/
dyspepsia, pseudomembranous colitis, gastritis, genital infusion, CHILD, 50 mg/kg; ADULT, 1 g.
candidiasis, vaginal discharge, vaginitis, eosinophilia, Central-line associated bloodstream infection, MSSA, by IV
hemolytic anemia, thrombocytopenia, neutropenia, injection/ infusion, ADULT, 2 g every 8 hours.
anaphylaxis, angioedema, arthralgia, arthritis, Dacryocystitis, by IV injection/ infusion, ADULT, 2 g every 8
arthropathy, hypersensitivity reactions hours for 7-14 days.
Rare: Erythema multiforme, Stevens Johnson syndrome,
toxic epidermal necrosis, nausea, vomiting, cholestatic Dose Adjustment:
jaundice, hepatitis (transient), interstitial nephritis Geriatric:
Refer to adult dosing.
Drug Interactions:
Avoid concomitant use with: Renal Impairment:

J
Reduces therapeutic effect of the following drugs: Adults:
BCG (intravesical), Sodium picosulfate, Typhoid vaccine CrCl 35-54 mL/minute or SrCr 1.6-3 mg%: Full dose every 8
hours or longer; ClCr 11-34 mL/minute or SrCr 3.1-4.5
Enhances therapeutic effect of Vitamin K antagonists e.g. mg%: 1/2 usual dose every 12 hours; CrCl ≤10
Warfarin mL/minute or SrCr ≥4.6 mg%: 1/2 usual dose every 18-
24 hours.
Increases serum concentration of Cefalexin: Pediatrics:
Metformin, Probenecid CrCl 41-70 mL/minute: 60% of usual dose given in equally
divided doses every 12 hours; CrCl 21-40 mL/minute:
Decreases serum concentration of Cefalexin: 25% of usual dose given in equally divided doses every
Multivitamins/Minerals (with ADEK, folate, iron) 12 hours; CrCl ≤5-20 mL/minute: 10% of usual dose
given in equally divided doses every 24 hours.
Reduces absorption of Cefalexin:
Zinc salts Precautions:
Monitor patients for: Elevated INR, Penicillin Allergy,
Administration: Take without regard to food. If GI distress, Superinfection;
take with food. Give around­the­clock to promote less Use with caution in patients with: Renal Impairment, Seizure
variation in peak and trough serum levels. Disorders.

Pregnancy Category: B Adverse Drug Reactions: Diarrhea, oral candidiasis,

stomach cramps, anorexia, anaphylaxis, eosinophilia,
ATC Code: J01DB01 itching, skin rash, leukopenia, thrombocytopenia,
hepatitis, genital or anal pruritus

CEFAZOLIN Drug Interactions:

Rx Increases serum concentration of Cefazolin:
WHO anti-biotic category: ACCESS
Probenecid
Inj.: 500 mg and 1 g vial (as sodium salt) (IM, IV)
Increases risk of adverse or toxic effects of the following
Indications: Treatment of staphylococcal toxic shock drugs:
syndrome, osteomyelitis, septic bursitis, prosthetic joint Fosphenytoin, Phenytoin, Vitamin K Antagonists e.g.
infection, native valve infective endocarditis, central-line Warfarin
associated bloodstream infection, dacryocystitis, and
dental prophylaxis Reduces therapeutic effect of the following drugs:
BCG Vaccine (Immunization), Typhoid Vaccine
Contraindication: Known allergy to the cephalosporin group
of antibiotics. Administration:
For IM: Inject deep IM into large muscle mass.
Dose: For IV: Inject direct IV over 5 minutes or may infuse as an
Staphylococcal toxic shock syndrome, by IV injection/ intermittent infusion over 30­60 minutes.
infusion, CHILD, 75-100 mg/kg in divided doses every 8
hours; maximum daily dose: 3-6 g. Pregnancy Category: B
Osteomyelitis, contiguous focus, MSSA, mild to moderate,
by IV injection/ infusion, CHILD, 50 mg/kg in 3 doses; ATC Code: J01DB04
maximum daily dose: 4 g;

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 ANTI-INFECTIVES FOR SYSTEMIC USE

SECOND-GENERATION CEPHALOSPORINS NOTE: Alternative recommendations: 2g within 60 minutes

prior to surgical incision; Doses may be repeated in 2
hours if procedure is lengthy or if there is excessive blood
Rx CEFOXITIN loss.

CHILD and INFANT >3 months old, 30-40 mg/kg 30-60

Inj.: 1 g vial (as sodium salt) (IM, IV)
minutes prior to surgical incision followed by 30-40
1 g powder for injection (as sodium) + 4% Dextrose
mg/kg/dose every 6 hours for no more than 24 hours
Solution for injection (IV infusion)
after surgery depending on the procedure.
Indications: Treatment of serious infections wherein
NOTE: Alternative recommendations: Children ≥1 years old:
anaerobes are suspected or documented including
40 mg/kg within 60 minutes prior to surgical incision
those of the lower respiratory tract, skin and skin
(maximum: 2000 mg/dose), doses may be repeated in 2
structure, bone and joint, and urinary tract; septicemia;
hours if procedure is lengthy or if there is excessive blood
Gynecologic infections; intra­abdominal infections
loss.
caused by susceptible bacteria; perioperative
prophylaxis
Dose Adjustment:
Renal Impairment:
Contraindications: Hypersensitivity to cefoxitin, any
IV: CrCl 30-50mL/minute: 1-2g every 8-12 hours; CrCl 10-
component of the formulation, or other cephalosporins.
29mL/minute: 1-2g every 12-24 hours; CrCl 5-9
J

mL/minute: 0.5-1g every 12-24 hours; CrCl

Dose:
<5mL/minute: 0.5-1g every 24-48 hours; Hemodialysis:
General dosing information, by IV push/ infusion,
Loading dose: 1-2g after each hemodialysis;
ADOLESCENT, CHILD, and INFANT >3 months, 80-160
Maintenance dose as noted above based on creatinine
mg/kg/day divided every 4-6 hours (max. daily dose: 12
clearance.
g).
Precautions:
NOTE: Alternative dose: Mild­to­moderate infection: Infants
Monitor patients for: Hypersensitivity, Superinfection; Use
>3 months old and Children, 80 mg/kg/day in divided
with caution in patients with: Gastrointestinal disease;
doses every 6-8 hours (maximum daily dose: 4000
renal impairment; seizure disorders; Discontinuation of
mg/day);
therapy: In pediatric patients ≥3 months old, higher
Severe infection: Infants >3 months old and Children, 160
doses have been associated with an increased incidence
mg/kg/day in divided doses every 4-6 hours (maximum
of eosinophilia and elevated AST.
dose: 12 g/day).
Adverse Drug Reactions:
Susceptible infections, by IV push/ infusion, ADULT, 1-2 g
Local reactions, rash, pruritus, fever, dyspnea, hypotension,
every 6-8 hours.
diarrhea, pseudomembranous colitis, exacerbation of
myasthenia gravis, eosinophilia, leukopenia,
NOTE: IM injection is painful
thrombocytopenia, bone marrow depression
Gas gangrene, by IV push/ infusion, ADULT, 2 g every 4
Drug Interactions:
hours or 3 g every 6 hours (max. daily dosage: 12 g).
Increases serum concentration of Cefoxitin:
Intra­abdominal infection, complicated community-
Probenecid
acquired, by IV push/ infusion, ADULT, Mild to moderate:
2 g every 6 hours for 4-7 days;
Increases risk of adverse or toxic effects of the following
Moderately severe or severe infections: 1 g every 4 hours or
drugs:
2 g every 6-8 hours (max. daily dosage: 8 g);
Aminoglycosides e.g. Streptomycin
Extra-biliary complicated intra- abdominal infections: 2 g
Vitamin K Antagonists e.g. Warfarin
every 6 hours.
Pelvic inflammatory disease for inpatients, by IV push/
Reduces therapeutic effect of the following drugs:
infusion, ADULT, 2 g every 6 hours plus doxycycline for at
BCG Vaccine, Typhoid Vaccine
least 24 hours after clinical improvement, followed by
doxycycline to complete 14 days;
Administration:
For outpatients, by IM injection, ADULT, 2 g with oral
For IM: Inject deep IM into large muscle mass.
probenecid, followed by doxycycline (with or without
For IV: Can be administered IVP over 3-5 minutes or by IV
concomitant metronidazole) for 14 days.
intermittent infusion over 10-60 minutes.
Surgical (perioperative) prophylaxis, by IV push/ infusion,
ADULT and ADOLESCENT, procedures other than
Pregnancy Category: B
Cesarean section, 2g 30-60 minutes prior to surgical
incision, followed by 2g every 6 hours for no more than
ATC Code: J01DC01
24 hours after surgery depending on the procedure;
Cesarean section: 2g as soon as umbilical cord is clamped
as a single dose or 2g as soon as umbilical cord is
clamped followed by 2g at 4 and 8 hours after the initial
dose;

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ANTI-INFECTIVES FOR SYSTEMIC USE

Continuous renal replacement therapy (CRRT): 1 g every 12

Rx CEFUROXIME hours.

Oral: 500 mg tablet (as axetil) Precautions:

125 mg/5 mL granules for suspension (as axetil), 70 WARNING: Use with caution in patients with a history of
mL penicillin allergy.
250 mg/5 mL granules for suspension, 50 mL and
120 mL
Inj.: 250 mg and 750 mg vial (IM, IV) May be associated with increased INR, especially in
1.5 g VIAL (as sodium salt) (IV infusion) nutritionally-deficient patients, prolonged treatment,
hepatic or renal disease; Prolonged use may result in
Indications: Treatment of infections caused by methicillin fungal or bacterial superinfection, including C. difficile-
sensitive staphylococci, group B. streptococcus, H. associated diarrhea (CDAD) and pseudomembranous
influenzae (type A and B), E. coli, Enterobacter, colitis; CDAD has been observed >2 months post-
Salmonella, and Klebsiella; treatment of susceptible antibiotic treatment.
infections of the upper and lower respiratory tract, otitis
media Adverse Drug Reactions:
Common: Diarrhea
Contraindications: Hypersensitivity to cefuroxime, any Less Common: Diaper rash, nausea, vomiting, vaginitis,
component of the formulation, or other cephalosporins. eosinophilia

J
Rare: Anaphylaxis, angioedema, chest pain, cholestasis,
Dose: colitis, dyspnea, erythema multiforme, fever, GI bleeding,
Acute otitis media, no anaphylaxis, by mouth, CHILD, 30 hemolytic anemia, hepatitis, hives, hyperbilirubinemia,
mg/kg every 12 hours for 10 days (<2 years old), 7 days hypersensitivity, interstitial nephritis, jaundice,
(2-5 years old), 5-7 days (>5 years old); ADULT, 500 mg- leukopenia, neutropenia, pain at injection site,
1 g in divided doses every 12 hours for 7 days. pancytopenia, positive Coombs test,
Acute otitis media, clinical failure after 3 days, by mouth, pseudomembranous colitis, rash, renal dysfunction,
CHILD, 30 mg/kg in divided doses every 12 hours for 10 seizure, SJS, stomach cramps, tachycardia,
days (2yrs old OR severe symptoms regardless of age), thrombocytopenia, tongue swelling, toxic epidermal
5-7 days (>2yrs with mild or moderate disease). necrolysis, urticaria.
Acute bacterial exacerbation of chronic bronchitis (ABECB),
by mouth, ADULT, 500 mg twice a day for 5-10 days Drug Interactions:
Community-acquired pneumonia, non-severe, by mouth, Decreases serum concentration of Cefuroxime:
CHILD >40 kg, 20-30 mg/kg in divided doses every 12 Antacids
hours for 7 days;
Severe, with no Hib vaccination or incomplete or Reduces therapeutic effect of the following drugs:
unknown vaccination history, by mouth, CHILD, 100 BCG, Typhoid vaccine (Only the live attenuated Ty21a
mg/kg in divided doses every 8 hours. strain is affected.)
With stable co-morbid illness, by mouth, ADULT, 500 mg
twice a day for 5-7 days or 3-5 days if using with Increases serum concentration of Cefuroxime:
azithromycin. Probenecid
Recurrent pharyngitis, by mouth, CHILD, 20 mg/kg in
divided doses every 12 hours for 10 days; ADULT, 500 Reduces absorption of Cefuroxime:
mg-1 g every 12 hours for 10 days. H2-antagonists e.g. Cimetidine (Separate oral doses by
Deep neck abscess/ Retropharyngeal abscess, by mouth, at least 2 hours.)
CHILD, 20-30 mg/kg in divided doses every 12 hours
with metronidazole 10 mg/kg in divided doses every 6 Administration:
hours for at least 7 days; ADULT, 500 mg twice daily with For Oral suspension: Administer with food. Shake well
metronidazole 500 mg every 8 hours for at least 7 days. before use.
Acute bacterial rhinosinusitis, with severe penicillin allergy, For IM: Inject deep IM into large muscle mass.
by mouth, CHILD, 30 mg/kg in divided doses every 12 For IV: Inject direct IV over 3-5 minutes. Infuse intermittent
hours for 10 days; ADULT, 500 mg twice daily for 5-7 infusion over 15-30 minutes.
days.
Acute sinusitis (clinical failure after 3 days), by mouth, Pregnancy Category: B
ADULT, 500 mg twice daily for 7-10 days.
ATC Code: J01DC02
Dose Adjustment:
Geriatric:
Refer to adult dosing.

Renal Impairment:
CrCl 10-20mL/minute: Administer every 12 hours.
CrCl <10mL/minute: Administer every 24 hours.
Hemodialysis: Dialyzable (25%).
Peritoneal dialysis: Dose every 24 hours.

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 ANTI-INFECTIVES FOR SYSTEMIC USE

THIRD-GENERATION CEPHALOSPORINS thrombocytopenia, toxic epidermal necrolysis, urticaria,

vaginitis, vomiting.

Rx CEFIXIME Drug Interactions:

WHO anti-biotic category: ACCESS and WATCH
Reduces therapeutic effect of the following drugs:
BCG, Typhoid vaccine (Only the live attenuated Ty21a strain
Oral: 200 mg capsule and 400 mg capsule
is affected)
20 mg/mL granules for drops (suspension), 10 mL
100 mg/5 mL granules for suspension, 60 mL
Increases serum concentration of Cefixime:
Probenecid
Indications: Second line therapy for uncomplicated typhoid
fever, salmonella gastroenteritis, uncomplicated
Administration:
gonococcal infections of the cervix, urethras, rectum and
May be administered with or without food; administer with
conjunctiva. Step down therapy for severe/complicated
food to decrease GI distress.
typhoid fever
Shake oral suspension well before use.
Dose:
Pregnancy Category: B
Gonococcal conjunctivitis, CHILD, by mouth, 8 mg/kg/day
with 10- 12 mg/kg/day of azithromycin
ATC Code: J01DD08
Uncomplicated typhoid fever (second line), by mouth,
J

CHILD, 15-20 mg/kg/day every 12 hours for 7-10 days;

maximum daily dose: 12 g; ADULT, 200mg every 12
hours for 7-10 days. Rx CEFOTAXIME
Step down therapy, Severe complicated typhoid fever, by WHO anti-biotic category: ACCESS and WATCH
mouth, CHILD, 15-20 mg/kg every 12 hours for 7-10
days; maximum daily dose: 200 mg 1 tablet every 12 Inj.: 250 mg vial (as sodium salt) + 2 mL diluent (IM, IV)
hours; ADULT, 200 mg 1 tablet every 12 hours for 7-10 500 mg vial (as sodium salt) + 2 mL diluent (IM, IV)
days.
Salmonella gastroenteritis, by mouth, CHILD, 15 mg/kg in Indications: Treatment of serious bone and joint infections,
divided doses every 12 hours for 7-10 days; maximum meningitis and other central nervous system infections,
daily dose: 400 mg. serious lower respiratory tract infections (including
Uncomplicated gonococcal infections of the cervix, urethras pneumonia), bacteremia/septicemia, serious skin and
and rectum, ADULT, 400 mg per dose with 1g of skin structure infections, multi drug resistant or
azithromycin per dose, CHILD, by mouth, 8 mg/kg/day complicated typhoid fever and other infections caused by
with 10-12 mg/kg/day of azithromycin Salmonella, infections caused by Vibrio
parahaemolyticus or V. vulnificus.
Dose Adjustment:
Renal Impairment: Dose:
CrCl 21-60 mL/ minute: Administer 75% of the standard Bacterial purulent pericarditis, by IV bolus/ infusion, CHILD,
dose. 200-300 mg/kg in divided doses every 6 to 8 hours;
CrCl <20 mL/minute: Administer 50% of the standard dose. maximum daily dose: 12 g.
10% removed by hemodialysis. Community acute bacterial meningitis, by deep IM injection
or IV bolus/ infusion, NEONATE 0-7 days old and <2kg,
50 mg/kg every 12 hours; NEONATE 0-7 days old and
Precautions: ≥2kg, 50 mg/kg every 8 hours; NEONATE >7 days old
and <2kg, 50 mg/kg every 8 hours; NEONATE >7 days
WARNING: Use with caution in patients with a history
old and ≥2kg, 50 mg/kg every 6 hours; duration
of penicillin allergy, especially IgE-mediated
dependent on the etiology of bacterial meningitis.
reactions.
Neonatal Sepsis, by deep IM injection or IV bolus/ infusion,
NEONATE ≤7 days old ≤2kg, 50 mg/kg every 12 hours;
Prolonged use may result in fungal or bacterial NEONATE 8-28 days old ≤2kg, 50 mg/kg every 8-12
superinfection, including C. difficile-associated diarrhea hours; NEONATE ≤7 days old >2kg, 50 mg/kg every 12
(CDAD) and pseudomembranous colitis. CDAD has been hours; NEONATE 8-28 days old >2kg, 50 mg/kg every 8
observed >2 months post-antibiotic treatment; Use with hours; with gentamicin OR amikacin with or without
caution in patients with renal impairment; modify oxacillin OR vancomycin.
dosage. Clinical sepsis without focus, by deep IM injection or IV
bolus/ infusion, CHILD, 200-225 mg/kg in divided doses
Adverse Drug Reactions: every 4-6 hours for 10-14 days or longer depending on
Common: Diarrhea established foci of infection.
Less Common: Abdominal pain, nausea, dyspepsia, Immunocompetent children, Urinary source, by IV bolus/
flatulence, loose stools. infusion, CHILD, 200-225 mg/kg in divided doses every
Rare: Acute renal failure, anaphylactic reactions, 4-6 hours; maximum daily dose: 8-12 g.
angioedema, candidiasis, dizziness, drug fever, Immunocompetent children, Intra-abdominal source, by IV
eosinophilia, erythema multiforme, facial edema, fever, bolus/ infusion, CHILD, 200-225 mg/kg in divided doses
headache, hepatitis, hyperbilirubinemia, jaundice, every 4-6 hours; maximum daily dose: 8-12 g.
leukopenia, neutropenia, pseudomembranous colitis,
rash, seizure, serum sickness-like reaction, SJS,

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ANTI-INFECTIVES FOR SYSTEMIC USE

Post-splenectomy, by IV bolus/ infusion, CHILD, 200-225 function) and should not supersede clinical judgment:
mg/kg in divided doses every 4-6 hours; maximum daily Continuous veno-venous hemofiltration: 1-2 g every 8-12
dose: 8-12 g. hours; Continuous veno-venous hemodialysis: 1-2 g
Non-typhoidal salmonellosis, by IV bolus/ infusion, CHILD, every 8 hours; Continuous venovenous
100-200 mg/kg in divided doses every 6 hours for 5-14 hemodiafiltration: 1-2 g every 6-8 hours.
days; maximum daily dose: 8-12 g.
Leptospirosis, moderate to severe, by IV bolus/ infusion, Children:
CHILD, 100-150 mg/kg every 6-8 hours for 7 days; NOTE: Glomerular filtration rate should be estimated using
maximum daily dose: 1 g every 6 hours. an acceptable pediatric method (eg, Schwartz equation,
Orbital Cellulitis, by IV bolus/ infusion, CHILD, 100-200 Traub­Johnson equation, or a height/weight nomogram).
mg/kg in 3-4 doses with linezolid for 7-14 days
depending on clinical response; maximum daily dose: 2g. Dose Adjustment:
Osteomyelitis, hematogenous, by IV bolus/ infusion, INFANT Glomerular filtration rate 30-50 mL/minute/1.73m2: 35-70
0-4 weeks and <1.2kg, 100 mg/kg in 2 doses; INFANT mg/kg/dose every 8-12 hours; Glomerular filtration rate
<7 days old and 1.2-2kg, 100 mg/kg in 2 doses; INFANT 10 to 29 mL/minute/1.73m2: 35-70 mg/kg/dose every
>7 days old and 1.2-2kg, 150 mg/kg in 3 doses; INFANT 12 hours; Glomerular filtration rate <10
<7 days old and >2kg, 100 mg/kg in 2 doses; INFANT >7 mL/minute/1.73m2: 35 to 70 mg/kg/dose every 24
days old and >2kg, 150-200 mg/kg in 3-4 doses; CHILD, hours; Intermittent hemodialysis: 35-70 mg/kg/dose
100-200 mg/kg in 1-2 doses; maximum daily dose: 8 g. every 24 hours; Peritoneal dialysis: 35-70 mg/kg/dose
Prosthetic valve infective endocarditis, gram negative every 24 hours; Continuous renal replacement therapy:

J
enteric bacilli, by IV bolus/ infusion, CHILD, 200 mg/kg 35-70 mg/kg/dose every 12 hours.
in divided doses every 6 hours daily for 6 weeks with
gentamicin; maximum daily dose: 12 g. Precautions:
Suppurative arthritis, gram stain is negative OR if gram stain Monitor patients for: arrhythmia, granulocytopenia,
is positive for gram-positive cocci, by IV bolus/ infusion, penicillin allergy, tissue inflammation, superinfection;
CHILD, 100-200 mg/kg in 3-4 doses with vancomycin; Use with caution in patients with colitis and renal
maximum daily dose: 12 g. impairment.
Suppurative arthritis, gram stain is positive for gram-
negative organisms, by IV bolus/ infusion, CHILD, 100- Adverse Drug Reactions:
200 mg/kg in 3-4 doses; maximum daily dose: 12 g. Injection-site reactions (e.g., pain, induration, tenderness,
inflammation)
Dose Adjustment:
Geriatric: Drug Interactions:
Refer to adult dosing. Increases serum concentration of Cefotaxime:
Probenecid
Renal Impairment:
Note: Renal function may be estimated using Increases risk of adverse or toxic effects of the following
Cockcroft­Gault formula for dosage adjustment drugs:
purposes. Aminoglycosides, Vitamin K Antagonists (e.g. Warfarin)

CrCl <20mL/minute/1.73 m2: dose should be decreased by Reduces therapeutic effect of the following drugs:
50%. BCG Vaccine (Immunization), Typhoid Vaccine
Alternative recommendation:
Adults: Administration:
Glomerular Filtration Rate >50 mL/minute: Administer For IM: Inject deep IM into large muscle mass. Individual
every 6 hours; Glomerular Filtration Rate 10-50 doses of 2 g may be given if the dose is divided and
mL/minute: Administer every 6-12 hours; Glomerular administered in different IM sites.
Filtration Rate <10 mL/minute: Administer every 24 For IV: Inject directly IV as a bolus over at least 3-5 minutes.
hours or decrease the dose by 50% (and administer at Infuse intermittent infusion over 15-30 minutes.
usual intervals); Intermittent hemodialysis: Administer 1-
2 g every 24 hours (on dialysis days, administer after Pregnancy Category: B
hemodialysis).
ATC Code: J01DD01
NOTE: Dosing dependent on the assumption of 3 times a
week, complete intermittent hemodialysis sessions.

Peritoneal dialysis: 1 g every 24 hours

Continuous renal replacement therapy: Drug clearance is
highly dependent on the method of renal replacement,
filter type, and flow rate. Appropriate dosing requires
close monitoring of pharmacologic response, signs of
adverse reactions due to drug accumulation, as well as
drug concentrations in relation to target trough (if
appropriate). The following are general
recommendations only (based on dialysate flow
ultrafiltration rates of 1-2 L/h and minimal residual renal

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 ANTI-INFECTIVES FOR SYSTEMIC USE

CEFTAZIDIME every 8 hours infused for 15-30 minutes with

Rx vancomycin OR linezolid.
WHO anti-biotic category: WATCH
Pathogen-specific treatment, P. aeruginosa, by IV push/
Inj.: 250 mg, 500 mg, and 1 g vial (as pentahydrate) (IM, infusion, CHILD, 100-150 mg/kg in divided doses every
IV) 8 hours with amikacin OR gentamicin; ADULT, 2 g every
2 g vial (as pentahydrate) (IV infusion) 8 hours with amikacin OR gentamicin OR aztreonam;
Achromobacter, by IV push/ infusion, CHILD, 100-150
Indications: Treatment of documented susceptible mg/kg in divided doses every 8 hours with trimethoprim-
Pseudomonas aeruginosa infection and infections due sulfamethoxazole;
to other susceptible aerobic gram-negative organisms; Burkholderia pseudomallei, by IV push/ infusion, CHILD,
neonatal sepsis, osteomyelitis, bone and joint infections, 100-150 mg/kg in divided doses every 8 hours with
necrotizing otitis externa, dacryocystitis, acute sinusitis, trimethoprim-sulfamethoxazole for 12-24 weeks; ADULT,
infective endocarditis. 2 g every 6 hours for 10-14 days.

Dose: Dose Adjustment:

Neonatal Sepsis, by deep IM injection or IV push/ infusion, Geriatric:
NEONATE ≤7 days old ≤2 kg, 50 mg/kg every 12 hours; IM, IV: Dosage should be based on renal function with a
NEONATE 8-28 days old ≤2 kg, 50 mg/kg every 8-12 dosing interval not more frequent than every 12 hours.
hours; NEONATE ≤7 days old >2 kg, 50 mg/kg every 12
hours; NEONATE 8-28 days old >2 kg, 50 mg/kg every 8 Renal Impairment:
J

hours; with gentamicin OR amikacin. CrCl 30-50mL/minute: Administer every 12 hours.

Healthcare-associated sepsis, by deep IM injection or IV CrCl 10-30mL/minute: Administer every 24 hours.
push/ infusion, CHILD, 150-200 mg/kg in divided doses CrCl <10mL/minute: Administer every 48-72 hours.
every 8 hours with or without amikacin OR vancomycin; Intermittent hemodialysis (IHD) (administer after
maximum daily dose: 6 g. hemodialysis on dialysis days): Dialyzable (50% to
Osteomyelitis, hematogenous, long bones, by IV push/ 100%): 0.5-1 g every 24 hours or 1-2 g every 48-72
infusion, ADULT, 2 g every 8 hours with vancomycin OR hours. Note: Dosing dependent on the assumption of 3
oxacillin for 6-12 weeks. times/week, complete IHD sessions.
Osteomyelitis, contiguous without vascular insufficiency, Peritoneal dialysis (PD): Loading dose of 1 g, followed by
foot bone, by IV push/ infusion, ADULT, 2 g every 8 hours. 500 mg every 24 hours.
Long bone or spinal implant, by IV push/ infusion, ADULT, Continuous renal replacement therapy (CRRT): Drug
2 g every 8 hours with vancomycin 15-20 mg/kg every 8- clearance is highly dependent on the method of renal
12 hours. replacement, filter type, and flow rate. Appropriate
Acute bacterial arthritis (gram negative bacilli), by IV push/ dosing requires close monitoring of pharmacologic
infusion, ADULT, 2 g every 8 hours. response, signs of adverse reactions due to drug
Bone and joint infections, by IV push/ infusion, ADULT, 2 g accumulation, as well as drug concentrations in relation
every 12 hours for 4-6 weeks. to target trough (if appropriate). The following are general
Native valve infective endocarditis, healthcare-associated, recommendations only (based on dialysate
by IV push/ infusion, CHILD, 100-150 mg/kg in divided flow/ultrafiltration rates of 1-2 L/hour and minimal
doses every 8 hours with vancomycin and gentamicin; residual renal function) and should not supersede
maximum daily dose: 2-4 g; ADULT, 2 g every 8 hours clinical judgment:
with vancomycin and gentamicin. CVVH: Loading dose of 2 g followed by 1-2 g every 12
Prosthetic valve infective endocarditis, gram-negative hours.
enteric bacilli, by IV push/ infusion, CHILD, 100-150 CVVHD/CVVHDF: Loading dose of 2 g followed by either
mg/kg in divided doses every 8 hours for 6 weeks; 1 g every 8 hours or 2 g every 12 hours. Note: Dosage of
maximum daily dose: 2-4 g. 1 g every 8 hours results in similar steady-state
Impaired host, burn, neutropenic, by IV push/ infusion, concentrations as 2 g every 12 hours and is more cost
ADULT, 2 g every 8 hours with vancomycin. effective. Dosage of 2 g every 8 hours may be needed for
Anatomic defects, neurological complications, open head gram-negative rods with MIC ≥4 mg/L.
trauma, by deep IM injection or IV push/ infusion, CHILD, Note: For patients receiving CVVHDF, some recommend
150 mg/kg in divided doses every 8 hours with giving a loading dose of 2 g followed by 3 g over 24 hours
vancomycin; ADULT, 2 g every 8 hours with vancomycin. as a continuous IV infusion to maintain concentrations
Brain abscess in the presence of chronic otitis media, ≥4 times the MIC for susceptible pathogens.
sinusitis, or mastoiditis, by deep IM injection or IV push/
infusion, CHILD, 150 mg/kg in divided doses every 8 Precautions:
hours with metronidazole; ADULT, 2 g every 8 hours with WARNING: Use with caution in patients with a history of
metronidazole. penicillin allergy, especially IgE-mediated reactions.
Dacryocystitis, by IV push/ infusion, CHILD, 100 mg/kg
divided in 3 doses for 7-14 days. Prolonged use may result in fungal or bacterial
Acute sinusitis, by IV push/ infusion, ADULT, 2 g every 8 superinfection, including C. difficile-associated diarrhea
hours with vancomycin. (CDAD) and pseudomembranous colitis; CDAD has been
Necrotizing otitis externa, by IV push/ infusion, CHILD, 100- observed >2 months post-antibiotic treatment;
150 mg/kg in divided doses every 8 hours. Use with caution in patients with renal impairment modify
Hospital-acquired and ventilator-associated pneumonia, by dosage in severe impairment); Use with caution in
IV infusion, CHILD, 100-150 mg/kg in divided doses patients with a history of seizure disorder, high levels,

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ANTI-INFECTIVES FOR SYSTEMIC USE

particularly in the presence of renal impairment, may approximately 5-7 days after clinical signs and symptoms
increase risk of seizures. of infection have disappeared.
Clinical sepsis without focus, by IV infusion, CHILD, 100
Adverse Drug Reactions: mg/kg in divided doses every 12-24 hours with or
Less Common: Diarrhea, pain at injection site, without oxacillin OR vancomycin for 10-14 days or longer
hypersensitivity reactions. depending on foci of infection.
Rare: Anaphylaxis, angioedema, asterixis, candidiasis, Immunocompetent children, urinary source, by IV infusion,
dizziness, encephalopathy, eosinophilia, erythema CHILD, 100 mg/kg in divided doses every 12-24 hours
multiforme, hyperbilirubinemia, pruritus, toxic epidermal with gentamicin OR amikacin.
necrolysis, vaginitis, vomiting. Immunocompetent children, intra-abdominal source, by IV
infusion, CHILD, 100 mg/kg in divided doses every 12-
Drug Interactions: 24 hours with metronidazole OR clindamycin.
Reduces therapeutic effect of the following drugs: Post-splenoctomy, by IV infusion, CHILD, 100 mg/kg in
BCG, Typhoid vaccine (Only the live attenuated Ty21a divided doses every 12-24 hours.
strain is affected.) Streptococcal toxic shock syndrome, by IV infusion, CHILD,
100 mg/kg in divided doses every 12-24 hours with
Increases serum concentration of Ceftazidime: clindamycin and IVIG for 10-14 days or longer depending
Probenecid on the infection.
Sepsis, suspect intra-abdominal source, by IV infusion,
Administration: ADULT, 2 g every12 hours with metronidazole.

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Any carbon dioxide bubbles that may be present in the Sepsis, suspect urinary tract infection, by IV infusion,
withdrawn solution should be expelled prior to injection. ADULT, 1 g every 24 hours.
Administer around the clock to promote less variation in Sepsis, suspect meningococcemia, by IV infusion, ADULT, 2
peak and trough serum levels. g every 12 hours.
Ceftazidime can be administered deep IM into large mass Sepsis, post splenoctomy, by IV infusion, ADULT, 2 g every
muscle, IVP over 3-5 minutes, or IV intermittent infusion 12 hours.
over 15-30 minutes. Do not admix with aminoglycosides Sepsis, Streptococcal toxic shock, by IV infusion, ADULT, 2 g
in same bottle/bag. Final concentration for IV every 24 hours with clindamycin and IVIG for a minimum
administration should not exceed 100 mg/mL. of 14 day with bacteremia.
Complicated typhoid fever, by IV infusion, CHILD, 75 mg/kg
Pregnancy Category: B for 10-14 days; ADULT, 1-2 g for 10-14 days.
Non-typhoidal salmonellosis, Samonella gastroenteritis, by
ATC Code: J01DD02 IV infusion, CHILD, 75 mg/kg for 7 days;
Extra-intestinal infections, by IV infusion, CHILD, 100
mg/kg in divided doses every 6 hours for 10-14 days
CEFTRIAXONE (Bacteremia), 4 weeks (Meningitis), 4-6 weeks
Rx (Osteomyelitis).
WHO anti-biotic category: ACCESS and WATCH
Leptospirosis, moderate to severe, by IV infusion, CHILD,
Inj.: 250 mg vial (as disodium / sodium salt) + 2 mL 1% 80-100 mg/kg every 24 hours for 7 days.
lidocaine solution (IM) Osteomyelitis, hematogenous, by IV infusion, NEONATE 0-4
500 mg vial (as disodium / sodium salt) + 2 mL 1% weeks and <2kg, 50 mg/kg in 1 dose; NEONATE 0-7 days
lidocaine solution (IM) old and >2kg, 50 mg/kg in 1 dose; NEONATE >7 days old
250 mg vial (as disodium / sodium salt), vial + 5 mL and <1.2kg, 75 mg/kg in 1 dose; INFANT and CHILD,
diluent (IV) 100-200 mg/kg in 1-2 doses; for 3-6 weeks;
1 g vial (as disodium / sodium salt) + 3.5 mL 1% Long bones, gram-negative bacilli seen on gram stain, by
lidocaine solution (IM) IV infusion, ADULT, 2 g every 24 hours with vancomycin
1 g vial (as disodium / sodium salt), vial + 10 mL or oxacillin for 4-6 weeks.
diluent (IV) Vertebral, by IV infusion, ADULT, 2 g every 24 hours with
vancomycin or oxacillin for 6-12 weeks.
Indications: Treatment of lower respiratory tract infections, Suppurative arthritis, gram stain is negative or if gram stain
acute bacterial otitis media, skin and skin structure is positive for gram-positive cocci, by IV infusion, CHILD,
infections, bone and joint infections, intra-abdominal 100 mg/kg in 1-2 doses with vancomycin for 2-3 weeks.
and urinary tract infections, pelvic inflammatory disease Suppurative arthritis, gram stain is positive for gram-
(PID), uncomplicated gonorrhea, bacterial septicemia, negative organisms, by IV infusion, CHILD, 100 mg/kg in
and meningitis; used in surgical prophylaxis. 1-2 doses for 2-3 weeks.
Acute bacterial arthritis, monoarticular, at risk for STI, by IV
Contraindications: Do NOT use in hyperbilirubinemic infusion, ADULT, 1 g every 24 hours for 7 days minimum.
neonates, particularly those who are premature since Acute bacterial arthritis, monoarticular, not at risk for STI, by
ceftriaxone is reported to displace bilirubin from albumin IV infusion, ADULT, 1 g every 24 hours for 2-4 weeks.
binding sites; concomitant use with intravenous calcium- Acute bacterial arthritis, polyarticular, at risk for STI, by IV
containing solutions/products in neonates (≤28 days). infusion, ADULT, 1 g every 24 hours.
Prosthetic joint infections, P. acnes, by IV infusion, ADULT,
Dose: 2 g every 24 hours for 4-6 weeks.
Neonatal sepsis, by IM injection or IV infusion, CHILD, 50 Native valve infective endocarditis, S. viridans or S. bovis,
mg/kg every 24 hours with gentamicin OR amikacin with with Penicillin G MIC ≤0.12 mcg/mL, by IM injection or IV
or without oxacillin OR vancomycin for 7-10 days or infusion, CHILD, 100 mg/kg in divided doses or 80

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 ANTI-INFECTIVES FOR SYSTEMIC USE

mg/kg for 4 weeks; by IV infusion, ADULT, 2 g every 24 Peritonsillar abscess, by IV infusion, CHILD, 50-75 mg/kg
hours for 4 weeks. every 12-24 hours with metronidazole; ADULT, 2 g every
Native valve infective endocarditis, S. viridans or S. bovis, 24 hours with metronidazole.
with Penicillin G MIC >0.12 mcg/mL to ≤0.5 mcg/mL, by Deep neck abscess, by IV infusion, CHILD, 50-75 mg/kg
IM injection or IV infusion, CHILD, 100 mg/kg in divided every 12-24 hours with metronidazole for at least 7 days;
doses or 80 mg/kg with gentamicin for 4 weeks; ADULT, ADULT, 2 g every 24 hours with metronidazolefor at least
2 g every 24 hours for 4 weeks. 7 days.
Native valve infective endocarditis, Enterococci, penicillin- Gonococcal pharyngitis, by deep IM injection, CHILD <45 kg,
susceptible, aminoglycoside-resistant (Gentamicin MIC 125mg; ADULT and CHILD >45 kg, 250 mg.
>500 mcg/mL), streptomycin susceptible, by IM Jugular vein suppurative phlebitis, by IV infusion, ADULT, 2g
injection or IV infusion, CHILD, 100 mg/kg in divided with metronidazole.
dose every 12 hours or 80 mg/kg with ampicillin; by IV Acute epiglottitis, by IV infusion, CHILD, 50-100 mg/kg in
infusion, ADULT, 2 g in divided doses every 12 hours with divided doses every 12-24 hours for 7-10 days; ADULT,
ampicillin for 6 weeks. 2 g every 24 hours for 7-10 days.
Native valve infective endocarditis, Haemophilus sp, Acute mastoiditis, by IV infusion, CHILD, 100 mg/kg in
Aggregatibacter sp, Cardiobacterium hominis, Eikenella divided doses every 12 hours with oxacillin; ADULT, 2 g.
corrodens, and Kingella species (HACEK), by IM injection Community-acquired pneumonia, severe, with no Hib
or IV infusion, CHILD, 100 mg/kg in divided doses every vaccination or incomplete or unknown vaccination
12 hours or 80 mg/kg for 4 weeks; by IV infusion, ADULT, history, by IV infusion, INFANT and CHILD up to 5 years,
2 g every 24 hours for 4 weeks. 100 mg/kg in divided doses every 12 hours;
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Prosthetic valve infective endocarditis, gram-negative Moderate risk, by IV infusion, ADULT, 2 g every 24 hours for
enteric bacilli, by IV infusion, CHILD, 100 mg/kg in 7-10 days;
divided doses every 12 hours or 80 mg/kg in divided High-risk, by IV infusion, ADULT, 2 g every 24 hours with
doses every 12-24 hours for 6 weeks. azithromycin or levofloxacin.
Dental prophylaxis, by IM injection or IV infusion, CHILD, 50 Acute emphysema, by IV infusion, CHILD, 50-100 mg/kg
mg/kg; ADULT, 1 g. every 24 hours for 10-30 minutes with clindamycin for 2-
Bacterial purulent pericarditis, S. aureus, Group A 4 weeks; ADULT, 2 g every 24 hours with vancomycin and
Streptococcus, Enterobacteriaceae, S. pneumoniae, by metronidazole for 2-4 weeks.
IV infusion, CHILD, 100 mg/kg in divided doses every 12- Lung abscess, by IV infusion, CHILD, 50-100 mg/kg every
24 hours with vancomycin; ADULT, 2 g every 24 hours 24 hours for 10-30 minutes with clindamycin for 4-6
with vancomycin. weeks; ADULT, 2g every 24 hours with
Bacterial purulent pericarditis, S. pneumoniae (including clindamycin/ampicillin sulbactam and
penicillin-resistant strains), N. meningitidis, H. influenzae metronidazole/piperacillin tazobactam for 4-6 weeks.
type B (for children who may be inadequately
immunized), by IV infusion, CHILD, 100 mg/kg in divided Dose Adjustment:
doses every 12-24 hours. Geriatric:
Community acute bacterial meningitis, by IV infusion, CHILD Refer to adult dosing.
>2 months-5 years, 100 mg/kg in divided doses every
12-24 hours; by IV infusion, CHILD >5-18 years, 100 Precautions:
mg/kg in divided doses every 12 hours; add rifampin for Severe cases (including some fatalities) of immune-related
<10 years old with confirmed Hib meningitis; ADULT, 2g hemolytic anemia have been reported in patients
every 12 hours; ADULT >50 years old, 2 g every 12 hours receiving cephalosporins, including ceftriaxone;
with ampicillin. Secondary to biliary obstruction, pancreatitis has been
Brain abscess in the presence of dental infection, by IM reported rarely;
injection or IV infusion, CHILD, 100 mg/kg in divided Use with caution in patients with a history of penicillin
doses every 12 hours with penicillin G; by IV infusion, allergy, especially IgE-mediated reactions;
ADULT, 2 g every 12 hours with penicillin G. Prolonged use may result in fungal or bacterial
Brain abscess in the presence of head trauma, by IM superinfection, including C. difficile-associated diarrhea
injection or IV infusion, CHILD, 100 mg/kg in divided (CDAD) and pseudomembranous colitis; CDAD has been
doses every 12 hours with vancomycin; by IV infusion, observed >2 months post-antibiotic treatment.
ADULT, 2 g every 12 hours with vancomycin.
Brain abscess in the presence of congenital heart disease, Adverse Drug Reactions:
by IM injection or IV infusion, CHILD, 100 mg/kg in Common: Induration, tightness, warmth.
divided doses every 12 hours with metronidazole; by IV Less Common: Rash, diarrhea, eosinophilia,
infusion, ADULT, 2 g every 12 hours with metronidazole. thrombocytosis, leukopenia, tenderness at injection site,
Buccal cellulitis, by IV infusion, CHILD, 50 mg/kg every 24 pain.
hours for 7-14 days. Rare: Abdominal pain, agranulocytosis, allergic dermatitis,
Orbital cellulitis, by IV infusion, CHILD, 100 mg/kg in 1-2 allergic pneumonitis, anaphylaxis, anemia, basophilia,
doses with vancomycin for 7-14 days; ADULT, stage II-IV biliary lithiasis, bronchospasm, chills, colitis,
MRSA considered, 1 g every 12 hours with vancomycin diaphoresis, dizziness, dysgeusia, dyspepsia, edema,
for 10-21 days. epistaxis, erythema multiforme, exanthema, fever,
Conjunctivitis, N. gonorrhoeae, by IV infusion, NEONATE, 25- flatulence, flushing, gallbladder sludge, gallstones,
50 mg/kg; maximum dose: 125 mg. glossitis, hemolytic anemia, jaundice, Lyell’s syndrome,
Gonococcal conjunctivitis, by IM injection or IV infusion, monocytosis, oliguria, palpitation, renal and pulmonary
ADULT, 1g with azithromycin and ceftriaxone-calcium precipitations, seizure, serum
levofloxacin/tobramycin/erythromycin.

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sickness, Stevens-Johnson syndrome, stomatitis, toxic Pneumonia, nosocomial (HAP/VAP), by IV injection/

epidermal necrolysis, vaginitis, vomiting. infusion, ADULT, 2 g every 8-12 hours with azithromycin
and gentamicin/amikacin for 7-28 days;
Drug Interactions: Multi-drug resistant, by IV injection/ infusion, CHILD,
Reduces therapeutic effect of the following drugs: 100-150 mg/kg every 8 hours; ADULT, 2g every 8 hours
BCG, Typhoid vaccine (Only the live attenuated Ty21a with or without levofloxacin/ amikacin and
strain is affected.) vancomycin/linezolid.
Pathogen-specific treatment, P. aeruginosa, by IV injection/
Enhances therapeutic effect of Vitamin K antagonists e.g. infusion, CHILD, 150 mg/kg every 6 hours with
Warfarin ceftazidime; ADULT, 2g every 8-12 hours with
amikacin/gentamicin OR aztreonam;
Administration: Enterobacter, by IV injection/ infusion, CHILD, 100-150
Do not admix with aminoglycosides in same bottle/bag. Do mg/kg every 8-12 hours; ADULT, 2 g every 8 hours.
not reconstitute, admix, or co-administer with calcium-
containing solutions. Infuse intermittent infusion over 30 Dose Adjustment:
minutes. Geriatric:
Refer to adult dosing.
Pregnancy Category: B
Renal Impairment:
ATC Code: J01DD04 Intermittent hemodialysis (IHD) (administer after

J
hemodialysis on dialysis days): IV: Initial: 1 g (single dose)
on day 1. Maintenance: 0.5-1g every 24 hours or 1-2 g
FOURTH-GENERATION CEPHALOSPORINS every 48-72 hours. Note: Dosing dependent on the
assumption of 3 times/week, complete IHD sessions.
Peritoneal dialysis (PD): Removed to a lesser extent than
Rx CEFEPIME hemodialysis; administer normal recommended dose
WHO anti-biotic category: RESERVE
every 48 hours.
Continuous renal replacement therapy (CRRT): Drug
Inj.: 500 mg, 1 g, and 2 g vial (as hydrochloride) (IM, IV)
clearance is highly dependent on the method of renal
replacement, filter type, and flow rate. Appropriate
Indications: Treatment of complicated urinary tract
dosing requires close monitoring of pharmacologic
infections, including pyelonephritis caused by E. coli,
response, signs of adverse reaction due to drug
Klebsiella pneumoniae, or Proteus mirabilis;
accumulation, as well as drug concentrations in relation
monotherapy for febrile neutropenia; complicated skin
to target trough (if appropriate). The following are general
and skin structure infections caused by S. pyogenes or
recommendations only (based on dialysate
methicillin-susceptible staphylococci; moderate-to-
flow/ultrafiltration rates of 1-2 L/hour and minimal
severe pneumonia caused by S. pneumoniae, P.
residual renal function) and should not supersede
aeruginosa, Klebsiella pneumoniae, or Enterobacter
clinical judgment:
species; complicated intra-abdominal infections caused
CVVH: Loading dose of 2 g followed by 1-2 g every 12
by E.coli, P. aeruginosa, K. pneumoniae, Enterobacter
hours.
species against methicillin-susceptible staphylococci,
CVVHD/CVVHDF: Loading dose of 2 g followed by either
Enterobacter sp, and many other gram negative bacilli.
1 g every 8 hours or 2 g every 12 hours. Note: Dosage of
1 g every 8 hours results in similar steady-state
Dose:
concentrations as 2 g every 12 hours and is more cost
Healthcare-associated sepsis, by IV injection/ infusion,
effective.
CHILD, 100-150 mg/kg in divided doses every 8 hours
with or without amikacin/vancomycin.
Precautions:
Febrile neutropenia, monotherapy, by IV injection/ infusion,
Use with caution in patients with a history of penicillin
ADULT, 2 g every 8 hours for 7 days or until the
allergy, especially IgE- mediated reactions; Prolonged
neutropenia resolves; CHILD, 150 mg/kg in divided
use may result in fungal or bacterial superinfection,
doses every 8 hours for 7 days or until neutropenia
including C. difficile-associated diarrhea (CDAD) and
resolves.
pseudomembranous colitis, CDAD has been observed
Osteomyelitis, contiguous focus, by IV injection/ infusion,
>2 months post-antibiotic treatment; Use with caution in
CHILD, 100-150 mg/kg in 2-3 doses with clindamycin or
patients with a history of gastrointestinal disease,
vancomycin for 6 weeks.
especially colitis; Use with caution in patients with renal
Prosthetic joint infections, P. aeruginosa, by IV injection/
impairment; dosage adjustments recommended.
infusion, ADULT, 2 g every 12 hours for 4-6 weeks.
Native valve infective endocarditis, healthcare-associated,
Adverse Drug Reactions:
by IV injection/ infusion, CHILD, 100-150 mg/kg in
Common: Positive Coombs test without hemolysis.
divided doses every 8-12 hours with vancomycin and
Less Common: Fever, headache, rash, pruritus,
gentamicin; ADULT, 2 g every 8 hours with vancomycin
hypophosphatemia, diarrhea, nausea, vomiting,
and gentamicin.
inflammation, phlebitis.
Impaired host, neutropenic, by IV injection/ infusion, ADULT,
Rare: Agranulocytosis, anaphylactic shock, colitis, coma,
2 g every 8 hours with amikacin.
confusion, encephalopathy, hallucinations,
Chronic or recurrent mastoiditis, intracranial extension
hyper/hypocalcemia, hyperkalemia,
suspected, by IV injection/ infusion, CHILD, 150 mg/kg
every 8 hours.

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hyperphosphatemia, leucopenia, moniliasis, stupor, Precautions:

vaginitis. Rare cross-allergenicity to penicillins and cephalosporins
has been reported;
Drug Interactions: Prolonged use may result in fungal or bacterial
Reduces therapeutic effect of the following drugs: superinfection, including C. difficile-associated diarrhea
BCG, Typhoid vaccine (Only the live attenuated Ty21a (CDAD) and pseudomembranous colitis. CDAD has been
strain is affected.) observed >2 months post-antibiotic treatment;
Use the injectable formulation with caution in patients with
Increases serum concentration of Cefepime: renal impairment, dosing adjustment required.
Probenecid
Adverse Drug Reactions:
Administration: Rash, diarrhea, nausea, vomiting, thrombophlebitis, pain at
May be administered with IM or IV. injection site, abdominal cramps, abnormal taste,
Inject deep IM into large muscle mass. Inject direct IV over anaphylaxis, anemia, angioedema, breast tenderness,
5 minutes. Infuse intermittent infusion over 30 minutes. bronchospasm, chest pain, diaphoresis, dizziness,
dermatitis, fever, flushing, pancytopenia, paresthesia,
Pregnancy Category: B petechiae, pruritus, purpura, sneezing, tinnitus, urticaria,
vaginitis, vertigo, wheezing.
ATC Code: J01DE01
Drug Interactions:
J

Reduces therapeutic effect of the following drugs:

MONOBACTAMS BCG, Typhoid vaccine (Only the live attenuated Ty21a
strain is affected.)

Rx AZTREONAM Administration:
WHO anti-biotic category: RESERVE
For IM: Administer by deep injection into large muscle mass,
such as upper outer quadrant of gluteus maximus or the
Inj.: 1 g powder for injection
lateral part of the thigh.
For IV: Administer by slow IV push over 3-5 minutes or by
Indications: Treatment of hospital-acquired and ventilator-
intermittent infusion over 20-60 minutes.
associated pneumonia, and pathogen-specific infections
Pregnancy Category: B
Contraindications: Hypersensitivity to aztreonam or any
component of the formulation.
ATC Code: J01DF01
Dose:
Hospital-acquired and ventilator-associated pneumonia, not
at high risk of mortality but with factors increasing the CARBAPENEMS
likelihood of MRSA, by IV push/ infusion, ADULT, 2 g
every 8 hours with vancomycin OR linezolid;
Rx ERTAPENEM
High risk of mortality and with risk factor for MDR, by IV WHO anti-biotic category: WATCH
push/ infusion, ADULT, 2 g every 8 hours with
levofloxacin/amikacin and vancomycin/linezolid for 7 Inj.: 1 g powder, vial (as sodium salt)
days.
Community acute bacterial meningitis with severe penicillin Indications: Treatment of sepsis and pneumonia,
allergy, by IV push/ infusion, ADULT, 2 g every 6-8 hours community-acquired with or without lung abscess.
with vancomycin.
Contraindications: Anaphylactic reactions to beta-lactam
Pathogen-specific treatment, by IV push/ infusion, ADULT, antibiotics. If using intramuscularly, known
2g every 6 hours with piperacillin-tazobactam OR hypersensitivity to local anesthetics of the amide type
ceftazidime OR cefepime OR meropenem OR (lidocaine is the diluent).
levofloxacin OR ciprofloxacin.
Dose:
Dose Adjustment: NOTE: Children ≥13 years: Refer to adult dosing
Geriatric:
Refer to adult dosing. Sepsis, suspect urinary tract infection, by IV infusion,
ADULT, 1 g every 24 hours.
Renal Impairment: Community-acquired pneumonia, high risk, no risk for P.
IM, IV: Adults: Following initial dose, maintenance doses aeruginosa, by IV infusion, ADULT, 1 g every 24 hours
should be given as follows: with azithromycin OR levofloxacin for 10-14 days.
CrCl 10-30 mL/minute: 50% of usual dose at the usual Pneumonia, anaerobic or aspiration with or without lung
interval. abscess, by IV infusion, ADULT, 1 g every 24 hours with
CrCl <10 mL/minute: 25% of usual dosage at the usual piperacillin-tazobactam OR ceftriaxone.
interval.
Dose Adjustment:
Geriatric:
Refer to adult dosing.

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ANTI-INFECTIVES FOR SYSTEMIC USE

Renal Impairment: MEROPENEM

Adults: CrCl >30 mL/minute/1.73m2: No adjustment Rx
WHO anti-biotic category: WATCH
required.
CrCl ≤30 mL/minute/1.73m2: and ESRD: 500 mg/day. Inj.: 500 mg and 1 g powder, vial (as trihydrate)
Hemodialysis: When the daily dose is given within 6 hours
prior to hemodialysis, a supplementary dose of 150 mg Indications: Treatment of intra-abdominal infections,
is required following hemodialysis. meningitis, and skin and skin structure infections,
respiratory tract infections, septicemia, and urinary tract
Precautions: infections caused by susceptible bacteria; empiric anti-
Serious hypersensitivity reactions, including anaphylaxis, infective therapy in febrile neutropenic patients.
have been reported; Carbapenems have been
associated with CNS adverse effects, including Contraindication: Patients who have experienced
confusional states and seizures. Use caution with CNS anaphylactic reactions to beta-lactams.
disorders and adjust dose in renal impairment to avoid
drug accumulation, which may increase seizure risk; Dose:
Prolonged use may result in fungal or bacterial Healthcare-associated sepsis, by IV injection/ infusion,
superinfection, include C. difficile-associated diarrhea CHILD, 60-120 mg/kg in divided doses every 8 hours
(CDAD) and pseudomembranous colitis. CDAD has been with or without amikacin OR vancomycin.
observed >2 months post-antibiotic treatment. Severe sepsis and septic shock, by IV injection/ infusion,
CHILD, 60-120 mg/kg in divided doses every 8 hours

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Adverse Drug Reactions: with vancomycin for 10-14 days.
Less Common: Edema, chest pain, hypertension, Febrile neutropenia, by IV injection/ infusion, CHILD, 60-
hypotension, tachycardia, headache, altered mental 120 mg/kg in divided doses every 8 hours; ADULT, 1-2 g
status, decreased mental acuity, changed mental status, every 8 hours with aminoglycoside/
fatigue, anxiety, rash, pruritus, diarrhea, vomiting, fluoroquinolone/vancomycin and antifungal treatment
dyspepsia, oral candidiasis. for 4-6 weeks.
Rare: Anaphylactoid reactions, arrhythmia, asthma, Sepsis, non-neutropenic, by IV injection/ infusion, ADULT,
asystole, atrial fibrillation, bradycardia, cholelithiasis, 1g every 8 hours with vancomycin.
delirium, DRESS syndrome, gout, facial edema, heart Acute sinusitis, by IV injection/ infusion, ADULT, 1 g every 8
failure, heart murmur, hemoptysis, hypoxemia, pleural hours with or without vancomycin
effusion, renal insufficiency, seizure, septicemia, Acute mastoiditis, caused by a multidrug-resistant
subdural hemorrhage, syncope, ventricular tachycardia. Pseudomonas sp, by IV injection/ infusion, ADULT, 1 g
every 8 hours.
Drug Interactions: Community-acquired pneumonia, multi-drug resistant
Reduces therapeutic effect of the following drugs: pathogens, by IV injection/ infusion, CHILD, 300 mg/kg
BCG, Typhoid vaccine (Only the live attenuated Ty21a in divided does every 6 hours; 120 mg/kg/day every 8
strain is affected.) hours if with meningitis.
Hospital-acquired pneumonia, Not at high risk of mortality
Decreases serum concentration of the following drugs: and no factors increasing the likelihood of MRSA, by IV
Divalproex, Valproic acid injection/ infusion, ADULT, 1 g every 8 hours;
Not at high risk of mortality but with factors increasing
Increases serum concentration of Ertapenem: the likelihood of MRSA, by IV injection/ infusion, ADULT,
Probenecid 1 g every 8 hours with vancomycin OR linezolid;
High risk of mortality and with risk factor for MDR; by IV
Administration: injection/ infusion, ADULT, 1 g every 8 hours with
For IM: Avoid injection into a blood vessel. Make sure vancomycin/ linezolid and levofloxacin/ amikacin;
patient does not have an allergy to lidocaine or another Ventilator-associated pneumonia, No risk factors for MDR
anesthetic of the amide type. Administer by deep IM VAP and no structural lung disease, by IV injection/
injection into a large muscle mass. Do not administer IM infusion, ADULT, 1 g every 8 hours;
preparation or drug reconstituted for IM administration With risk factors for MRD VAP and with structural lung
intravenously. disease, by IV injection/ infusion, ADULT, 1 g every 8
For IV: Infuse over 30 minutes. hours with vancomycin/ linezolid and levofloxacin/
amikacin for 7 days or longer.
Pregnancy Category: B Pathogen-specific treatment, P. aeruginosa, by IV injection/
infusion, ADULT, 1 g every 8 hours with levofloxacin/
ATC Code: J01DH03 ciprofloxacin OR aztreonam;
Acinetobacter species, by IV injection/ infusion, CHILD,
60 mg/kg in divided doses every 8 hours with amikacin
OR gentamicin; ADULT, 1 g every 8 hours with ampicillin-
sulbactam;
Klebsiella pneumoniae, by IV injection/ infusion, CHILD,
60 mg/kg in divided doses every 8 hours;
Achromobacter, by IV injection/ infusion, CHILD, 60
mg/kg in divided doses every 8 hours with trimethoprim-
sulfamethoxazole; ADULT, 1 g every 8 hours;

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Burkholderia cepacia, by IV injection/ infusion, CHILD, hyperbilirubinemia, cholestatic jaundice, hepatic failure,
60 mg/kg in divided doses every 8 hours with amikacin jaundice, sepsis, inflammation at injection site, back
or gentamicin; ADULT, 1 g every 8 hours; pain, weakness, renal failure, pharyngitis, pneumonia,
Burkholderia pseudomallei, by IV injection/ infusion, apnea, asthma, cough, dyspnea, hypoxia, pleural
CHILD, 60 mg/kg in divided doses every 8 hours for 7-14 effusion, pulmonary edema, respiratory tract disease,
days with trimethoprim-sulfamethoxazole for 12-24 fever
weeks;
Escherichia coli, by IV injection/ infusion, CHILD, 60 Drug Interactions:
mg/kg in divided doses every 8 hours with amikacin or Monitor closely with:
gentamicin; Enhances therapeutic effect of Aminoglycosides e.g.
Enterobacter, by IV injection/ infusion, CHILD, 60 mg/kg Streptomycin
in divided doses every 8 hours with amikacin or
gentamicin; ADULT, 500 mg – 1 g every 8 hours. Avoid concomitant use with:
Increases serum concentration of Meropenem:
Dose Adjustment: Probenecid
Geriatric:
Dosage adjustment is not necessary for geriatric patients Decreases serum concentration of Valproic acid
with creatinine clearances >50 mL/minute; For geriatric
patients with reduced renal function, dosage should be Administration:
adjusted according to the guidelines for other adults with For IV: injections of meropenem should be given over a 3-5
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renal impairment. minutes period; infusions of meropenem should be given

over approximately 15–30 minutes.
Renal Impairment: Infants <3 months old: Administer as an IV infusion over 30
Adults: minutes;
CrCl 26-50 mL/minute: Administer recommended dose Infants ≥3 months old, children, adolescents, and adults:
based on indication every 12 hours. Administer IV infusion over 15-30 minutes; IV bolus
CrCl 10-25 mL/minute: Administer one­half recommended injection (5-20 mL) over 3-5 minutes; Extended infusion
dose based on indication every 12 hours. administration:
CrCl <10 mL/minute: Administer one­half recommended Adults: Administer over 3 hours.
dose based on indication every 24 hours.
Children: Note: Must consider meropenem’s limited room
Glomerular Filtration Rate 30-50 mL/minute: Administer temperature stability if using extended infusions.
20-40 mg/kg every 12 hours.
Glomerular Filtration Rate 10-29 mL/minute: Administer Pregnancy Category: B
10-20 mg/kg every 12 hours.
Glomerular Filtration Rate <10 mL/minute: Administer 10- ATC Code: J01DH02
20 mg/kg every 24 hours. Intermittent hemodialysis
(IHD): 10-20 mg/kg every 24 hours administer after
hemodialysis on dialysis days). SULFONAMIDES AND TRIMETHOPRIM
Peritoneal dialysis: 10-20 mg/kg every 24 hours.
Continuous renal replacement therapy: 20-40 mg/kg every
12 hours.
COTRIMOXAZOLE
Rx (SULFAMETHOXAZOLE +
Precautions: TRIMETHOPRIM)
Monitor patients for: anaphylaxis/hypersensitivity reactions, WHO anti-biotic category: ACCESS
central nervous system effects (including confusional
states and seizures), superinfection; Oral: 400 mg sulfamethoxazole + 80 mg trimethoprim
Use with caution in patients with renal Impairment, elderly, tablet / capsule
pediatrics (Safety and efficacy not established in children 800 mg sulfamethoxazole + 160 mg trimethoprim
<3 months old). tablet / capsule
200 mg sulfamethoxazole + 40 mg trimethoprim per
Adverse Drug Reactions: 5 mL suspension, 70 mL and 120 mL
Peripheral vascular disease, shock, bradycardia, cardiac 400 mg sulfamethoxazole + 80 mg trimethoprim per
arrest, cardiac failure, chest pain, hypertension, 5 mL suspension, 60 mL
hypotension, myocardial infarction, peripheral edema, Inj.: 400 mg sulfamethoxazole + 80 mg trimethoprim, 5
pulmonary embolism, syncope, tachycardia, headache, mL ampule (IV infusion)
convulsions, pain, agitation, anxiety, chills, confusion,
delirium, depression, dizziness, drowsiness, Indications: Treatment of uncomplicated typhoid fever,
hallucination, insomnia, nervousness, paresthesia, internal hordeolum, dacrocystitis, pertussis, and
seizure, skin rash, pruritus, dermal ulcer, diaphoresis, pathogen-specific infections such Pneumocystis jirovecii
urticaria, hypoglycemia, hypervolemia, nausea, diarrhea,
constipation, vomiting, oral candidiasis, gastrointestinal Contraindications: Infants <2 months of age; severe renal
disease, glossitis, abdominal pain, anorexia, dyspepsia, or hepatic failure; megaloblastic anemia (due to folic
enlargement of abdomen, flatulence, intestinal acid deficiency); blood dyscrasias; acute porphyria; late
obstruction, dysuria, pelvic pain, urinary incontinence, pregnancy (due to risk of neonatal kernicterus, hemolytic
vulvovaginal candidiasis, anemia, hypochromic anemia, anemia and jaundice).

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ANTI-INFECTIVES FOR SYSTEMIC USE

Dose: Rare: Arthralgia, aseptic meningitis, Clostridium difficile-

Uncomplicated typhoid fever, by mouth, ADULT, 800/180 associated disease, convulsions, depression, erythema,
mg every 12 hours for 14 days; CHILD, 8 mg/kg of hallucinations, hepatic necrosis, hepatitis,
Trimethoprim in 2 divided doses every 12 hours for 14 hypoglycemia, jaundice, lowered mental acuity,
days. megaloblastic anemia, myalgia, myocarditis,
Internal hordeolum, MRSA, by mouth, ADULT, 800/160 mg pancreatitis, peripheral neuropathy, pulmonary
every 12 hours. infiltrates, SJS, SLE, toxic epidermal necrolysis, urinary
Dacrocystitis, by mouth, ADULT, 2 double strenght tablets obstruction with anuria or oliguria, uveitis, vasculitis,
twice a day. vertigo.
Pertussis, by mouth, CHILD ≥ 2 months old, 8/40 mg/kg in
2 divided doses for 14 days; ADULT, 160/800 mg twice Drug Interactions:
daily for 14 days. Monitor closely with:
Pathogen-specific treatment, Achromobacter, by mouth, Drugs causing potassium retention e.g. ACE inhibitors,
CHILD, 8 mg/kg in divided doses every 12 hours with Other nephrotoxic drugs e.g., gentamicin and
ceftazidime; streptomycin
Burkholderia cepacia, by mouth, CHILD, 8 mg/kg in
divided doses every 12 hours; Administration:
Burkholderia pseudomallei, by mouth, CHILD, 8 mg/kg in Should be taken WITH food; this is best taken after meals
divided doses every 12 hours for 12-24 weeks. with an adequate amount of fluid.
Enterobacter, by mouth, CHILD, 8 mg/kg in divided

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doses every 12 hours. Pregnancy Category: C

Dose Adjustment: ATC Code: J01EE01

Renal Impairment:
For mild to moderate renal impairment, dose reduction is
warranted; contraindicated for severe impairment. MACROLIDES, LINCOSAMIDES, AND
STREPTOGRAMINS
Hepatic Impairment:
Contraindicated in significant hepatic impairment.
MACROLIDES
Precautions:
HIV infection; Rx AZITHROMYCIN
Photosensitivity, slow acetylator phenotype; WHO anti-biotic category: WATCH
Treatment with oral typhoid vaccine;
Systemic Lupus Erythematosus (SLE); Renal impairment Oral: 250 mg capsule (as base / as dihydrate)
(avoid if severe and if plasma sulfamethoxazole 250 mg and 500 mg tablet (as base / as dihydrate/as
concentration cannot be monitored), monohydrate)
Low urine pH increases risk of crystalluria (maintain 200 mg/5 mL powder for suspension (as base /as
adequate fluid intake to prevent crystalluria); dehydrate/as monohydrate), 15 mL and 60 mL
Hepatic impairment (avoid if severe); Inj.: 500 mg powder vial (as base / as dihydrate) (IV
Blood disorders (avoid unless under specialist supervision; infusion)
monitor blood count and discontinue immediately if
blood disorder develops); Indications: Suspected uncomplicated genital chlamydial
Rash (discontinue treatment immediately); infections (e.g., urethritis, cervicitis, trachoma); low-risk
Asthma; community-acquired pneumonia (CAP-LR) in adults,
G6PD deficiency; when Legionella, Chlamydia or Mycoplasma is
Elderly (increased risk of blood dyscrasias and skin suspected, or when there is hypersensitivity to the beta-
disorders); lactams; non-severe CAP in child with hypersensitivity to
Pregnancy (first trimester: teratogenic effects which include amoxicillin.
anencephaly, hypoplastic left heart syndrome, choanal
atresia, transverse limb defect, diaphragmatic hernia; Contraindications: With history of cholestatic jaundice or
third trimester: neonatal hemolysis and hepatic impairment associated with prior azithromycin
methemoglobinemia); use.
Breastfeeding (monitor infant for jaundice: small risk of
kernicterus in jaundiced infants); Dose:
G6PD-deficient infants (risk for hemolysis due to Uncomplicated typhoid fever, by mouth, CHILD, 20 mg/kg
sulfamethoxazole). for 5-7 days; ADULT, 500 mg-1g for 5-7 days.
Caution in ill or premature infants and avoid in infants <6 Complicated typhoid fever, by mouth, CHILD, 20 mg/kg for
weeks. 5-7 days, ADULT, 500 mg 1-2 tablets for 5-7 days
Leptospirosis, mild, by mouth, CHILD, 1 g loading dose then
Adverse Drug Reactions: 10 mg/kg for 2 days;
Common: Anorexia, diarrhea, fever, hyperkalemia, Moderate to severe, by mouth, CHILD, 500 mg for 5 days.
hyponatremia, itch, nausea, rash, sore mouth, Prophylaxis, by mouth, CHILD, 10 mg/kg; If children are
thrombocytopenia, vomiting. exposed for more than 7 days, the dose should be
Less Common: Drowsiness, headache, neutropenia, repeated after 1 week.
photosensitivity.

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 ANTI-INFECTIVES FOR SYSTEMIC USE

Acute bacterial arthritis, monoarticular, by mouth, ADULT, Rare: Acute renal failure, agitation, angioedema, cholestatic
1g for 7 days minimum. jaundice, convulsions, disturbances in taste and vision,
Dental prophylaxis, allergic to penicillin or ampicillin, by hemolytic anemia, hepatic necrosis and failure,
mouth, CHILD, 15 mg/kg; ADULT, 500 mg. interstitial nephritis, seizures, syncope.
Conjunctivitis, Chlamydia trachomatis, by mouth, NEONATE
3-10 days, 20 mg/kg every 24 hours for 3 days. Drug Interactions:
Gonococcal conjunctivitis, for presumptive Chlamydia co- NOTE: Macrolides inhibit P-glycoprotein, which may lead to
infection, by mouth, ADULT, 1 g per day PLUS with topical drug interactions.
levofloxacin OR tobramycin OR erythromycin ointment
every 4 days for 2-3 weeks or until resolution of Monitor closely with:
symptoms. Reduces absorption of Azithromycin:
Pharyngitis or tonsilitis, penicillin allergy, by mouth, CHILD, Antacids (e.g. aluminum or magnesium hydroxide)
12 mg/kg for 5 days; ADULT, 500 mg then 250 mg for 4
days or 500 mg for 3 days Reduces therapeutic effect of Contraceptives (Oral)
Pertussis, by mouth, INFANT <1 month, 10 mg/kg every 24
hours for 5 days; INFANT >2 months, 10 mg/kg on day 1 Avoid concomitant use with:
then 5 mg/kg every 24 hours for 4 days; ADULT, 500 mg Increases serum concentration of Digoxin
on day 1 then 250 mg every 24 hours on day 2 to 5.
Acute bacterial exacerbation of chronic bronchitis (ABECB), Increases risk of adverse or toxic effects of the following
severe, by mouth, ADULT, 500 mg every 24 hours for 3 drugs:
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days. Amiodarone, Artemether + Lumefantrine

Community-acquired pneumonia, by mouth, CHILD, 10
mg/kg for 3 days or 10 mg/kg on day 1 then 5 mg/kg on Administration:
day 2 to 5; Capsules should be taken at least 1 hour before, or 2 hours
Low-risk, without co-morbid illness, by mouth, ADULT, after, food; oral suspension can be taken with food to
500 mg for 3-5 days; reduce GI discomfort and increase tolerability.
Low-risk, with stable co-morbid illness, by mouth, ADULT,
500 mg with co-amoxiclav OR cefuroxime for 3-5 days; NOTE: Oral suspensions (100 mg/5 mL and 200 mg/5 mL)
Moderate-risk, by mouth, ADULT, 500 mg with ampicillin- may be stored for 10 days post-reconstitution and taken
sulbactam or cefuroxime. without regard to food.
High-risk, risk for P. aeruginosa, by IV infusion, ADULT,
500 mg with piperacillin-tazobactam/ Pregnancy Category: B
cefepime/meropenem and gentamicin/amikacin.
ATC Code: J01FA10
Dose Adjustment:
Renal Impairment:
For severe impairment – refer to specialist CLARITHROMYCIN
Rx
WHO anti-biotic category: WATCH
Hepatic Impairment:
(except for Contraindications stated above): Oral: 250 mg and 500 mg base tablet
For severe impairment – reduce dose 125 mg/5 mL and 250 mg/5 mL granules / powder
for suspension, 50 mL
Precautions:
Cardiac conditions: congenital long QT syndrome and family Indications: Management of low risk community-acquired
history of QT prolongation; torsades de pointes, pneumonia in adults (CAP-LR) due to Legionella,
ventricular arrhythmia and other arrhythmias, congestive Chlamydia or Mycoplasma; non-severe PCAP with
heart failure, recent MI; Proarrhythmic conditions (e.g., hypersensitivity to amoxicillin; Helicobacter pylori
hypokalemia, hypomagnesemia); Renal impairment infection. In combination with other drugs. Alternative in
Exacerbations of myasthenia gravis penicillin allergic patients.
Elderly patients (may be more susceptible to drug-
associated QT prolongation); Contraindications: Severe hepatic failure; hypokalemia;
Breastfeeding (limited drug information available – use only patients with history of QT prolongation or ventricular
if adequate alternatives are not available). cardiac arrhythmias; cholestatic jaundice or hepatic
dysfunction with prior clarithromycin use.
Adverse Drug Reactions:
Common: Abdominal pain, arthralgia, cramping, diarrhea, Dose:
dizziness, dyspepsia, flatulence, headache, malaise, Dental prophylaxis, by mouth, CHILD, 15 mg/kg; ADULT,
nausea, pruritic, rash, vaginitis, vomiting. 500 mg.
Less Common: Abnormal heart rhythm, allergic reaction, Pharyngitis or tonsillitis, penicillin allergy, by mouth, CHILD,
anorexia, anxiety, chest pain, conjunctivitis, constipation, 15 mg/kg in divided doses every 12 hours for 10 days;
drowsiness, edema, enteritis, fatigue, gastritis, ADULT, 250 mg every 12 hours for 10 days.
hyperkinesia, hypesthesia, hypotension, insomnia, Acute bacterial rhinosinusitis (ABRBS), severe penicillin
leukopenia, liver disorders, myasthenia gravis, allergy, by mouth, CHILD, 15 mg/kg in divided doses
neutropenia, palpitations, pancreatitis, paresthesia, every 12 hours.
photosensitivity, rash, sleep disturbances, somnolence, Acute otitis media (AOM), by mouth, CHILD, 15 mg/kg every
thrombocytopenia, tinnitus, urticaria, vertigo. 12 hours.

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ANTI-INFECTIVES FOR SYSTEMIC USE

Pertussis, by mouth, INFANT >1 month, 7.5 mg/kg every 12

hours for 7 days; ADULT, 500 mg twice daily for 7 days. Increases risk of adverse or toxic effects Clarithromycin:
Acute bacterial exacerbation of chronic bronchitis (ABECB), Class IA antiarrhythmics e.g. Procainamide
severe, by mouth, ADULT, 500 mg twice daily for 5-10 Class III antiarrhythmics e.g., Amiodarone, Sotalol or
days. drugs which prolong QT interval
Community-acquired pneumonia, by mouth, CHILD >5 years
old, suspension 15 mg/kg in divided doses every 12 Increases risk of adverse or toxic effects of Hypoglycemic
hours for 10 days. agents e.g. Insulin
Low-risk, without co-morbid illness, by mouth, ADULT,
500 mg twice daily for 5-7 days; Increases serum concentration of the following drugs:
Low-risk, with stable co-morbid illness, by mouth, ADULT, Anticoagulants e.g. Warfarin, Phosphodiesterase
500 mg twice daily with co-amoxiclav OR cefuroxime for inhibitors e.g., Sildenafil, Theophylline
5-7 days;
Moderate-risk, by mouth, ADULT, 500 mg twice daily with Avoid concomitant use with:
ampicillin-sulbactam OR cefuroxime OR ceftriaxone for 7- Decreases metabolism of Calcineurin inhibitors e.g.
28 days; Tacrolimus
Eradication of H. pylori, by mouth, ADULT, 500 mg twice
daily for 7 days in a combination treatment Increases risk of adverse or toxic effects of the following
drugs:
Dose Adjustment: Ergot alkaloids e.g. ergotamine, HMG-CoA reductase

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Renal Impairment: inhibitors e.g. simvastatin (rhadomyolysis)
For mild-to-moderate renal impairment, dose reduction is
warranted; for severe impairment, the patient should be Increases serum concentration of the following drugs:
referred to a specialist. HMG-CoA reductase inhibitors e.g. simvastatin

Precautions: Administration:
The regular tablet and liquid can be taken with or without
WARNING: Increased risk of cardiac deaths.
food; whereas, the long-acting tablet is usually taken with
food. Immediate release tablets are usually taken with or
Patients with a predisposition to QT interval prolongation, without food. The tablet should be taken with a full glass
including electrolyte disturbances (e.g., uncorrected of water; while the long-acting tablet is swallowed whole
hypokalemia or hypomagnesemia) and concomitant use (do not split, chew or crush). Shake the suspension well
of drugs that prolong QT interval; History of ischemic before use.
heart disease, severe cardiac insufficiency, ventricular
arrhythmia including torsades de pointes, bradycardia Pregnancy Category: C
(treatment risk-benefit should be considered);
Hepatic dysfunction (discontinue immediately if signs and ATC Code: J01FA09
symptoms of hepatitis occur);
Antibiotic-associated colitis,
Myasthenia gravis (may be aggravated); ERYTHROMYCIN
Elderly patients may be more susceptible to drug-associated Rx
WHO anti-biotic category: WATCH
QT prolongation;
Breastfeeding (safety has not been established). Oral: 500 mg tablet (as stearate)
200 mg/5 mL granules / powder for suspension (as
NOTE: Macrolides inhibit P-glycoprotein, which may lead to ethyl succinate), 60 mL
drug interactions; CYP3A-based interactions 400 mg/5 mL granules / powder for suspension (as
clarithromycin (a CYP3A inhibitor) may increase or ethyl succinate), 50 mL and 60 mL
prolong both therapeutic and adverse effects of drugs
primarily metabolized by CYP3A enzymes. Indications: Alternative to penicillin in hypersensitive
patients such as in secondary prevention of rheumatic
Adverse Drug Reactions: fever and tonsillitis; conjunctivitis, pharyngitis, pertussis,
Common: Taste disturbance. chlamydia infections and community-acquired
Less Common: Abdominal discomfort, diarrhea, pneumonia.
hepatotoxicity (including cholestatic jaundice), nausea,
rash, tinnitus, vomiting. Contraindications: Porphyria; severe hepatic impairment;
Rare: Antibiotic-associated colitis, arrhythmias, QT prolongation and ventricular cardiac arrhythmias.
pancreatitis, pulmonary infiltration with QT interval
prolongation, SJS, torsades de pointes, toxic epidermal Dose:
necrolysis. Conjunctivitis, Chlamydia trachomatis, by mouth, NEONATE,
12.5 mg/kg every 6 hours for 14 days.
Drug Interactions: Pharyngitis, penicillin allergy, by mouth, CHILD, 40 mg/kg in
Monitor closely with: divided doses every 6 hours for 10 days; ADULT, 400 mg
Decreases metabolism of Benzodiazepines e.g. Midazolam every 6-12 hours for 10 days.
Pertussis, by mouth, INFANT <1 month, 40 mg/kg in 4
Increases metabolism of Clarithromycin: divided doses for 14 days; ADULT, 500 mg four times
CYP3A4/5 inducers, Rifampicin daily for 14 days.

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 ANTI-INFECTIVES FOR SYSTEMIC USE

Secondary prevention, acute rheumatic fever, ADULT, 20 ATC Code: J01FA01

mg/kg/day twice a day
Community-acquired pneumonia, by mouth, CHILD >5
years, 50 mg/kg in divided doses every 6-8 hours for 10- LINCOSAMIDES
14 days.

Dose Adjustment:
Rx CLINDAMYCIN
Renal Impairment:
For mild-to-moderate renal impairment, dose reduction is Oral: 150 and 300 mg capsule (as hydrochloride)
warranted; for severe impairment, the patient should be 75 mg/5 mL granules for suspension (as palmitate
referred to a specialist. hydrochloride), 60 mL
Inj.: 150 mg/mL (as phosphate), 2 mL ampule / vial and
Precautions: 4 mL ampule (IM, IV)
Risk of sudden cardiac death from cardiac causes when oral
erythromycin used concomitantly with drugs that inhibit Indications: Skin and soft tissue infections caused by
CYP3A4; community-associated methicillin-resistant
Caution in ventricular cardiac arrhythmia and QT Staphylococcus aureus (MRSA); alternative for
prolongation; anaerobic infections. Alternative to macrolides for severe
Hepatic impairment (may cause idiosyncratic penicillin allergy; recurrent pharyngitis
hepatotoxicity), predisposition to QT interval
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prolongation, including electrolyte disturbances and Contraindications: History of ulcerative or

concomitant use of drugs that prolong the QT interval; pseudomembranous colitis.
Breastfeeding (small amounts found in milk – not known to
be harmful; may cause loose bowel in infants). Dose:
Immunocompetent children, intra-abdominal source, by IV
Adverse Drug Reactions: injection, CHILD, 20-40 mg/kg in divided doses every 6-
Common: Abdominal pain, candida infections, cramps, 8 hours with ampicillin and gentamicin/amikacin for 10-
diarrhea, nausea, vomiting. 14 days.
Less Common: Headache, rash, urticaria. Staphylococcal toxic shock syndrome, by IV injection, CHILD,
Rare: Blood dyscrasias, cardiac effects, cholestatic 30-40 mg/kg in divided doses every 6-8 hours with
jaundice, C. difficile-associated disease, hypersensitivity oxacillin/cefazolin/vancomycin and IVIG for 10-14 days.
reactions; anaphylaxis; infantile hypertrophic pyloric Streptococcal toxic shock syndrome, by IV injection, CHILD,
stenosis, myasthenia-like syndrome, pancreatitis, 30-40 mg/kg in divided doses every 6-8 hours with
psychiatric disturbances, ototoxicity, toxic epidermal penicillin G sodium/ceftriaxone and IVIG for 10-14 days.
necrolysis. Febrile neutropenia, low-risk, penicillin allergy, by mouth,
Frequency not defined: Torsades de pointes, ventricular ADULT, 300 mg every 6 hours with
arrhythmias, ventricular tachycardia. ciprofloxacin/levofloxacin until patient is afebrile and
absolute neutrophil count >500cells/μL.
Drug Interactions: Osteomyelitis, hematogenous, by IV injection, NEONATE 0-4
NOTE: Macrolides inhibit P-glycoprotein, which may lead to weeks old and <1.2kg, 10 mg/kg in 2 doses; NEONATE
drug interactions. 0-7 days old and 1.2-2kg, 10 mg/kg in 2 doses;
NEONATE >7 days old and 1.2-2kg, 15 mg/kg in 3 doses;
Monitor closely with: NEONATE 0-7 days old and >2kg, 15 mg/kg in 3 doses;
Reduces therapeutic effect of Contraceptives (Oral) NEONATE >7 days old and >2kg, 20 mg/kg in 4 doses;
CHILD and NEONATE >28 days old, 25-40 mg/kg in 3-4
Avoid concomitant use with: doses; with cefotaxime OR ceftriaxone.
Increases serum concentration of Erythromycin: Osteomyelitis, contiguous focus, by IV injection, CHILD, 25-
CYP3A4 inhibitors, Verapamil 40 mg/kg in 3-4 doses.
Suppurative arthritis, by IV injection, CHILD 3 months to 14
Increases serum concentration of HMG-CoA reductase years, 25-40 mg/kg in 3-4 doses with cefotaxime OR
inhibitors e.g., Atorvastatin, Simvastatin ceftriaxone for 3-6 weeks.
Dental prophylaxis, allergic to penicillin or ampicillin, by
Increases risk of adverse or toxic effects of the following mouth, CHILD, 20 mg/kg; ADULT, 500 mg; by IV IM/IV
drugs: injection, CHILD, 20 mg/kg; ADULT, 600 mg.
HMG-CoA reductase inhibitors (e.g. Atorvastatin, Dentoalveolar infection or peri-apical abscess, by mouth,
Simvastatin) (myopathy and rhabdomyolysis) [stop CHILD,10 mg/kg every 8 hours for 7-14 days; ADULT,
medication temporarily], Artemether + Lumefantrine 300mg every 8 hours for 7-14 days.
Acute gingivitis, by mouth, by IV injection, ADULT, 300 mg
Decreases metabolism of Hydrocortisone with penicillin V potassium every 8 hours for 7-10 days.
Acute necrotizing ulcerative gingivitis, by mouth, by IV
Administration: injection, ADULT, 300 mg every 8 hours for 10 days.
Tablets and capsules should be swallowed WHOLE; best Periodontal abscess, by mouth, CHILD, 10 mg/kg every 8
taken on an empty stomach 1 hour before, or 2 hours, hours for 7 days; ADULT, 150-300 mg every 8 hours for
after meals. 7 days.

Pregnancy Category: B

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ANTI-INFECTIVES FOR SYSTEMIC USE

Ludwig’s angina, by mouth, CHILD, 17-25 mg/kg in 3-4 Frequency not defined: Agranulocytosis, C. difficile-
equally divided doses for 2-3 weeks; by IV injection, associated diarrhea, eosinophilia (transient),
ADULT, 600 mg every 6-8 hours for 2-3 weeks. esophagitis, fungal overgrowth, granulocytopenia,
Orbital cellulitis, stage II-IV, by IV injection, ADULT, 600 mg hypersensitivity, neutropenia, polyarthritis,
every 8 hours with piperacillin-tazobactam OR pseudomembranous colitis, SJS, thrombocytopenia,
ciprofloxacin for 10-21 days. renal dysfunction.
Peritonsillar abscess, penicillin allergy, by IV injection,
CHILD, 40 mg/kg in divided doses every 6-8 hours; Drug Interactions:
ADULT, 600-900 mg every 6-8 hours. Monitor closely with:
Parapharyngeal space infection, by IV injection, ADULT, Reduces therapeutic effect of Conjugated estrogens or
600-900 mg every 8 hours with metronidazole. estradiol or ethinylestradiol
Jugular vein suppurative phlebitis, by IV injection, ADULT,
600-900 mg every 8 hours. Enhances therapeutic effect of the following drugs:
Acute epiglottitis, by IV injection, ADULT, 600-900 mg every Digoxin, Warfarin (decreased vitamin-K producing
6-8 hours with levofloxacin for 7-10 days. intestinal flora may increase INR after a few days)
Acute emphysema, by IV injection, CHILD, 25-40 mg/kg in
divided doses every 6-8 hours with ceftriaxone for 2-4 Increases risk of adverse or toxic effects of Neuromuscular
weeks; ADULT, 600 mg every 8 hours with ceftriaxone for blockers (e.g., pancuronium) (possible serious or life-
2-4 weeks. threatening interaction; risk of respiratory depression)
Lung abscess, by IV injection, CHILD, 25-40 mg/kg in [use alternatives if possible]

J
divided doses every 6-8 hours with ceftriaxone for 4-6
weeks; ADULT, 600 mg every 8 hours for 4-6 weeks. Avoid concomitant use with:
Pneumonia, anaerobic or aspiration with or without lung Reduces therapeutic effect of the following drugs:
abscess, by mouth, ADULT, 300-450 mg thrice a day for Typhoid vaccine (Live) (antagonistic effects) (high
3-4 weeks or longer; by IV injection, ADULT, 600 mg every likelihood of serious or life-threatening interaction), BCG
8 hours with ceftriaxone OR ampicillin-sulbactam for 3-4 vaccine (Live) (antagonistic effects) (high likelihood of
weeks or longer. serious or life-threatening interaction), Erythromycin
Recurrent pharyngitis, ADULT, by mouth, 200 mg/kg/day (antagonistic effects)
twice a day
Administration:
Dose Adjustment: May be taken with food. Do not refrigerate reconstituted oral
Hepatic Impairment: solution since the solution will thicken; reconstituted
Use with caution in hepatic impairment, monitor for hepatic solution is stable for 2 weeks at room temperature.
abnormalities.
Pregnancy Category: B
Precautions:
ATC Code: J01FF01
WARNING: Clostridium difficile-associated diarrhea
(CDAD) has been reported and may range in severity
from mild diarrhea to fatal colitis. This may occur during
treatment or for 2 months after discontinuation of
AMINOGLYCOSIDE ANTIBACTERIALS
treatment. (more likely to be refractory to antimicrobial
therapy and may require colectomy). Rx AMIKACIN
Reserve clindamycin for serious infection where less toxic WHO anti-biotic category: ACCESS
antibiotics are inappropriate.
Avoid use for non-bacterial infection including most upper Inj.: 50 mg/mL, 100 mg/mL, 125 mg/mL, and 250
respiratory tract infections. mg/mL (as sulfate), 2 mL ampule / vial (IM, IV)
100 mg, 250 mg, 500 mg, and 1 g (as sulfate), vial
(IM, IV)
Risk of potentially fatal pseudomembranous colitis, fungal
or bacterial superinfection on prolonged use, Indications:
discontinue therapy if significant abdominal cramps, Used in combination with beta lactams for the treatment of
diarrhea or passage of blood and mucus occur; potential and neonatal sepsis, bacterial purulent
Severe skin reactions (e.g. toxic epidermal necrolysis), some pericarditis, acute bacterial meningitis in infants,
with fatal outcome, have been reported, permanently community-acquired pneumonia, hospital-acquired
discontinue in these situations; pneumonia, ventilator-associated pneumonia, and
Parenteral product contains benzyl alcohol which may pathogen-specific infections
cause “gasping syndrome” and death in newborn;
May increase the risk for antimicrobial-resistant bacteria if Dose:
used in the absence of proven or strongly suspected Potential sepsis, by IM injection or IV infusion, NEONATE ≤7
susceptible bacteria; days old ≤2 kg, 15 mg/kg every 48 hours; NEONATE 8-
Lactation: possibly unsafe. 28 days old ≤2 kg, 15 mg/kg every 24 hours; NEONATE
≤7 days old >2 kg, 15 mg/kg every 24 hours; NEONATE
Adverse Drug Reactions: 8-28 days old >2 kg, 17.5 mg/kg every 24 hours; with
Common: Abdominal pain, diarrhea, hypotension, jaundice, ampicillin
nausea, pruritus, rash, urticaria, vomiting. Neonatal sepsis, by deep IM injection or IV infusion,
NEONATE ≤7 days old ≤2kg, 15 mg/kg every 48 hours;

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 ANTI-INFECTIVES FOR SYSTEMIC USE

NEONATE 8-28 days old ≤2kg, 15 mg/kg every 24 hours; Reduced dose at fixed interval; Serum amikacin should be
NEONATE ≤7 days old >2kg, 15 mg/kg every 24 hours; measured to avoid concentrations higher than 35
NEONATE 8-28 days old >2kg, 17.5 mg/kg every 24 mcg/mL. If serum assay determinations are not available
hours; with cefotaxime/ceftriaxone with or without and the patient’s condition is stable, serum creatinine
oxacillin/vancomycin. and clearance values are the most readily available
Immunocompetent children, intra-abdominal source, by IV indicators of the degree of renal impairment.to use as
infusion, CHILD, 15-22.5 mg/kg in divided doses every guide for dosage.
8-12 hours or 15-20 mg/kg daily with ampicillin and
metronidazole OR clindamycin for 10-14 days or longer. Precautions:
Immunocompetent children, urinary source, by IV infusion,
CHILD, 15-22.5 mg/kg in divided doses every 8-12 hours WARNING: Neurotoxicity, manifested as vestibular and
or 15-20 mg/kg daily with ceftriaxone OR cefotaxime for permanent bilateral auditory ototoxicity, can occur in
10-14 days or longer. patients with preexisting renal damage in patients with
Bacterial purulent pericarditis, S. aureus, Group A normal renal function treated at higher doses and/or
Streptococcus, Enterobacteriaceae, S. pneumoniae, by periods longer than those recommended.
IV infusion, CHILD, 15 mg/kg with vancomycin.
Impaired host, neutropenic, by IV infusion, CHILD, 15 mg/kg Aminoglycosides are potentially nephrotoxic. The risk of
with cefepime OR ceftazidime. nephrotoxicity is greater in patients with impaired renal
Community acute bacterial meningitis, by IM injection or IV function and in those who receive high doses or
infusion, INFANT, 15 mg/kg with ampicillin OR prolonged therapy;
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cefotaxime dependent on the etiology of bacterial Neuromuscular blockade and respiratory paralysis have
meningitis. been reported following parenteral injection, topical
Community-acquired pneumonia, severe, by IV infusion, instillation, and following oral use of aminoglycosides;
NEONATE, 15 mg/kg with ampicillin OR penicillin G;
Prolonged use may result in fungal or bacterial
High-risk, risk for P. aeruginosa, by IV infusion, ADULT,
superinfection, including C. difficile-associated diarrhea
15 mg/kg with azithromycin and piperacillin- (CDAD) and pseudomembranous colitis; CDAD has been
tazobactam/cefepime/meropenem. observed >2 months post-antibiotic treatment.
Hospital-acquired pneumonia, P. aeruginosa, A. baumanii,
K. pneumoniae; Klebsiella spp., E. coli, Enterobacter Adverse Drug Reactions:
spp.; Proteus spp.; Serratia marcesens, by IV infusion, Less Common: Neurotoxicity, nephrotoxicity, auditory
CHILD, 15 mg/kg with ceftazidime; ototoxicity, vestibular ototoxicity.
High risk of mortality and with risk factor for Multiple Rare: Arthralgia, drowsiness, drug fever, dyspnea,
Drug Resistance, by IV infusion, ADULT, 15-20 mg/kg eosinophilia, headache, hypersensitivity reaction,
with vancomycin/linezolid AND piperacillin-tazobactam/ hypotension, nausea, paresthesia, skin rash, tremor,
cefepime/ meropenem/ aztreonam for 7 days or longer. vomiting, weakness
Ventilator-associated pneumonia, with risk factors for Multi-
drug resistant VAP and with structural lung disease, by IV Drug Interactions:
infusion, ADULT, 15-20 mg/kg with vancomycin/linezolid Monitor closely with:
AND piperacillin-tazobactam/ cefepime/ meropenem/ Increases risk of adverse or toxic effects Amikacin:
aztreonam for 7 days or longer. Amphotericin B, Cephalosporins, Loop diuretics,
Pathogen—specific treatment, P. aeruginosa, by IV infusion, Vancomycin
CHILD, 15 mg/kg with ceftazidime; ADULT, 15 mg/kg
with levofloxacin OR ciprofloxacin; Increases risk of adverse or toxic effects of the following
Acinetobacter species, by IV infusion, CHILD, 15 mg/kg drugs:
in divided doses every 8 hours with meropenem; Bisphosphonates e.g., Alendronate, Carboplatin
Burkholderia cepacia, by IV infusion, CHILD, 15 mg/kg
Neuromuscular-blocking agents
with meropenem;
Escherichia coli, by IV infusion, CHILD, 15 mg/kg with Reduces therapeutic effect of the following drugs:
ceftriaxone; BCG vaccine, Typhoid vaccine
Enterobacter, by IV infusion, CHILD, 15 mg/kg with
meropenem or cefepime. Enhances therapeutic effect of Amikacin:
Capreomycin
Dose Adjustment:
Geriatric: Decreases excretion of Amikacin:
Refer to adult dosing. NSAIDs
Renal Impairment: Avoid concomitant use with:
Doses may be adjusted in patients with impaired renal Reduces therapeutic effect of Cholera vaccine
function either by administering normal doses at
prolonged intervals or by administering reduced doses at Increases risk of adverse or toxic effects Amikacin:
fixed intervals. Neither method should be used when Foscarnet, Mannitol
dialysis is being performed.
Normal dose at prolonged intervals: If serum creatinine Administration:
concentration is 2mg/100mL, the recommended single For IM: Administer IM injection in large muscle mass.
dose (7.5 mg/kg) should be administered every 18
hours.

234
ANTI-INFECTIVES FOR SYSTEMIC USE

For IV: Infuse over 30 to 60 minutes (children, adolescents ADULT, 1 mg/kg every 8 hours with vancomycin for 6
and adults) or over 1 to 2 hours (infants). weeks.
Prosthetic valve infective endocarditis, by IV infusion,
Pregnancy Category: D CHILD, 3-6 mg/kg in divided doses every 8 hours with
vancomycin; ADULT, 1 mg/kg every 8 hours with
ATC Code: J01GB06 vancomycin and rifampin for 6 weeks;
MSSA, by IM injection or IV infusion, CHILD, 3-6 mg/kg in
3 divided doses with oxacillin and rifampin for 2 weeks;
GENTAMICIN ADULT, 1 mg/kg every 8 hours with oxacillin and rifampin
Rx for 2 weeks;
WHO anti-biotic category: ACCESS
Gram-negative enteric bacilli, by IV infusion, CHILD, 3-6
Inj.: 10 mg/mL (as sulfate), 2 mL ampule/vial (IM, IV) mg/kg in divided doses every 8 hours with
40 mg/mL (as sulfate), 2 mL ampule / vial (IM, IV) ceftazidime/cefotaxime/ceftriaxone.
Bacterial purulent pericarditis, S. aureus, Group A
Indications: Used in combination with beta lactams for the Streptococcus, Enterobacteriaceae, S. pneumoniae, by
treatment of potential sepsis, sepsis neonatorum, IV infusion, ADULT, 5 mg/kg with vancomycin and
immunocompetent children due to specific sources, ceftriaxone/levofloxacin.
native valve infective endocarditis, prosthetic valve Community acute bacterial meningitis, by IM injection or IV
infective endocarditis, bacterial purulent pericarditis, infusion, INFANT, 5 mg/kg with ampicillin OR cefotaxime
community acute bacterial meningitis, brain abscess in dependent on the etiology of bacterial meningitis.

J
the presence of endocarditis, chronic or recurrent Brain abscess in the presence of endocarditis, native valve,
mastoiditis, community-acquired pneumonia, hospital- by IM injection or IV infusion, ADULT and CHILD, 3-6
acquired pneumonia, and pathogen-specific infections. mg/kg with ceftriaxone.
Brain abscess in the presence of endocarditis, prosthetic
Contraindications: Perforated ear drum; hepatic valve, by IM injection or IV infusion, ADULT and CHILD, 3-
impairment; myasthenia gravis. 6 mg/kg with vancomycin.
Chronic or recurrent mastoiditis, by IV infusion, CHILD, 7.5
Dose: mg/kg in divided doses every 8 hours with piperacillin-
Potential sepsis, by IV infusion, NEONATE ≤7 days old ≤2 kg, tazobactam.
5 mg/kg every 48 hours; NEONATE 8-28 days old ≤2 kg, Community-acquired pneumonia, severe, by IV infusion,
5 mg/kg every 36 hours; NEONATE ≤7 days old >2 kg, 4 NEONATE, 5 mg/kg with ampicillin OR penicillin G;
mg/kg every 24 hours; NEONATE 8-28 days old >2 kg, 4- High-risk, risk for P. aeruginosa, by IV infusion, ADULT, 5-
5 mg/kg every 24 hours; with ampicillin. 7 mg/kg with azithromycin and piperacillin-
Neonatal sepsis, by IV infusion, NEONATE ≤7 days old ≤2 kg, tazobactam/cefepime/meropenem.
5 mg/kg every 48 hours; NEONATE 8-28 days old ≤2 kg, Hospital-acquired pneumonia, P. aeruginosa, A. baumanii,
5 mg/kg every 36 hours; NEONATE ≤7 days old >2 kg, 4 K. pneumoniae; Klebsiella spp., E. coli, Enterobacter
mg/kg every 24 hours; NEONATE 8-28 days old >2 kg, 4- spp.; Proteus spp.; Serratia marcesens, by IV infusion,
5 mg/kg every 24 hours; with cefotaxime/ceftriaxone CHILD, 5 mg/kg with ceftazidime;
with or without oxacillin/vancomycin. Pathogen—specific treatment, P. aeruginosa, by IV infusion,
Immunocompetent children, intra-abdominal source, by IV CHILD, 5-7 mg/kg with ceftazidime; ADULT, 5-7mg/kg
infusion, CHILD, 6-7.5 mg/kg in divided doses every 8 with levofloxacin OR ciprofloxacin;
hours or 5-7.5 mg/kg daily with ampicillin and Acinetobacter species, by IV infusion, CHILD, 5 mg/kg
metronidazole OR clindamycin for 10-14 days or longer. with meropenem;
Immunocompetent children, urinary source, by IV infusion, Burkholderia cepacia, by IV infusion, CHILD, 5-7 mg/kg
CHILD, 6-7.5 mg/kg in divided doses every 8 hours or 5- with meropenem;
7.5 mg/kg daily with ceftriaxone OR cefotaxime for 10- Escherichia coli, by IV infusion, CHILD, 5 mg/kg with
14 days or longer. ceftriaxone;
Native valve infective endocarditis, community-acquired, by Enterobacter, by IV infusion, CHILD, 5-7 mg/kg with
IM injection or IV infusion, CHILD, 3-6 mg/kg in divided meropenem or cefepime.
doses every 8 hours with ampicillin-sulbactam; ADULT, 1
mg/kg every 8 hours with ampicillin-sulbactam; Dose Adjustment:
Healthcare-associated, by IM injection or IV infusion, Neonates and Infants:
CHILD, 3-6 mg/kg every 8 hours with vancomycin; Adjust dosage; avoid prolonged use.
ADULT, 1 mg/kg every 8 hours with vancomycin and
cefepime/ceftazidime; Geriatric:
S. viridans or S. bovis (S. gallolyticus) with penicillin G For mild-to-moderate renal impairment, dose reduction or
MIC ≤0.12 mcg/mL, by IV infusion, ADULT, 3 mg/kg with dose interval extension is warranted; for severe
penicillin G OR ceftriaxone for 2 weeks; impairment, the patient should be referred to a
S. viridans or S. bovis (S. gallolyticus) with penicillin G specialist.
MIC >0.12 to ≤0.5mcg/mL, by IV infusion, CHILD, 3-6
mg/kg in divided doses every 8 hours with ampicillin OR Renal Impairment:
ceftriaxone for 2 weeks; ADULT, 3 mg/kg with penicillin For mild-to-moderate renal impairment, dose reduction is
G for 2 weeks; warranted; for severe impairment, the patient should be
Enterococci, penicillin-resistant aminoglycoside- referred to a specialist.
sensitive, by IV infusion, CHILD, 3-6 mg/kg in divided
doses every 8 hours with vancomycin for 6 weeks;

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 ANTI-INFECTIVES FOR SYSTEMIC USE

Precautions: QUINOLONE
WARNING: Neurotoxicity, manifested as both bilateral
auditory and vestibular ototoxicity, can occur in patients FIRST-GENERATION QUINOLONES
with pre-existing renal damage and in patients with (NON-FLUORINATED)
normal renal function treated at higher doses and/or
for periods longer than those recommended.
Aminoglycosides are potentially nephrotoxic. Risk is Rx NALIDIXIC ACID
greater in patients with impaired renal function and in
those who receive high doses or prolonged therapy. Oral: 500 mg tablet
Use with caution premature infants and neonates 250 mg/5 mL suspension, 60 mL
because of renal immaturity and the resulting
prolongation of serum half-life of the drug. Decrease Indications: Treatment of acute or chronic urinary tract and
dose. gastrointestinal tract infections caused by susceptible
Neuromuscular blockade and respiratory paralysis have gram-negative organisms.
been reported following parenteral injection of
aminoglycosides. Use with caution when giving in Contraindications: Hypersensitivity to any quinolones,
patients with neuromuscular diseases e.g. myasthenia children under 3 months old and pregnant women.
gravis.
Dose:
J

Obesity (use ideal body weight to calculate dose and Shigellosis, by mouth, ADULT, 1 g every 6 hours for 5 days;
CHILD ≥3 months, 15 mg/kg (maximum 1 g) every 6
monitor serum gentamicin concentration closely);
Pregnancy (second and third trimesters: auditory or hours for 5 days.
vestibular nerve damage; reserve for severe or life-
threatening infections for which safer drugs are Dose Adjustment:
inappropriate; if administered, monitor serum-
Geriatric:
Risk of toxic reactions may be greater in patients with
gentamicin concentration),
impaired renal function.
Breastfeeding (amount probably too small to be harmful;
monitor infant for thrush and diarrhea).
Renal Impairment:
Adverse Drug Reactions: The normal dosage of nalidixic acid may be employed in
Common: Edema, gait instability, ototoxicity (auditory and patients with creatinine clearance more than 20
vestibular damage), nephrotoxicity, reddening of the mL/minute. Dosage should be halved in patients with
skin, skin itching. creatinine clearance 20 mL/minute or less.
Less Common: Rash.
Precautions:
Rare: Anaphylaxis, antibiotic-associated colitis, blood
disorders, bronchospasm, CNS effects, electrolyte WARNING: May cause toxic psychosis, convulsions,
disturbances, nausea, neuromuscular blockade, oliguria, increased intracranial pressure, or metabolic acidosis.
peripheral neuropathy, photosensitivity, stomatitis, Use with caution in patients with known or suspected
vomiting. CNS disorders e.g cerebral arteriosclerosis or epilepsy,
or other factors which predispose seizures
Drug Interactions:
Monitor closely with: Serious and occasionally fatal hypersensitivity
Increases risk of adverse or toxic effects of Gentamicin: (anaphylactoid) reactions, some following the first dose,
Ototoxic and nephrotoxic drugs e.g. Streptomycin have been reported in patients receiving quinolone
therapy.
Avoid concomitant use with:
Increases risk of adverse or toxic effects of Gentamicin: Adverse Drug Reactions:
Diuretics e.g. Furosemide Common: Nausea and vomiting.
Less Common: Visual disturbances, headache, rashes,
Administration: eosinophilia, and photosensitivity.
Infuse gentamicin over 30-60 minutes; doses <120 mg may Rare: Hepatic and renal disturbances.
be given as IV injection over 3-5 minutes. Final
concentration of IV infusion should not exceed 10 Drug Interactions:
mg/mL. Monitory closely with:
Enhances therapeutic effect of Warfarin
Pregnancy Category: D
Reduces therapeutic effect of Nalidixic Acid:
ATC Code: J01GB03 Probenecid

Reduces absorption of Nalidixic Acid:

Antacids

Avoid concomitant use with:

Increases risk of adverse or toxic effects of Melphalan

236
ANTI-INFECTIVES FOR SYSTEMIC USE

Increases serum concentration of Cyclosporine Community-acquired pneumonia, high risk, risk for P.
aeruginosa, by IV infusion, ADULT, 400 mg every 8-12
Administration: Can be taken with or without meals. hours with azithromycin and gentamicin/ amikacin and
Patients should be advised to drink fluids liberally and piperacillin-tazobactam /meropenem/ cefepime.
not take antacids. Pathogen-specific treatment, P. aeruginosa, by IV infusion,
CHILD, 20-30 mg/kg in divided doses every 12 hours
Pregnancy Category: C with amikacin/ gentamicin and piperacillin-tazobactam/
meropenem; ADULT, 400 mg every 8 hours with
ATC Code: J01MB02 amikacin/ gentamicin;
MDR Acinetobacter, by IV infusion, CHILD, 20-30 mg/kg
in divided doses every 12 hours;
SECOND-GENERATION FLUOROQUINOLONES Klebsiella pneumoniae, by IV infusion, CHILD, 20-30
mg/kg in divided doses every 12 hours;
Burkholderia cepacia, by IV infusion, CHILD, 20-30
Rx CIPROFLOXACIN mg/kg in divided doses every 12 hours; ADULT, 400 mg
WHO anti-biotic category: WATCH
every 12 hours;
Enterobacter, by IV infusion, CHILD, 20-30 mg/kg in
Oral: 250 mg and 500 mg tablet (as hydrochloride)
divided doses every 12 hours.
Inj.: 2 mg/mL (as lactate), 100 mL vial (IV infusion)
400 mg/200 mL (IV infusion)
Dose Adjustment:

J
Renal Impairment:
Indications: Restricted use of treatment of severe infections
For mild-to-moderate renal impairment, dose reduction is
of the GI tract including MDR typhoid fever and Shigella
warranted; for severe impairment, the patient should be
dysentery, chancroid; febrile neutropenia, alternative
referred to a specialist.
treatment of acute uncomplicated cystitis;
meningococcal meningitis prophylaxis.
Hepatic Impairment:
Same dosage as in patients with normal hepatic function
Contraindications: Known history of tendon disorders
may be used in patients with mild-to-moderate hepatic
related to quinolone use; children; concurrent tizanidine
impairment; for severe impairment, refer to a specialist.
use.
Precautions:
Dose:
Sepsis suspect intra-abdominal source, by IV infusion, WARNING: Associated with an increased risk of tendinitis
ADULT, 400 mg every 12 hours with metronidazole. and tendon rupture; this risk is further increased in
Febrile neutropenia, low risk, by mouth, Adult, 750 mg twice older patients, usually those older than 60 years; in
daily with amoxicillin-clavulanic acid until patient is kidney, heart, and lung transplant recipients; and with
afebrile and absolute neutrophil count >500cells/μL. the concomitant use of steroid therapy. If tendinitis is
Antibacterial prophylaxis, by mouth, ADULT, 500-750 mg; by suspected, the quinolone should be discontinued
IV infusion, ADULT, 400 mg every 12 hours. immediately. Quinolones are contraindicated in
Uncomplicated typhoid fever, by mouth, CHILD, 30 mg/kg in patients with a history of quinolone-related tendon
divided doses every 12 hours for 7-10 days; ADULT, 500 disorders.
mg 1 tablet every 12 horus for 7-10 days. May exacerbate muscle weakness in patients with
Complicated typhoid fever, by IV infusion, CHILD, 30 mg/kg myasthenia gravis; avoid quinolones with known history
in divided doses every 12 hours for 7-10 days; ADULT, of myasthenia gravis.
400 mg every 12 hours for 7-10 days.
Chronic carrier, by IV infusion, CHILD, 30 mg/kg in divided
doses every 12 hours for 4 weeks; by mouth, ADULT, History of epilepsy or conditions that predispose to seizures,
500-750 mg every 12 hours for 28 days. myasthenia gravis, G6PD deficiency (increased risk of
Non-typhoidal salmonellosis, Salmonella gastroenteritis, by hemolytic anemia),
IV infusion, INFANT ≤3 months old, 10-20 mg/kg in Risk of crystalluria (avoid excessive alkalinity of urine and
divided doses every 12 hours for 7-10 days. ensure adequate fluid intake)
Osteomyelitis, foot bone, by mouth, ADULT, 750 mg twice a Renal impairment;
day, photosensitivity (discontinue if photosensitivity occurs);
Community acute bacterial meningitis, for severe penicillin Pregnancy (avoid use; arthropathy reported in animal
allergy, by IV infusion, ADULT, 400 mg with vancomycin; studies; safer alternatives are available);
For confirmed meningococcal meningitis and not treated Breastfeeding (amount too small to be harmful; use
with Ceftriaxone, by mouth, ADULT, 500 mg. alternative drugs if possible).
Orbital cellulitis, with serious allergy to Penicillin and/or USE IN CHILDREN: Ciprofloxacin causes arthropathy in
cephalosporins, by mouth, CHILD, 20-30 mg/kg in 2 weight-bearing joints of immature animals, and is
divided doses with vancomycin; therefore generally not recommended for use in children
Stage II-IV MRSA not considered, by IV infusion, ADULT, and growing adolescents. However, the significance of
400 mg every 8-12 hours with clindamycin for 10-21 this effect in humans is uncertain and in some specific
days; circumstances, short-term use of ciprofloxacin in
Serious allergy to penicillin and/or cephalosphorin, by children may be justified.
mouth, ADULT, 500-750 mg twice a day with vancomycin
for 10-21 days; by IV infusion, ADULT, 400 mg every 12 SKILLED TASKS: May impair ability to perform skilled tasks,
hours with vancomycin for 10-21 days. e.g., operating machinery or driving.

237
 ANTI-INFECTIVES FOR SYSTEMIC USE

Adverse Drug Reactions: OFLOXACIN

Common: Abdominal pain, diarrhea, dyspepsia, flatulence, Rx
WHO anti-biotic category: WATCH
itch, nausea, rash, vomiting.
Less Common: agitation, anorexia, arthralgia, arthritis, Oral: 200 mg tablet
confusion, decreased appetite and food intake,
depression, dizziness, drowsiness, hallucinations, fever, Indications: Treatment of acute exacerbations of chronic
headache, myalgia, superinfections, fever, headache, bronchitis, community-acquired pneumonia, skin and
myalgia, superinfections, restlessness, sleep and taste skin structure infections (uncomplicated), urethritis and
disorders, urticaria. cervicitis (non-gonococcal) due to Chlamydia
Rare: Agranulocytosis, anaphylaxis, bone marrow trachomatis infection, mixed infections of the urethra
depression, C. difficile-associated disease, dyspnea, and cervix, pelvic inflammatory disease (acute), cystitis
edema, erythema multiforme, erythema, hematuria, (uncomplicated), urinary tract infections (complicated),
fixed drug eruptions, hearing loss, hemolytic anemia, prostatitis.
hepatitis, hyperglycemia, hypoglycemia, hypotension,
interstitial nephritis, jaundice, leukopenia, neutropenia, Dose:
pancreatitis, pancytopenia, petechiae, photosensitivity Cervicitis/urethritis, by mouth, non-gonococcal (due to
reactions, psychotic reactions, renal impairment, Chlamydia trachomatis), ADULT, 300 mg twice daily for
seizures, serum sickness-like reactions, SJS, syncope, 7 days
tachycardia, tendonitis, thrombocytopenia, toxic Chronic bronchitis (acute exacerbation), community-
epidermal necrolysis, vasculitis. acquired pneumonia, skin and skin structure infections
J

(uncomplicated), by mouth, ADULT, 400 mg every 12

Drug Interactions: hours for 10 days.
NOTE: Ciprofloxacin inhibits CYP1A2, and may affect drugs Pelvic inflammatory disease (acute), by mouth, ADULT, 400
metabolized by this enzyme. mg every 12 hours for 10 to 14 days.
Prostatitis, by mouth, ADULT, 300 mg every 12 hours for 6
Monitor closely with: weeks.
Increases risk of adverse or toxic effects of Ciprofloxacin: Urinary tract infection, by mouth, ADULT, uncomplicated,
Ibuprofen 200 mg every 12 hours for 3 to 7 days; complicated, 200
mg every 12 hours for 10 days.
Reduces therapeutic effect of Phenytoin
Dose Adjustment:
Decreases metabolism of Theophylline Geriatric:
Refer to adult dosing.
Enhances therapeutic effect of Warfarin
Renal Impairment:
Increases risk of adverse or toxic effects of Warfarin (risk of After a normal initial dose, adjust as follows:
bleeding) [monitor INR] CrCl >20 mL/minute: Administer usual recommended dose
every 24 hours.
Avoid concomitant use with: CrCl <20 mL/minute: Administer half the usual
Reduces absorption of Ciprofloxacin: recommended dose every 24 hours.
Antacids (e.g. aluminum or magnesium hydroxide) [give Intermittent hemodialysis (IHD): 100 to 200 mg after
it at least 2 hours, before, or 4-6 hours after, the antacid], dialysis.
Calcium [separate doses by at least 2 hours], Iron Peritoneal dialysis: 200 mg every 24 hours.
[separate doses by at least 2 hours], Sucralfate, Zinc Continuous renal replacement therapy (CRRT): 300 mg
salts [separate doses by at least 2 hours] every 24 hours.

Increases risk of adverse or toxic effects of Ciprofloxacin: Hepatic Impairment:

Seizure-inducing drugs, Artemether + Lumefantrine Use with caution for patients with severe impairment (e.g.,
cirrhosis with or without ascites).
Administration:
May be taken with or without food; do not take with Precautions:
antacids, iron or dairy products. WARNING: Significant hypoglycemia and certain mental
health side effects. Low blood sugar levels can lead to
Pregnancy Category: C coma; and the mental health side effects to be added
or updated across all fluoroquinolones are
ATC Code: J01MA02 disturbances in attention, disorientation, agitation,
nervousness, memory impairment, and serious
disturbances in mental abilities called delirium.
Associated with an increased risk of tendinitis and tendon
rupture in all ages. This risk is further increased in older
patients (usually older than 60 years), patients taking
corticosteroid drugs, and patients with kidney, heart, or
lung transplants.

238
ANTI-INFECTIVES FOR SYSTEMIC USE

May exacerbate muscle weakness in persons with BCG Vaccine, Lactobacillus, Estriol, Sodium Picosulfate,
myasthenia gravis. Avoid ofloxacin in patients with a Typhoid Vaccine
known history of myasthenia gravis.
Increases risk of adverse or toxic effects Ofloxacin:
Fluoroquinolones may prolong QTc interval, avoid use in Corticosteroids
patients with a history of QTc prolongation, uncorrected
hypokalemia, hypomagnesemia, or concurrent Decreases excretion of Ofloxacin:
administration of other medications known to prolong Probenecid
the QT interval (including Class Ia and Class III
antiarrhythmics, cisapride, erythromycin, antipsychotics, Avoid concomitant use with:
and tricyclic antidepressants); Increases risk of adverse or toxic effects Ofloxacin:
Tremor, restlessness, confusion and very rare Nadifloxacin
hallucinations, increased intracranial pressure or
seizures may occur (use with caution in patients with Increases risk of adverse or toxic effects of Aminolevulinic
known or suspected CNS disorder. Discontinue in Acid
patients who experience significant CNS adverse
effects); Reduces therapeutic effect of the following drugs:
Severe, sometimes, fatal, hypersensitivity reactions, BCG, Cholera Vaccine
including anaphylaxis, have occurred with quinolone
therapy. (Prompt discontinuation of drug should occur if Enhances therapeutic effect of the following drugs:

J
skin rash or other symptoms arise); Hydroxychloroquine, Mifepristone, Probucol, QTc-
Peripheral neuropathy (discontinue if symptoms of sensory Prolonging Agents
of sensorimotor neuropathy occur);
Photosensitivity (discontinue use if photosensitivity occurs); Decreases serum concentration of Ofloxacin:
Prolonged use may result in fungal or bacterial Strontium Ranelate
superinfection, including C. difficile-associated diarrhea
(CDAD) and pseudomembranous colitis. Administration: Administer with or without food; do not take
within 2 hours of sucralfate, didanosine, iron, zinc, or
Adverse Drug Reactions: antacids containing magnesium, calcium, or aluminum.
Less Common: Chest pain, headache, insomnia, dizziness,
fatigue, drowsiness, sleep disorder, nervousness, trunk Pregnancy Category: C
pain, pruritus, skin rash, genital pruritus, nausea,
diarrhea, vomiting, abdominal cramps, constipation, ATC Code: J01MA01
decreased appetite, dysgeusia, flatulence,
gastrointestinal distress, xerostomia, vaginitis, visual
disturbances, pharyngitis, fever. THIRD-GENERATION FLUOROQUINOLONES
Rare: Abnormal dreams, anaphylaxis, anxiety, auditory
disturbance, blurred vision, chills, cognitive dysfunction, LEVOFLOXACIN
cough, depression, ecchymosis, edema, erythema Rx
WHO anti-biotic category: WATCH
nodosum, euphoria, exacerbation of myasthenia gravis,
Gilles de la Tourette’s syndrome, hallucination, hepatic Oral: 250 mg, 500 mg, and 750 mg tablet
insufficiency, hepatic failure, hepatitis, hepatotoxicity, Inj.: 5 mg/mL solution for IV infusion, 100 mL and 150 mL
hyperglycemia, hypoglycemia, hypertension, increased vial
intracranial pressure, polydipsia, interstitial nephritis,
limb pain, malaise, palpitations, paresthesia, peripheral Indications: Treatment of community-acquired pneumonia,
neuropathy, photophobia, pneumonitis, pseudotumor including multidrug resistant strains of S. pneumoniae;
cerebri, psychotic reaction, rhabdomyolysis, rupture of nosocomial pneumonia; acute bacterial exacerbation of
tendon, seizure, skin photosensitivity, SJS, syncope, chronic bronchitis; skin or skin structure infections
tendonitis, tinnitus, torsades de pointes, toxic epidermal (uncomplicated or complicated); antibacterial
necrolysis, vasculitis, vasodilation, vertigo, weakness, prophylaxis; pathogen-specific treatment
weight loss.
Dose:
Drug Interactions: Note: Sequential therapy (IV to oral) may be instituted based
Monitor closely with: on prescriber's discretion.
Enhances therapeutic effect of the following drugs:
Glucose Lowering Agents e.g. Insulin Sepsis, intra-abdominal source, by IV infusion, ADULT, 750
Delamanid, Fluoxetine, Porfimer, QTc-Prolonging mg every 24 hours with metronidazole.
Agents, Tacrolimus, Vitamin K Antagonists e.g. Warfarin Febrile neutropenia, low risk, by mouth, ADULT, 750 mg with
amoxicillin-clavulanic acid until patient is afebrile and
Reduces absorption of Ofloxacin: absolute neutrophil count >500cells/μL.
Antacids (except: sodium bicarbonate), Calcium Salts Antibacterial prophylaxis, by mouth, by IV infusion, ADULT,
(except: calcium chloride), Phosphate binder e.g. 500-750 mg.
Sevelamer Osteomyelitis, hematogenous, vertebral, MRSA likely, by IV
infusion, ADULT, 750 mg every 24 hours with
Reduces therapeutic effect of the following drugs: vancomycin;

239
 ANTI-INFECTIVES FOR SYSTEMIC USE

MRSA unlikely, by IV infusion, ADULT, 750 mg every 24 CrCl 20 to 49 mL/minute: Administer 750 mg every 48
hours with oxacillin. hours.
Osteomyelitis, foot bone, by mouth, ADULT, 750 mg every CrCl 10 to 19 mL/minute: Administer 750 mg initial dose,
24 hours. followed by 500 mg every 48 hours.
Bacterial purulent pericarditis, S. aureus, Group A Hemodialysis/chronic ambulatory peritoneal dialysis
Streptococcus, Enterobacteriaceae, S. pneumoniae, by (CAPD): Administer 750 mg initial dose, followed by 500
IV infusion, ADULT, 750 mg every 24 hours with mg every 48 hours; supplemental doses are not required
vancomycin. following either hemodialysis or CAPD.
Acute epiglottitis, by IV infusion, ADULT, 750 mg every 24
hours with clindamycin. Normal renal function dosing of 750 or 1,000 mg daily
Acute sinusitis, clinical failure after 3 days, by mouth, (treatment of tuberculosis only) (CDC 2003): CrCl <30
ADULT, 500 mg for 5 days; by IV infusion, ADULT, 750 mL/minute: Administer 750 or 1,000 mg 3 times per
mg for 7-10 days. week (in hemodialysis patients administer after dialysis
Acute otitis media (AOM), with anaphylaxis, by mouth, on dialysis days).
ADULT, 750 mg every 24 hours for 5 days.
Acute otitis media, clinical failure after 3 days, severe Continuous renal replacement therapy (CRRT): Drug
penicillin allergy, by mouth, ADULT, 750 mg twice daily clearance is highly dependent on the method of renal
for 5 days. replacement, filter type, and flow rate. Appropriate
Acute mastoiditis, by IV infusion, ADULT, 750 mg daily. dosing requires close monitoring of pharmacologic
Acute bacterial exacerbation of chronic bronchitis (ABECB), response, signs of adverse reactions due to drug
J

severe, by mouth, ADULT, 500 mg every 24 hours for 5- accumulation, as well as drug concentrations in relation
10 days. to target trough (if appropriate). The following are general
Acute bacterial exacerbation (bronchiectasis), by mouth, recommendations only (based on dialysate
ADULT, 500 mg every 24 hours for 7-10 days. flow/ultrafiltration rates of 1 to 2 L/hour and minimal
Community-acquired pneumonia, moderate risk, by mouth, residual renal function) and should not supersede
ADULT, 750 mg with ampicillin-sulbactam/ cefuroxime clinical judgment:
sodium/ ceftriaxone for 7-28 days; CVVH: Loading dose of 500 to 750 mg followed by 250
High risk, no risk for P. aeruginosa, by IV infusion, ADULT, mg every 24 hours.
750 mg with ceftriaxone or ertapenem; CVVHD: Loading dose of 500 to 750 mg followed by 250
High risk, risk for P. aeruginosa, by IV infusion, ADULT, to 500 mg every 24 hours.
750 mg with gentamicin/amikacin and azithromycin and CVVHDF: Loading dose of 500 to 750 mg followed by
piperacillin-tazobactam/ cefepime/ meropenem. 250 to 750 mg every 24 hours.
Hospital-acquired pneumonia, high risk of mortality and with
risk factor for MDR, by IV infusion, ADULT, 750 mg with Precautions:
vancomycin/linezolid and piperacillin-tazobactam/ WARNING: Fluoroquinolones are associated with
cefepime/ meropenem for 7 days or longer. disabling and potentially irreversible serious adverse
Ventilator-associated pneumonia, with risk factors for MRD reactions that may occur together, including tendinitis
VAP and with structural lung disease, by IV infusion, and tendon rupture, peripheral neuropathy, and CNS
ADULT, 750 mg with vancomycin/linezolid and effects. Discontinue levofloxacin immediately and
piperacillin-tazobactam/ cefepime/ meropenem/ avoid use of fluoroquinolones in patients who
aztreonam for 7 days or longer. experience any of these serious adverse reactions.
Pathogen-specific treatment, P. aeruginosa, by IV infusion, Patients of any age or without preexisting risk factors
ADULT, 750 mg with amikacin OR gentamicin; have experienced these reactions; may occur within
Klebsiella pneumoniae, by IV infusion, ADULT, 750 mg hours to weeks after initiation.
every 24 hours.
QTc prolongation (avoid use in patients with a history of QTc
Dose Adjustment: prolongation, uncorrected hypokalemia,
Geriatric: hypomagnesemia, or concurrent administration of other
Refer to adult dosing. medications known to prolong the QT interval e.g, Class
Ia and Class III antiarrhythmics, cisapride, erythromycin,
Renal Impairment: antipsychotics, and tricyclic antidepressants;
Normal renal function dosing of 250 mg daily: Hypoglycemia/hyperglycemia (Patients should be
CrCl 20 to 49 mL/minute: No dosage adjustment required. monitored closely for signs/symptoms of disordered
CrCl 10 to 19 mL/minute: Administer 250 mg every 48 glucose regulation particularly severe hypoglycemia);
hours (except in uncomplicated UTI, where no dosage Severe hepatotoxicity (including acute hepatitis and
adjustment is required). fatalities) has been reported. (Discontinue therapy
Normal renal function dosing of 500 mg daily: immediately if signs and symptoms of hepatitis occur);
CrCl 20 to 49 mL/minute: Administer 500 mg initial dose, Severe hypersensitivity reactions, including anaphylaxis
followed by 250 mg every 24 hours. (Prompt discontinuation of drug should occur if skin rash
CrCl 10 to 19 mL/minute: Administer 500 mg initial dose, or other symptoms arise;
followed by 250 mg every 48 hours. Photosensitivity (Discontinue use if photosensitivity occurs);
Hemodialysis/chronic ambulatory peritoneal dialysis Prolonged use may result in fungal or bacterial
(CAPD): Administer 500 mg initial dose, followed by 250 superinfection, including C. difficile-associated diarrhea
mg every 48 hours; supplemental doses are not required (CDAD) and pseudomembranous colitis.
following either hemodialysis or CAPD
Normal renal function dosing of 750 mg daily:

240
ANTI-INFECTIVES FOR SYSTEMIC USE

Adverse Drug Reactions: Avoid concomitant use with:

Less Common: Chest pain, edema, headache, insomnia, Incrases risk of adverse or toxic effects Levofloxacin:
dizziness, skin rash, pruritus, nausea, diarrhea, Nadifloxacin
constipation, abdominal pain, dyspepsia, vomiting,
vaginitis, candidiasis, injection site reaction, dyspnea Reduces therapeutic effect of the following drugs:
Rare: abnormal gait, acute generalized exanthematous BCG, Cholera Vaccine
pustolosis, acute renal failure, ageusia, agitation,
agranulocytosis, altered sense of smell, anaphylactoid Enhances therapeutic effect of the following drugs:
reaction, aplastic and hemolytic anemia, anorexia, Hydroxychloroquine, Macimorelin, Mifepristone,
anosmia, anxiety, arthralgia, blurred vision, Probucol, Promazine, QTc-Prolonging Agents
bronchospasm, cardiac arrest, cardiac arrhythmia
(including ventricular tachycardia/ fibrillation and Decreases serum concentration of Levofloxacin:
torsades de pointes), Clostridium difficile-associated Strontium Ranelate
diarrhea, confusion, convulsions, crystalluria, decreased
visual acuity, depression, dermatological disease, Administration:
drowsiness, dysgeusia, epistaxis, erythema multiforme, For oral: Tablets may be administered without regard to
esophagitis, exacerbation of myasthenia gravis, fever, meals. Oral solution should be administered at least 1
gastritis (including gastroenteritis), glossitis, hour before or 2 hours after meals. Maintain adequate
granulocytopenia, hallucination, hepatic failure (some hydration of patient to prevent crystalluria. Administer at
fatal), hepatic insufficiency, hepatitis, hepatotoxicity least 2 hours before or 2 hours after antacids containing

J
(idiosyncratic), hyperglycemia, hyperkalemia, magnesium or aluminum, sucralfate, metal cations (e.g.
hyperkinesia, hypersensitivity pneumonitis, iron), multivitamin preparations with zinc, or didanosine
hypersensitivity reaction (including anaphylaxis, chewable/buffered tablets or the pediatric powder for
angioedema, rash, pneumonitis, and serum sickness), solution.
hypertension, hypertonia, hypoacusis, hypoglycemia, For IV: Infuse 250 to 500 mg IV solution over 60 minutes;
hypotension, increased intracranial pressure, interstitial infuse 750 mg IV solution over 90 minutes. Too rapid of
nephritis, intestinal obstruction, jaundice, leukocytosis, infusion can lead to hypotension. Avoid administration
leukopenia, leukorrhea, lymphadenopathy, multiorgan through an intravenous line with a solution containing
failure, muscle injury, muscle spasm, myalgia, multivalent cations (eg, magnesium, calcium). Maintain
palpitations, pancreatitis, pancytopenia, paralysis, adequate hydration of patient to prevent crystalluria.
paranoia, paresthesia, peripheral neuropathy (may be
irreversible), phlebitis, phototoxicity, prolonged Pregnancy Category: C
prothrombin time, prolonged QT interval, pseudotumor
cerebri, psychosis, restlessness, rhabdomyolysis, ATC Code: J01MA12
rupture of tendon, scotoma, seizure, skeletal pain, skin
photosensitivity, sleep disorder (including abnormal
dreams and nightmares), SJS, stomatitis, suicidal FOURTH-GENERATION FLUOROQUINOLONES
ideation, syncope, tachycardia, tendonitis, tinnitus, toxic
epidermal necrolysis, toxic psychosis, thrombocytopenia
(including thrombotic thrombocytopenic purpura), Rx MOXIFLOXACIN
tremor, urticaria, uveitis, vasculitis, vasodilatation, WHO anti-biotic category: WATCH
vertigo, visual disturbance (including diplopia), voice
disorder Oral: 400 mg film coated tablet

Drug Interactions: Indications: Treatment of multidrug resistant tuberculosis

Monitory closely with: (MDRTB); mild to moderate community-acquired
Enhances therapeutic effect of the following drugs: pneumonia, including multidrug-resistant Streptococcus
Blood Glucose Lowering Agents, Delamanid, Fluoxetine, pneumoniae; acute bacterial exacerbation of chronic
QTc-Prolonging Agents e.g. Tacrolimus, Vitamin K bronchitis; acute bacterial sinusitis; complicated and
Antagonists e.g. Warfarin uncomplicated skin and skin structure infections;
complicated intra-abdominal infections; prophylaxis and
Reduces absorption of Levofloxacin: treatment of plague, including pneumonic and
Antacids (except: sodium bicarbonate), Calcium Salts septicemic plague, due to Yersinia pestis.
(except: calcium chloride), Sevelamer
Dose:
Reduces therapeutic effect of the following drugs: Acute bacterial rhinosinusitis, by mouth, ADULT, 400 mg
BCG Vaccine, Lactobacillus, Estriol, Sodium Picosulfate, every 24 hours for 10 days (manufacturer’s labeling) or
Typhoid Vaccine 5 to 7 days. (Note: Recommended in patients with beta-
lactam allergy; may also be used if initial therapy fails, in
Increases risk of adverse or toxic effects Levofloxacin: areas with high endemic rates of penicillin non
Corticosteroids susceptible S. pneumoniae, those with severe infections,
age >65 years, recent hospitalization, antibiotic use
Decreases excretion of Levofloxacin: within the past month, or who are
Probenecid immunocompromised).
Chronic bronchitis, acute bacterial exacerbation, by mouth,
ADULT, 400 mg every 24 hours for 5 days

241
 ANTI-INFECTIVES FOR SYSTEMIC USE

Community-acquired pneumonia (CAP) (including MDRSP, confusion, depression, disorientation, drowsiness, facial
by mouth, ADULT, 400 mg every 24 hours for 7 to 14 pain, fatigue, hallucination, hypoesthesia, lethargy,
days malaise, nervousness, noncardiac chest pain, pain,
Intra-abdominal infections, complicated, by mouth, ADULT, paresthesia, restlessness, vertigo, erythema,
400 mg every 24 hours for 5 to 14 days (initiate with IV); hyperhidrosis, night sweats, pruritus, skin rash, urticaria,
Note: 2010 IDSA guidelines recommend a treatment hypokalemia, dehydration, hyperglycemia,
duration of 4 to 7 days (provided source controlled) for hyperlipidemia, abdominal discomfort, abdominal
community-acquired, mild to moderate IAI distension, anorexia, decreased appetite, dysgeusia,
Plague, by mouth, ADULT, 400 mg every 24 hours for 10 to flatulence, gastritis, gastroenteritis, gastroesophageal
14 days reflux disease, oral candidiasis, tinnitus, blurred vision,
Skin and skin structure infections (Complicated), by mouth, fever, asthma, hypersensitivity reaction
ADULT, 400 mg every 24 hours for 7 to 21 days Rare: agranulocytosis, anaphylactic shock, anaphylaxis,
Skin and skin structure infections (Uncomplicated), by angioedema, aplastic anemia, ataxia, auditory
mouth, ADULT, 400 mg every 24 hours for 7 days impairment, cholestatic jaundice, Clostridium difficile
associated diarrhea, deafness (reversible), exacerbation
Dose Adjustment: of myasthenia gravis, facial edema, hemolytic anemia,
Geriatric: hepatic failure, hepatic necrosis, hepatitis,
Refer to adult dosing. hypoglycemia, increased intracranial pressure,
interstitial nephritis, jaundice, laryngeal edema,
Hepatic Impairment: myasthenia, nightmares, pancytopenia, paranoia,
J

No dosage adjustment necessary; however, use with peripheral neuropathy (may be irreversible), pharyngeal
caution in this patient population secondary to the risk of edema, phototoxicity, pneumonitis (allergic),
QT prolongation. polyneuropathy, pseudomembranous colitis,
pseudotumor cerebri, psychotic reaction, renal
Precautions: insufficiency, rupture of tendon, seizure, serum sickness,
WARNING: Fluoroquinolones are associated with skin photosensitivity, SJS, suicidal ideation, suicidal
disabling and potentially irreversible serious adverse tendencies, tendonitis, thrombotic thrombocytopenic
reactions that may occur together, including tendinitis purpura, toxic epidermal necrolysis, ventricular
and tendon rupture, peripheral neuropathy, and CNS tachyarrhythmias (including torsades de pointes and
effects. Discontinue moxifloxacin immediately and cardiac arrest
avoid use of fluoroquinolones in patients who
experience any of these serious adverse reactions. Drug Interactions:
Patients of any age or without pre-existing risk factors Monitory closely with:
have experienced these reactions; may occur within Enhances therapeutic effect of the following drugs:
hours to weeks after initiation. Blood Glucose Lowering Agents, Fluoxetine, Porfimer,
QTc-Prolonging Agents, Tacrolimus, Verteporfin, Vitamin
QTc prolongation (avoid use in patients with a history of QTc K Antagonists (e.g. Warfarin)
prolongation, uncorrected hypokalemia,
hypomagnesemia, or concurrent administration of other Reduces absorption of Moxifloxacin:
medications known to prolong the QT interval e.g. Class Antacids (except: sodium bicarbonate), Calcium Salts
Ia and Class III antiarrhythmics, cisapride, erythromycin, (except: calcium chloride), Sevelamer
antipsychotics, and tricyclic antidepressants;
Hypoglycemia/hyperglycemia (Patients should be Reduces therapeutic effect of the following drugs:
monitored closely for signs/symptoms of disordered BCG Vaccine, Lactobacillus and Estriol, Sodium
glucose regulation particularly severe hypoglycemia); Picosulfate, Typhoid Vaccine
Severe hepatotoxicity (including acute hepatitis and
fatalities) has been reported. (Discontinue therapy Increases risk of adverse or toxic effects Moxifloxacin:
immediately if signs and symptoms of hepatitis occur); Corticosteroids
Severe hypersensitivity reactions, including anaphylaxis
(Prompt discontinuation of drug should occur if skin rash Decreases excretion of Moxifloxacin:
or other symptoms arise; Probenecid
Photosensitivity (Discontinue use if photosensitivity occurs);
Prolonged use may result in fungal or bacterial Avoid concomitant use with:
superinfection, including C. difficile-associated diarrhea Increases risk of adverse or toxic effects Moxifloxacin:
(CDAD) and pseudomembranous colitis. Nadifloxacin

Adverse Drug Reactions: Reduces therapeutic effect of the following drugs:

Common: headache, dizziness, insomnia, hyperchloremia, BCG, Cholera Vaccine
nausea, diarrhea, constipation, vomiting, abdominal
pain, decreased hemoglobin, eosinopenia, leukocytosis, Enhances therapeutic effect of the following drugs:
hypoxia Hydroxychloroquine, Macimorelin, Mifepristone,
Less Common: angina pectoris, atrial fibrillation, Probucol, Promazine, QTc-Prolonging Agents, Vinflunine
bradycardia, cardiac arrest, cardiac failure, chest pain,
edema, hypertension, hypotension, palpitations, Decreases serum concentration of Moxifloxacin:
peripheral edema, phlebitis, prolonged Q-T interval on Strontium Ranelate
ECG, syncope, tachycardia, agitation, anxiety, chills,

242
ANTI-INFECTIVES FOR SYSTEMIC USE

Administration: Administer without regard to meals. Acute bacterial arthritis, monoarticular, not at risk for STI,
Administer at least 4 hours before or 8 hours after gram-positive cocci, by IV infusion, ADULT, 15-20 mg/kg
products containing magnesium, aluminum, iron, or zinc, every 8-12 hours;
including antacids, sucralfate, multivitamins, and Negative on gram-stain, by IV infusion, ADULT, 15-20
didanosine (buffered tablets for oral suspension or the mg/kg every 8-12 hours with ceftazidime OR piperacillin-
pediatric powder for oral solution). tazobactam.
Septic bursitis, MRSA, by IV infusion, ADULT, 15-20 mg/kg
Pregnancy Category: C every 8-12 hours for 14-21 days.
Prosthetic joint infections, Methicillin-resistant S. aureus or
ATC Code: J01MA14 epidermidis, by IV infusion, ADULT, 15-20 mg/kg every 8-
12 hours with rifampin and debridement, antibiotics and
implant retention (DAIR) followed by
GLYCOPEPTIDE ANTIBACTERIALS levofloxacin/ciprofloxacin and rifampin for 3 months;
Enterococci (penicillin-resistant), by IV infusion, ADULT,
15 mg/kg every 12 hours for 4-6 weeks.
Rx VANCOMYCIN Native valve infective endocarditis, healthcare-associated,
WHO anti-biotic category: ACCESS and WATCH
by IV infusion, CHILD, 60 mg/kg in divided doses every 6
hours with gentamicin; ADULT, 15-20 mg/kg every 8-12
Inj.: 500 mg and 1 g vial (as hydrochloride) (IV)
hours with gentamicin and cefepime/ceftazidime;
Enterococci, Penicillin-resistant aminoglycoside-
Indications: Treatment of early-onset prosthetic valve

J
sensitive, by IV infusion, CHILD, 60 mg/kg in divided
diphtheroid endocarditis in combination; Treatment of
doses every 6 hours with gentamicin for 6 weeks; ADULT,
enterococci (e.g. Enterococcus faecalis) endocarditis, in
15-20 mg/kg every 8-12 hours with gentamicin for 6
combination; Treatment of staphylococcal endocarditis;
weeks.
Treatment of streptococcal endocarditis, as
MRSA, by IV infusion, CHILD, 60 mg/kg in divided doses
monotherapy or in combination; Treatment of serious or
every 6 hours; ADULT, 15-20 mg/kg every 8-12 hours for
severe infections (e.g. septicemia, bone infections, lower
6 weeks.
respiratory tract infections, skin and skin structure
Prosthetic valve infective endocarditis, empiric therapy, by
infections) caused by susceptible strains of methicillin-
IV infusion, CHILD, 40-60 mg/kg in divided doses every
resistant staphylococci; empiric therapy of suspected
6-8 hours with gentamicin and rifampin for 6 weeks;
methicillin-resistant staphylococci infections
ADULT, 15-20 mg/kg every 8-12 hours with gentamicin
Dose:
and rifampin for 6 weeks;
Severe sepsis and septic shock, by IV infusion, CHILD, 40-
MRSA, by IV infusion, CHILD, 40 mg/kg in 2-3 divided
60 mg/kg in divided doses every 6 hours for 10-14 days;
doses with gentamicin and rifampin for 6 weeks; ADULT,
meningitis, by IV infusion, NEONATE ≤28 days old, 15
15-20 mg/kg every 8-12 hours with gentamicin and
mg/kg with piperacillin-tazobactam OR meropenem for
rifampin for 6 weeks.
10-14 days;
Bacterial purulent pericarditis, S. aureus, Group A
Bacteremia, by IV infusion, NEONATE ≤28 days old, 10
Streptococcus, Enterobacteriaceae, S. pneumoniae, by
mg/kg with piperacillin-tazobactam OR meropenem for
IV infusion, CHILD, 60 mg/kg in divided doses every 6
10-14 days.
hours with ceftriaxone; ADULT, 15-20 mg/kg every 8-12
Staphylococcal toxic shock syndrome, MRSA, by IV infusion,
hours with ceftriaxone OR levofloxacin OR gentamicin OR
CHILD, 40-60 mg/kg in divided doses every 6 hours daily
amikacin.
drip for 1 hours with clindamycin and IV IG for 10-14
Methicillin-resistant S. aureus is isolated and/or with
days; ADULT, 25-30 mg/kg loading dose then 1 g every
history and clinical features for MRSA infection; S.
8 hours with clindamycin and IV IG for 2-3 days.
pneumoniae resistant to extended-spectrum
Sepsis, non-neutropenic and/or suspect illicit IV drug use
cephalosporins, or nosocomial infections, by IV infusion,
source, by IV infusion, ADULT, 25-30 mg/kg loading dose
CHILD, 60 mg/kg every 6 hours; empirical and
then 1 g every 8 hours with piperacillin-tazobactam.
determined partly by the nature of concomitant infection.
Osteomyelitis, hematogenous, MRSA likely, long bones, by
Once a pathogen is isolated and the antimicrobial
IV infusion, ADULT, 15-20 mg/kg every 8-12 hours for 4-
susceptibilities are known, the most specific
6 weeks;
antimicrobial agent is continued IV for 3-4 weeks.
Vertebral, by IV infusion, ADULT, 15-20 mg/kg every 8-
Central line-associated bloodstream infection (CLABSI), by
12 hours with ceftriaxone OR piperacillin-tazobactam,
IV infusion, CHILD, 60 mg/kg in divided doses every 6
OR levofloxacin.
hours with piperacillin-tazobactam and aminoglycoside;
Osteomyelitis, contiguous without vascular insufficiency,
ADULT, 15-20 mg/kg every 8-12 hours.
long bone or spinal implant, by IV infusion, ADULT, 15-20
Impaired host, neutropenic, by IV infusion, ADULT, 15-20
mg/kg every 8-12 hours with ceftazidime OR piperacillin-
mg/kg every 8-12 hours with cefepime OR ceftazidime
tazobactam;
OR piperacillin-tazobactam.
Sternum, post-surgery, by IV infusion, ADULT, 15-20
Community-acute bacterial meningitis, severe penicillin
mg/kg every 8-12 hours.
allergy, by IV infusion, ADULT, 15-20 mg/kg every 8-12
Osteomyelitis, contiguous focus, by IV infusion, CHILD, 45-
hours with aztreonam or ciprofloxacin.
60 mg/kg in 3-4 doses with ceftazidime OR cefepime.
Anatomic defects, neurosurgical complications, and open
Suppurative arthritis, gram stain is negative OR if gram stain
head trauma, by IM injection or IV infusion, CHILD, 60
is positive for gram-positive cocci, by IV infusion, CHILD
mg/kg in divided doses every 6 hours with ceftazidime;
3 months-14 years, 40-60 mg/kg in 3-4 doses with
ADULT, 15-20 mg/kg every 8-12 hours with ceftazidime.
cefotaxime OR ceftriaxone.

243
 ANTI-INFECTIVES FOR SYSTEMIC USE

Brain abscess in the presence of head trauma, by IV Redosing based on pre-HD concentrations:
infusion, CHILD, 60 mg/kg in divided doses every 6 hours <10 mg/L: Administer 1,000 mg after HD
with ceftriaxone; ADULT, 15-20 mg/kg every 8-12 hours 10 to 25 mg/L: Administer 500 to 750 mg after HD
with ceftriaxone. >25 mg/L: Hold vancomycin
Brain abscess in the presence of endocarditis, by IV Redosing based on post-HD concentrations: <10 to 15
infusion, CHILD, 60 mg/kg in divided doses every 6 hours mg/L: Administer 500 to 1,000 mg
with gentamicin; ADULT, 15-20 mg/kg every 8-12 hours Peritoneal dialysis (PD): 1 g every 4 to 7 days
with gentamicin.
Spinal abscess, by IV infusion, CHILD, 60 mg/kg in divided Continuous renal replacement therapy (CRRT): Drug
doses every 6 hours; ADULT, 15-20 mg/kg every 8-12 clearance is highly dependent on the method of renal
hours. replacement, filter type, and flow rate. Appropriate
Dacrocystitis, by IV infusion, CHILD, 40 mg/kg 3-4 in divided dosing requires close monitoring of pharmacologic
doses with ceftazidime for 7-14 days; response, signs of adverse reactions due to drug
With signs and symptoms of orbital cellulitis, ADULT, 15- accumulation, as well as drug concentrations in relation
20 mg/kg every 8-12 hours with ceftriaxone or cefepime to target trough (if appropriate). The following are general
for 7-14 days. recommendations only (based on dialysate
Acute mastoiditis, by IV infusion, CHILD, 45-60 mg/kg in flow/ultrafiltration rates of 1 to 2 L/hour and minimal
divided doses every 6 hours. residual renal function) and should not supersede
Acute emphysema, by IV infusion, ADULT, 40 mg/kg in clinical judgment:
divided doses every 6 hours with ampicillin-sulbactam CVVH: Loading dose of 15 to 25 mg/kg, followed by
J

for 2-4 weeks. either 1,000 mg every 48 hours or 10 to 15 mg/kg every

Lung abscess, by IV infusion, CHILD, 40 mg/kg in divided 24 to 48 hours
doses every 6 hours with ceftriaxone and metronidazole CVVHD: Loading dose of 15 to 25 mg/kg, followed by
for 4 weeks. either 1,000 mg every 24 hours or 10 to 15 mg/kg every
Hospital-acquired pneumonia, not at high risk of mortality 24 hours
but with factors increasing the likelihood of MRSA, by IV CVVHDF: Loading dose of 15 to 25 mg/kg, followed by
infusion, ADULT, loading dose of 25-30 mg/kg then 15- either 1,000 mg every 24 hours or 7.5 to 10 mg/kg every
20 mg/kg every 8-12 hours with goal to target trough 12 hours
level to 15-20 mg/mL with piperacillin-tazobactam/ Note: Consider redosing patients receiving CRRT for
cefepime/ meropenem/ aztreonam; vancomycin concentrations <10 to 15 mg/L.
High risk of mortality and with risk factor for MDR, by IV
infusion, ADULT, loading dose of 25-30 mg/kg then 15- Precautions:
20 mg/kg every 8-12 hours with goal to target trough IV vancomycin is an irritant; ensure proper needle or
level to 15-20 mg/mL with piperacillin-tazobactam/ catheter placement prior to and during infusion; avoid
cefepime/ meropenem/ aztreonam and extravasation. If thrombophlebitis occurs, slow infusion
levofloxacin/amikacin for 7 days. rates, dilute solution (eg, 2.5 to 5 g/L) and rotate infusion
Ventilator-associated pneumonia, with risk factors for MRD sites;
VAP and with structural lung disease, by IV infusion, May cause nephrotoxicity; usual risk factors include
ADULT, loading dose of 25-30mg/kg then 15-20 mg/kg preexisting renal impairment, concomitant nephrotoxic
every 8-12 hours with goal to target trough level to 15- medications, advanced age, and dehydration (If multiple
20 mg/mL with piperacillin-tazobactam/ cefepime/ sequential (≥2) serum creatinine concentrations
meropenem/ aztreonam and levofloxacin/ amikacin for demonstrate an increase of 0.5 mg/dL or ≥50% increase
7 days. from baseline (whichever is greater) in the absence of an
Pathogen-specific treatment, by IV infusion, CHILD, 40-60 alternative explanation, the patient should be identified
mg/kg in divided doses every 6 hours with goal to target as having vancomycin-induced nephrotoxicity);
trough level to 15-20 mg/mL; ADULT, 15-20 mg/kg. Prolonged therapy and use of concomitant drugs that cause
neutropenia may increase the risk (monitor leukocyte
Dose Adjustment: counts periodically in these patients. Prompt reversal of
Geriatric: neutropenia is expected after discontinuation of
Refer to adult dosing. therapy);
Ototoxicity is rarely associated with monotherapy (Serial
Renal Impairment: auditory function testing may be helpful to minimize risk.
Poorly dialyzable by intermittent hemodialysis; however, use Ototoxicity may be transient or permanent; discontinue
of high-flux membranes and continuous renal treatment if signs of ototoxicity occur);
replacement therapy (CRRT) increases vancomycin Prolonged use may result in fungal or bacterial
clearance, and generally requires replacement dosing superinfection, including C. difficile infection (CDI); CDI
(Launay-Vacher 2002). has been observed >2 months post-antibiotic treatment.
End-stage renal disease (ESRD) on intermittent
hemodialysis (IHD) (administer after hemodialysis on Adverse Drug Reactions:
dialysis days): Following loading dose of 15 to 25 mg/kg, Common: Hypotension (accompanied by flushing)
give either 500 to 1,000 mg or 5 to 10 mg/kg after each Less Common: Local phlebitis, chills, drug fever, skin rash,
dialysis session (Heintz 2009). Note: Dosing dependent eosinophilia, neutropenia (reversible)
on the assumption of 3 times/week, complete IHD Rare: DRESS syndrome (drug rash with eosinophilia and
sessions. systemic symptoms), ototoxicity (use of other ototoxic
agents may increase risk), renal failure (limited data

244
ANTI-INFECTIVES FOR SYSTEMIC USE

suggesting direct relationship), SJS, thrombocytopenia, CBA/kg/day, CHILD, 2.5 to 5 mg CBA/kg/day in 2 to 4

vasculitis divided doses; maximum: 5 mg CBA/kg/day

Drug Interactions: Dose Adjustment:

Monitory closely with: Geriatric:
Increases risk of adverse or toxic effects of the following Refer to adult dosing
drugs: Renal Impairment:
Aminoglycosides e.g. Streptomycin Note: Dosage expressed in terms of colistin base activity
Colistimethate (CBA); although reported conversions have varied slightly
in the literature, CBA 1 mg is defined to be equivalent to
Reduces therapeutic effect of the following drugs: colistimethate sodium (CMS) 30,000 units
BCG Vaccine, Lactobacillus and Estriol
Sodium picosulfate, Typhoid Vaccine CrCl ≥80 mL/minute: No dosage adjustment necessary;
maximum: 5 mg CBA/kg/day
Reduces therapeutic effect of Vancomycin: CrCl 50 to 79 mL/minute: 2.5 to 3.8 mg CBA/kg/day in
Bile Acid Sequestrants 2 divided doses
CrCl 30 to 49 mL/minute: 2.5 mg CBA/kg/day once daily
Enhances therapeutic effect of Neuromuscular-Blocking or in 2 divided doses
Agents CrCl 10 to 29 mL/minute: 1.5 mg CBA/kg every 36 hours
Intermittent hemodialysis (IHD) (administer after

J
Avoid concomitant use with: hemodialysis on dialysis days) - 1.5 mg CBA/kg every 24
Reduces therapeutic effect of the following drugs: to 48 hours
BCG, Cholera Vaccine Continuous renal replacement therapy (CRRT) - Drug
clearance is highly dependent on the method of renal
Administration: Administer vancomycin with a final replacement, filter type, and flow rate. Appropriate
concentration not to exceed 5 mg/mL by IV intermittent dosing requires close monitoring of pharmacologic
infusion over at least 60 minutes (recommended response, signs of adverse reactions due to drug
infusion period of ≥30 minutes for every 500 mg accumulation, as well as drug concentrations in relation
administered; in adult patients in need of fluid to target trough (if appropriate).
restriction, a concentration up to 10 mg/mL may be CVVH/CVVHD/CVVHDF - 2.5 mg CBA/kg every 24 to 48
used, but risk of infusion-related reactions is increased. hours (frequency dependent upon site or severity of
NOT for IM administration. infection or susceptibility of pathogen). Note: These are
general recommendations only (based on dialysate
Pregnancy Category: B flow/ultrafiltration rates of 1 to 2 L/hour and minimal
residual renal function) and should not supersede
ATC Code: J01XA01 clinical judgment. More recent data among patients
receiving CVVHDF suggest that the daily dose at least
equal or even exceed that of patients with normal renal
POLYMYXINS function.
Sustained low-efficiency dialysis (SLED): IV: May consider
using the following calculations; however, although
Rx COLISTIN derived from critically ill patients, the use of this
WHO anti-biotic category: RESERVE
algorithm has not been prospectively evaluated in the
critically ill (Nation 2017):
Inj.: 2,000,000 IU lyophilized powder for injection (IV
infusion)
Loading dose of colistin base activity (mg) = Target
average colistin steady-state plasma concentration (in
Indications: For extended-spectrum beta-lactamase (ESBL)
mg/L) x 2 x weight (in kg) (maximum loading dose: 300
or carbapenemase-producing multidrug-resistant (MDR)
mg CBA). For patient weight, use the lower of ideal or
gram-negative bacillus; Treatment of acute or chronic
actual body weight expressed in kg. Application of these
infections due to sensitive strains of certain gram-
equations has not been evaluated in obese patients.
negative bacilli (particularly Pseudomonas aeruginosa)
which are resistant to other antibacterials or in patients
Maintenance dose of colistin base activity (mg): Add 10%
allergic to other antibacterials
per 1 hour of SLED replacement to the baseline daily
dose (refer to equation in IHD section above; administer
NOTE: Its use is restricted only to health facilities able to
in 2 divided doses administered 12 hours apart). For
satisfy the following criteria:
example, in a patient receiving 10 hours nocturnal SLED
(1) Presence of an Infection Control Committee whose
session each day with a goal colistin steady-state
chairperson is a physician and DOH-trained on
concentration of 2 mg/L, the suggested CBA dose is: 130
antimicrobial stewardship
mg + 10 hours * 13 mg = 260 mg CBA/day. SLED
(2) Presence of a board certified infectious disease
session should begin 1 to 2 hours after the
specialist who shall authorize the use of the drug as
afternoon/evening dose.
clinically needed
Precautions:
Dose:
Transient, reversible neurological disturbances (e.g.,
Susceptible infections, for IV injection, ADULT, 2.5 to 5 mg
dizziness, numbness, paresthesia, generalized pruritus,
CBA/kg/day in 2 to 4 divided doses; maximum: 5 mg

245
 ANTI-INFECTIVES FOR SYSTEMIC USE

slurred speech, tingling, vertigo) may occur. (Patients IMIDAZOLE DERIVATIVES

must be cautioned about performing tasks which require
mental alertness (e.g., operating machinery or driving).
Dose reduction may reduce neurologic symptoms; Rx METRONIDAZOLE
WHO anti-biotic category: ACCESS
monitor closely);
Dose-dependent nephrotoxicity has been reported,
Oral: 250 and 500 mg tablet
generally reversible upon discontinuation of treatment.
125 mg base/5 mL (200 mg/5 mL) (as benzoate)
Withhold treatment if signs of renal impairment occur
suspension, 60 mL
during treatment;
Inj.: 5 mg/mL, 100 mL vial (IV infusion)
Respiratory arrest has been reported with use; impaired
renal function may increase the risk for neuromuscular
Indications: Eradication of H. pylori; Treatment of acute
blockade and apnea;
intestinal amebiasis (amebic dysentery) and amebic liver
Prolonged use may result in fungal or bacterial
abscess; Treatment of bacterial septicemia; Treatment
superinfection, including C. difficile-associated diarrhea
(adjunctive therapy) of bone and joint infections;
(CDAD) and pseudomembranous colitis; CDAD has been
Treatment of CNS infections, including meningitis and
observed >2 months postantibiotic treatment.
brain abscess; Treatment of gynecologic infections
including endometritis, endomyometritis, tubo-ovarian
Adverse Drug Reactions:
abscess, or postsurgical vaginal cuff infection; Treatment
Common: Nephrotoxicity, acute, renal failure
of intra-abdominal infections, including peritonitis, intra-
Less Common: neurotoxicity
J

abdominal abscess and liver abscess; Treatment of

lower respiratory tract infections, including pneumonia,
Drug Interactions:
empyema and lung abscess
Monitory closely with:
Increases risk of adverse or toxic effects Colistin:
Dose:
Aminoglycosides e.g. Streptomycin; Amphotericin B
Sepsis, suspect intra-abdominal source, by IV infusion,
Cefazedone, Cephalothin, Vancomycin
ADULT, 1 g loading dose then 500 mg every 6 hours or 1
g every 12 hours. CHILD, 30-50 mg/kg every 6 hours with
Reduces therapeutic effect of the following drugs:
ampicillin and gentamicin/amikacin for 10-14 days.
BCG Vaccine, Lactobacillus and Estriol, Sodium
Brain abscess in the presence of chronic otitis media,
Picosulfate, Typhoid Vaccine
sinusitis, or mastoiditis, by IM injection or IV infusion,
CHILD and ADULT, 7.5 mg/kg every 6 hours or 15 mg/kg
Enhances therapeutic effect of Colistin:
every 12 hours with ceftazidime.
Capreomycin, Polymyxin B
Brain abscess, no focus or in the presence of congenital
heart disease, CHILD and ADULT, 7.5 mg/kg every 6
Enhances therapeutic effect of Neuromuscular-Blocking
hours or 15 mg/kg every 12 hours with ceftriaxone.
Agents
Acute gingivitis, oral anaerobes, by mouth, CHILD >12 years
old, 30 mg/kg in divided doses every 6 hours with
Avoid concomitant use with:
penicillin for 7-10 days; ADULT, 500 mg every 8 hours
Increases risk of adverse or toxic effects of the following
with penicillin V potassium for 7-10 days.
drugs:
Acute necrotizing ulcerative gingivitis, oral anaerobes, by
Bacitracin, Methoxyflurane
mouth, ADULT, 500 mg every 8 hours with penicillin V
potassium for 10 days.
Reduces therapeutic effect of the following drugs:
Juvenile periodontitis, by mouth, CHILD <8 years old, 50
BCG, Cholera Vaccine
mg/kg in divided doses every 8 hours for 7 days.
Ludwig’s angina, by IV infusion, CHILD, 22.5-40 mg/kg in 3
Administration: Administer by IM, direct IV injection over 3
divided doses with ampicillin-sulbactam OR penicillin G
to 5 minutes, intermittent infusion over 30 minutes or by
for 2-3 weeks; ADULT, 500 mg every 6-8 hours with
continuous IV infusion.
penicillin G for 2-3 weeks.
For continuous IV infusion, one-half of the total daily dose is
Jugular vein suppurative phlebitis (Lumierre’s syndrome), by
administered by direct IV injection over 3 to 5 minutes
mouth or IV infusion, ADULT, 500 mg every 8 hours with
followed 1 to 2 hours later by the remaining one-half of
ceftriaxone.
the total daily dose diluted in a compatible IV solution
infused over 22 to 23 hours. The final concentration for
Dose Adjustment:
continuous infusion administration should be based on
Geriatric:
the patient's fluid needs; infusion should be completed
Refer to adult dosing
within 24 hours of preparation.
Renal Impairment:
Pregnancy Category: C
Severe impairment: There are no dosage adjustments
provided in the manufacturer’s labeling; metronidazole
ATC Code: J01XB01
metabolites may accumulate; monitor for adverse
events.
ESRD requiring dialysis: Metronidazole metabolites may
accumulate; monitor for adverse events. Accumulated
metabolites may be rapidly removed by dialysis:

246
ANTI-INFECTIVES FOR SYSTEMIC USE

Intermittent hemodialysis (IHD): If administration cannot Enhances therapeutic effect of Vecuronium

be separated from hemodialysis, consider supplemental
dose following hemodialysis. Avoid concomitant use with:
Peritoneal dialysis (PD): No dosage adjustment Increases risk of adverse or toxic effects of the following
necessary. drugs:
Alcohol (Ethyl), Carbocisteine, Products Containing
Hepatic Impairment: Propylene Glycol
Severe impairment (Child-Pugh class C):
Extended-release tablets: Use is not recommended. Increases risk of adverse or toxic effects Metronidazole:
Immediate-release capsules: Disulfiram, Mebendazole, Ritonavir
Amebiasis: 375 mg 3 times daily
Trichomoniasis: 375 mg once daily Reduces therapeutic effect of the following drugs:
Immediate-release tablets, injection: BCG, Cholera Vaccine
Reduce dose by 50%
Administration:
Precautions: For IV: Infuse intravenously over 30 to 60 minutes. Avoid
contact of drug solution with equipment containing
WARNING: Possibly carcinogenic based on animal
aluminum.
data. Unnecessary use should be avoided.
For oral: Immediate-release tablets and capsules may be
administered with food to minimize stomach upset.

J
Clinical and laboratory monitoring recommended in course Extended-release tablets should be administered on an
lasting longer than 10 days; empty stomach (1 hour before or 2 hours after meals);
Hepatic impairment and hepatic encephalopathy; Renal do not split, crush, or chew.
impairment;
Congestive heart failure; Pregnancy Category: B
History of blood dyscrasias;
History of CNS disorders and seizures; ATC Code: J01XD01
Severe neurological disturbances, including aseptic
meningitis (may occur within hours of a dose), cerebellar
symptoms, convulsive seizures, encephalopathy, optic NITROFURAN DERIVATIVES
neuropathy, and peripheral neuropathy (usually
symmetric and of sensory type) have been reported;
CNS symptoms and CNS lesions are generally reversible Rx NITROFURANTOIN
WHO anti-biotic category: ACCESS
within days to weeks of discontinuation of therapy;
peripheral neuropathy symptoms may be prolonged after
Oral: 50 mg and 100 mg capsule (as macrocrystals)
discontinuation. (Monitor for neurologic symptoms and
discontinue therapy if any abnormal neurologic
symptoms occur); Indications: Treatment of acute, uncomplicated cystitis in
Prolonged use may result in fungal or bacterial non-pregnant women, asymptomatic bacteruria;
recurrent urinary tract infection in non-pregnant women
superinfection, including C. difficile-associated diarrhea
(for asymptomatic bacteriuria in pregnancy, urine culture
(CDAD) and pseudomembranous colitis; CDAD has been
is necessary).
observed >2 months post-antibiotic treatment.
Candidiasis infection (known or unknown) may be more
Contraindications: Previous history of cholestatic jaundice
prominent during metronidazole treatment, antifungal
or hepatic dysfunction associated with prior
treatment required.
Pregnancy (avoid use in early pregnancy); lactation nitrofurantoin use; for infants <1 month of age
(increased risk of hemolytic anemia); G6PD-deficiency,
(significant amounts excereted in breastmilk; may cause
including breast-feeding of affected infants (only small
bitterness in milk)
amounts in milk but may be enough to produce
Adverse Drug Reactions: hemolysis in G6PD-deficient infants); pregnancy at term
Common: Headache, nausea, vaginitis (third trimester: may produce neonatal hemolysis if used
Less Common: Metallic taste, dizziness, genital pruritus, at term); porphyria.
abdominal pain, diarrhea, xerostomia, dysmenorrhea,
urine abnormality, urinary tract infection, bacterial Dose:
infection, candidiasis, flu-like symptoms, upper Asymptomatic bacteriuria, by mouth, ADULT, in non-
respiratory tract infection, pharyngitis, sinusitis pregnant patients 100 mg 4 times daily for 7-14 days; in
pregnant women, 100 mg 4 times daily for 7 days.
Drug Interactions: Acute uncomplicated cystitis in non-pregnant women, by
Monitory closely with: mouth, ADULT, 100 mg 4 times daily for 5 days; in
Reduces therapeutic effect of the following drugs: pregnant women, 100 mg 4 times daily for 7 days; CHILD
BCG Vaccine, Lactobacillus and Estriol, Sodium >1year, 5-7 mg/kg/day divided in 4 doses (maximum
Picosulfate, Typhoid Vaccine dose, 400 mg).
Recurrent urinary tract infection in non-pregnant women, by
Increases risk of adverse or toxic effects of the following mouth, ADULT (women), 100 mg at bedtime for 6-12
months either continuously or as post-coital prophylaxis.
drugs:
Lithium, Lopinavir, Tipranavir

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 ANTI-INFECTIVES FOR SYSTEMIC USE

Dose Adjustment: Pregnancy Category: B

Renal Impairment:
Avoid use (peripheral neuropathy; ineffective because of ATC Code: J01XE01
inadequate urinary concentrations).

Hepatic Impairment: FOSFOMYCIN

Avoid use (cholestatic jaundice and chronic active hepatitis Rx
WHO anti-biotic category: RESERVE
have been reported).
Oral: 3 g granules for solution
Precautions:
This is NOT indicated for the treatment of pyelonephritis; it Indication: First-line treatment for acute uncomplicated
is ineffective in alkaline urine; cystitis
Pulmonary toxicity and disorders (monitor lung and liver
function on long-term therapy; discontinue use if the lung Dose:
function deteriorates; acute, subacute or chronic Cystitis, acute uncomplicated, by mouth, ADULT, 3 g as a
pulmonary reactions have been observed); single dose. Safety and effectiveness in the pediatric
Susceptibility to peripheral neuropathy (risk may be population have not been established.
increased in patients with anemia, renal impairment,
diabetes, vitamin B deficiency, debilitating disease, or Dose Adjustment:
electrolyte disturbance); Geriatric:
J

Risk of optic neuritis; Refer to adult dosing.

Hepatic reactions (monitor liver function tests periodically);
Hemolytic anemia; Precautions:
Neurological or allergic disorder; Prolonged use may result in fungal or bacterial
folate deficiency; prolonged use may result in fungal or superinfection, including C. difficile-associated diarrhea
bacterial superinfection; urine may be colored yellow or (CDAD) and pseudomembranous colitis; CDAD has been
brown. observed >2 months post-antibiotic treatment;
Elderly (monitor closely for toxicities during use). Potentially significant interactions may exist, requiring dose
Pregnancy (when given during second trimester until 32 or frequency adjustment, additional monitoring, and/or
weeks age of gestation) selection of alternative therapy.
NOTE: During long-term treatment, monitor:
Pulmonary function; Liver function every month for 3 Adverse Drug Reactions:
months, then every 3 months, since onset of Common: None.
hepatotoxicity may be insidious; Renal function; Less Common: Headache, pain, dizziness, skin rash,
Development of paresthesia (withdraw to prevent severe diarrhea, nausea, abdominal pain, dyspepsia, vaginitis,
neuropathy). dysmenorrhea, back pain, weakness, rhinitis,
pharyngitis.
Adverse Drug Reactions: Rare: Abnormal stools, anaphylaxis, angioedema, anorexia,
Common: Abdominal pain, allergic skin reactions, anorexia, aplastic anemia, cholestatic jaundice, constipation,
diarrhea, headache, nausea, vomiting. dermatological disease, drowsiness, dysuria, ear
Less Common: Dizziness, drowsiness, vertigo. disease, exacerbation of asthma, fatigue, fever,
Rare: Alopecia, anaphylaxis, arthralgia, benign intracranial flatulence, flu-like symptoms, hearing loss, hematuria,
hypertension; blood disorders, drug fever, cholestatic hepatic necrosis, insomnia, lymphadenopathy,
jaundice, erythema multiforme, exfoliative dermatitis, menstrual disease, migraine, myalgia, nervousness,
pancreatitis, peripheral neuropathy, pulmonary optic neuritis, paresthesia, pruritus, toxic megacolon,
reactions, SJS. vomiting, xerostomia
Drug Interactions: Drug Interactions:
NOTE: The bioavailability of nitrofurantoin is usually Monitory closely with:
increased by medicines that reduce gastric emptying Reduces therapeutic effect of the following drugs:
time, such as diphenoxylate and atropine. Sodium Picosulfate, Typhoid Vaccine
Monitor closely with: Avoid concomitant use with:
Increases risk of adverse or toxic effects of Aldosterone- Reduces therapeutic effect of the following drugs:
blocking agents e.g., eplerenone and spironolactone BCG Vaccine, Cholera Vaccine
(hyperkalemic effect)
Administration: Always mix with 3 to 4 oz (90 to 120 mL)
Enhances therapeutic effect of Sedatives (e.g. alcohol) cool water before ingesting; do not administer in its dry
(potentiative effect) form or mix with hot water. May be administered without
regard to meals.
Avoid concomitant use with:
Reduces absorption of Nitrofurantoin: Pregnancy Category: C
Antacids
ATC Code: J01XX01
Administration:
Take with food or milk.

248
ANTI-INFECTIVES FOR SYSTEMIC USE

SPECTINOMYCIN Staphylococcus aureus (MRSA) and complicated skin

Rx and soft tissue infections (cSSTI).
WHO anti-biotic category: ACCESS

Inj.: 2 g vial (IM) Contraindications: Concurrent or within 2 weeks of use of

MAO inhibitors; Hypersensitivity to linezolid or any
Indications: Treatment of acute gonorrheal urethritis and component of the formulation
proctitis in the male and acute gonorrheal cervicitis and
proctitis in the female when due to susceptible strains of Dose:
Neisseria gonorrhoeae. Men and women with known Methicillin-resistant staphylococcal infections, by IV
recent exposure to gonorrhea should be treated as those injection or by mouth, ADULT, 600 mg every 12 hours.
known to have gonorrhea. Complicated skin and soft tissue infections, by IV injection
or by mouth, ADULT, 600 mg every 12 hours for 10-14
Contraindications: Hypersensitivity to spectinomycin or any days; CHILD <12 years, 10 mg/kg every 8 hours for 10-
component of the formulation. 14 days; CHILD ≥12 years, 600 mg every 12 hours for
10-14 days.
Dose:
Gonococcal infection, by IM injection, ADULT, 2 g as a single Dose Adjustment:
dose. Max: 4 g, administer in two different injection sites; Renal impairment:
CHILD, beyond newborn period and <45 kg: 40 mg/kg as Mild to severe impairment- no dosage adjustment
a single dose. Max: 2 g. necessary.

J
End-stage renal disease on intermittent hemodialysis- no
Dose Adjustment: dosage adjustment necessary; administer after
Geriatric: hemodialysis.
Refer to adult dosing.
Hepatic impairment:
Precautions: Mild to moderate impairment- no dosage adjustment
Ineffective in the treatment of syphilis and may mask or necessary.
delay symptoms of incubating syphilis. Severe impairment- no dosage adjustments provided in the
manufacturer’s labeling.
Adverse Drug Reactions:
Common: Nausea, dizziness, fever and chills, insomnia, Precautions:
urticaria, mild to moderate pain after IM injection, May cause lactic acidosis, myelosuppression, peripheral
alterations in kidney and liver function, decrease in Hb and optic neuropathy, serotonin syndrome, and
and hematocrit. superinfection; use in caution in patients with carcinoid
Rare: Anaphylaxis or anaphylactoid reactions. syndrome, diabetes mellitus, hypertension,
hyperthyroidism, pheochromocytoma, and seizure
Drug Interactions: disorder.
Increases risk of adverse or toxic effects of Lithium
Adverse Drug Reactions:
Administration: Given by deep intramuscular injection as a Common: Diarrhea.
single dose equivalent to 2 g of spectinomycin, although Less Common: Headache, nausea, vomiting, dizziness,
a dose of 4 g may sometimes be required, divided rash, vaginal and oral moniliasis, taste alteration, fungal
between two injection sites. infection, localized and generalized abdominal pain,
tongue discoloration, anemia, thrombocytopenia, loose
Pregnancy Category: B stools, eosinophilia, pruritus, and vertigo.
Rare: Lactic acidosis, myelosuppression, peripheral
ATC Code: J01XX04 neuropathy, optic nerve disorder, and serotonin
syndrome.

Drug Interactions:
Rx LINEZOLID Avoid concomitant use with:
WHO anti-biotic category: ACCESS
Both drugs increase serotonin levels:
Oral: 600 mg tablet/film-coated tablet Fluoxetine, Cocaine, Dextromethorphan, Ergotamine,
Inj: 2 mg/mL (600 mg/300 mL), solution for infusion (IV) Escitalopram, Isoniazid, Levodopa, Lithium, Morphine,
Selegiline, Sertraline, Tramadol
Linezolid inhibits bacterial protein synthesis by binding to
bacterial 23S ribosomal RNA of the 50S subunit. This Decreases effects of BCG vaccine
prevents the formation of a functional 70S initiation
complex that is essential for the bacterial translation Increases effects of the following:
process Linezolid is bacteriostatic against enterococci Caffeine, Dobutamine, Dopamine, Ephedrine,
and staphylococci and bactericidal against most strains Epinephrine, Formoterol, Norepinephrine,
of streptococci. Phenylephrine, Terbutaline

Indications: Treatment of serious life-threatening gram- Increases toxicity of the following:

positive infections including methicillin-resistant Butorphanol, Codeine, Nalbuphine, Oxycodone,
Tramadol, Fentanyl

249
 ANTI-INFECTIVES FOR SYSTEMIC USE

Increases toxicity of Linezolid: Adverse Drug Reactions:

Carbamazepine Chills, fever, multiple organ failure, nausea and vomiting,
hypotension, respiratory failure, dyspnea, sepsis,
Administration: Oral: Administer with or without food. diarrhea, headache, cardiac arrest, hypertension,
IV: Administer intravenous infusion over 30-120 minutes. hypokalemia, kidney failure
Do not mix or infuse with other medications.
Drug Interactions:
Pregnancy Category: C Increases risk of adverse or toxic effects of the following
drugs:
ATC Code: J01XX08 Antineoplastics, Nephrotoxic drugs
Corticosteroids, Foscarnet

Increases risk of adverse or toxic effects of Amphotericin B:

ANTIFUNGALS FOR SYSTEMIC USE Aminoglycosides e.g Streptomycin; Cardiac glycosides
e.g. Digoxin; Colistimethate, Cyclosporine, Flucytosine
POLYENE ANTIFUNGAL Reduces therapeutic effect of Antifungal Agents (Azole
Derivatives, Systemic)
Rx AMPHOTERICIN B Administration:
J

IV: For patients who experience non-anaphylactic infusion-

Inj.: Lipid Complex: 50 mg and 100 mg vial (as cholesteryl related reactions, premedicate 30-60 minutes prior to
complex, colloidal dispersion) (lipid complex) (IV drug administration with a NSAID ± diphenhydramine or
infusion) acetaminophen with diphenhydramine or
Non-Lipid Complex: 50 mg vial lyophilized powder (as hydrocortisone. If the patient experiences rigors during
deoxycholate) (non-lipid complex) (IV infusion) the infusion, meperidine may be administered.
Administer over 2-6 hours. Invert infusion container
Indications: Treatment of invasive fungal infection including several times prior to administration and every 2 hours
candidiasis, cryptococcus, and aspergillosis and during infusion if it exceeds 2 hours. Do NOT use an in-
histoplasma infections. The lipid complex is only given in line filter during administration. Flush line with dextrose;
patients who are refractory to or intolerant of Normal saline may cause precipitate.
conventional amphotericin B (amphotericin B
deoxycholate) therapy. Pregnancy Category: B

Contraindications: Hypersensitivity to amphotericin or any ATC Code: J02AA01

component of the formulation.

Dose: TRIAZOLE DERIVATVES

For Non-lipid complex
CHILD, by IV, test dose: 0.1 mg/kg , not to exceed 1 mg, Azoles are synthetic compounds that can be classified as
administer over 20-60 min., initial dose, 0.25 either imidazoles or triazoles according to the number of
mg/kg/dose daily, maintenance dose, increase by 0.25 nitrogen atoms. Azoles exhibit activity by reducing the
mg/day increments as tolerated to 1-1.5 mg/kg/day ergosterol synthesis through inhibition of fungal
over 2-6 hrs, ADULT, by IV , test dose, 1 mg x 1 infused cytochrome P450 enzymes.
over 20-30 min, loading dose, 0.25-0.5 mg/kg infused
over 2-6 hr , maintenance dose, 0.25-1 mg/kg daily OR
up to 1.5 mg/kg every other day (may increase gradually
by 0.25 mg-increments/day) Rx FLUCONAZOLE
Lipid Complex
CHILD, by IV, 5 mg/kg daily, infuse IV at rate of 2.5 mg/hr, Oral: 50 mg, 150 mg, and 200 mg capsule
ADULT, by IV, 5 mg/kg daily; infuse IV at rate of 2.5 mg/hr Inj.: 2 mg/mL, 100 mL vial (IV infusion)

Dose Adjustment: Indications: Treatment of candidiasis (esophageal,

Geriatric: oropharyngeal, peritoneal, urinary tract, vaginal);
Refer to adult dosing. Systemic candida infections (e.g., candidemia,
disseminated candidiasis, and pneumonia);
Precautions: Cryptococcal meningitis; Antifungal prophylaxis in
allogeneic bone marrow transplant recipients.
WARNING: This drug should be used for treatment of
patients with progressive and potentially life-
Contraindications: Hypersensitivity to fluconazole or any
threatening fungal infections; it should not be used to
component of the formulation (crossreaction with other
treat noninvasive forms of fungal disease such as oral
azole antifungal agents may occur); Co-administration of
thrush, vaginal candidiasis, and esophageal
terfenadine in adult patients receiving multiple doses of
candidiasis in patients with normal neutrophil counts.
400mg or higher or with CYP3A4 substrates (e.g.,
Monitor patients for anaphylaxis and infusion reactions.

250
ANTI-INFECTIVES FOR SYSTEMIC USE

astemizole, cisapride, erythromycin, pimozide, or renal function) and should not supersede clinical
quinidine). judgment:
Continuous Veno-Venous Hemofiltration: Loading dose of
Dose: 400-800 mg followed by 200-400 mg every 24 hours
Candiasis, prophylaxis, by mouth, by IV infusion, ADULT, 400 Continuous venovenous hemodialysis / continuous veno-
mg daily until recovery of neutropenia. venous hemodiafiltration: Loading dose of 400-800 mg
Central line-associated bloodstream infection (CLABSI), followed by 400-800 mg every 24 hours (Continuous
Hyperalimentation, Candida spp., by mouth, by IV venovenous hemodialysis or continuous veno-venous
infusion, CHILD, 12 mg/kg as loading dose, then 6 hemodiafiltration) or 800 mg every 24 hours (continuous
mg/kg as acceptable alternative if not critically ill and veno-venous hemodiafiltration).
unlikely to have fluconazole-resistant Candida spp; up to NOTE: Higher maintenance doses of 400 mg every 24 hours
2 weeks after clearance of candidemia. (Continuous veno-Venous Hemofiltration), 800 mg every
Fungal meningitis, Cryptococcal meningitis, non-AIDS, 24 hours (continuous venovenous hemodialysis), and
consolidation phase, by mouth, ADULT, 200 mg 4 times 500-600 mg every 12 hours (continuous veno-venous
a day for 10-12 weeks after CSF culture is negative; hemodiafiltration) may be considered when treating
Less severely ill, by mouth, by IV infusion, CHILD, 6-12 resistant organisms and/or when employing combined
mg daily; ADULT, 400 mg; for 10-12 weeks after CSF ultrafiltration and dialysis flow rates of ≥2 L/hour for
culture is negative. continuous venovenous hemodialysis/ continuous veno-
Cryptococcal meningitis associated with HIV/AIDS, venous hemodiafiltration.
induction phase, by IV infusion, CHILD, 6-12 mg/kg with

J
amphotericin B deoxycholate for at least 2 weeks; by Precautions:
mouth, by IV infusion, ADULT, 800 mg with amphotericin
WARNING: Serious hepatotoxicity has been reported in
B deoxycholate for at least 2 weeks;
patients with severe underlying disease such as AIDS
Consolidation phase, by IV infusion, CHILD, 6-12 mg/kg
or malignancy.
for at least 8 weeks; by mouth, by IV infusion, ADULT,
400 mg for at least 8 weeks;
Suppression, by IV infusion, CHILD, 3 mg/kg for at least Monitor patients for: arrhythmias; central nervous system
1 year; by mouth, ADULT, 200 mg for at least 1 year. effects; hepatotoxicity, skin reaction. Use with caution in
Endophthalmitis, Candida sp., by mouth, ADULT, 800 mg patients with hepatic impairment. Formulation may
loading dose then 400-800 mg daily; CHILD, 12 mg/kg contain benzyl alcohol and derivatives.
loading dose then 6-12 mg/kg daily.
Adverse Drug Reactions:
Dose Adjustment: Common: gastrointestinal tract reactions such as
Geriatric: abdominal pain, diarrhea, flatulence, nausea and
Refer to adult dosing. vomiting, and taste disturbance.
Less Common: headache, dizziness, leukopenia,
Renal Impairment: thrombocytopenia, hyperlipidemia
NOTE: Renal function estimated using the Cockcroft-Gault Rare: anaphylaxis and angioedema.
formula.
For multiple dosing in adults, administer loading dose of 50- Drug Interactions:
400 mg, then adjust daily doses as follows (dosage Increases serum concentration of Fluconazole:
reduction in children should parallel adult Apixaban, Aripiprazole, Atorvastatin, Bosentan,
recommendations): Budesonide, Busulfan, Calcium Channel Blocker e.g.
CrCl >50 mL/minute: No dosage adjustment necessary Amlodipine; Carbamazepine, Carvedilol, Cilostazol,
CrCl ≤50 mL/minute (no dialysis): Reduce dose by 50% Colchicine, Cyclosporine, CYP2C9 Substrates, CYP3A4
Substrates, Domperidone, Doxorubicin, Dronabinol,
Endstage renal disease on intermittent hemodialysis: 100% Fentanyl, Fosphenytoin, HMG-Coa Reductase Inhibitors
of daily dose (according to indication) after each dialysis e.g. Simvastatin; Parecoxib, Phenytoin, Prednisone,
session; On nondialysis days, patient should receive a Propafenone, Proton Pump Inhibitors e.g. Omeprazole;
reduced dose according to their CrCl; Alternate Rifamycin Derivatives; Ruxolitinib, Salmeterol, Sildenafil,
recommendations: doses of 200-400 mg every 48-72 Sirolimus, Sulfonylureas e.g. Gliclazide; Tacrolimus,
hours or 100-200 mg every 24 hours have been Tipranavir, Tolvaptan, Vardenafil, Vitamin K Antagonists
recommended. e.g. Warfarin; Zidovudine, Zolpidem
NOTE: Dosing dependent on the assumption of 3 times per
week, complete intermittent hemodialysis sessions. Increases risk of adverse or toxic effects of Fluconazole:
Amitriptyline, Citalopram, Erythromycin, Qt-Prolonging
Continuous renal replacement therapy: Drug clearance is Agents, Methadone, Mifepristone, Oxycodone, Pimozide
highly dependent on the method of renal replacement,
filter type, and flow rate. Appropriate dosing requires Reduces therapeutic effect of Amphotericin B
close monitoring of pharmacologic response, signs of
adverse reactions due to drug accumulation, as well as Reduces therapeutic effect of Fluconazole:
drug concentrations in relation to target trough (if Clopidogrel
appropriate). The following are general
recommendations only (based on dialysate flow Decreases serum concentration of Fluconazole:
ultrafiltration rates of 1 to 2 L/hour and minimal residual Losartan

251
 ANTI-INFECTIVES FOR SYSTEMIC USE

Reduces absorption of Didanosine Use with caution in special population: Pediatric (the safety
and efficacy of itraconazole in children <18 years old
Decreases metabolism of Fluconazole: have not been established).
Buspirone, Quinidine, Solifenacin High potential for drug interactions: co-administration with
itraconazole can cause elevated plasma concentrations
Decreases active metabolite of Fluconazole: of certain drugs and can lead to QT prolongation and
Ifosfamide ventricular tachyarrhythmias, including torsades de
pointes.
Administration: Absorption of itraconazole capsules is reduced when gastric
For IV: Infuse over ~1-2 hours; Do not exceed 200 mg/hr; acidity is reduced (e.g., achlorhydria, acid suppressive
Do not add additional medication. therapy) administer with an acidic beverage (e.g. cola) in
For oral: May be administered without regard to meals. patients with reduced gastric acidity and separate
administration from acid suppressive therapy (refer to
Pregnancy Category: C (single 150 mg tablet use for vaginal drug interactions section). Monitor for response.
candidiasis) and D (all other indications) Appropriate use: Itraconazole should not be used for
voriconazole refractory aspergillosis because the same
ATC Code: J02AC01 antifungal and/or resistance mechanism(s) may be
shared by both agents.
Itraconazole capsule is not bioequivalent or
interchangeable to other oral itraconazole preparations.
J

Rx ITRACONAZOLE Due to variable bioavailability of oral preparations,

therapeutic drug monitoring is advisable.
Oral: 100 mg capsule
Adverse Drug Reactions:
Nausea and vomiting, edema, headache, rash, diarrhea,
Indications: Used in treatment of allergic bronchopulmonary
fatigue, fever, rhinitis, URTI, sinusitis, abdominal pain,
aspergillosis, second line treatment for cutaneous fungal
dizziness, hypertension, flatulence.
infections and prophylaxis of candidiasis
Drug Interactions:
Contraindications: Treatment of onychomycosis (or other
Avoid concurrent administration with astemizole, bepridil,
non-life-threatening indications) in patients with
colchicine, disopyramide, domperidone, dronedarone,
evidence of ventricular dysfunction, such as congestive
eplerenone, ergot derivatives, felodipine, fesoterodine,
heart failure (CHF) or a history of CHF; Treatment of
irinotecan, ivabradine, midazolam (oral), quinidine,
onychomycosis in women who are pregnant or intend to
ranolazine, simvastatin, solifenacin, ticagrelor,
become pregnant; Treatment of dermatomycosis (tinea
lercanidipine,
pedis, tinea cruris, tinea corporis, pityriasis versicolor) in
women who are pregnant or intend to become pregnant.
Increases serum concentration of Antiretroviral Agents
Dose:
Increases serum concentration of Itraconazole:
Prophylaxis of Candidiasis, by mouth, ADULT, 200 mg twice
Antiretroviral Agents, Aliskiren, Alprazolam
daily until recovery of neutropenia.
Aripiprazole, Benzodiazepines e.g. Diazepam; Bosentan,
Treatment of allergic bronchopulmonary aspergillosis, by
Budesonide, Calcium Channel Blocking Agents e.g.
mouth, ADULT, 200 mg twice daily for 16 weeks or
Amlodipine; Carbamazepine; Cardiac Glycoside e.g.
longer.
Digoxin; Cilostazol, Colchicine, Corticosteroids,
Tinea versicolor, by mouth, ADULT, 200 mg twice daily for 2-
Dabigatran etexilate, Disopyramide, Domperidone,
4 weeks, CHILD, by mouth, 5-10 mg/kg/day for 2-4
Doxorubicin, Dutasteride
weeks
Fexofenadine, Fluticasone, Fusidic Acid, Hydrocodone,
Medroxyprogesterone, Midazolam, Mifepristone,
Dose Adjustment:
Parecoxib, Propafenone, Repaglinide, Salmeterol,
Geriatric:
Saquinavir, Sildenafil, Tramadol, Vinblastine, Vitamin K
Refer to adult dosing.
Antagonists e.g. Warfarin; Zolpidem
Renal Impairment:
Increases risk of adverse or toxic effects of Calcium Channel
Use with caution in patients with renal impairment. Dosage
Blocking Agents e.g. Amlodipine
adjustment may be needed.
Increases risk of adverse or toxic effects of Itraconazole:
Precautions:
Antiarrhythmic Agents, Antilipidemic Agents,
WARNING: Congestive heart; High potential for drug Benzodiazepines e.g. Diazepam; Ergot Alkaloids e.g.
interactions. Ergotamine; Fentanyl, Pimozide, Phosphodiesterase
Type 5 Inhibitors e.g. Sildenafil; QT prolonging Agents,
Monitor patients for: Central Nervous System Depression; Oxycodone, Vincristine
Hearing Loss; Heart Failure; Hepatotoxicity;
Hypersensitivity; Neuropathy. Reduces therapeutic effect of Itraconazole:
Use with caution in patients with: Cystic Fibrosis; Amphotericin B
Dermatomycosis; Onychomycosis; Renal Impairment.
Increases serum concentration of the following drugs:

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ANTI-INFECTIVES FOR SYSTEMIC USE

Antacids, Non-nucleoside Reverse Transcriptase sinus bradycardia, existing symptomatic arrhythmias,

Inhibitors (NNRTIs), Carbamazepine, Isoniazid, concomitant use w/ drugs known to prolong QT interval;
Nevirapine Monitor & correct electrolyte imbalances (hypokalemia,
hypomagnesemia and hypocalcemia) prior to and during
Increases serum concentration of Itraconazole: therapy. Monitor for hepatic toxicity and lab evaluation of
Meloxicam hepatic function (AST/ALT) at least weekly for the 1st
month of therapy;
Reduces absorption of Sucralfate Acute renal failure & visual adverse events in severely ill
patients with underlying conditions and/or concomitant
Decreases metabolism of Itraconazole: medications;
Cyclosporine, Docetaxel Adults and children with risk factors for acute pancreatitis.
Rare exfoliative cutaneous reaction, photosensitivity;
Administration: squamous cell carcinoma of the skin & melanoma,
Itraconazole capsules should be administered with a full periostitis on long-term therapy;
meal to ensure maximal absorption of the drug. Oral Pregnancy and lactation.
doses >200 mg/day are given in 2 divided doses; Do not
administer with antacids. Take with food, it is best to Adverse Drug Reactions:
administer itraconazole after meals at the same time Pseudomembranous colitis, sinusitis, bone marrow failure,
each day. agranulocytosis, pancytopenia, thrombocytopenia,
The capsules should not be used for the treatment of leukopenia, anaemia, lymphadenopathy, eosinophilia,

J
oropharyngeal or esophageal candidiasis; Efficacy has anaphylactoid reaction, hypersensitivity, adrenal
not been established and this formulation may be less insufficiency, hypothyroidism, hyperthyroidism,
effective than the oral solution for these infections. hypoglycemia, hypokalemia, hyponatremia, peripheral
edema, depression, hallucination, anxiety, insomnia,
Pregnancy Category: C agitation, confusional state, hepatic encephalopathy,
brain edema, encephalopathy, syncope, extrapyramidal
ATC Code: J02AC02 disorder, tremor, hypertonia, Guillain-Barré syndrome,
peripheral neuropathy, ataxia, paresthesia,
hypoesthesia, nystagmus, dysgeusia, somnolence,
dizziness, headache, optic atrophy and nerve disorder,
Rx VORICONAZOLE papilloedema, retinal hemorrhage, oculogyric crisis,
corneal opacity, visual impairment, diplopia, scleritis,
Oral: 200 mg film-coated tablet blepharitis, hypoacusis, vertigo, tinnitus, torsades de
Inj.: 200 mg lyophilized powder for solution, 30 mL vial (IV pointes, thrombophlebitis, hypotension, phlebitis,
infusion) lymphangitis, acute respiratory distress syndrome,
pulmonary edema, peritonitis, pancreatitis, swollen
Indications: Treatment of candida endophthalmitis, reserve tongue, diarrhea, vomiting, duodenitis, cheilitis,
drug for the treatment of severe fungal infections; gastroenteritis, dyspepsia, abdominal pain, glossitis,
prophylaxis for aspergillus in patients undergoing constipation, gingivitis, nausea, hepatic failure, jaundice,
chemotherapy for AML/MDS with neutropenia and jaundice cholestatic, hepatitis, hepatomegaly,
allogeneic HSCT recipients cholecystitis, cholelithiasis, toxic epidermal necrolysis,
SJS, angioedema, pseudoporphyria, erythema
Contraindications: Hypersensitivity. Concomitant use of multiforme, dermatitis exfoliative, psoriasis, cutaneous
CYP3A4 substrates, terfenadine, astemizole, cisapride, lupus erythematosus, drug eruption, alopecia,
pimozide or quinidine; sirolimus, rifabutin, rifampicin, photosensitivity reaction, purpura, rash maculopapular,
carbamazepine, long-acting barbiturates, efavirenz, urticaria, rash, eczema, pruritus, back pain, arthritis,
ritonavir, ergot alkaloids renal failure acute, renal tubular necrosis, proteinuria,
nephritis, hematuria, chest pain, face edema, infusion
Dose: site reaction, flu like illness, asthenia, chills
Anti-aspergillus prophylaxis, by mouth, by IV infusion,
ADULT, 200 mg twice daily. Drug Interactions:
Endophthalmitis, Candida sp., by IV infusion, ADULT, 400 Decreases excretion of the following drugs:
mg twice a day for 2 doses loading dose then 300 mg, by Ergot alkaloids, Disopyramide
mouth or IV infusion, twice a day; CHILD, 12 mg/kg twice Simvastatin, Pimozide, Ranozaline, Sirolimus
a day for 2 doses loading dose then 4 mg/kg, by mouth
or IV infusion, twice a day. Decreases excretion of Voriconazole:
Efavirenz, Rifabutin, Rifampin, Rionavir, Carbamazepine,
Dose Adjustment: Phenobarbital
Geriatric:
Refer to adult dosing Administration: Should be taken on an empty stomach: Take
at least 1 hour before or after meals.
Precautions:
Hypersensitivity to other azoles. Infusion-related reactions; Pregnancy Category: D
patients with potentially proarrhythmic conditions e.g.,
congenital or acquired QT prolongation, cardiomyopathy, ATC Code: J02AC03

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 ANTI-INFECTIVES FOR SYSTEMIC USE

FLUCYTOSINE Drug Interactions:

Rx Increases risk of adverse or toxic effects of the following
(5-FLUOROCYTOSINE)
drugs:
Amphotericin B, Ganciclovir, Norfloxacin, Valganciclovir,
Oral: 250 mg tablet
Zidovudine
Indications: Adjunctive treatment of systemic fungal
Increases risk of adverse or toxic effects of Flucytosine:
infections (e.g., septicemia, endocarditis, urinary tract
Clozapine, Dipyrone, Hydroxyurea, Fluconazole,
infection, meningitis, or pulmonary) caused by
Itraconazole
susceptible strains of Candida or Cryptococcus.
Reduces therapeutic effect of Flucytosine:
Dose:
BCG Vaccine
Endocarditis, by mouth, CHILD, 100 mg/kg/day in 3 or 4
divided doses (with amphotericin B) for >4-6 weeks after
Reduces therapeutic effect of Cytarabine
valve replacement.
Administration:
Dose Adjustment:
Take orally; Administer around-the-clock to promote less
Geriatric:
variation in peak and trough serum levels.
Refer to adult dosing.
Pregnancy Category: C
Renal Impairment:
J

Adults (based upon dosing of 25 mg/kg every 6 hours):

ATC Code: J02AX01
CrCl >40 mL/minute: No dosage adjustment
recommended; CrCl 20-40 mL/minute: 50% of standard
dose every 6 hours; CrCl 10-20 mL/minute: 25% of
standard dose every 6 hours; End stage renal disease on Rx MICAFUNGIN
intermittent hemodialysis: 25-50 mg/kg every 48-72
hours, administer dose after hemodialysis.
Adults and Adolescents (HIV positive patients) (based upon Inj.: 50 mg lyophilized powder for infusion (IV)
dosing of 25 mg/kg every 6 hours): CrCl >40 mL/minute:
No dosage adjustment recommended; ClCr 20-40 Indications: For resistant candida and disseminated
mL/minute: 25 mg/kg every 12 hours; CrCl 10- ≤20 candidiasis
mL/minute: 25 mg/kg every 24 hours; CrCl <10
mL/minute: 25 mg/kg every 48 hours; End stage renal Contraindications: Hypersensitivity to micafungin, other
disease on intermittent hemodialysis: 25-50 mg/kg echincandins, or any component of the formulation.
every 48-72 hours, administer dose after hemodialysis.
Infants, Children, and non-HIV positive Adolescents (based Dose:
upon dosing of 100-150 mg/kg/day divided every 6 Anticandidal prophylaxis, by IV infusion, ADULT, 150 mg
hours): until recovery or neutropenia.

NOTE: Flucytosine should be avoided in children with severe Dose Adjustment:

renal impairment. Geriatric:
Refer to adult dosing.
CrCl 30-50 mL/minute: 25-37.5 mg/kg every 8 hours;
CrCl 10-29 mL/minute: 25-37.5 mg/kg every 12 hours; Precautions:
CrCl <10 mL/minute: 25-37.5 mg/kg every 24 hours; WARNING: Cases of hypersensitivity reactions including
Hemodialysis: 25-37.5 mg/kg every 24 hours; anaphylactoid reactions and anaphylaxis with shock
Peritoneal dialysis: 25 to 37.5 mg/kg every 24 hours; have been reported in patients who receive micafungin.
Continuous renal replement therapy: 25-37.5 mg/kg every
8 hours (monitor serum concentrations).
Use with caution to avoid anaphylactic reactions, hemolytic
Precautions: anemia, hepatic failure and renal impairment.

WARNING: Use with extreme caution in patients with renal Adverse Drug Reactions:
impairment. Close monitoring of hematologic, renal Common: Fever, headache, hypokalemia,
and hepatic status of all patients is essential. hypomagnesemia, diarrhea, nausea, vomiting, mucosal
inflammation, constipation.
Use with caution in patients with: Bone Marrow Depression; Less Common: Hypotension, tachycardia, hypertension,
Hematologic Disease; Patients who have been treated peripheral edema, edema, bradycardia, atrial fibrillation,
with radiation or drugs that suppress the bone marrow; insomnia, anxiety.
Hepatic Impairment; Renal Dysfunction.
Drug Interactions: No known significant interactions
Adverse Drug Reactions:
Myocardial toxicity, chest pain, dyspnea, rash, pruritus, Administration:
urticaria, nausea, jaundice, renal failure, azotemia, For IV use only; infuse over 1 hour. Flush line with NS prior
crystalluria, anemia, leukopenia, ataxia, confusion. to administration.

254
ANTI-INFECTIVES FOR SYSTEMIC USE

Pregnancy Category: C
ANTIMYCOBACTERIALS
ATC Code: J02AX05
Antimycobacterial drugs are used in the treatment of
diseases caused by members of the Mycobacterium
genus, including tuberculosis (TB) and leprosy.
Rx NYSTATIN Combination chemotherapy is essential to kill
heterogeneous populations of bacterial cells located in
Oral: 100,000 units/mL suspension, 30 mL different conditions within the host, and to prevent drug
resistance.
Indication: Treatment of oral candidiasis
DRUGS FOR TREATMENT
Contraindications: Hypersensitivity to nystatin or any OF TUBERCULOSIS
component of the formulation.
DRUGS FOR TUBERCULOSIS
Dose:
Oral candidiasis, Candida albicans, by mouth, ADULT, oral
suspension 100,000 U/mL, 4mL 4 times daily for 7-14 Rx ETHAMBUTOL
days.

J
Precautions: Oral: 200 mg and 400 mg tablet
Not for use in systemic mycoses. Discontinue therapy if 100 mg tablet (pediatric)
irritation or sensitization observed during use.
Indication: Treatment of tuberculosis in combination with
Adverse Drug Reactions: isoniazid, rifampicin and pyrazinamide
Localized sensitization; hypersensitivity reactions.
Contraindications: Hypersensitivity to ethambutol or any
Drug Interactions: component of the formulation; optic neuritis; children <6
Enhances erratic release of Nystatin: years
Progesterone Intravaginal Gel
Dose:
Administration: NOTE: Doses may need adjustment if significant weight gain
Shake well before use. Swish about the mouth and retain in occurs during treatment. Use doses below for the first 2
the mouth for as long as possible (several minutes) months of the 6-month multi-drug regimen.
before swallowing. For neonates and infants, paint Tuberculosis, by mouth, ADULT, 15 mg/kg (range: 15-20
nystatin suspension into recesses of the mouth. mg/kg) daily, not to exceed 1.2 g daily; CHILD, 20 mg/kg
(range: 15-25 mg/kg) daily, not to exceed 1.2 g daily.
Pregnancy Category: A
Dose Adjustment:
ATC Code: G01AA01 Renal Impairment:
For adult patients with creatinine clearance <30 mL/minute
or for adult patients receiving hemodialysis: 15-25
mg/kg dose three times per week (not daily).

Precautions:
Ocular examination is recommended before, and during,
treatment; warn patients to report visual changes;
elderly; young children; further deterioration in vision
may occur where there are visual defects (e.g. diabetic
retinopathy, cataract); renal impairment (monitor plasma
ethambutol concentration); gout (acute attack may
occur).
Pregnancy (not known to be harmful); breastfeeding
(amount too small to be harmful).
NOTE: Patients should report visual disturbances
immediately and discontinue treatment; children who
are incapable of reporting symptomatic visual changes
accurately should be given alternative therapy, as
should, if possible, any patients who cannot understand
warnings about visual adverse effects.

Adverse Drug Reactions:

Common: Retrobulbar neuritis (resulting in loss of visual
acuity and red-green color blindness).

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 ANTI-INFECTIVES FOR SYSTEMIC USE

Less Common: Abdominal pain, anorexia, confusion, Elderly patients;

disorientation, hallucinations, headache, malaise, Hepatic impairment (increased risk of hepatotoxicity,
nausea, vomiting. monitor liver function regularly, and frequently in the first
Rare: Acute gout, hypersensitivity reaction, anaphylaxis, 2 months); Patients with liver disorder
hyperuricemia, neutropenia, peripheral neuritis, renal Renal impairment (risk of ototoxicity and peripheral
failure, thrombocytopenia. neuropathy);
Epilepsy (isoniazid may cause seizures; ensure adequate
Drug Interactions: control);
Avoid concomitant use with: Slow acetylator status (increased risk of adverse effects);
Reduces absorption of Ethambutol: History of psychosis;
Aluminum salts Porphyria;
Pregnancy (not known to be harmful);
Administration: Breasfeeding (monitor infant for possible toxicity;
Tablets should be taken WITH food. theoretical risk of convulsions and neuropathy)

Pregnancy Category: C Adverse Drug Reactions:

Common: Acne, fever, GI disorders (e.g., nausea, vomiting,
ATC Code: J04AK02 diarrhea), hepatitis, rash, reduced alertness, skin
eruptions, tiredness.
Less Common: Atrophy, dryness of mouth, optic neuritis,
J

memory impairment, peripheral neuritis, seizures, toxic

Rx ISONIAZID encephalopathy, toxic psychosis.
Rare: Agranulocytosis, amenorrhea, aplastic anemia,
Oral: 300 mg and 400 mg tablet arthritic symptoms, convulsions, difficulty with
200 mg/ 5 mL syrup, 120 mL micturition, gynecomastia, hemolytic anemia,
hyperglycemia, hypersensitivity reactions, lupus-like
Indications: Treatment of tuberculosis in combination with syndrome, pancreatitis, pellagra, pure red cell aplasia,
rifampicin, pyrazinamide and ethambutol; primary thrombocytopenia, urinary retention.
regimen for latent tuberculosis.
Drug Interactions:
Contraindications: Known hypersensitivity to isoniazid or Monitor closely with:
any component of the formulation; drug-induced hepatic Decreases metabolism of Carbamazepine
disease.
Reduces therapeutic effect of the following drugs:
Dose: Drug increasing blood glucose concentration (e.g.,
Tuberculosis, treatment, by mouth, ADULT, 5 mg/kg (range: glucocorticoids, antipsychotics, calcineurin inhibitors,
4-6 mg/kg) daily, not to exceed 400 mg daily, not to and high-dose thiazide diuretics)
exceed 300 mg daily. Oral contraceptives
NOTE: Patients at risks of developing peripheral neuropathy
as a result of malnutrition, alcoholism or diabetes Increases risk of adverse or toxic effects of Paracetamol
mellitus should additionally receive pyridoxine, 10 mg (more studies needed)
daily. Pregnant and patients with renal failure should
also receive pyridoxine while on isoniazid therapy. Increases risk of adverse or toxic effects of Isoniazid:
Rifampicin
Dose Adjustment:
Renal Impairment: Avoid concomitant use with:
For adult patients with creatinine clearance <30 mL/min or Reduces absorption of Isoniazid:
for adult patients receiving hemodialysis: 15-25 mg/kg Antacids (e.g., aluminum or magnesium hydroxide)
per dose three times per week.
Decreases metabolism of Diazepam
Precautions:
Increases metabolism of Ketoconazole
WARNING: Severe and sometimes fatal hepatitis may be
associated with isoniazid therapy which is age-related. Administration:
Patients or their caregivers should be told how to Absorbed best if taken on an empty stomach (1 hour before,
recognize signs of liver disorder, and advised to or 2 hours after a meal).
discontinue treatment and seek immediate medical
attention if symptoms such as nausea, vomiting, Pregnancy Category: C
malaise or jaundice develop.
Very high doses can induce CNS adverse effects (e.g., ATC Code: J04AC01
seizures, ataxia, stupor, psychosis).

Malnutrition;
Chronic alcohol dependence;
Diabetes mellitus and HIV infection (risk of peripheral
neuritis);

256
ANTI-INFECTIVES FOR SYSTEMIC USE

Rx PYRAZINAMIDE Rx RIFAMPICIN

Oral: 500 mg tablet Oral: 300 mg, 450 mg, and 600 mg tablet / capsule
250 mg/5 mL and 500 mg/5 mL suspension, 12O mL 200 mg/5 mL suspension, 120 mL

Indication: Treatment of tuberculosis in combination with Indications: Treatment of tuberculosis in combination with
isoniazid, rifampicin and ethambutol. isoniazid, pyrazinamide and ethambutol, treatment of
leprosy using combination therapy
Contraindications: Severe hepatic impairment; porphyria;
acute gout. Contraindications: Hypersensitivity to rifamycins, or any
component of the formulation; jaundice.
Dose:
Tuberculosis, by mouth, ADULT, 25 mg/kg (range: 20-30 Dose:
mg/kg) daily, not to exceed 2 g daily; CHILD, 30 mg/kg Tuberculosis, by mouth, ADULT, 10 mg/kg (range: 8-12
(range: 20-40 mg/kg) daily, not to exceed 2 g daily. mg/kg) daily, not to exceed 600 mg daily; CHILD, 15
mg/kg (range: 10-20 mg/kg) daily; not to exceed 600 mg
Dose Adjustment: daily.
Renal Impairment: Leprosy, by mouth, ADULT, 600 mg
For adult patients with creatinine clearance <30 mL/minute

J
or for adult patients receiving hemodialysis: 25-35 Dose Adjustment:
mg/kg per dose three times per week. Monitor for gout. Hepatic Impairment:
Dose reduction is warranted (maximum, 8 mg/kg/day).
Precautions:
Liver Disorders (Patients or their caregivers should be told Precautions:
how to recognize signs of liver disorder, and advised to Alcohol dependency, the elderly, and in prolonged therapy;
discontinue treatment and seek immediate medical daily alcohol intake (may increase the risk of drug-
attention if symptoms, such as persistent nausea, induced hepatotoxicity); renal impairment; hepatic
vomiting, malaise or jaundice, develop.); impairment (impaired elimination; monitor liver
Acute gout; function); porphyria; it discolors soft lenses.
Hepatic impairment (monitor hepatic function); IMPORTANT: Advise patient on hormonal contraceptives to
Renal impairment; use additional means (effectiveness is reduced);
Diabetes mellitus (monitor blood glucose; may change alternative family planning advice shall be offered.
suddenly); LIVER DISORDERS: Monitor liver function and blood count
Pregnancy (use it only if potential benefits outweigh risks); in liver disorder. Patients or their caregivers should be
Breastfeeding (amount too small to be harmful). told how to recognize signs of liver disorders and advised
to discontinue treatment and seek immediate medical
Adverse Drug Reactions: attention if symptoms such as persistent nausea,
Common: Hyperuricemia, nausea, polyarthralgia, vomiting. vomiting, malaise, or jaundice develop.
Less Common: Allergic reactions, anorexia, diarrhea, fever, Pregnancy (first trimester: very high doses are teratogenic
flushing, hepatotoxicity (including hepatomegaly, in animal studies; third trimester: risk of neonatal
jaundice, liver tenderness, liver failure, malaise, and bleeding may be increased); and breastfeeding (amount
splenomegaly), itch, rash, urticaria too small to be harmful; may cause loose bowel
Rare: Acute gout, acute porphyric crisis, dysuria, pellagra, movement in babies).
photosensitivity, sideroblastic anemia, NOTE: Resumption of rifampicin treatment after a long
thrombocytopenia. interval may cause serious immunological reactions,
resulting in renal impairment, hemolysis, or
Drug Interactions: thrombocytopenia – discontinue permanently if serious
Monitor closely with: adverse effects occur.
Reduces therapeutic effect of Anti-gout drugs e.g.,
allopurinol, colchicine Adverse Drug Reactions:
Common: Anorexia, cramps, diarrhea, epigastric distress,
Increases risk of adverse or toxic effects of Rifampicin flatulence, increased hepatic enzymes, nausea, orange-
(severe, or even fatal, liver injury has been reported in red coloration of body fluids (urine, tears, saliva and
patients using these two drugs as a 2-month treatment sputum), pancreatitis, rash, staining of soft contact
regimen for latent TB infection). lenses, vomiting.
Less Common: Ataxia, behavioral changes, dizziness,
Administration: edema, fatigue, flu-like syndrome (characterized by
Should be taken with food. fever, chills, myalgia), flushing, headache, heartburn,
menstrual disturbances, numbness.
Pregnancy Category: C Rare: Acute renal failure, cerebral hemorrhage, C. difficile-
associated disease, collapse, exfoliative dermatitis,
ATC Code: J04AK01 hemolytic anemia, hepatitis, jaundice, leukopenia,
myopathy, pemphigoid reactions, psychosis, respiratory
symptoms, shock, thrombocytopenic purpura, toxic
epidermal necrolysis.

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 ANTI-INFECTIVES FOR SYSTEMIC USE

Drug Interactions: Precautions:

NOTE: Enzyme induction: accelerates the metabolism of WARNING: May cause nephrotoxicity and neurotoxicity.
various substrates, thus possibly decreasing their Avoid concurrent use of nephrotoxic/neurotoxic drugs;
effects. may cause neuromuscular blockade and respiratory
paralysis, especially when given after anesthesia or
Monitor closely with: muscle relaxants.
Reduces therapeutic effect of the following drugs:
Azole antifungal e.g. ketoconazole Children (painful injection, avoid use if possible);
Beta blockers e.g., metoprolol, propranolol Renal impairment (monitor plasma concentration);
Cotrimoxazole, Digoxin, Doxycycline, Theophylline Infants, and the elderly (adjust dose and monitor renal,
auditory, and vestibular function and plasma
Increases metabolism of the following drugs: streptomycin concentrations);
Corticosteroids e.g., hydrocortisone, prednisone, Pregnancy (second and third trimester: auditory and
prednisolone; Thyroid hormones e.g. Thyroxine vestibular damage in the fetus; avoid unless essential; if
given, serum-streptomycin concentration monitoring is
Avoid concomitant use with: essential);
Reduces absorption of Rifampicin: Breastfeeding (present in milk; continue breastfeeding and
Antacids (e.g., aluminum and magnesium hydroxide) monitor infant for thrush and diarrhea).
Reduces therapeutic effect of Oral Contraceptives Adverse Drug Reactions:
J

Common: Fever, hearing loss, hypersensitivity reactions,

Increases metabolism of Praziquantel nausea, rash, sterile abscess and pain at injection site,
vertigo, vomiting.
Administration: Less Common: Albuminuria, high frequency range hearing
Take dose at least 30 minutes before a meal (absorption is impairment, numbness around mouth, tinnitus, urinary
reduced when taken with food). casts, vestibular damage and toxicity.
Rare: Agranulocytosis, anaphylactic shock, aplastic anemia,
Pregnancy Category: C C. difficile-associated disease, exfoliative dermatitis,
hemolytic anemia, hypomagnesemia, nephrotoxicity,
ATC Code: J04AB02 paresthesia, of the mouth, tubular necrosis,
thrombocytopenia.

Rx STREPTOMYCIN Drug Interactions:

Monitor closely with:
Increases risk of adverse or toxic effects of the following
Inj.: 1 g vial (as sulfate) (IM) drugs:
Ototoxic and nephrotoxic drugs e.g., other
Indication: Treatment of tuberculosis, as an alternative to aminoglycoside antibiotics, furosemide, cephalosporins
ethambutol in combination with isoniazid, rifampicin and and vancomycin
pyrazinamide.
Enhances therapeutic effect of Streptomycin:
Contraindications: Hypersensitivity to streptomycin or any Magnesium sulfate
component of the formulation; hearing disorders (e.g.,
vestibular disturbances and impaired hearing); Avoid concomitant use with:
myasthenia gravis Increases risk of adverse or toxic effects of Streptomycin:
H1 receptor blocker e.g. Diphenhyadramine
Dose:
Tuberculosis, by deep IM injection, ADULT, 15 mg/kg Administration:
(range: 12-18 mg/kg) daily, not to exceed 1 g daily Solutions retain their potency for 48 hours after
(patients over 60 years, or those weighing <50 kg may reconstitution at room temperature and for up to 14 days
not tolerate doses above 500-750 mg daily); CHILD, 30 when refrigerated.
mg /kg (range: 20-40 mg/kg) daily, not to exceed 1 g
daily. Pregnancy Category: D

Dose Adjustment: ATC Code: A07AA04; J01GA01

Renal Impairment:
For adult patients with creatinine clearance <30 mL/minute
or for adult patients receiving hemodialysis: 12-15
mg/kg per dose two or three times per week.
If possible, streptomycin should be avoided in patients with
renal failure.

258
ANTI-INFECTIVES FOR SYSTEMIC USE

COMBINATIONS OF DRUGS FOR ATC Code: J04AM07

TREATMENT OF TUBERCULOSIS

ISONIAZID + RIFAMPICIN +
Rx ISONIAZID + RIFAMPICIN Rx
PYRAZINAMIDE

Oral: 75 mg isoniazid + 150 mg rifampicin tablet Oral: 50 mg isoniazid + 75 mg rifampicin + 150 mg

50 mg isoniazid + 75 mg rifampicin dispersible fixed- pyrazinamide dispersible fixed-dose
dose combination tablet (pediatric) combination tablets (pediatric)

Indication: Treatment of tuberculosis Indication: Treatment of tuberculosis

Contraindications: Combined preparations may not be Contraindications: Combined preparations may not be
suitable for use in young children. suitable for use in children; see under Single Dose
Formulation: Ethambutol, Isoniazid, Pyrazinamide and
Dose: Rifampicin.
Tuberculosis, by mouth, ADULT, refer to the Tables in the
section on Recommended Treatment Regimen for Dose:
Tuberculosis. Tuberculosis, by mouth, ADULT, refer to the Tables in the
section on Recommended Treatment Regimen for

J
Dose Adjustments, Precautions, Adverse Drug Reactions, Tuberculosis.
and Drug Interactions:
Dose Adjustment, Precautions, Adverse Drug Reactions and
See under Single Dose Formulation: Isoniazid and Drug Interactions:
Rifampicin for other information.
See under Single Dose Formulation: Isoniazid, Rifampicin
Administration: and Ethambutol.
Take on an empty stomach with full glass of water.
Administration:
Pregnancy Category: C Take on an empty stomach with full glass of water.

ATC Code: J04AM02 Pregnancy Category: C

ATC Code: J04AM05

ISONIAZID + RIFAMPICIN +
Rx
ETHAMBUTOL
ISONIAZID + RIFAMPICIN +
Oral: 75 mg isoniazid + 150 mg rifampicin + 275 mg Rx PYRAZINAMIDE +
ethambutol tablet ETHAMBUTOL
Indication: Treatment of tuberculosis Oral: 75 mg isoniazid + 150 mg rifampicin + 400 mg
pyrazinamide + 275 mg ethambutol tablet
Contraindications:
Combined preparations may not be suitable for use in young Indications: Treatment of tuberculosis
children see under Single Dose Formulation: Isoniazid,
Rifampicin and Ethambutol. Contraindications: Combined preparations may not be
suitable for use in young children.
Dose:
Tuberculosis, by mouth, ADULT, refer to the section on Dose:
Recommended Treatment Regimen for Tuberculosis. Tuberculosis, by mouth, ADULT, refer to the Tables in the
section on Recommended Treatment Regimen for
Dose Adjustments, Precautions, Adverse Drug Reactions Tuberculosis.
and Drug Interactions:
Dose Adjustment:
See under Single Dose Formulation: Isoniazid, Rifampicin Renal and Hepatic Impairment:
and Ethambutol. For severe impairment, dose reduction may be warranted.

Drug Interactions: Precautions, Adverse Drug Reactions, and Drug

Refer to individual monographs of components. Interactions:

Administration: See under Ethambutol, Isoniazid, Pyrazinamide and

Take on an empty stomach with full glass of water. Rifampicin.
For more information, refer to individual monographs of
Pregnancy Category: C components.

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 ANTI-INFECTIVES FOR SYSTEMIC USE

Administration: Dose Adjustment:

Should be taken on an empty stomach; take 1 hour before, Geriatric:
or 2 hours after meals. Refer to adult dosing. Use with caution due to the increased
potential for pre-existing renal dysfunction or impaired
Pregnancy Category: C hearing.

ATC Code: J04AM06 Renal Impairment:

Adults (max: 1g/dose)
CrCl 110 mL/min: 13.9 mg/kg every 24 hours.
DRUGS FOR MULTIDRUG RESISTANT CrCl 100 mL/min: 12.7 mg/kg every 24 hours.
TUBERCULOSIS (MDRTB) CrCl 80 mL/min: 10.4 mg/kg every 24 hours.
CrCl 60 mL/min: 8.2 mg/kg every 24 hours.
CrCl 50mL/min: 7mg/kg every 24 hours or 14 mg/kg every
Rx AMIKACIN 48 hours.
WHO anti-biotic category: ACCESS CrCl 30 mL/min: 5.9 mg/kg every 24 hours or 11.7 mg/kg
every 48 hours.
Inj.: 50 mg/mL, 100 mg/mL, 125 mg/mL, and 250 CrCl 20 mL/min: 3.6 mg/kg every 24 hours or 7.2 mg/kg
mg/mL (as sulfate), 2 mL ampule / vial (IM, IV) every 48 hours or 10.7 mg/kg every 72 hours.
100 mg, 250 mg, 500 mg and 1 g vial (as sulfate) (IM, CrCl 10 mL/min:2.4mg/kg every 24 hours or 4.9 mg/kg
IV) every 48 hours or 7.3 mg/kg every 72 hours.
J

CrCl 0mL/min: 1.3 mg/kg every 24 hours or 2.6 mg/kg

Indication: Second line for the treatment of multi-drug every 48 hours or 3.9 mg/kg every 72 hours.
resistant tuberculosis in conjunction with at least
three other anti-tuberculosis agent. Precautions:

Contraindications: Cross-sensitivity may exist with other WARNING: Use caution in patients with pre-existing
aminoglycosides. auditory impairment due to risk of additional eighth
nerve impairment and should be weighed against the
Dose: benefits. Use caution in patients with renal
NOTE: Individualization is critical because of the low impairment.
therapeutic index.
Tuberculosis, by IM injection or IV infusion, ADULT and Other parenteral anti-tuberculosis agents (i.e. streptomycin)
CHILD, 5-7.5 mg/kg/dose every 8 hours. also have similar and sometimes irreversible toxic
effects, particularly on the eighth cranial nerve and renal
See Amikacin under Aminoglycoside Antibacterials in function, simultaneous administration of these agents
Chapter 07: Anti-infectives for other information. with capreomycin is not recommended;
Safety has not been established in children and pregnant
Pregnancy Category: D
women.
ATC Code: J01GB06
Adverse Drug Reactions:
Common: Ototoxicity and nephrotoxicity
Less Common: Eosinophilia
Rx CAPREOMYCIN Rare: Acute tubular necrosis, Bartter syndrome,
hypersentivity, hypocalcemia, hypokalemia,
hypomagesemia, injection site reactions, leukocytosis,
Inj.: 1 g powder for injection (IV, IM) leukopenia, renal injury, thrombocytopenia, tinnitus,
toxic nephritis, urinary sediment abnormal, vertigo.
Indication: Second line treatment of multi-drug resistant
tuberculosis in conjunction with at least one three other Drug Interactions:
anti-tuberculosis agent Monitor closely with:
Enhances therapeutic effect of the following drugs:
Contraindications: Hypersensitivity to capreomycin or any Aminoglycosides e.g. Streptomycin; Neuromuscular-
component of the formulation. blocking agents e.g. Pancuronium; Polymyxin B
Dose: Enhances toxic effect of Capreomycin:
Tuberculosis, by deep IM injection or IV infusion, ADULT, 1 Non-tuberculosis drugs (i.e. aminoglycosides) (ototoxic
g/day (max: 20 mg/kg/day) for 60-120 days, followed by or nephrotoxic effect)
1 g 2-3 times/week or 15 mg/kg/day (max: 1 g/dose) for
2-4 months, followed by 15 mg/kg (max: 1 g/dose) 2-3 Reduces therapeutic effect of BCG Vaccine
times/week; CHILD <15 years and ≤40kg: 15-30
mg/kg/day (max: 1 g/day) for 2-4 months, followed by Administration:
15-30 mg/kg (max: 1 g/day) twice weekly; CHILD ≥15 Administer by deep IM injection into large muscle mass.
years or >40kg: 15 mg/kg/day (max: 1 g/dose) for 2-4 Infuse IV over 60 minutes.
months followed by 15 mg/kg (max: 1 g/dose) 2-3
times/week. Pregnancy Category: C

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ANTI-INFECTIVES FOR SYSTEMIC USE

ATC Code: J04AB30

Rx KANAMYCIN

Inj.: 1 g vial (as sulfate) (IM)

Rx CYCLOSERINE
Indication: Second line treatment for Mycobacterium
Oral: 250 mg capsule tuberculosis in combination with atleast 3 other agents.

Indication: Secondline treatment for multidrug resistant Contraindications: Hypersensitivity to kanamycin, any
tuberculosis in combination with at least three other component of the formulation or other aminoglycosides;
agents. pregnancy.

Contraindications: Hypersensitivity to cycloserine or any Dose:

component of the formulation. NOTE: Dosing should be based on ideal body weight.
Tuberculosis, by IM injection or IV infusion, ADULT and
Dose: CHILD, 5-7.5 mg/kg/dose in divided doses every 8-12
NOTE: Some of the neurotoxic effects may be relieved or hours (<15 mg/kg/day).
prevented by the concomitant administration of
pyridoxine. Dose Adjustment:
Tuberculosis, by mouth, ADULT, initial 250 mg every 12 Geriatric:

J
hours for 14 days, then give 500 mg to 1 g/day in 2 Tuberculosis, by deep IM injection or IV infusion, initial dose
divided doses for 18-24 months (max daily dose: 1 g). should be 5-7.5 mg/kg based on ideal body weight;
CHILD, 10-20 mg/kg/day in 2 divided doses up to 1000 maintenance dose and interval should be adjusted for
mg/day for 18-24 months. estimated renal function; dosing interval in most older
patients is every 12-24 hours.
Dose Adjustment:
Geriatric: Renal Impairment:
Refer to adult dosing. CrCl 50-80 mL/minute: Administer 60% to 90% of dose or
administer every 8-12 hours.
Renal Impairment: CrCl 10-50 mL/minute: Administer 30% to 70% of dose or
CrCl 10-50mL/min: Administer every 12-24 hours. administer every 12 hours.
CrCl <10mL/min: Administer every 24 hours. CrCl <10 mL/minute: Administer 20% to 30% of dose or
administer every 24-48 hours.
Precautions:
WARNING: May cause CNS toxicity and Precautions:
superinfection. WARNING: May cause nephrotoxicity and
neurotoxicity.
Has been associated with CNS toxicity, including seizures,
psychosis, depression, and confusion; May cause neuromuscular blockade and respiratory
Decrease dosage or discontinue use if occurs; paralysis especially when given soon after anesthesia or
Prolonged use may result in fungal or bacterial muscle relaxants;
superinfection, including C. difficile-associated diarrhea Prolonged use may result in fungal or bacterial infection,
(CDAD) and pseudomembranous colitis; CDAD has been including C. difficile-associated diarrhea (CDAD) and
observed >2 months post-antibiotic treatment. pseudomembranous colitis; CDAD has been observed
>2 months post-antibiotic treatment;
Adverse Drug Reactions: Not intended for long-term therapy due to toxic hazards
Rare: Cardia arrhythmia, drowsiness, headache, dizziness, associated with extended administration.
vertigo, seizure, confusion, psychosis, paresis, coma,
rash, vitamin B12 deficiency, folate deficiency, tremor. Adverse Drug Reactions:
Rare: Edema, neurotoxicity, drowsiness, headache,
Drug Interactions: pseudomotor cerebri, skin itching, redness, rash,
Reduces therapeutic effect of the following drugs: photosensitivity, erythema, nausea, vomiting, diarrhea,
BCG, Typhoid vaccine malabsorption syndrome, anorexia, weight loss,
enterocolitis, burning weakness, tremor, muscle cramps.
Increases risk of adverse or toxic effects Cycloserine:
Isoniazid Drug Interactions:
Monitor closely with:
Administration: Enhances therapeutic effect of the following drugs:
Administer orally with meals. Botulinum toxin type A, RimabotulinumtoxinB,
Colistimethate
Pregnancy Category: C
Increases risk of adverse or toxic effects Kanamycin:
ATC Code: J04AB01 Amphotericin B, Vancomycin, Cisplatin

Enhances therapeutic effect of Kanamycin:

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 ANTI-INFECTIVES FOR SYSTEMIC USE

Capreomycin
Rx OFLOXACIN
Decreases excretion of Kanamycon:
NSAIDs Oral: 200 mg tablet

Increases risk of adverse or toxic effects of Kanamycin: Indications: Quinolone antibiotic for the treatment of acute
Amphotericin B, Vancomycin, Cisplatin exacerbation of chronic bronchitis, community-acquired
Loop diuretics e.g. Furosemide pneumonia, skin and skin structure infections

Increases risk of adverse or toxic effects of the following Dose:

drugs: Tuberculosis, by mouth, ADULT and CHILD, 200–400 mg
Bisphosphonate derivatives e.g. Alendronate every 12 hours.
Carboplatin, Cyclosporine
Gallium nitrate Dose Adjustment:
Geriatric:
Avoid concomitant use with: Tuberculosis, by mouth, 200-400 mg per day (based on
Reduces therapeutic effect of the following drugs: estimated renal function) for 7 days to 6 weeks
BCG, Typhoid vaccine depending on indication.

Decreases serum concentration of Kanamycin: See Ofloxacin unde Second Generations Fluorquinolones in
J

Penicillins Chapter number 07: Anti-infectives title for other

information.
Administration:
Administer intramuscularly, deeply in upper outer quadrant Pregnancy Category: C
of the gluteal muscle. Infuse IV over 30-60 minutes.
ATC Code: J01MA01
Pregnancy Category: D

ATC Code: J01GB04

Rx PARA-AMINOSALICYLIC ACID

Rx LEVOFLOXACIN Oral: 4 g enteric-coated delayed-release granules, sachet

WHO anti-biotic category: WATCH
Indications: Adjunctive treatment of tuberculosis used in
Oral: 250 mg, 500 mg, and 750 mg tablet combination with other anti-tubercular agents.
Inj.: 5 mg/mL solution for IV infusion, 100 mL and 150 mL
vial Dose:
Tuberculosis, by mouth, ADULT, 150 mg/kg/day in 2-3
Indications: Used for drug-resistant tuberculosis or equally divided doses; CHILD, 200-300 mg/kg/day in 3-
intolerance to first-line agents in combination with other 4 equally divided doses.
agents.
Dose Adjustment:
Contraindications: Hypersensitivity to levofloxacin, any Geriatric:
component of the formulation, or other quinolones. Refer to adult dosing.

Dose: Renal Impairment:

Tuberculosis, by mouth, ADULT, 500-1000 mg daily; CHILD, CrCl 10-50 mL/minute: Administer 50% to 75% of dose.
15-25 mg/kg daily (maximum dose of 1000 mg). CrCl <10 mL/minute: Administer 50% of dose.
NOTE: Levofloxacin should be taken during the intensive (6 Administer after hemodialysis: Administer 50% of dose.
month) and continuation (12-18 months) phases of Continuous arteriovenous hemofiltration: Dose for CrCl <10
treatment. mL/minute.

See Levofloxacin under Third Generations Fluoroquinolones Precautions:

in Chapter 07: Anti-infectives for other information. Patients with sensitivity to tartrazine dyes, nasal polyps, and
asthma may have an increased risk of salicylate
Pregnancy Category: C sensitivity;
Use with caution in patients with gastric ulcer, hepatic
ATC Code: J01MA12 impairment, and renal impairment.

Adverse Drug Reactions:

Pericarditis, vasculitis, encephalopathy, fever, skin
eruptions, goiter, hypoglycemia, abdominal pain,
diarrhea, nausea, vomiting, agranulocytosis, anemia,
leukopenia, hepatitis, jaundice, optic neuritis,
eosinophilic pneumonia.

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ANTI-INFECTIVES FOR SYSTEMIC USE

Drug Interactions: Isoniazid

Monitor closely with:
Reduces therapeutic effect of the following drugs: Administration:
ACE inhibitors e.g., Enalapril, Loop diuretics e.g., Administer WITH meals.
Furosemide, Probenecid
Pregnancy Category: D
Increases risk of adverse or toxic effects of Sulfonylureas
ATC Code: J04AD01
Enhances therapeutic effect of the following drugs:
Anticoagulants, Drotrecogin alfa, Corticosteroids,
Vitamin K antagonists
Rx RIFABUTIN
Avoid concomitant use with:
Increases risk of adverse or toxic effects of the following Oral: 150 mg capsule
drugs:
Carbonic anhydrase inhibitors, Thrombolytic agents, Indications: Alternative to the macrolides for the prophylaxis
NSAIDs of Mycobacterium avium complex (MAC) infection in
immunocompromised patients. Alternative to rifampicin
Increases risk of adverse or toxic effects of Para- in the treatment of tuberculosis in HIV patients in
aminosalicylic acid: combination with other mycobacterial agents.

J
Influenza virus vaccine
Dose:
Administration: Disseminated Mycobacterium Avium Complex in advanced
May be administered orally with food. Do not use granules HIV infection, by mouth, ADULT, Prophylaxis: 300 mg
if packet is swollen or if granules are discolored. once a day or 150 mg 2 times a day; Treatment: 300
Granules may be sprinkled in applesauce or yogurt or mg/day as an optional add-on to primary therapy of
suspended in tomato or orange juice. clarithromycin and ethambutol.

Pregnancy Category: C Dose Adjustment:

Geriatric:
ATC Code: J04AA01 Refer to adult dosing.

Renal Impairment:
ClCr <30 mL/minute: Reduce dose by 50%.
Rx PROTHIONAMIDE
Precautions:
Oral: 250 mg film-coated tablet WARNING: Use with caution in patients with hepatic
impairment, renal impairment.
Indication: Treatment of multi-drug resistant tuberculosis
(MDRTB) Monitor patients for: Hematologic Toxicity, Hypersensitivity
Reactions, Superinfection; Uveitis, potentially significant
Contraindication: Severe liver disease due to risk of further interactions may exist, requiring dose or frequency
hepatotoxicity. adjustment, additional monitoring, and/or selection of
alternative therapy;
Dose: Must not be administered for Mycobacterium Avium
Tuberculosis, by mouth, ADULT/CHILD, 15-20 mg/kg Complex prophylaxis to patients with active tuberculosis
(maximum: 1 g) once daily. since its use may lead to the development of TB resistant
to both rifabutin and rifampin. Caution that active TB in
Dose Adjustment: the HIVpositive patient may present atypically (negative
Geriatric: PPD or extrapulmonary manifestations); Remove soft
Refer to adult dosing. contact lenses during therapy since permanent staining
may occur.
Adverse Drug Reactions: Urine, feces, saliva, sweat, tears, sputum, and skin may be
Common: Nausea, vomiting, diarrhea, anorexia, excessive discolored to brown/orange.
salivation, metallic test, stomatitis, and abdominal pain.
Less Common: dizziness, encephalopathy, peripheral Adverse Drug Reactions:
neuropathy, psychotic disturbances, depression, Rash, gastrointestinal disturbances, neutropenia,
hypoglycemia, hypothyroidism. polyarthralgia arthritis, uveitis, asymptomatic corneal
Rare: acute hepatitis, optic neuritis. opacities, orangetan skin pigmentation, discolored urine,
flulike syndrome in Crohn's disease, hepatitis,
Drug Interactions: leucopenia, neutropenia, epigastric pain, ageusia, fever,
Increases risk of adverse or toxic effects of the following vomiting.
drugs:
Cycloserine, P-aminosalicylic acid, Rifampicin Drug Interactions:
Increases serum concentration of the following drugs:
Increases serum concentration of Prothionamide:

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 ANTI-INFECTIVES FOR SYSTEMIC USE

Antifungal Agents (Azole Derivatives), Voriconazole DRUGS FOR TREATMENT OF LEPRA

Increases risk of adverse or toxic effects Rifabutin:
Clarithromycin, Clopidogrel, Ifosfamide, Isoniazid Rx CLOFAZIMINE
Reduces therapeutic effect of Rifabutin:
Oral: 50 mg and 100 mg capsule (available under DOH
BCG (Intravesical), BCG Vaccine (Immunization), Sodium
program)
Picosulfate, Typhoid Vaccine
Indiations: Multibacillary leprosy; type 2 lepra reactions
Decreases serum concentration of Rifabutin:
(Erythema Nodosum Leprosum).
Abiraterone Acetate, Antihepaciviral Combination
Products, Apixaban, Aripiprazole, Axitinib, Bedaquiline,
Dose:
Boceprevir, Bortezomib, Bosentan, Bosutinib,
Multibacillary leprosy (in combination with dapsone and
Brentuximab Vedotin, Brexpiprazole, Buspirone,
rifampicin), by mouth, ADULT, 50 mg once daily and 300
Cabozantinib, Calcium Channel Blockers, Ceritinib,
mg once a month; CHILD 10-14 years, 50 mg on
Clozapine, Contraceptives (Estrogens), Contraceptives
alternate days, and 150 mg once a month; CHILD <10
(Progestins), Corticosteroids, Crizotinib, Cyclosporine,
years, required appropriate dosage adjustments (e.g., 50
CYP3A4 Substrates, Daclatasvir, Dapsone, Dasatinib,
mg twice a week and, 100 mg once a month); continue
Deferasirox, Dexamethasone, Doxorubicin, Dronabinol,
treatment for 12 months.
Dronedarone, Eliglustat, Enzalutamide, Erlotinib,
Type 2 lepra reactions, by mouth, ADULT and CHILD, 200-
J

Etoposide, Etravirine, Everolimus, Exemestane, Fentanyl,

300 mg daily in 2 or 3 divided doses for a maximum of 3
Gefitinib,, Guanfacine, HMG-CoA Reductase Inhibitors,
months; 4-6 weeks treatment may be required before
Hydrocodone, Hydrocortisone, Ibrutinib, Imatinib,
any effect is seen.
Irinotecan, Itraconazole, Ivabradine, Lapatinib,
Ledipasvir, Linagliptin, Lumefantrine,
Dose Adjustment:
Methylprednisolone, Mifepristone, Morphine,
Renal and Hepatic Impairment:
Mycophenolate, Netupitan, Nevirapine, Nifedipine,
Use drug with caution for mild-to-moderate impairment; for
Nilotinib, Nimodipine, Palbociclib, Pazopanib,
severe impairment, the patient should be referred to a
Perampanel, Praziquantel, Prednisolone, Prednisone,
specialist.
Propafenone, Quetiapine, Quinidine, Raltegravir,
Ramelteon, Ranolazine, Regorafenib, Rilpivirine,
Precautions:
Rivaroxaban, Roflumilast, Rolapitant, Saxagliptin,
Patients with pre-existing GI symptoms and problems
Siltuximab, Simeprevir, Sofosbuvir, Sorafenib, Sunitinib,
(reduce the dose, increase the dose interval or
Tacrolimus, Tadalafil, Tamoxifen, Telaprevir,
discontinue if symptoms develop during treatment);
Temsirolimus, Ticagrelor, Tocilizumab, Tofacitinib,
avoid use if abdominal pain and diarrhea persist; may
Tolvaptan, Ulipristal, Vincristine, Vitamin K Antagonists
discolor soft contact lenses; avoid treatment with daily
(e.g. Warfarin), Vortioxetine, Zolpidem
doses exceeding 100 mg; Pregnancy (use with caution
during first trimester); breastfeeding (crosses placental
Decreases serum concentration of Efavirenz
barrier and excreted in breast milk; can cause reversible
skin discoloration in nursing infant).
Decreases metabolism of Rifabutin:
Barbiturates
Adverse Drug Reactions:
Common: Abdominal pain, conjunctival discoloration,
Decreases metabolism of Macrolide Antibiotics
diarrhea, dryness of skin, eye irritation, ichthyosis, itch
nausea, pink to brownish-black discoloration of skin,
Administration:
rash, red-brown coloration of body fluids, vomiting.
Administer WITH meals.
Less Common: Constipation, dizziness, drowsiness,
eosinophilic enteritis, GI bleeding, splenic infarction,
Pregnancy Category: C
taste disturbances.
Rare: Enteropathy (due to the deposition of clofazimine
ATC Code: J04AB04
crystals in the GI mucosa and lymph nodes),
phototoxicity.

Drug Interactions:
Monitor closely with:
Reduces absorption of Rifampicin

Avoid concomitant use with:

Reduces therapeutic effect of Clofazimine:
Dapsone

Administration:
Medicines used in the treatment of leprosy should always
be used in combination (essential to prevent the
emergence of resistance); Clofazimine is best absorbed
when given right after a meal.

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ANTI-INFECTIVES FOR SYSTEMIC USE

Pregnancy Category: C Adverse Drug Reactions:

Common: Asymptomatic methemoglobinemia, GI
ATC Code: J04BA01 symptoms, hemolytic anemia (occurs in most patients
taking more than 200 mg daily); rash (in HIV patients).
Less Common: Allergy, anorexia, fever, headache, insomnia,
nausea, nervousness, vomiting.
Rx DAPSONE Rare: Agranulocytosis, albuminuria, aplastic anemia,
blurred vision, Dapsone syndrome (resembling
Oral: 100 mg tablet mononucleosis), hepatitis, Jarisch-Herxheimer reactions,
neutropenia, paresthesia, peripheral neuropathy (with
Indications: Paucibacillary and multibacillary leprosy; doses more than 200 mg daily); psychosis, severe skin
dermatitis herpetiformis. reactions (e.g. exfoliative dermatitis).

Contraindications: Severe anemia; porphyria. Drug Interactions:

Avoid concomitant use with:
Dose: Increases risk of adverse or toxic effects Dapsone:
Dermatitis herpetiformis, by mouth, ADULT, start at 50 mg Antimalarial agents (chloroquine and/or primaquine)
daily, increase to 300 mg daily (or higher to achieve full
control). Reduces therapeutic effect of Clofazimine

J
NOTE: reduce dosage to minimum level as soon as possible.
Multibacillary leprosy (in combination with rifampicin and Administration:
clofazimine), by mouth, continued for 12 months, ADULT, This may be administered with meals if GI upset occurs; do
100 mg daily; CHILD 10-14 years, 50 mg daily; CHILD NOT administer with antacids, alakine foods, or drugs.
<10 years, 50 mg every other day.
Paucibacillary leprosy (in combination with rifampicin), by NOTE: Stop dapsone if serious skin reaction or muscle
mouth, continued for 6 months, ADULT, 10-14 years, 50 weakness occurs.
mg daily; CHILD <10 years, 50 mg every other day.
Pregnancy Category: C
Dose Adjustment:
Renal and Hepatic Impairment: ATC Code: J04BA02
Use drug with caution for mild to moderate impairment; for
severe impairment, the patient should be referred to a
specialist.
Rx RIFAMPICIN
Precautions:
Sulfonamide allergy (may predispose to dapsone allergy; Oral: 300 mg, 450 mg, and 600 mg tablet / capsule
begin with low dose of dapsone and monitor closely for 200 mg/5 mL suspension, 120 mL
adverse effects);
Cardiopulmonary disease or HIV and PCP (tolerate Indications: First line of treatment for tuberculosis, in
hemolytic anemia and methemoglobinemia); combination with other drugs; treatment of leprosy, in
Susceptibility to hemolysis, including G6PD deficiency, or in combination.
patients receiving drugs capable of inducing hemolysis
(including breastfeeding affected infants); Dose:
Hemoglobin M deficiency; Leprosy, Paucibacillary leprosy, by mouth, ADULT 50-70kg,
Methemoglobin reductase deficiency; 600mg/months with dapsone (100mg/ day); duration of
In patients with hepatic or renal disease; dermatologic treatment: >6months;
reactions (serious reactions are rare, but potentially Multibacillary leprosy, by mouth, ADULT 50- 70 kg, 600mg/
occurring); month with dapsone (100mg/day) and Clofazimine
Peripheral neuropathy (motor loss and muscle weakness (50mg/day + 300mg/month); Duration of treatment: >2
have been reported with use); years and, when monitoring is feasible, until skin smears
Prolonged use may result in fungal or bacterial are negative.
superinfection; Note: Supervised use of Rifampicin.
Pregnancy (supplementation with folic acid may be
necessary if use is warranted; possible risk of See Rifampicin, in Drugs for Tuberculosis under Chapter 07
hyperbilirubinemia in neonates);
Breastfeeding (avoid use) Pregnancy Category: C

BLOOD DISORDERS. On long-term treatment, patients and ATC Code: J04AB02

their caregivers should be told how to recognize blood
disorders, and advised to seek immediate medical
attention of symptoms, such as fever, sore throat, rash,
mouth ulcers, purpura, bruising, or bleeding develop.

265
 ANTI-INFECTIVES FOR SYSTEMIC USE

Precautions:
ANTIVIRALS FOR SYSTEMIC USE
WARNING: May aggravate renal sufficiency due to intra-
tubular obstruction with acyclovir microcrystals.
NUCLEOSIDES AND NUCLEOTIDES,
EXCLUDING REVERSE TRANSCRIPTASE Use with caution in patients with dehydration, renal disease,
INHIBITORS electrolyte abnormalities, underlying neurologic
diseases, hepatic dysfunction or renal impairment,
ANTIHERPES AGENTS maintain adequate hydration (especially with infusion or
high doses, or during renal impairment) to minimize renal
adverse effects; Suppressive therapy of genital herpes
Rx ACICLOVIR (ACYCLOVIR) should be considered only if patient is severely affected
(periodic evaluation is recommended), and cross-
resistance may occur between agents due to their similar
Oral: 200 mg, 400 mg, and 800 mg tablet mechanisms of action and activation pathways;
200 mg/5 mL suspension, 60 mL and 120 mL Prolonged or repeated courses of acyclovir in severely
Inj.: 25 mg/mL, 10 mL vial (IV infusion) immunocompromised patients may result in selection of
resistant viruses associated with infections which may
An acyclic, purine nucleoside analogue, which has a high not respond, the elderly (at increased risk of neurological
degree of specificity, and is active against herpes adverse effects; likely to have reduced renal function),
simplex virus and varicella-zoster virus. pediatrics (safety and effectiveness in children <2 years
J

of age have not been adequately studied)

Indications: Initial treatment and prophylaxis of recurrent
mucosal and cutaneous herpes (HSV1, HSV2) infections; Adverse Drug Reactions:
acute chickenpox (varicella zoster) in Common: Diarrhea, hallucinations, headache, nausea,
immunocompromised patients; herpes zoster infections vomiting.
(shingles). Less Common: Abdominal pain, agitation, arthralgia,
confusion, constipation, dizziness, drowsiness, edema,
Contraindications: Serious adverse reactions to individual fatigue, pruritus, photosensitivity, rash, renal
drug or metabolite; should not be used to treat severe impairment, sore throat, urticaria, vertigo, weakness.
HSV infections in children with low resistance to disease. Rare: Acute renal failure, anaphylaxis, anemia, anorexia,
coma, crystalluria, dyspnea, fatigue, fever, hepatitis,
Dose: jaundice, leukopenia, neutropenia, psychosis, seizures,
Antiviral prophylaxis, by mouth, ADULT, 800 mg twice a day SJS, thrombocytopenia, toxic epidermal necrolysis,
OR 400 mg 3-4 times a day. tremor.
Encephalitis, herpes simplex, by IV infusion, CHILD <12
years old, 20 mg/kg infused over 1 hour every 8 hours Drug Interactions:
for 14-21 days; ADULT, 10 mg/kg infused over 1 hour Monitor closely with:
every 8 hours for 14-21 days. Decreases metabolism of Acyclovir:
Herpes simplex virus gingivostomatitis, herpes simplex virus Probenecid
1 and 2, by IV infusion, CHILD, 15 mg/kg every 8 hours
for 5-7 days. Increases risk of adverse or toxic effects of Theophylline
Conjunctivitis, Herpes simplex types 1 and 2, by IV infusion,
NEONATE, 60 mg/kg in divided doses every 8 hours for Enhances therapeutic effect of Zidovudine
14 days.
Herpes keratitis, with recurrent infections, by mouth, ADULT Avoid concomitant use with:
>12 years old, 400 mg twice a day for 2 months. Reduces therapeutic effect of Zoster vaccine
Varicella zoster ophthalmicus, by mouth, ADULT, 800 mg 5
times a day for 10 days. Administration:
Acute retinal necrosis, varicella zoster virus, by IV infusion, For dosage taken 5 times daily, take every 4 hours during
ADULT, 10-12 mg/kg every 8 hours for 7-10 days until waking hours. Make sure that the patient drinks plenty
disease stabilizes THEN by mouth, ADULT, 800 mg 5 of fluids (at least 1.5-2 L daily). This medication may
times a day for a minimum of 6 weeks. make the patient feel dizzy or confused; advise not to
Vesicular, viral ulcerative pharyngitis, Coxsackie A9, B1-5; drive or operate machinery if the patient is affected.
ECHO viruses (multiple types); Enterovirus 71; Herpes
simplex virus (HSV) 1, 2, For HSV 1 and 2 in Pregnancy Category: B
immunocompromised host, by IV infusion, CHILD <12
years old, 10 mg/kg for 1-3 hours every 8 hours for 7-14; ATC Code: J05AB01
CHILD >12 years old, 5 mg/kg for 1-3 hours every 8
hours for 7-14; by mouth, ADULT, 400 mg five times a
day for 5 days.

Dose Adjustment:
Renal Impairment:
For mild-to-moderate renal impairment, dose reduction is
warranted; for severe impairment, the patient should be
referred to a specialist.

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ANTI-INFECTIVES FOR SYSTEMIC USE

Pregnancy Category: B
Rx VALACICLOVIR (VALACYLOVIR)
ATC Code: J05AB11
Oral: 500 mg tablet (as hydrochloride)

Indications: Treatment of herpes zoster and herpes simplex ANTICYTOMEGALOVIRUS

infections of the skin and mucous membranes, including
genital herpes.
Rx GANCICLOVIR
Dose:
Herpes simplex virus gingivostomatitis, herpes simplex virus Inj.: 500 mg vial (as sodium) (IV infusion)
1 and 2, by mouth, ADULT, 2 g every in 2 divided doses
every 12 hours for 7 days. Indications: Treatment of CMV retinitis in
Varicella zoster ophthalmicus, by mouth, ADULT, 1g thrice a immunocompromised individuals, including patients
day for 10 days. with acquired immunodeficiency syndrome; prophylaxis
Acute retinal necrosis, varicella zoster virus, by mouth, of CMV infection in transplant patients.
ADULT, 1 g thrice a day.
Vesicular, viral ulcerative pharyngitis, Coxsackie A9, B1-5; Dose:
ECHO viruses (multiple types); Enterovirus 71; Herpes CMV Retinitis, by slow IV infusion, ADULT and CHILD,
simplex virus (HSV) 1, 2, For HSV 1 and 2 in induction therapy: 5mg/kg/dose every 12 hours for 14-

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immunocompromised host, by IV infusion, CHILD> 12 21 days followed by maintenance therapy of
years old, 4 g per day every 12 hours; 5mg/kg/day as a single daily dose for 7 days/week or
Recurrent herpes labialis, by IV infusion, CHILD >12 6mg/kg/day for 5 days/week.
years old, 4g per day every 12 hours; by mouth, ADULT, Prevention of CMV disease in transplant patients, by slow IV
500 mg twice daily for 7 days. infusion, ADULT and CHILD, same initial and
maintenance dose as CMV retinitis except duration of
Dose Adjustment: initial course is 7-14 days, duration of maintenance
Geriatric: therapy is dependent on clinical condition and degree of
Refer to adult dosing. immunosuppression.
Renal Impairment: Dose Adjustment:
CrCl 30-49mL/minute: 1g every 12 hours; Geriatric:
CrCl 1029mL/minute: 1g every 24 hours; Refer to adult dosing
CrCl <10mL/minute: 500mg every 24 hours.
Renal Impairment:
Precautions: IV (induction):
WARNING: Monitor patients for CNS adverse effects and CrCl 50-69mL/min: 2.5 mg/kg/dose every 12 hours.
thrombotic thrombocytopenic purpura/ hemolytic CrCl 25-49mL/min: 2.5 mg/kg/dose every 24 hours.
uremic syndrome. CrCl 10-24mL/min: 1.25 mg/kg/dose every 24 hours.
CrCl <10mL/min: Administer 1.25mg/kg/dose
Use with caution in patients with renal impairment; 3 times/week following hemodialysis.
IV (maintenance):
Adverse Drug Reactions: CrCl 50-69mL/min: 2.5 mg/kg/dose every 24hours.
Common: Diarrhea, hallucinations (high dose), headache, CrCl 25-49mL/min: 1.25 mg/kg/dose every 24 hours
nausea, vomiting. CrCl 10-24mL/min: 0.625 mg/kg/dose every 24 hours.
Less Common: Abdominal pain, agitation, arthralgia, CrCl >10mL/minute: 0.625 mg/kg/dose 3 times/week
confusion, constipation, dizziness, drowsiness, edema, following hemodialysis.
fatigue, pruritus, photosensitivity, rash, renal
impairment, sore throat, urticaria, vertigo, weakness. Precautions:
Rare: Acute renal failure, anaphylaxis, anemia, anorexia, WARNING: Animal studies have demonstrated
coma, crystalluria, dyspnea, fatigue, fever, hepatitis, carcinogenic and teratogenic effects, and
jaundice, leukopenia, neutropenia, psychosis, seizures, inhibition of spermatogenesis.
SJS, thrombocytopenia, toxic epidermal necrolysis,
tremor. Granulocytopenia (neutropenia);
Anemia and thrombocytopenia may occur;
Drug Interactions: Use with caution in patients with renal impairment (dosage
Monitor closely with: adjustment or interruption of therapy may be necessary).
Decreases excretion of Tenofovir
Adverse Drug Reactions:
Avoid concomitant use with: Common: Fever, diarrhea, anorexia, vomiting,
Reduces therapeutic effect of Zoster vaccine thrombocytopenia, leukopenia, anemia, neutropenia,
retinal detachment, sepsis, diaphoresis.
Administration: Less Common: Chills, neuropathy, pruritus.
If gastrointestinal upset occurs, administer with meals. Rare: Anaphylaxis, alopecia, arrhythmia, bronchospasm,
cardiac arrest, cataracts, cholestasis, coma, dyspnea,

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edema, encephalopathy, exfoliative dermatitis, Renal Impairment:

extrapyramidal symptoms, hepatitis, hepatic failure, CrCl 40-59mL/min: 450 mg every 12 hours (induction),
pancytopenia, pulmonary fibrosis, seizure, urticaria, SJS, THEN 450mg/day.
torsades de pointes, renal failure, visual loss. CrCl 25-39mL/min: 450 mg daily (induction), THEN 450 mg
every 2 days.
Drug Interactions: CrCl 10-24mL/min: 450 mg every 2 days (induction), THEN
Monitor closely with: 450 mg 2 times per week.
Increases risk of adverse or toxic effects of Imipenem <10mL/minute (on hemodialysis): Not recommended.

Increases serum concentration of Mycophenolate Precautions:

WARNING: May cause dose- or therapy-limiting
Increases serum concentration of Ganciclovir: granulocytopenia, anemia, and/or
Probenecid thrombocytopenia. May be teratogenic,
carcinogenic and cause aspermatogenesis.
Avoid concomitant use with:
Increases risk of adverse or toxic effects of Reverse Monitor patients for hematologic toxicity; female infertility,
Transcriptase Inhibitors aspermatogenesis;
Use with caution in patients with preexisting cytopenias;
Increases serum concentration of Tenofovir concomitant use nephrotoxic drugs;
May be teratogenic or embryotoxic;
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Administration: Avoid pregnancy; male patients advised to use barrier

Should NOT be administered by IM, subcutaneously, or method during and for 90 days after treatment;
rapid IV push; administer by slow IV infusion over at least Maintain adequate hydration.
1 hour. Too rapid infusion can cause increased toxicity
and excessive plasma levels. Adverse Drug Reactions:
Common: Fever, diarrhea, anorexia, vomiting,
Pregnancy Category: C thrombocytopenia, leukopenia, anemia, neutropenia,
retinal detachment, sepsis, diaphoresis.
ATC Code: J05AB06 Less Common: Chills, neuropathy, pruritus.
Rare: Anaphylaxis, alopecia, arrhythmia, bronchospasm,
cardiac arrest, cataracts, cholestasis, coma, dyspnea,
Rx VALGANCICLOVIR edema, encephalopathy, exfoliative dermatitis,
extrapyramidal symptoms, hepatitis, hepatic failure,
pancytopenia, pulmonary fibrosis, seizure, urticaria, SJS,
Oral: 450 mg tablet torsades de pointes, renal failure, visual loss.

Indication: Treatment of cytomegalovirus (CMV) retinitis in Drug Interactions:

patients with acquired immunodeficiency syndrome Monitor closely with:
(AIDS). Increases risk of adverse or toxic effects of Imipenem

Dose: Avoid concomitant use with:

Cytomegalovirus Retinitis in Patients with AIDS, by mouth, Increases risk of adverse or toxic effects of Reverse
ADULT, induction dose 900 mg every 12 hours for 21 Transcriptase Inhibitors
days. Maintenance dose 900 mg every day following
induction treatment, or in patients with inactive Increases serum concentration of Tenofovir
Cytomegalovirus retinitis.
Cytomegalovirus prevention in solid organ transplant: Administration:
Kidney and kidney-pancreas transplantation, by mouth, Administer orally with food. Do NOT break or crush the
ADULT, 900 mg once a day; begin within 10 days of tablets. Maintain adequate hydration.
transplant until 200 days post-transplant; INFANT, <4
months old: Safety and efficacy not established; CHILD, Pregnancy Category: C
4 months-16 years old, daily dose (mg) = 7 x BSA x CrCl; NOTE: Females of reproductive potential should use
not to exceed 900mg/day; begin within 10 days of effective contraception during treatment and for at least
transplant and continue until 200 days post-transplant. 30 days following treatment. Males should be advised to
Heart transplantation, by mouth, ADULT, 900 mg once a practice barrier contraception during and for at least 90
day. Begin within 10 days of transplant until 100 days days following treatment. Temporary or permanent
post transplant. CHILD, 1 month-16 years old, daily dose female and male infertility may occur.
(mg) = 7 x BSA x CrCl; not to exceed 900 mg/day; begin
within 10 days of transplant and continue until 100 days ATC Code: J05AB14
post-transplant.

Dose Adjustment:
Geriatric:
Start at lower end of dosing range.

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NUCLEOSIDE AND NUCLEOTIDE Drug Interactions:

REVERSE TRANSCRIPTASE INHIBITORS Avoid concomitant use with:
Increases risk of adverse or toxic effects of Reverse
NRTIs or nucleoside analogues act by competitive inhibition Transcriptase Inhibitors e.g. Lamivudine
of HIV-1 reverse transcriptase; incorporation into the
growing viral DNA chain causes premature chain Increases risk of adverse or toxic effects Abacavir:
termination due to inhibition of binding with the incoming Ribavirin
nucleotide.
Administration:
May be administered with or without food.
ANTIRETROVIRAL AGENTS
Pregnancy Category: C
Rx ABACAVIR ATC Code: J05AF06

Oral: 300 mg tablet (as sulfate)

Indication: First-line treatment for children with Human Rx ENTECAVIR

Immunodeficiency Virus (HIV) infection as combination
therapy. Oral: 500 micrograms and 1 mg tablet / film-coated tablet

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0.05 mg/mL oral solution
Contraindications: Hypersensitivity to abacavir or any
component of the formulation; Moderate-to-severe Indications: Treatment of chronic hepatitis B infection, with
hepatic impairment. compensated or decompensated liver disease, in adults
with evidence of active viral replication.
Dose:
HIV treatment, by mouth, ADULT, 300 mg twice daily or 600 Dose:
mg once daily in combination with other antiretroviral HIV/HBV coinfection, by mouth, ADULT and CHILD ≥16
agents.; CHILD 3 months to 16 years, 8 mg/kg twice daily years, recommended in patients who cannot take
(maximum of 300 mg twice daily) in combination with tenofovir, 0.5 mg once daily.
other antiretroviral agents.
Dose Adjustment:
Dose Adjustment: Geriatric:
Geriatric: Refer to adult dosing.
Refer to adult dosing.
Renal Impairment:
Hepatic Impairment: Dosage adjustments depends on creatinine clearance of
Mild hepatic dysfunction, 200 mg twice daily (oral solution patient.
is recommended) while for moderate-to-severe
dysfunction, use is contraindicated. Hepatic Impairment:
Decompensated liver disease, 1 mg once daily.
Precautions:
WARNING: Serious and sometimes fatal hypersensitivity Precautions:
reactions have occurred. Lactic acidosis and severe WARNING: Lactic acidosis and severe hepatomegaly with
hepatomegaly with steatosis have been reported with steatosis. May cause development of HIV resistance in
nucleoside analogues, including fatal cases.) chronic hepatitis B patients with unrecognized or
untreated HIV infection.
May cause redistribution of fat (e.g., buffalo hump,
peripheral wasting with increased abdominal girth, Use with caution in patients with renal impairment or
cushingoid appearance); patients receiving concomitant therapy which may
Patients may develop immune reconstitution syndrome reduce renal function, dose adjustment recommended
resulting in the occurrence of an inflammatory response for ClCr <50mL/minute;
to an indolent or residual opportunistic infection (further Cross-resistance may develop in patients failing previous
evaluation and treatment may be required). therapy with lamivudine.

Adverse Drug Reactions: Adverse Drug Reactions:

Common: Headache, nausea. Common: Peripheral edema, pyrexia, ascites
Less common: Depression, fever/chills, anxiety, rash, Less Common: Headache, fatigue, dizziness,
diarrhea, vomiting, and hypersensitivity reactions. hyperglycemia, diarrhea, dyspepsia, nausea, hepatic
Rare: Erythema multiforme, fat redistribution, hepatic encephalopathy, hematuria, glycosuria, upper
steatosis, hepatomegaly, hepatotoxicity, lactic acidosis, respiratory tract infection.
pancreatitis, SJS, toxic epidermal necrolysis. Rare: Alopecia, anaphylactoid reaction, hepatomegaly,
hypoalbuminemia, insomnia, lactic acidosis, rash, renal
failure, somnolence, thrombocytopenia, vomiting.

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 ANTI-INFECTIVES FOR SYSTEMIC USE

Drug Interactions: Administration:

Decreases serum concentration of Protease inhibitors e.g. Administer orally with no regard to meals.
Lopinavir
Pregnancy Category: C
Avoid concomitant use with:
Increases risk of adverse or toxic effects of Reverse ATC Code: J05AF05
Transcriptase Inhibitors

Increases risk of adverse or toxic effects Abacavir: TENOFOVIR ALAFENAMIDE

Ribavirin (hepatotoxic) Rx
FUMARATE
Administration:
Oral: 25 mg tablet
Administer on an EMPTY stomach (2 hours before or after a
meal). Do not dilute or mix oral solution with water or
The active moiety of Tenofovir alafenamide inhibits
other beverages; use calibrated oral dosing syringe. Oral
replication of HBV by inhibiting HBV polymerase.
solution and tablet are bioequivalent on a mg-to-mg
basis.
Indication: Treatment of chronic hepatitis B
Pregnancy Category: C
Dose:
Chronic hepatitis B, by mouth, ADULT, 25 mg tab once daily.
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ATC Code: J05AF10

Dose Adjustment:
Renal impairment:
Rx LAMIVUDINE CrCl >15 mL/min: no dosage adjustment necessary.
CrCl <15 mL/min: use is not recommnended.
Oral: 100 mg tablet and 150 mg tablet / film-coated tablet Hepatic impairment:
10 mg/mL suspension, 240 mL bottle Mild impairment: no dosage adjustment necessary.
Decompensated cirrhosis: use is not recommended.
Indications: Treatment of HIV infection when antiretroviral
therapy is warranted; should always be used as part of a Precautions:
multidrug regimen (at least three antiretroviral agents). May cause lactic acidosis, hepatomegaly, renal toxicity,
hepatitis B acute exacerbation;
Dose: Use is not recommended in patients with hepatic and renal
HIV infection, ADULT, oral dose of 150 mg twice daily or 300 impairment, HIV-1 and HBV co-infection.
mg once daily. CHILD, 1-3 months, 4 mg/kg/dose twice
daily. 3 months to 16 years, 4 mg/kg/dose twice daily. Adverse Drug Reactions:
Common: Headache and decreased bone mineral density.
Dose Adjustment: Less Common: Fatigue, skin rash, glycosuria, abdominal
Geriatric: pain, nausea, diarrhea, dyspepsia, flatulence, vomiting,
Refer to adult dosing. back pain, arthralgia, cough
Precautions: Drug Interactions:
WARNING: Lactic acidosis and severe hepatomegaly Monitor closely with:
with steatosis. Increases the level or effect of Tenofovir:
Daclatasvir, Sofosbuvir/Velpatasvir
Do not use as monotherapy in treatment of HIV. Lamivudine
combined with emtricitabine is not recommended as a Administration: Administer with food.
dual-NRTI combination due to similar resistance patterns
and negligible additive antiviral activity; Pregnancy Category: B
Use with caution in patients with renal impairment (dosage
reduction recommended). ATC Code: J05AF13

Adverse Drug Reactions:

Headache, nausea, malaise, fatigue, nasal signs and
symptoms, diarrhea, cough, fever

Drug Interactions:
Monitor closely with:
Decreases excretion of Lamivudine:
Trimethoprim

Avoid concomitant use with:

Enhances risk of adverse or toxic effects of Lamivudine:
Ganciclovir, Valganciclovir, Ribavirin

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ANTI-INFECTIVES FOR SYSTEMIC USE

TENOFOVIR DISOPROXIL Stage Renal Disease on Intermittent Hemodialysis

Rx (admin dose after dialysis on dialysis days): 100mg every
FUMARATE
6-8 hours, alternate dosing: 100mg 3 times a day or
300mg/day. Peritoneal Dialysis: 100mg every 6-8 hours.
Oral: 300 mg tablet
Precautions:
Indications: First-line treatment for HIV infection; treatment
of chronic hepatitis B virus. WARNING: Hematologic toxicity; Lactic
acidosis/severe hepatomegaly.
Dose:
HIV infection, by mouth, ADULT, 300 mg once daily, in Monitor patients for: Fat Redistribution; Hematologic
combination with other antiretrovirals. CHILD, ≥12 years Toxicity, Immune Reconstitution Syndrome), Lactic
and ≥35 kg, 300 mg once daily. Acidosis, Severe Hepatomegaly with Steatosis,
Myopathy.
Precautions:
WARNING: Black box warning of chronic hepatitis B and Adverse Drug Reactions:
lactic acidosis or hepatomegaly. Common: Headache, malaise, nausea, anorexia, vomiting.
Less common: Constipation, anemia, muscle weakness.
Use with caution in patients with risk factors for liver disease Rare: Cardiomyopathy, rash, body fat redistribution,
(risk may be increased with female sex, obesity, abdominal pain, hepatitis, hearing loss.

J
pregnancy or prolonged exposure) and suspend
treatment in any patient who develops clinical or Drug Interactions:
laboratory findings suggestive of lactic acidosis or Monitor closely with:
hepatotoxicity. Increases risk of adverse or toxic effects of Zidovudine:
Aciclovir, Valaciclovir, Divalproex, Fluconazole,
Adverse Drug Reactions: Interferons, Protease inhibitors, Rifamycin
Common: Insomnia, abdominal pain, muscle weakness.
Less Common: Chest pain, fatigue, hyperglycemia. Avoid concomitant use with:
Rare: Neutropenia, diaphoresis. Reduces therapeutic effects of Stavudine

Drug Interactions: Increases risk of adverse or toxic effects of the following

Avoid concomitant use with: drugs:
Reduces therapeutic effect of Didanosine Ribavirin, Ganciclovir, Valganciclovir, Doxorubicin,
Clarithromycin
Administration: May be administered orally without meals.
Administration:
Pregnancy Category: B May be administered orally without regard to meals. Take
around the clock to promote less variation in peak and
ATC Code: J05AF07 trough serum levels.

Pregnancy Category: C

Rx ZIDOVUDINE ATC Code: J05AF01

Oral: 100 mg capsule

300 mg tablet, 60 per bottle NON-NUCLEOSIDE REVERSE
50 mg/5 mL suspension, 240 mL bottle TRANSCRIPTASE INHIBITORS (NNRTI)

Indication: Treatment of HIV-1 infection in combination with NNRTIs under Antiretroviral (ARV) HIV drug class act by
at least two other antiretroviral agents. binding directly to HIV-1 reverse transcriptase, resulting
in allosteric inhibition of RNA- and DNA-dependent DNA
Contraindications: Neutrophil count <750/mm3 or polymerase activity.
hemoglobin <7.5g/dL (4.65mmol/L).
ANTIRETROVIRAL AGENTS
Dose:
HIV infection, by mouth, ADULT, 200 mg three times daily or
300 mg twice a day. Rx EFAVIRENZ
For treatment of HIV infection, by mouth, ADULT >18 years
old, dose calculated by body weight or body surface area: Oral: 50 mg, 100 mg, 200 mg and 600 mg tablet / capsule
240 mg/m2 every 12 hours or 160 mg/m2/dose every 8
hours, with a maximum dose of 200 mg every 8 hours. Indications: First-line treatment for HIV infection; alternative
drug for patients who cannot tolerate nevirapine.
Dose Adjustment:
Renal Impairment: Contraindications: Concurrent use of bepridil, cisapride,
CrCl <15mL/minute: 100mg every 6-8 hours, alternate midazolam, pimozide, triazolam, voriconazole, or ergot
dosing: 100mg 3 times a day or 300 mg once a day; End- alkaloids.

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 ANTI-INFECTIVES FOR SYSTEMIC USE

Dose:
HIV infection, in combination with tenofovir and Rx NEVIRAPINE
emtricitabine, by mouth, ADULT, 600 mg once daily.
Dosage adjustment for concomitant use of voriconazole Oral: 200 mg tablet
to 300 mg once daily and increase voriconazole to 400 50 mg/5 mL suspension, 240 mL
mg every 12 hours; CHILD ≥3 years and 10kg to <15kg,
200mg once daily; CHILD ≥3 years and 15kg to <20kg, Indication: In combination therapy with other antiretroviral
250mg once daily; CHILD ≥3 years and 20kg to <25kg, agents for the treatment of HIV-1.
300mg once daily; CHILD ≥3 years and 25kg to <32.5kg,
350mg once daily; CHILD ≥3 years and 32.5kg to <40kg, Contraindications: Moderate-to-severe hepatic impairment;
400mg once daily; CHILD ≥3 years and ≥40kg, 600mg use in occupational or non-occupational post-exposure
once daily. prophylaxis regimen

Dose Adjustment: Dose:

Hepatic Impairment: Treatment of HIV-1 infection, by mouth, ADULT, 200 mg
Do not use for moderate-to-severe hepatic impairment. once daily for the first 14 days of therapy. Dose should
then be increased to 200 mg twice daily in patients who
Precautions: do not experience rash or liver function test
May cause CNS depression; symptoms usually begin within abnormalities with the lower dosage; CHILD 15 days of
1-2 days after starting efavirenz, and generally resolve age or older, the usual initial dosage of nevirapine oral
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within 2-4 weeks of continues therapy, avoid potentially suspension or immediate-release tablets is 150 mg/m2
hazardous tasks such as driving or operating machinery; once daily for the first 14 days of therapy. Dosage should
Serious psychiatric side effects have been associated then be increased to 150 mg/m2 twice daily in patients
with use, including severe depression, suicide, paranoia, who do not experience rash or liver function test
and mania, use with caution in patients with a history of abnormalities with the lower dosage. Dose should not
mental illness/drug abuse. exceed 400 mg/day.
Not recommended in moderate-to-severe hepatic
impairment. Dose Adjustment:
Geriatric:
Adverse Drug Reactions: Refer to adult dosing.
Common: Dizziness, fever, depression, insomnia, anxiety,
pain, headache, rash, diarrhea, nausea, vomiting, cough. Renal Impairment:
Less Common: Impaired concentration, somnolence, Patients requiring dialysis: Administer additional 200 mg
fatigue, abnormal dreams, nervousness, hallucinations, dose after each dialysis treatment.
pruritus, hyperglycemia, dyspepsia, abdominal pain,
anorexia Hepatic Impairment:
Rare: Allergic reaction, aggressive reaction, agitation, Moderate to severe: Not recommended for use.
arthralgia, ataxia, balance disturbances, body fat
accumulation/redistribution. Precautions:
Patients taking nevirapine should be closely monitored for
Drug Interactions: adverse skin reactions and hepatotoxicity during the first
Monitor closely with: 18 weeks of treatment, extra vigilance is advised during
Increases metabolism of the following drugs: the first 6 weeks of treatment. Use with extreme caution
CYP2B6 inducers, CYP3A4 inducers in patients with moderate hepatic impairment,
contraindicated in those with severe hepatic impairment,
Decreases metabolism of the following drugs: Treatment should be permanently stopped in patients
CYP2C19 substrates, CYP3A4 substrates, CYP2B6 who suffer a severe rash, rash accompanied by
inhibitors constitutional symptoms, hypersensitivity reactions or
clinical hepatitis.
Administration:
Administer on an EMPTY stomach. Dosing at or before Adverse Drug Reactions:
bedtime is recommended to limit central nervous system Common: Rash
effects. Tablets should NOT be broken. Less common: Hypersensitivity reactions
Rare: Hepatitis, hepatic failure, SJS, and toxic epidermal
Pregnancy Category: D necrolysis.

ATC Code: J05AG03 Drug Interactions:

Avoid concomitant use with:
Decreases serum concentration of the following drugs:
Aripiprazole, Caspofungin, Contraceptives, Dolutegravir,
Fosamprenavir, Indinavir, Itraconazole, Ketoconazole,
Lopinavir, Voriconazole

Decreases serum concentration of Nevirapine:

Carbamazepine, Dabrafenib, Mitotane, Rifampin

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ANTI-INFECTIVES FOR SYSTEMIC USE

Increases serum concentration of the following drugs: Hypersensitivity (Severe skin and hypersensitivity reactions
Rilpivirine, Tizanidine reported, including cases of drug reaction with
eosinophilia and systemic symptoms (DRESS).
Increases risk of adverse or toxic effects of Efavirenz
Adverse Drug Reactions:
Increases metabolism of Nevirapine: Common: Depression, headache, drowsiness, nausea
CYP2B6 Inducers (Strong), CYP3A4 Inducers (Strong) Less Common: Dizziness, insomnia, abnormal dreams,
fatigue, skin rash, abdominal pain, vomiting
Increases metabolism of Methadone Rare: Angioedema, conjunctivitis, DRESS syndrome, facial
edema, fever, hepatitis, hypersensitivity reaction,
Administration: localized vesiculation, nephrotic syndrome, and suicidal
Administered orally without regard to food. Therapy is ideation.
initiated using a low dosage of immediate-release
nevirapine for the first 14 days since this appears to Drug Interactions:
reduce the frequency of rash. Monitor closely with:
Increased toxicity of the following drugs:
Pregnancy Category: B Amiodarone, Artemether/Lumefantrine, Azithromycin,
Chlorpromazine, Ciprofloxacin, Clarithromycin,
ATC Code: J05AG01 Erythromycin, Escotalopram, Fluconazole, Fluoxetine,
Haloperidol, Indapamide, Levofloxacin, Lopinavir,

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Moxifloxacin, Octreotide, Ofloxacin, Paliperidone,
Quetiapine, Quinine, Risperidone, Tacrolimus,
Rx RILPIVIRINE Voriconazole

Avoid concomitant use with:

Oral: 25 mg tablet (as hydrochloride) Decreases levels of Rilpivirine:
Carbamazepine, Dexamethasone, Efavirenz, Nevirapine,
Rilpivirine has activity against HIV-1 by binding to reverse Oxcarbazepine, Phenobarbital, Phenytoin, Rifampin,
transcriptase. It consequently blocks the RNA-dependent Rifabutin
and DNA dependent DNA polymerase activities, including
HIV-1 replication. Administration: Must be taken with a normal to high calorie
meal. Taking with a protein supplement drink alone does
Indications: Treatment of human immunodeficiency virus not increase absorption. Swallow tablet whole with
type 1 (HIV 1) infection in combination with other water.
antiretroviral agents in treatment-naïve patients with
HIV-1 RNA <100,000 copies/mL. Pregnancy Category: B
Contraindications: Hypersensitivity to rilpivirine or any ATC Code: J05AG05
component of the formulation.

Dose:
HIV-1 infection, by mouth, ADULT and CHILD ≥ 12 years, 25 COMBINATIONS OF ANTIVIRALS FOR THE
mg once daily; CHILD <12 years, safety and efficacy not TREATMENT OF HIV INFECTIONS
established.

Dose Adjustment: Rx LAMIVUDINE + TENOFOVIR

Dosage adjustment for concomitant therapy with rifabutin:
Increase to 50 mg once daily in patients on concomitant Oral: 300 mg lamivudine + 300 mg tenofovir tablet
rifabutin. Decrease to 25 mg once daily when rifabutin is
stopped. Indication: First-line treatment for HIV infection which
consists of at least 3 agents
Precautions:
Depressive disorders (may cause depression, mood Contraindications: Hypersensitivity to tenofovir, lamivudine
changes, negative thoughts, suicide attempts, or suicidal or any excipient in the formulation
ideation);
Fat redistribution (e.g., central obesity, buffalo hump, facial Dose:
wasting, peripheral wasting, breast enlargement, and Treatment of HIV-1 infection, by mouth, ADULT, one tablet
cushingoid appearance); taken once daily
Hepatotoxicity (Patients with underlying hepatitis B or C, or
marked increased transaminases prior to treatment may Dose Adjustment:
be at increased risk); Renal Impairment:
Immune reconstitution syndrome (During initial HIV Not recommended for patients with moderate or severe
treatment, patient may develop immune reconstitution renal impairment, may require dose interval adjustment
syndrome resulting in the occurrence of an indolent or of lamivudine and tenofovir that cannot be achieved with
residual opportunistic infection, or autoimmune combination tablet.
disorders later in therapy.)

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 ANTI-INFECTIVES FOR SYSTEMIC USE

Precautions:
WARNING: Chronic hepatitis B and lactic acidosis or Should not be administered concomitantly with other
hepatomegaly may occur. cytidine analogues such as Emtricitabine.

Refer to individual drug monographs of Tenofovir,

Should not be administered concomitantly with other
Lamivudine and Efavirenz.
Cytidine analogues such as Emtricitabine.
Adverse Drug Reactions:
Refer to individual drug monographs of lamivudine, and Refer to individual drug monographs of Lamivudine,
tenofovir. Tenofovir, and Efavirenz.
Adverse Drug Reactions:
Drug Interactions:
Refer to individual drug monographs of lamivudine, and
Refer to individual monographs of Lamivudine, Tenofovir,
tenofovir. and Efavirenz.
Drug Interactions: Administration: Tablet should be swallowed whole with
Refer to individual drug monographs of lamivudine, and water, taken on an empty stomach since food may
tenofovir. increase efavirenz exposure and may lead to an increase
in the frequency of adverse reactions.
Administration: Tablet should be swallowed WHOLE with
Not recommended for administration to CHILDREN.
J

water, taken on an empty stomach since food may

increase Efavirenz exposure and may lead to an increase Pregnancy Category: D
in the frequency of adverse reactions.
Not recommended for administration to CHILDREN. ATC Code: J05AR11
Pregnancy Category: C

ATC Code: J05AR12 Rx LAMIVUDINE + ZIDOVUDINE

Oral: 150 mg lamivudine + 300 mg zidovudine tablet

LAMIVUDINE + TENOFOVIR +
Rx
EFAVIRENZ Indication: First-line treatment for HIV infection which
consists of at least 3 agents.
Oral: 300 mg lamivudine + 300 mg tenofovir + 600 mg
efavirenz Dose:
Treatment of HIV infection, by mouth, ADULT and CHILD,
A combination of three antiviral drugs used to treat HIV ≥30 kg, 1 tablet twice daily (refer to adult dosing)
infection in adults and adolescents.
Dose Adjustment:
Indication: First-line treatment for HIV infection. Renal Impairment:
Not recommended for use.
Contraindications: Patients with clinically significant
hypersensitivity to tenofovir, lamivudine, efavirenz or any Hepatic Impairment:
of the excipients contained in the formulation. Not recommended for use.

Dose: Precautions:
Treatment of HIV-1 infection, by mouth, ADULT, one tablet
taken once daily WARNING: Zidovudine is associated with hematologic
toxicity including neutropenia and severe anemia.
Dose Adjustment: Lactic acidosis and severe hepatomegaly with
Geriatric: steatosis.
Should be administered with caution.

Renal Impairment: Prolonged use of Zidovudine has been associated with

Not recommended for patients with moderate or severe symptomatic myopathy and myositis; Monitor closely for
renal impairment, may require dose interval adjustment chronic hepatitis B for several months following
of lamivudine and tenofovir that cannot be achieved with discontinuation of therapy in patients co-infected with
combination tablet. HBV and HIV.

Hepatic Impairment: Refer to individual drug monographs of Lamivudine and

Monitor closely for adverse reactions, especially nervous Zidovudine.
system symptoms related to Efavirenz.
Adverse Drug Reactions:
Precautions: Refer to individual drug monographs of Lamivudine and
Zidovudine.
WARNING: Chronic hepatitis B and lactic acidosis or
hepatomegaly may occur.

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ANTI-INFECTIVES FOR SYSTEMIC USE

Drug Interactions: Administration:

Refer to individual monographs of Lamivudine and May be taken with or without food
Zidovudine.
Pregnancy Category: C
Administration:
May be taken with or without food ATC Code: J05AR05

Pregnancy Category: C

ATC Code: J05AR01 Rx LOPINAVIR + RITONAVIR

Oral: 200 mg lopinavir + 50 mg ritonavir tablet / capsule

LAMIVUDINE + ZIDOVUDINE +
Rx Indications: First-line treatment for HIV infection in children
NEVIRAPINE
less than 3 years; second-line treatment for HIV infection
Oral: 150 mg lamivudine + 300 mg zidovudine + 200 mg in older children and adults
nevirapine tablet
Contraindications: Co-administration with medications
Indication: First-line treatment for HIV-1 infection highly dependent upon CYP3A4 for clearance.

J
Contraindications: Severe Anemia (< 7.5 g/dL or 4.65 Dose:
mmol/L); Neutropenia (< 0.75 x 109/L); Permanent liver HIV infection, by mouth, ADULT, twice daily dosing lopinavir
disease or marked changes in liver function; History of 400 mg/ ritonavir 100 mg. NOTE: This regimen is
liver inflammation; History of skin rash or liver injury preferred in pregnant therapy-naïve patients.
while on treatment with nevirapine-containing products; Once daily dosing for therapy-naïve or experience patients
Medication therapy with rifampicin; Children <25kg. with <3 lopinavir resistance-associated substitutions:
lopinavir 800 mg/ritonavir 200 mg once daily; by mouth,
Dose: CHILD <15 kg, 12 mg/kg twice daily; CHILD 15-40 kg, 10
NOTE: This fixed combination replaces the three mg/kg twice daily; CHILD >40 kg, lopinavir 400
components (lamivudine, nevirapine and zidovudine) mg/ritonavir 100 mg twice daily.
used separately in similar dosages. Treatment must be
started with lamivudine, zidovudine, and nevirapine Dose Adjustment:
separately for the first 6-8 weeks the patients is stable Geriatric:
on nevirapine 200mg 2 times a day and adequate Use with caution due to possible decreased hepatic, renal
tolerability to lamivudine, zidovudine and nevirapine has and cardiac function.
been demonstrated.
Renal Impairment:
Treatment of HIV infection, by mouth, ADULT and CHILD, Decrease in clearance is not expected. Do not use once
>25kg: 1 tablet 2 times a day. daily dosing in hemodialysis patients.

Dose Adjustment: Hepatic Impairment:

Renal Impairment: Use caution in hepatic impairment. AUC of lopinavir may be
It is recommended that separate preparations of increase ~30% in mild-to-moderate impairment.
Lamivudine, Zidovudine and Nevirapine be
administered. Precautions:
May alter cardiac conduction and prolong the QT and/or PR
Hepatic Impairment: interval, second- and third-degree AV block and torsade
Contraindicated in severe hepatic impairment. de pointes have been observed;
Patients may develop immune reconstitution syndrome
Precautions: resulting in the occurrence of an inflammatory response
Monitor patients for: liver damage, blood disorders (anemia to an indolent or residual opportunistic infection, further
and neutropenia), hypersensitivity reactions, lactic evaluation and treatment may be required;
acidosis, immune reactivation syndrome, osteonecrosis; Increases in total cholesterol and triglycerides have been
It is recommended that separate preparations of reported, screening should be done prior to therapy and
Lamivudine, Zidovudine and Nevirapine be administered periodically throughout treatment.
when any dosage adjustment is necessary.
Adverse Drug Reactions:
Refer to individual drug monographs of Lamivudine, Common: Rash, hypercholesterolemia, diarrhea, abnormal
Zidovudine and Nevirapine taste, vomiting, nausea, abdominal pain
Adverse Drug Reactions: Less Common: Vasodilation, insomnia, hyperglycemia,
Refer to individual drug monographs of Lamivudine, hyperuricemia, dyspepsia, flatulence, weight loss,
Zidovudine and Nevirapine muscular weakness,
Rare: Abdominal distention, Cushing’s syndrome, diabetes
Drug Interactions: mellitus, dry skin, dyskinesia, eczema, esophagitis,
Refer to individual drug monographs of Lamivudine, exfoliative dermatitis, extrapyramidal symptoms, facial
Zidovudine and Nevirapine paralysis, folliculitis, rhinitis, skin discoloration,

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 ANTI-INFECTIVES FOR SYSTEMIC USE

somnolence, splenomegaly, SJS, weight gain, Adverse Drug Reactions:

xerostomia. Common: Abdominal pain, conjunctivitis, ear disorder,
epistaxis, insomnia, nausea, vomiting, vertigo.
Drug Interactions: Less Common: Aggravation of diabetes, anemia,
Monitor closely with: arrhythmia, confusion, delirium, hemorrhagic colitis,
Use with caution in patients taking CYP3A4 inhibitors, hepatitis, humerus fracture, peritonsillar abscess,
inducers and substrates. pneumonia, pseudomembranous colitis, pyrexia, rash,
seizure, increased transaminase, toxic epidermal
Avoid concomitant use with: necrolysis, unstable angina, swelling of face or tongue.
Incompatible with Colchicine Hypothermia also reported.

Increases risk of averse or toxic effects of Salmeterol Administration:

May be taken with meals to reduce GI side effects. Capsule
Administration: may be opened and mixed with sweetened food
May be taken with or without food. Swallow WHOLE; do NOT products. To prepare 100 mL of 6 mg/mL suspension,
break, crush or chew. May be taken with didanosine put 7 mL of distilled water into a glass or
when taken without food. Tablets are recommended in polyethyleneterephthalate (PET) bottle then empty
patients <15kg. contents of eight 75 mg capsules (= 600 mg) into the
bottle. Swirl the suspension for at least 2 minutes then
Pregnancy Category: C slowly add 91 mL of syrup, sweetened condensed milk,
J

or yogurt. Shake well for 30 minutes. Instruct patient to

ATC Code: J05AR10 shake mixture well before using. Swallow mixture
immediately after preparation.

NEURAMINIDASE INHIBITORS NOTE: Suspension can remain stable for 5 days at room
temperature or 5 weeks if refrigerated at 2-8 degrees
ANTI-INFLUENZA A AND B Centigrade.

Pregnancy Category: C
Rx OSELTAMIVIR
ATC Code: J05AH02

Oral: 75 mg capsule (as phosphate)

ANTIVIRALS FOR TREATMENT OF HCV INFECTIONS
Indications: Prophylaxis of influenza A and B (not a
substitute for flu vaccination); treatment of
uncomplicated acute illness due to influenza A and B Rx DACLATASVIR
infection in patients who have been symptomatic for no
more than 2 days.
Oral: 60 mg tablet
Dose:
Treatment of influenza (must be given within 2 days of onset Daclatasvir binds to the N-terminus within Domain 1 of HCV
of flu symptoms), by mouth, ADULT, 75 mg every 12 nonstructural protein 5A (NS5A) and inhibits viral RNA
hours for 5 days; INFANT 2 weeks-11 months old, 3 replication and virion assembly.
mg/kg twice a day for 5 days; CHILD ≤15kg, 30 mg twice
a day for 5 days; CHILD >15-23kg, 45 mg twice a day for Indications: Treatment of hepatitis C genotypes 1, 2, 3, and
5 days; CHILD >23-40kg, 60 mg twice a day for 5 days; 4 in combination of sofosbuvir with or without ribavirin.
CHILD>40kg and ADULT, 75 mg twice a day for 5 days;
Contraindications: Concurrent use with strong inducers of
Dose Adjustment: CYP3A4 and P-glycoprotein.
Renal Impairment:
Administer with caution in moderate to severe renal Dose:
impairment. Chronic hepatits C genotype 1a or 1b, by mouth, ADULT,
treatment-naïve without cirrhosis: 60 mg once daily with
Precautions: concomitant sofosbuvir for 12 weeks;
peginterferon/ribavirin-experienced patients without
WARNING: Severe hypersensitivity reactions have
cirrhosis: 60 mg once daily with concomitant sofosbuvir
been associated with use.
for 12 weeks; decompensated cirrhosis: 60 mg once
daily with concomitant sofosbuvir and ribavirin for 12
Most effective when used within 24-48 hours of onset of weeks.
symptoms; Age <1 year: safety and efficacy for Chronic hepatits C genotype 2, by mouth, ADULT, treatment-
prophylaxis of influenza has not been established; Age naïve without cirrhosis: 60 mg once daily with
≤2 weeks: safety and efficacy for treatment of influenza concomitant sofosbuvir for 12 weeks; treatment-naïve
has not been established; Increased risk of serious skin with compensated cirrhosis: 60 mg once daily with
reactions; Reports of potentially fatal neuropsychiatric concomitant sofosbuvir for 16-24 weeks;
adverse events in patients with flu. peginterferon/ribavirin-experienced without cirrhosis: 60
mg once daily with concomitant sofosbuvir for 12 weeks;

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ANTI-INFECTIVES FOR SYSTEMIC USE

peginterferon/ribavirin-experienced with compensated Tacrolimus, Telmisartan, Tenofovir, Testosterone,

cirrhosis: 60 mg once daily with concomitant sofosbuvir Valsartan, Verapamil, Vinblastine, Vincristine, Warfarin
for 16-24 weeks; patients with decompensated cirrhosis:
60 mg once daily with concomitant sofosbuvir and Increases the level or effect of Daclatasvir:
ribavirin for 12 weeks, and 24 weeks for patients not Ciprofloxacin, Fluconazole, Itraconazole, Verapamil
eligible for ribavirin; liver transplant recipients with or
without cirrhosis: 60 mg once daily with concomitant Increases toxicity of Amiodarone
sofosbuvir and ribavirin for 12 weeks; kidney transplant
recipients with or without compensated cirrhosis: 60 mg Avoid concomitant use with:
once daily with sofosbuvir and ribavirin for 12 weeks. Decreases the level or effect of Daclatasvir:
Carbamazepine, Oxcarbazepine, Phenobarbital,
Chronic hepatits C genotype 3, by mouth, ADULT, treatment- Phenytoin, Rifabutin, Rifampin, Dexamethasone,
naïve without cirrhosis: 60 mg once daily with Efavirenz
concomitant sofosbuvir for 12 weeks; treatment-naïve
with compensated cirrhosis: 60 mg once daily with Increases the level or effect of Daclatasvir:
concomitant sofosbuvir with or without ribavirin, for 24 Clarithromycin, Colchicine, Imatinib, Isoniazid,
weeks; peginterferon/ribavirin-experienced without Ketoconazole, Nicardipine, Voriconazole
cirrhosis: 60 mg once daily with concomitant sofosbuvir
for 12 weeks; patients with decompensated cirrhosis: 60 Increases the level or effect of Sofosbuvir
mg once daily with concomitant sofosbuvir and ribavirin

J
for 12 weeks, and 24 weeks for patients not eligible for Administration: May be taken with or without food.
ribavirin; liver transplant recipients with or without
cirrhosis: 60 mg once daily with concomitant sofosbuvir Pregnancy Category: C
and ribavirin for 12 weeks; kidney transplant recipients
with or without compensated cirrhosis: 60 mg once daily ATC Code: J05AP07
with sofosbuvir and ribavirin for 12 weeks.
Chronic hepatits C genotype 4, by mouth, ADULT, patients
with decompensated cirrhosis: 60 mg once daily with
concomitant sofosbuvir and ribavirin for 12 weeks, and Rx RIBAVIRIN
24 weeks for patients not eligible for ribavirin; liver
transplant recipients with or without cirrhosis: 60 mg Oral: 200 mg, 500 mg and 600 mg tablet
once daily with concomitant sofosbuvir and ribavirin for
12 weeks; kidney transplant recipients with or without Although not completely understood, Ribarivin appears to
compensated cirrhosis: 60 mg once daily with sofosbuvir interfere with RNA and DNA synthesis and subsequently
and ribavirin for 12 weeks. inhibit protein synthesis and viral replication.

Dose Adjustment: Indication: Treatment of chronic hepatitis C (HCV)

Renal and Hepatic impairment:
No dosage adjustment necessary. Contraindications: Women who are or may become
pregnant; male partners of pregnant women,
Precautions: autoimmune hepatitis, hemoglobinopathies; creatinine
May cause bradycardia; use in caution patients with clearance <50 mL/minute.
cardiovascular disease, hepatic disease, hepatitis B
virus reactivation; not to be used as monotherapy, use Dose:
only in combination with other antihepatitis C virus drugs. Chronic HCV infection, in combination with peg-interferon
alfa-2a, by mouth, ADULT, genotype 1, 4, HIV-free: <75
Adverse Drug Reactions: kg, 1000 mg daily, divided into 2 doses x 48 weeks, ≥75
Common: Fatigue, headache, nausea, and anemia. kg, 1200 mg daily, divided into 2 doses x 48 weeks;
Less Common: Drowsiness, insomnia, skin rash, diarrhea genotype 2/3, HIV-free: 800 mg daily divided into 2
Rare: Reactivation of hepatitis B virus. doses x 24 weeks; HIV-HCV co-infection: 800 mg daily,
divided into 2 doses plus peg-interferon alfa-2a 180 mcg
Drug Interactions: SC every week x 24 weeks; CHILD 5-17 years old, 15
Monitor closely with: mg/kg divided into 2 doses with weekly SC peg-
Increased level or effect due to Daclatasvir: interferon alfa-2a.
Atorvastatin, Azithromycin, Budesonide, Carvedilol,
Cetirizine, Ciprofloxacin, Cyclosporine, Dexamethasone, Dose Adjustment:
Digoxin, Diltiazem, Docetaxel, Doxorubicin, Erythromycin, Renal impairment:
Etoposide, Everolimus, Fentanyl, Hydrocortisone, CrCl ≥50 mL/min: dose adjustment not necessary.
Idarubicin, Imatinib, Irinotecan, Lansoprazole, CrCl <50 mL/min: use is contraindicated.
Ledipasvir/Sofosbuvir, Levothyroxine, Lidocaine,
Loreramide, Loratadine, Methotrexate, Hepatic impairment:
Methylprednisolone, Morphine, Nicardipine, Avoid use in decompensated hepatic disease;
Nitrofurantoin, Omeprazole, Ondansetron, Paclitaxel, contraindicated in HCV-HIV co-infected patients with
Paliperidone, Prednisone, Quinine, Ranitidine, Rifampin, cirrhosis and baseline Child-Pugh score ≥6.
Rifaximin, Risperidone, Rosuvastatin,
Sacubitril/Valsartan, Sertraline, Simvastatin, Precautions:

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 ANTI-INFECTIVES FOR SYSTEMIC USE

HCV treatment regimens (Do not use ribavirin alone for Contraindications: Hypersensitivity to sofosbuvir or any
treatment of chronic HCV infection); component of the formulation; males whose female
Fetal/neonatal morbidity and mortality (Teratogenic and/or partners may become pregnant.
embroyocidal. Exercise extreme care to avoid pregnancy
in female patients and in female partners of male Dose:
patients); Hepatitis C genotype 1, by mouth, ADULT, treatment-naïve
Hematologic effects (Hemolytic anemia reported in patients or peginterferon + ribavirin treatment-experienced
receiving oral ribavirin in conjunction with interferon alfa; without cirrhosis: 400 mg once daily in combination with
anemia usually occurs 1-2 weeks after initiation of simeprevir or daclatasvir for 12 weeks; patients with
therapy); decompensated cirrhosis: 400 mg once daily in
Cardiovascular effects (Fatal and nonfatal MI reported in combination with daclatasvir and ribavirin for 12 weeks;
patients with anemia due to oral ribavirin.); liver transplant recipients without cirrhosis or with
Hepatic failure (Patients with chronic HCV infection and compensated cirrhosis: 400 mg once daily in
cirrhosis may be at risk of hepatic decompensation and combination with daclatasvir and ribavirin or simeprevir
death during interferon alfa therapy); with or without ribavirin for 12 weeks.
Pancreatitis (Temporarily interrupt oral ribavirin in patients Hepatitis C genotype 2, by mouth, ADULT, treatment-naïve
with manifestations of pancreatitis.); or peginterferon + ribavirin treatment-experienced
Dental and periodontal disorders; patients: 400 mg once daily in combination with
Pregnancy (Take extreme care to avoid pregnancy). daclatasvir for 12 weeks (without cirrhosis) or 16-24
weeks (with compensated cirrhosis); patients with
J

Adverse Drug Reactions: decompensated cirrhosis: 400 mg once daily in

Common: Fatigue, headache, hemolysis, myalgia, nausea, combination with daclatasvir and ribavirin for 12 weeks;
rigors, fever, insomnia, depression, decreased Hgb, liver transplant recipients with or without cirrhosis,
hyperbilirubinemia, arthralgia, alopecia, irritability, including decompensated cirrhosis: 400 mg once daily in
musculoskeletal pain, rash, anorexia, dizziness, pruritus, combination with daclatasvir and ribavirin for 12 weeks;
flu-like syndrome, dyspnea, nasal congestion, dyspepsia, renal transplant recipients without cirrhosis or with
impaired concentration, thrombocytopenia, sinusitis, compensated cirrhosis: 400 mg once daily in
vomiting, emotional liability, and decreased WBC. combination with daclatasvir and ribavirin for 12 weeks.
Less Common: Hemolytic anemia, weakness, chest pain, Hepatitis C genotype 3, by mouth, ADULT, treatment-naïve
taste perversion, and nervousness. or peginterferon + ribavirin treatment-experienced
Rare: Dehydration, hearing impairment, hearing loss, retinal without cirrhosis: 400 mg once daily in combination with
detachment, pure red cell aplasia, serious skin daclatasvir for 12 weeks; treatment-naïve patients with
reactions, liver and renal graft rejection, homicidal compensated cirrhosis: 400 mg once daily in
ideation, and growth inhibition in pediatric patients. combination with daclatasvir with or without ribavirin for
24 weeks; patients with decompensated cirrhosis: 400
Drug Interactions: mg once daily in combination with daclatasvir and
Monitor closely with: ribavirin for 12 weeks; liver transplant recipients with or
Increases toxicity of the following drugs: without cirrhosis, including decompensated cirrhosis:
Lamivudine, Tobramycin (Inhalation) 400 mg once daily, in combination with daclatasvir and
for 12 weeks; renal transplant recipients without
Avoid concomitant use with: cirrhosis or with compensated cirrhosis: 400 mg once
Increases toxicity of Abacavir daily in combination with daclatasvir and ribavirin for 12
weeks.
Decreases effects of Zidovudine Hepatitis C genotype 4, by mouth, ADULT, patients with
decompensated cirrhosis: 400 mg once daily in
Administration: Take tablet with food. Do not crush or break combination with daclatasvir and ribavirin for 12 weeks;
tablet. liver transplant recipients without cirrhosis or with
compensated cirrhosis: 400 mg once daily, in
Pregnancy Category: X combination with daclatasvir and ribavirin or simeprevir
with or without ribavirin for 12 weeks.
ATC Code: J05AP01 Hepatitis C genotype 5 and 6, by mouth, ADULT, liver
transplant recipients without cirrhosis or with
compensated cirrhosis: 400 mg once daily in
combination with daclatasvir and ribavirin for 12 weeks;
Rx SOFOSBUVIR renal transplant recipients without cirrhosis or with
compensated cirrhosis: 400 mg once daily in
Oral: 400 mg tablet combination with daclatasvir and ribavirin for 12 weeks.

Sofosbuvir inhibits HCV NS5B RNA-dependent RNA Dose Adjustment:

polymerase, essential for viral replication, and acts as a Renal impairment:
chain terminator. No dosage adjustments provided in the manufacturer’s
labeling.
Indications: Treatment of hepatitis C genotypes 1, 2, 3, 4, 5,
and 6 in combination with other direct acting antivirals. Hepatic impairment:
No dosage adjustment necessary.

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ANTI-INFECTIVES FOR SYSTEMIC USE

Precautions: non-NS5A inhibitor, sofosbuvir containing regimen-

Hepatitis B virus reactivation has been reported in HBsAg experienced patients without cirrhosis: one tablet once
positive patients and in patients with serologic evidence daily with concomitant ribavirin for 12 weeks;
of resolved HBV infection. decompensated cirrhosis: one tablet once daily with
concomitant ribavirin for 12 weeks, 24 weeks if ribavirin-
Adverse Drug Reactions: ineligible; decompensated cirrhosis in patients with
Common: Fatigue, headache, insomnia, chills, irritability, sofosbuvir or NS5A-based treatment failure: one tablet
pruritus, skin rash, nausea, decreased appetite, once daily with concomitant ribavirin for 24 weeks; liver
diarrhea, anemia, neutropenia, asthenia, myalgia, flu- transplant recipients with or without cirrhosis: one tablet
like symptoms, and fever. once daily with concomitant ribavirin for 12 weeks;
Less Common: Thrombocytopenia kidney transplant recipients without cirrhosis or with
Rare: Angioedema, bradycardia, pancytopenia, reactivation compensated cirrhosis: one tablet once daily for 12
of HBV, severe depression, and suicidal ideation. weeks.
Hepatitis C genotype 4, by mouth, ADULT, treatment-naïve
Drug Interactions: patients without cirrhosis or with compensated cirrhosis
Monitor closely with: and peginterferon/ribavirin treatment-experienced
Increases the level or effect of Tenofovir: patients without cirrhosis: one tablet once daily for 12
Sofosbuvir weeks; peginterferon/ribavirin treatment-experienced
patients with compensated cirrhosis: one tablet once
Increases toxicity of Warfarin daily with concomitant ribavirin for 12weeks;

J
decompensated cirrhosis: one tablet once daily with
Avoid concomitant use with: concomitant ribavirin for 12 weeks, 24 weeks if ribavirin-
Decreases the level or effect of Sofosbuvir: ineligible; decompensated cirrhosis in patients with
Carbamazepine, Oxacarbazepine, Phenobarbital, sofosbuvir or NS5A-based treatment failure: one tablet
Phenytoin, Rifabutin, Rifampin. once daily with concomitant ribavirin for 24 weeks; liver
transplant recipients with or without cirrhosis: one tablet
Increases toxicity of Amiodarone once daily with concomitant ribavirin for 12 weeks;
kidney transplant recipients without cirrhosis or with
Increases the level or effect of Sofosbuvir: compensated cirrhosis: one tablet once daily for 12
Daclatasvir weeks.
Hepatitis C genotype 5 or 6, by mouth, ADULT, treatment-
Administration: Administer with or without food. naïve and peginterferon/ribavirin treatment-experienced
patients without cirrhosis or with compensated cirrhosis:
Pregnancy Category: B one tablet once daily for 12 weeks; decompensated
cirrhosis: one tablet once daily with concomitant ribavirin
ATC Code: J05AP08 for 12 weeks, 24 weeks if ribavirin-ineligible;
decompensated cirrhosis in patients with sofosbuvir or
NS5A-based treatment failure: one tablet once daily with
concomitant ribavirin for 24 weeks; liver transplant
Rx SOFOSBUVIR + LEDIPASVIR recipients with or without cirrhosis: one tablet once daily
with concomitant ribavirin for 12 weeks.
Oral: 400 mg sofosbuvir + 90 mg ledipasvir tablet
Dose Adjustment:
Ledipasvir inhibits the HCV NS5A protein necessary for viral Renal impairment:
replication; sofosbuvir inhibits NS5B RNA-dependent No dosage adjustments provided in the manufacturer’s
RNA polymerase essential for viral replication, and acts labeling.
as a chain terminator.
Hepatic impairment:
Indications: For the treatment of hepatitis C genotypes 1, 4, No dosage adjustment necessary.
5, and 6.
Precautions:
Contraindications: Hypersensitivity to any component of the Hepatitis B virus reactivation has been reported in HBsAg
formulation. positive patients and in patients with serologic evidence
of resolved HBV infection.
Dose:
Hepatitis C genotype 1, by mouth, ADULT, treatment-naïve Adverse Drug Reactions:
patients without cirrhosis or with compensated cirrhosis Common: Headache, fatigue, and weakness.
or peginterferon/ribavirin treatment-experienced Less Common: Irritability, insomnia, dizziness, depression,
patients without cirrhosis: one tablet once daily for 12 nausea, diarrhea, hyperbilirubinemia, myalgia, increased
weeks; peginterferon/ribavirin treatment-experienced creatine phosphokinase, cough, and dyspnea.
patients with compensated cirrhosis: one tablet once Rare: Angioedema, reactivation of HBV, and skin rash.
daily with concomitant ribavirin for 12weeks; NS3
protease inhibitor + peginterferon/ribavirin treatment- Drug Interactions:
experienced patients: without cirrhosis, one tablet once Monitor closely with:
daily for 12 weeks, with compensated cirrhosis, one Increased toxicity due to Sofosbuvir/Ledipasvir:
tablet once daily with concomitant ribavirin for 12 weeks; Amiodarone, Warfarin

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 ANTI-INFECTIVES FOR SYSTEMIC USE

Avoid concomitant use with: Omeprazole, Oxcarbazepine, Phenobarbital, Phenytoin,

Increases the level/ effect of Colchicine Rifabutin, Rifampin, Vinblastine.

Decreases levels of Sofosbuvir/Ledipasvir: Administration: Administer with or without food.

Carbamazepine, Oxcarbamazepine, Phenobarbital,
Phenytoin, Rifabutin, And Rifampin Pregnancy Category: B

Administration: Administer with or without food. ATC Code: J05AP55

Pregnancy Category: B

ATC Code: J05AP51 IMMUNE SERA AND

IMMUNOGLOBULINS

Rx SOFOSBUVIR + VELPATASVIR IMMUNE SERA

Oral: 400 mg sofosbuvir + 100 mg velpatasvir tablet Rx ANTI-RABIES SERUM (EQUINE)

Velpatasvir inhibits the HCV NS5A protein necessary for viral
J

replication while sofosbuvir inhibits NS5B RNA- Inj.: 200 IU/mL, 5 mL vial (IM)
dependent RNA polymerase and acts as a chain 400 IU/mL, 5 mL vial (IM)
terminator.
Indications: For the seroprophylaxis of rabies in individuals
Indications: Treatment of chronic hepatitis C genotypes 1, who are suspected to have been exposed to the rabies
2, 3, 4, 5, and 6. virus, when rabies immunoglobulin (human) is
unavailable or unaffordable.
Contraindications: Hypersensitivity to sofosbuvir,
velpatasvir, or any component of the formulation. NOTE: The lethal risk associated with rabies overcomes any
potential.
Dose:
Chronic hepatitis C genotypes 1, 2, 3, 4, 5, and 6, by mouth, Dose:
ADULT, 400/100 mg tablet once daily. Prophylaxis of rabies from suspected individuals, by
filtration, ADULT and CHILD, 40 IU/kg of body weight in
Dose Adjustment: and around the cleansed wound; if infiltration of whole
Renal and Hepatic impairment: volume is not possible, give the remainder by IM injection
No dosage adjustment required. slowly (wounds in certain anatomical sites, such as
fingertips, should be infiltrated with care to prevent a
Precautions: local increase in pressure in the tissue).
May cause hepatitis B reactivation.
NOTE: When the volume required to infiltrate the wound(s)
Adverse Drug Reactions: exceeds the recommended dose, some clinicians
Common: Headache, and fatigue. recommend diluting the calculated dose in saline to yield
Less Common: Irritability, insomnia, depression, skin rash, a two- to threefold increase in solution volume to ensure
nausea, weakness that all wound areas receive adequate infiltration.
Rare: Reactivation of hepatitis B virus and angioedema.
Precautions:
Drug Interactions: Do NOT administer intravenously; ensure that the needle
Monitor closely with: has not penetrated a blood vessel; do not give repeated
Increases level/effect of the following drugs: doses once rabies vaccine is given as this may reduce
Alprazolam, Atorvastatin, Clonidine, Colchicine, the immunologic response to the vaccine; despite the
Diazepam, Digoxin, Doxorubicin, Enalapril, Ergotamine, high degree of purification of the serum, it is
Everolimus, Fentanyl, Imatinib, Irinotecan, Methotrexate, recommended to perform a skin test before
Midazolam, Mitoxantrone, Nitrofurantoin, Rosuvastatin, administering rabies antiserum; if the recommended
Simvastatin, Tacrolimus, Valsartan, Warfarin. dosage is not strictly observed (i.e. overdosage), there is
a risk of immunosuppressive interference with rabies
Decreases levels/effects of Sofosbuvri/Velpatasvir: vaccine
Aspirin, Antacids In patients with a history of bleeding disorders, including
thrombocytopenia, and patients on anticoagulant
Avoid concomitant use with: therapy.
Increases toxicity of Amiodarone
NOTE: Immunoglobulins may interfere with the immune
Decreases leves/effects of Sofosbuvir/Velpatasvir: response to live virus vaccines.
Carbamazepine, Colchicine, Dexamethasone,
Doxorubicin, Efavirenz, Lansoprazole, Nevirapine,

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ANTI-INFECTIVES FOR SYSTEMIC USE

Adverse Drug Reactions: NOTE: Immunoglobulins may interfere with the immune
Common: Acute febrile reaction, injection site swelling and response of live virus vaccines which should normally be
pain, serum sickness-like reactions. given either at least 3 weeks before or at 3 months after
Rare: Anaphylaxis. administration of an immunoglobulin.

Drug Interactions: Adverse Drug Reactions:

Reduces therapeutic effect of Anti-rabies Serum: Common: Acute febrile reaction, injection site swelling and
Corticosteroids, Vaccines (Live, attenuated, virus) pain, serum sickness-like reactions.
Rare: Anaphylaxis.
Administration:
Administer as soon as possible, at the same time as the Drug Interactions:
rabies vaccine, or up to 7 days after vaccine injection; Avoid concomitant use with:
the remaining serum should be administered via the IM Reduces therapeutic effect of Anti-Tetanus Serum:
route (into the gluteal region) in a single injection. Vaccines (Live, attenuated, virus)

NOTE: Vaccines should be stored within the safe Administration:

temperature range of 2-8°C. Freezing is the most The serum should be administered via the IM route. If a
common cause of vaccine damage; do not use a large volume is required, it is recommended to
defrosted vaccine unless freezing is the recommended administer the serum in divided doses at different sites.
storage condition.

J
NOTE: Vaccines should be stored within the safe
Pregnancy Category: C temperature range of 2-8°C. Freezing is the most
common cause of vaccine damage; do not use a
ATC Code: J06AA06 defrosted vaccine unless freezing is the recommended
storage condition.

ANTI-TETANUS SERUM Pregnancy Category: C

Rx
(EQUINE)
ATC Code: J06AA02
Inj.: 4,000 IU/mL, 2.5 mL vial (IM)
1,500 IU/0.7 mL solution for injection, vial/ampule
(IM) Rx COBRA ANTIVENIN
1,500 IU/mL, 1 mL and 1.5 mL vial/ampule (IM)

Indications: Prophylaxis against tetanus in non-immune Inj.: 800 MU/4.8 mL, 1 mL ampule (IV infusion)
individuals after serious injury or bite when tetanus 800 IU/mL, 5 ml ampule (IV infusion)
immunoglobulin (human) is unavailable or unaffordable;
treatment of tetanus when tetanus immunoglobulin is Indications: Management of patients with Naja spp.
unavailable or unaffordable. Envenomations (i.e., N. philippinensis, N. samarensis
and N. sumatrana), signs of neurotoxicity or swelling
Contraindications: Known Hypersensitivity to tetanus involving more than half the bitten extremity.
antitoxin or any other component within the serum, and
any product prepared from horse serum. Contraindications: Allergy to horse-based products, or
antivenin by history or because of an appropriate
Dose: sensitivity test; hypersensitivity to any component of the
Post-exposure prophylaxis against tetanus, by IM injection, formulation, including papaya or papain; cross
3,000-5,000 IU. allergenicity with dust mite and latex allergens.
Treatment of tetanus infection, by IM injection, ADULT and
CHILD, 50,000-100,000 IU single dose; NEONATE, 500 Dose:
UNITS/KG OR 5,000-10,000 IU in tetanus neonatorum. Naja spp. envenomations, by IM injection, ADULT and
CHILD, usual dose is 0.5 mL, severe cases: initial dose of
NOTE: The above doses could be given ½ IV and the rest IM 5-10 vials IV and repeated every 1-2 hours until local
after appropriate testing for sensitivity and manifestations, coagulation tests, and systemic signs
desensitization, if necessary. are observed to be normal. The antivenin can be diluted
in 500 mL isotonic fluid to run for 1-2 hours, or given
Precautions: undiluted IV over 10-15 minutes.
WARNING: Increased risk of fatal prophylaxis in
NOTE: Begin infusion slowly, watching carefully for adverse
hypertensive individuals.
effects. Stop the infusion temporarily if these occur. If
there is no adverse reaction, increase the rate, aiming to
Informed consent and skin test are required (a negative skin give the entire infusion over about 15-20 minutes.
or eye test is not an absolute indication of the absence
of sensitivity), a syringe with 0.3 mL of 1:1000 aqueous
solution of epinephrine should be always at hand.

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 ANTI-INFECTIVES FOR SYSTEMIC USE

Precautions: Precautions:
WARNING: Antivenins should never be administered Regardless of allergic history or history of prior
prophylactically to asymptomatic patients. Pain and administration of preparations containing equine serum,
fang marks are not intrinsically signs of envenomation. sensitivity testing must be performed in all individuals
prior to administration of diphtheria antitoxin; Patients
Patients sensitive to antivenin or horse serum may develop should be carefully monitored for evidence of
anaphylaxis. Prior to IV or IM antivenin administration, hypotension and bronchoconstriction during sensitivity
proper skin test should be performed and interpreted testing and desensitization to diphtheria antitoxin and
(therapy may be modified if indicated); in life threatening during administration of the antitoxin.
situations, pre-treat with antihistamine
(diphenhydramine, 50-100 mg IV), followed by slow IV Adverse Drug Reactions:
infusion of very dilute antivenin. At the first sign of Common: Anaphylaxis or anaphylactoid reactions, chest
hypersensitivity reaction, stop infusion and administer discomfort, chills, dizziness, dyspnea, edema of the face,
subcutaneously 0.5-1.0 mL epinephrine (1:1000), pre- tongue, and throat, fever, flushing, headache,
existing renal, hepatic, cardiac, or respiratory treatment hypotension, pruritus, rash, serum sickness, tachypnea,
with anticoagulant or antiplatelet drugs (increased risk urticaria.
of serious outcomes, including death from snakebite), Less Common: Abdominal pain, angioedema, arthralgia,
the elderly (may require more vigorous treatment), bradycardia, bronchospasm, collapse, myalgia, nausea,
children (should not be given weight-adjusted doses, the neurological impairment, pain at the infusion site,
amount required depends on the amount of venom to be sweating, tachycardia, vertigo, vomiting, wheezing.
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neutralized). Rare: Cardiac arrest

STORAGE: Cold-chain management in hospitals. Administration: A test dose of diluted diphtheria antitoxin
should be given intradermally to exclude hypersensitivity.
Adverse Drug Reactions:
Common: Anaphylaxis or anaphylactoid reactions, chest STORAGE: It should be stored at 2-8°C and not be allowed
discomfort, chills, dizziness, dyspnea, edema of the face, to freeze.
tongue, and throat, fever, flushing, headache,
hypotension, pruritus, rash, serum sickness, tachypnea, Pregnancy Category: C
urticaria.
Less Common: Abdominal pain, angioedema, arthralgia, ATC Code: J06AA01
bradycardia, bronchospasm, collapse, myalgia, nausea,
neurological impairment, pain at the infusion site,
sweating, tachycardia, vertigo, vomiting, wheezing. IMMUNOGLOBULINS
Rare: Cardiac arrest
IMMUNOGLOBULINS, NORMAL HUMAN
Administration:
The treatment should begin as soon as possible and
IMMUNOGLOBULIN NORMAL,
preferably within 4-6 hours of envenomation; monitor for Rx
1 hour following the infusion. HUMAN IM (IGIM)

Pregnancy Category: C Inj.: 160 mg/mL, 2 mL, 5 mL, and 10 mL vial (IM)

ATC Code: J06AA03 Indications: Provide passive immunity in susceptible

individuals under the following circumstances:
Hepatitis A: Within 14 days of exposure and prior to
manifestation of disease;
Rx DIPHTHERIA ANTITOXIN Measles: For use within 6 days of exposure in an
unvaccinated person, who has not previously had
measles.
Inj.: 10,000 IU and 20,000 IU, 5 mL and 10 mL (IV)
Varicella: When varicella zoster immune globulin is not
available.
Indications: Treatment of probable or confirmed diphtheria,
Rubella: Post-exposure prophylaxis (within 72 hours)
recommended in exceptional circumstances for post-
exposure prophylaxis in individuals with known or
Contraindications: IgA deficiency; severe thrombocytopenia
suspected exposure to toxigenic Corynbacteria.
or coagulation disorders where IM injections are
contraindicated.
Contraindications: Hypersensitivity to immune globulin or
any component of the formulation.
Dose:
Hepatitis A, by IM injection, ADULT and CHILD, Pre-exposure
Dose:
prophylaxis upon travel into endemic areas (hepatitis A
Pharyngeal or laryngeal disease, by IV or IM injection, ADULT
vaccine preferred):
and CHILD, 20,000-40,000 units for 448 hours duration.
0.02mL/kg for anticipated risk of exposure <3 months,
Nasopharyngeal disease, by IV or IM injection, ADULT and
0.06mL/kg for anticipated risk of exposure ≥3 months,
CHILD, 40,000-60,000 units for 448 hours duration.
repeat approximate dose every 5 months if exposure
continues;

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ANTI-INFECTIVES FOR SYSTEMIC USE

Post-exposure prophylaxis: 0.02mL/kg/dose given IMMUNOGLOBULIN NORMAL,

within 14 days of exposure. IG is not needed of at least Rx
HUMAN IV (IGIV)
1 dose of hepatitis A, vaccine was given at ≥1 month
before exposure.
Inj.: 50 mg/mL, 10 mL, 20 mL, 50 mL, 100 mL, and 200
Measles, by IM injection, ADULT and CHILD, Prophylaxis,
mL vial (IV)
immunocompetent: 0.25mL/kg (maximum dose: 15mL)
1 g/bottle freeze-dried powder + 33 mL and 50 mL
given within 6 days of exposure followed by live
reconstitution fluid (IV)
attenuated measles vaccine in 5-6 months when
2.5 g/bottle freeze-dried powder + 100 mL
indicated;
reconstitution fluid (IV)
Prophylaxis, immunocompromised: 0.5mL/kg
5 g/bottle freeze-dried powder + 100 mL diluent vial
(maximum dose: 15mL) immediately following exposure.
(IV)
Rubella, by IM injection, ADULT and CHILD, Prophylaxis
10 g/bottle freeze-dried powder + 260 mL diluent vial
during pregnancy: 0.55mL/kg/dose within 72 hours of
(IV)
exposure.
Varicella, by IM injection, ADULT and CHILD, Prophylaxis:
Indications: Treatment of primary immunodeficiency
0.6-1.2mL/kg (varicella zoster immune globulin
syndromes, chronic inflammatory demyelinating
preferred) within 72 hours of exposure.
polyneuropathy (CIDP) and immune (idiopathic)
IgG deficiency, by IM injection, ADULT and CHILD,
thrombocytopenic purpura (ITP) and Kawasaki disease.
0.66mL/kg/dose every 3-4 weeks. A double dose may be
Prevention of bacterial infection in B-cell chronic
given at onset of therapy; some patients may require
lymphocytic leukemia (CLL).

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more frequent injections.
Contraindications: Hypersensitivity to immune globulin or
Precautions:
any component of the formulation; selective IgA
Hypersensitivity and anaphylactic reactions can occur;
deficiency; hyperprolinemia.
immediate treatment (including epinephrine 1:1000)
should be available;
Dose:
Product of human plasma; may potentially contain
Prevention of HIV infection, by IV infusion, CHILD, 400
infectious agents which could transmit disease;
mg/kg every 2-4 weeks.
Screening of donors, as well as testing and/or inactivation
Primary immunodeficiency disorder, by IV infusion, ADULT
or removal of certain viruses, reduces the risk; Skin
and CHILD, 200-800mg/kg per month.
testing should not be performed as local irritation can
B-cell chronic lymphocytic leukemia (CLL), by IV infusion,
occur and be misinterpreted as a positive reaction.
ADULT and CHILD, 400mg/kg/dose every 3-4 weeks.
Immune (idiopathic) thrombocytopenic purpura (ITP), acute,
Adverse Drug Reactions:
by IV infusion, ADULT and CHILD, 400mg/kg/day for 2-5
Flushing, angioedema, chills, lethargy, fever, urticaria,
days;
erythema, nausea, vomiting, tenderness, muscle
Chronic, by IV infusion, ADULT and CHILD, 400mg/kg as
stiffness at IM site, myalgia, hypersensitivity reactions.
needed to maintain platelet count ≥30,000/mm3 or to
control significant bleeding; may increase dose if needed
Drug Interactions:
(range: 800-1000mg/kg).
Avoid concomitant use with:
Chronic inflammatory demyelinating polyneuropathy (CIDP),
Reduces therapeutic effects of the following drugs:
by IV infusion, ADULT and CHILD, Loading dose:
Live vaccines (except: influenza virus vaccine
2000mg/kg divided over 2-4 consecutive days;
(live/attenuated); rotavirus vaccine; yellow fever vaccine;
Maintenance 1000mg/kg/day for 1 day every 3 weeks
zoster vaccine
or 500mg/kg/day for 2 consecutive days every 3 weeks.
Kawasaki disease, by IV infusion, ADULT and CHILD, initiate
Administration:
IVIG therapy within 10 days of disease onset; must be
NOT for IV administration.
used in combination with aspirin, 80-100mg/kg/day in 4
Administer IM in the anterolateral aspects of the upper thigh
divided doses for 14 days; when fever subsides, dose
or deltoid muscle of the upper arm. Avoid gluteal region
aspirin at 3-5mg/kg once daily for ≥6-8 weeks.
due to risk of injury to sciatic nerve; use upper outer
Hematopoietic stem cell transplantation with
quadrant only. Divide doses >10mL.
hypogammaglobulinemia, by IV infusion, CHILD,
400mg/kg per month; increase dose or frequency to
Pregnancy Category: C
maintain IgG levels >400mg/dL; ADULT,
500mg/kg/week.
ATC Code: J06BA01
Precautions:
WARNING: Acute renal dysfunction (increased serum
creatinine, oliguria, acute renal failure, osmotic
nephrosis) can rarely occur usually within 7 days of
use (more likely with products stabilized with
sucrose). Use with caution in the elderly, patients
with renal disease, diabetes mellitus, volume
depletion, sepsis, paraproteinemia, and nephrotoxic
medications due to risk of renal dysfunction.

283
 ANTI-INFECTIVES FOR SYSTEMIC USE

In patients at risk of renal dysfunction, the rate of infusion SPECIFIC IMMUNOGLOBULINS

and concentration of solution should be minimized.
Discontinue of renal function deteriorates;
High dose regimens (1000mg/kg for 1-2 days) are not HEPATITIS B
Rx
recommended for individuals with fluid overload or IMMUNOGLOBULIN (HUMAN)
where fluid volume may be of concern;
Hypersensitivity and anaphylactic reactions can occur, Inj.: 0.5 mL, 1 mL, and 2 mL vial (IM)
immediate treatment (including epinephrine 1:1000)
should be available; Indications: Passive prophylactic immunity to hepatitis B
Product of human plasma; may potentially contain following: Acute exposure to blood containing hepatitis B
infectious agents which could transmit disease. surface antigen (HBsAg); perinatal exposure of infants
born to HBsAg-positive mothers; sexual exposure to
Adverse Drug Reactions: HBsAg-positive persons; household exposure to persons
Chest tightness, edema, flushing of the face, hypertension, with acute HBV infection. Prevention of hepatitis B virus
hypotension, palpitation, tachycardia, anxiety, aseptic recurrence after liver transplantation in HBsAg-positive
meningitis syndrome, chills, dizziness, drowsiness, transplant patients.
fatigue, fever, headache, irritability, lethargy,
lightheadedness, malaise, migraine, pain, bruising, Contraindications: Hypersensitivity to hepatitis B immune
petechiae, pruritus, purpura, rash, urticaria, abdominal globulin or any component of the formulation; severe
cramps, abdominal pain, diarrhea, discomfort, allergy to gamma globulin or anti-immunoglobulin
J

dyspepsia, nausea, sore throat, vomiting, anemia, therapies.

autoimmune hemolytic anemia, hemolysis (mild),
hemorrhage, thrombocytopenia, bilirubin increased, pain Dose:
or irritation at the infusion site, autoimmune pure red cell Post-exposure prophylaxis, by IM injection, ADULT and
aplasia. CHILD ≥12 months, 0.06mL/kg as soon as possible after
exposure (i.e. within 24 hours of needlestick, ocular, or
Drug Interactions: mucosal exposure or within 14 days of sexual exposure);
Avoid concomitant use with: usual dose: 3-5mL; repeat at 28-30 days after exposure
Reduces therapeutic effects of the following drugs: in non-responders to hepatitis B vaccine or in patients
Live vaccines (except: influenza virus vaccine who refuse vaccination.
(live/attenuated); rotavirus vaccine; yellow fever vaccine; Prevention of hepatitis B virus recurrence after liver
zoster vaccine transplantation, by IV infusion, ADULT, 20,000 int.
units/dose according to the following schedule:
Administration: Anhepatic phase (Initial dose): One dose given with the
IV infusion over 2-24 hours; for initial treatment, a lower liver transplant;
concentration and/or a slower rate of infusion should be Week 1 post-op: One dose daily for 7 days (days 1-7);
used. Administer in separate infusion line from other Week 2 post-op: One dose every 2 weeks starting day 14;
medications; if using primary line, flush with saline prior Month 4 onwards: One dose monthly starting on month
administration. Refrigerated product should be warmed 4.
to room temperature prior to infusion. Some products
require filtration; refer to individual product labeling. Dose Adjustment:
Antecubital veins should be used, especially with Prevention of hepatitis B virus recurrence after liver
concentrations ≥10% to prevent injection site transplantation: Adjust dose to reach anti-HBs levels of
discomfort. Decrease dose, rate and/or concentration of 500 IU/L within the first week after transplantation. In
infusion in patients who may be at risk of renal failure. patients with surgical bleeding, abdominal fluid drainage
Decreasing the rate or stopping the infusion may help >500mL or those undergoing plasmapheresis,
relieve some adverse effects (flushing, changes in pulse administer 10,000 IU/dose every 6 hours until target
rate, changes in blood pressure). Epinephrine should be anti-HBs levels are reached.
available during administration.
Precautions:
Pregnancy Category: C Hypersensitivity and anaphylactic reactions can occur;
immediate treatment (including epinephrine 1:1000)
ATC Code: J06BA02 should be available;
Use with caution in patients with previous systemic
hypersensitivity to human immunoglobulins;
Use with caution in patients with thrombocytopenia or
coagulation disorders, IM injections may be
contraindicated;
Use with caution in patients with IgA deficiency;
Product of human plasma; may potentially contain
infectious agents which could transmit disease.

Adverse Drug Reactions:

Tremor and hypotension

Drug Interactions:

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ANTI-INFECTIVES FOR SYSTEMIC USE

Avoid concomitant use with: Live vaccines (except: influenza virus vaccine
Reduces therapeutic effects of the following drugs: (live/attenuated); rotavirus vaccine; yellow fever vaccine;
Live vaccines (except: influenza virus vaccine zoster vaccine
(live/attenuated); rotavirus vaccine; yellow fever vaccine;
zoster vaccine Administration:
Do not administer IV.
Administration: Post-exposure would infiltration: If anatomically feasible,
For IM: Post-exposure: Only in anterolateral aspect of upper the full rabies immune globulin dose should be infiltrated
thigh and deltoid muscle of upper arm to prevent injury around the wound; remaining volume should be
from injection, care should be taken when giving to administered IM in the deltoid muscle of the upper arm
patients with thrombocytopenia or bleeding disorders. or lateral thigh muscle. The gluteal area should be
For IV: Administer at 2mL/minute. Decrease infusion to ≤1 avoided to reduce the risk of sciatic nerve damage. Do
mL/minute for patient discomfort or infusion-related not administer rabies vaccine in the same syringe or at
adverse events. Actual volume of infusion is dependent the same administration site as rabies immunoglobulin.
upon potency labeled on each individual vial. If rabies vaccine was initiated without RIG, RIG may be
administered through the seventh day after the
Pregnancy Category: C administration of the first dose of the vaccine.
Administration of RIG is not recommended after the
ATC Code: J06BB04 seventh day post vaccine since an antibody response to
the vaccine is expected during this time period.

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RABIES IMMUNOGLOBULIN Pregnancy Category: C
Rx
(HUMAN)
ATC Code: J06BB05
Inj.: 150 IU/mL, 2 mL and 5 mL vial (IM)
150 IU/mL, 2 mL, 5 mL, and 10 mL ampule (IM)
TETANUS IMMUNOGLOBULIN
Rx
Indications: Part of post-exposure prophylaxis of persons (HUMAN)
with rabies exposure who lack a history of pre-exposure
or post-exposure prophylaxis with rabies vaccine or a Inj.: 1,000 IU/mL, 1.5 mL vial (IM)
recently documented neutralizing antibody response to 1,500 IU/mL, 1 mL ampule (IM)
previous rabies vaccination. 250 IU/mL, 1 mL, 2 mL, and 4 mL ampule (IM)
250 IU/mL, 1 mL pre-filled syringe (IM)
Dose: 250 units/mL, 1 mL and 2 mL vial (IM)
Post-exposure prophylaxis, by IM injection, ADULT and
CHILD, local would infiltration: 20 units/kg in a single Indications: Prophylaxis against tetanus following injury in
dose, RIG should always be administered as part of patients where immunization is not known or certain.
rabies vaccine regimen. If anatomically feasible, the full Passive immunization for TIG is recommended for the
rabies immune globulin dose should be infiltrated following:
around and into the wound/s; remaining volume should
be administered IM at a site distant from the vaccine Persons with a wound that is not clean or minor and in
administration site. whom contraindications to a tetanus-toxoid containing
vaccine exist and they have not completed a primary
Precautions: series of tetanus toxoid immunization;
Hypersensitivity and anaphylactic reactions can occur; Persons who are wounded in bombings or similar mass
immediate treatment (including epinephrine 1:1000) casualty events who have penetrating injuries or
should be available; nonintact skin exposure and who cannot confirm receipt
Use with caution in patients with isolated IgA deficiency or a of a tetanus booster within the previous 5 years. In case
history of systemic hypersensitivity to human of shortage, use should be reserved for persons ≥60
immunoglobulins; years of age.
Use with caution in patients with thrombocytopenia or
coagulation disorders, IM injections may be Dose:
contraindicated; Prophylaxis of tetanus, by IM injection, CHILD <7 years, 4
Product of human plasma; may potentially contain units/kg; some recommend 250 units to small children;
infectious agents which could transmit disease. CHILD ≥7 years and ADULT, 250 units.
Treatment of tetanus, by IM injection, CHILD and ADULT,
Adverse Drug Reactions: 500-6000 units; infiltration of part of the dose around
Fever, headache, malaise, angioedema, rash, urticaria, the wound is recommended.
soreness at injection site, tenderness, stiffness,
nephrotic syndrome, anaphylaxis.

Drug Interactions:
Avoid concomitant use with:
Reduces therapeutic effects of the following drugs:

285
 ANTI-INFECTIVES FOR SYSTEMIC USE

Tetanus Prophylaxis in Wound Management mothers do not have evidence of immunity to varicella;
Number of Clean, minor All other hospitalized premature infants born at <28 weeks of
Prior wounds wounds gestation or who weigh 1,000 g at birth, regardless of
Tetanus their mothers' evidence of immunity to varicella. In
Toxoid Td TIG Td TIG pregnant women, for the prevention or reduction in
Doses severity of maternal infection within 4 days of exposure
Unknown or to the varicella zoster virus.
Yes No Yes Yes
<3
≥3 No No No No Contraindications: Severe reaction associated with past
human immune globulin administration; IgA deficiency.
Precautions:
Hypersensitivity and anaphylactic reactions can occur; Dose:
immediate treatment (including epinephrine 1:1000) Prevention or reduction of maternal infection, by IM/IV
should be available; injection, ADULT, 125 int. units/10kg Administer within
Use with caution in patients with isolated IgA deficiency or a 96 hours of exposure.
history of systemic hypersensitivity to human
immunoglobulins; Dose Adjustment:
Use with caution in patients with thrombocytopenia or No dosage adjustments necessary.
coagulation disorders, IM injections may be
contraindicated; Precautions:
J

Product of human plasma; may potentially contain Hypersensitivity and anaphylactic reactions can occur;
infectious agents which could transmit disease. immediate treatment (including epinephrine 1:1000)
should be available;
Adverse Drug Reactions: Use with caution in patients with isolated IgA deficiency or a
Temperature increased, angioneurotic edema, pain at history of systemic hypersensitivity to human
injection site, soreness, tenderness, nephritic syndrome, immunoglobulins;
anaphylactic shock Use with caution in patients with thrombocytopenia or
coagulation disorders, IM injections may be
Drug Interactions: contraindicated;
Avoid concomitant use with: Product of human plasma, may potentially contain
Reduces therapeutic effects of the following drugs: infectious agents which could transmit disease.
Live vaccines (except: influenza virus vaccine
(live/attenuated); rotavirus vaccine; yellow fever vaccine; Adverse Drug Reactions:
zoster vaccine Common: Headache, injection site pain.
Less Common: Dizziness, fever, pain, chills, fatigue,
Administration: flushing, insomnia, rash, dermatitis, erythematous rash,
Do not administer IV. nausea, dysgeusia, injection site bruising, itching,
Administer in the anterolateral aspects of the upper thigh or tenderness, neck pain, myalgia.
the deltoid muscle of the upper arm. Avoid gluteal region
due to risk of injury to sciatic nerve; if gluteal region is Drug Interactions:
used, administer only in the upper outer quadrant. If Avoid concomitant use with:
tetanus vaccine and TIG are administered Reduces therapeutic effects of the following drugs:
simultaneously, separate sites should be used for each Live vaccines (except: influenza virus vaccine
injection. When used for the treatment of tetanus, (live/attenuated); rotavirus vaccine; yellow fever vaccine;
infiltration of part of the dose around the wound is zoster vaccine
recommended.
Administration: Bring to room temperature prior to use.
Pregnancy Category: C Should be given as soon as possible following exposure;
efficacy has not been established for use >96 hours
ATC Code: J06BB02 following exposure.
For IM injection, administer into deltoid muscle or
anterolateral aspect of upper thing; avoid gluteal region.
For IV administration, inject over 3-5 minutes.
VARICELLA ZOSTER
Rx
IMMUNOGLOBULIN (VZIG) Pregnancy Category: A
Inj.: 125 units/1.25 mL vial (IM) ATC Code: J06BB03
An immune globulin specific for varicella zoster virus.

Indications: Post exposure prophylaxis in the following :

immunocompromised patients without evidence of
immunity; newborn infants whose mothers have signs
and symptoms of varicella around the time of delivery
(i.e., 5 days before to 2 days after).; hospitalized
premature infants born at ≥28 weeks of gestation whose

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ANTI-INFECTIVES FOR SYSTEMIC USE

Avoid concomitant use with:

VACCINES Reduces therapeutic effect of the following drugs:
Anti-infectives
Immunosuppressive Agents e.g. Corticosteroids
BACTERIAL VACCINES Antineoplastic (decreases antibody response)

TEST INTERACTION. May suppress response to tuberculin

Rx BCG VACCINE test if given within 4–6 weeks of vaccination.

Inj.: Freeze-dried power, 100 micrograms/0.1 mL, 1 mL, Administration: Give by ID injection. Stretch skin between
1.5 mL and 2 mL vial (ID) thumb and finger above the insertion of the deltoid
500 microgram/mL vial + 1 mL diluent in ampule (ID), muscle onto the humerus.
20 doses
Store at 2-8°C. Freezing is the most common cause of
A vaccine prepared from bacillus Calmette-Guerin, an vaccine damage. Do NOT use a defrosted vaccine unless
attenuated strain of Mycobacterium bovis, which freezing is the recommended storage condition.
reduces the incidence of meningeal and military TB in
early childhood. Pregnancy Category: C

Indication: Active immunization against tuberculosis ATC Code: J07AN01

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Contraindications: Known hypersensitivity to the vaccine or
any of its components; previous TB infection, or
tuberculin reactions >5 mm; HIV infection; significant Rx DIPHTHERIA-TETANUS TOXOIDS (DT)
fever (give at least 1 month after fever subsides);
patients receiving immunosuppressive therapy; primary Inj.: 30 IU diphtheria toxoid + 40 IU tetanus toxoid per 0.5
and secondary immune deficiency states; generalized mL ampule (IM)
septic skin conditions; burns; pregnancy.
A combination vaccine that promotes active immunity to
Dose: diphtheria and tetanus by inducing production of specific
Immunization against tuberculosis, by ID injection, ADULT antibodies.
and CHILD >12 months 0.1 mL; INFANT up to 12 months,
0.05 mL. Indication: For primary and booster immunization against
diphtheria and tetanus in infants and children 6 weeks
NOTE: Tuberculin test must be done before vaccination up to 7 years of age.
(except in infants <6 months); give vaccine if induration
is <5 mm 48-72 hours after dose of 10 tuberculin units. NOTE: For less than 10 years old

Vaccine is preferably given at birth, or any time after Contraindication: Hypersensitivity to diphtheria, tetanus
birth; may be given at the same time as other live toxoid, or any component of the formulation
vaccines, if not given simultaneously, should be given 4
weeks apart; when given to infants, no need to delay Dose:
primary immunizations. Primary immunization, by IM injection, CHILD 6 weeks to ≤6
years, 0.5-mL administered as follows:
Precautions: First 3 doses at 2, 4, and 6 months of age; may be given
Eczema and scabies; as early as 6 weeks of age and repeated every 4–8
Patients at high risk for HIV infection. weeks;
Pregnancy (first trimester: theoretical risk of congenital Fourth dose at ~15 to 18 months of age, but at least 6
malformations; but the need for vaccination may, months after third dose; may be given as early as 12
sometimes, outweigh the possible risk to fetus). months of age, but at least 6 months after third dose and
the fourth dose;
Adverse Drug Reactions: Fifth dose at 4–6 years of age, prior to starting school or
Common: Enlargement of regional lymph nodes, ulcer at kindergarten; if the fourth dose is given at ≥4 years of
injection site (2–6 weeks after vaccination) age, fifth dose may be omitted [NOTE: For use when
Less Common: Fainting, fever, injection site reactions (pain, pertussis-containing vaccine is contraindicated].
redness, itching, small hard lump that may persist for Booster immunization, by IM injection, CHILD, refer to
some weeks) Diphtheria and Tetanus Toxoids and Acellular Pertussis
Rare: Abscess, allergic reactions including anaphylaxis, Vaccine monograph for additional information.
disseminated infection, keloid formation, lymphadenitis,
osteitis Precautions:
Anaphylactoid or hypersensitivity reactions;
Drug Interactions: Arthus-type hypersensitivity; syncope (has been reported
Monitor closely with: with use);
Reduces therapeutic effect of the following drugs: Acute illness;
Other vaccines and immunoglobulins [administer at Bleeding disorders, including thrombocytopenia;
least 4 weeks apart] Guillain-Barré syndrome;

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 ANTI-INFECTIVES FOR SYSTEMIC USE

Altered immunocompetence (may have a reduced response same bleeding risks and treated as those with clotting
to vaccination); factor disorders.
Children (pediatric dosage form (DT) should only be used in
patients 6 weeks to ≤6 years of age; Pregnancy Category: C
Administer Td for children ≥7 years of age; apnea has
occurred following administration in premature infants). ATC Code: J07AM51
Pregnancy (reproduction studies have not been conducted);
Lactation (not known if excreted into breast milk;
inactivated vaccines do not affect the safety of
breast­feeding for the mother or the infant). Rx DIPHTHERIA-TETANUS TOXOID (Td)

Adverse Drug Reactions: Inj.: ≥ 2 IU diphtheria toxoid + ≥ 40 IU tetanus toxoid per

Common: Headache, tiredness, chills, fever, rash, lymph 0.5 mL ampule (IM) (For 7 yrs. old and above)
node swelling, nausea, vomiting, diarrhea, injection site ≥ 2 IU diphtheria toxoid + ≥ 40 IU tetanus toxoid per
reactions (pain, erythema, swelling), body ache, muscle 0.5 mL (IM), multidose vial (10 doses per vial)
weakness, sore or swollen joints
Less Common: Allergic reactions, anaphylactic reactions, A combination vaccine that promotes active immunity to
arthralgia, dizziness, fatigue, injection site reactions diphtheria and tetanus by inducing production of specific
(cellulitis, induration, nodules, warmth), antibodies.
lymphadenopathy, musculoskeletal stiffness, myalgia,
J

pain, pain in extremities, paresthesia, peripheral edema, Indication: Tetanus and diphtheria toxoids adsorbed for
seizure, syncope, weakness adult use

Drug Interactions: NOTE: For 10 years old and above.

Avoid concomitant use with:
Reduces therapeutic effect of Diphtheria-Tetanus Toxoids: Contraindications: Hypersensitivity to diphtheria, tetanus
Belimumab toxoid, or any component of the formulation
Fingolimod [administer at least 2 weeks apart; if
vaccinated during fingolimod therapy, revaccinate 2–3 Dose:
months after fingolimod discontinuation] Primary immunization, by IM injection, ADULT (NOT
Immunosuppressants [Cytarabine, Liposomal] previously immunized), 2 primary doses of 0.5 mL each,
[administer at least 2 weeks apart; if vaccinated during given at an interval of 8 weeks, then a third (reinforcing)
immunosuppressant therapy, revaccinate at least 3 dose of 0.5 mL 6–8 months later.
months after immunosuppressant discontinuation] Booster immunization, by IM injection, ADULT (with
Meningococcal Polysaccharide (Groups A / C / Y and complete primary immunization series), 0.5 mL every 10
W­135) Tetanus Toxoid Conjugate Vaccine [administer years; CHILD 11–12 years, 0.5 mL as a single dose when
the meningococcal polysaccharide (groups A / C / Y and at least 5 years have elapsed since last dose of toxoid-
W135) tetanus toxoid conjugate vaccine either together containing vaccine; subsequent routine doses are not
with or at least one month before a tetanus toxoids- recommended more often than every 10 years [NOTE: If
containing vaccine] Tdap is given as part of catch­up dosing at 7–10 years of
age, the 11–12 year booster is not needed; regular Td
Administration: For IM administration only. Administer into booster immunizations should begin 10 years after the
the anterolateral aspect of the thigh or the deltoid last dose of the primary series].
muscle. Do NOT inject in the gluteal area. Do NOT inject Tetanus prophylaxis in wound management should be
by IV or SC. based on if the status of the wound (clean or
contaminated) and the immunization status of the
Shake suspension well before use. Do NOT mix with patient. Wound management includes proper use of
other vaccines or injections. Use different needles and tetanus toxoid and/or tetanus immune globulin (TIG),
syringes for each injection. wound cleaning, and (if required) surgical debridement
and the proper use of antibiotics.
Administer while patient is seated or lying down to
prevent syncope related injuries. History of Clean, Minor
All Other Wounds
Tetanus Wounds
NOTE: For patients at risk of hemorrhage following IM Immuniza Tetanu
injection, administer by IM only if, in the opinion of the Tetanus
tion TIG s TIG
physician familiar with the patient's bleeding risk, the Doses Toxoid
Toxoid
vaccine can be administered by this route with
Uncertain
reasonable safety. Use a fine needle (23 gauge or
or <3 Yes No Yes Yes
smaller) and apply firm pressure to the site (without
doses
rubbing) for at least 2 minutes.
No
If the patient receives anti-hemophilia or other similar Yes if No
therapy, intramuscular vaccination can be scheduled 3 or more ≥10 Yes if
No No
shortly after such therapy is administered. Patients on doses years ≥5
anticoagulant therapy should be considered to have the since years
last dose

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ANTI-INFECTIVES FOR SYSTEMIC USE

Administration: For IM administration only into the deltoid Anaphylactoid or hypersensitivity reactions (immediate
muscle. Do NOT administer by IV or SC administration. treatment, including epinephrine 1:1000 should be
Shake suspension well before use. Do NOT mix with available during vaccine use);
other vaccines or injections. Use different needles and Arthus-type hypersensitivity; syncope (has been reported
syringes for each injection. with use);
Acute illness;
Administer while patient is seated or lying down to Bleeding disorders, including Guillain-Barré syndrome;
prevent syncope related injuries. Neurologic disorders;
Thrombocytopenia;
NOTE: For patients at risk of hemorrhage following IM Immunodeficiency.
injection, administer by IM only if, in the opinion of the Elderly (frequency of adverse effects increases with age and
physician familiar with the patient's bleeding risk, the number of injections);
vaccine can be administered by this route with Children with proven, or suspected, underlying active or
reasonable safety. Use a fine needle (23 gauge or progressive neurologic disorders;
smaller) and apply firm pressure to the site (without Pregnancy (adult vaccine may be used if necessary).
rubbing) for at least 2 minutes.
Adverse Drug Reactions:
If the patient receives anti-hemophilia or other similar Common: Crying, drowsiness, irritability, limb swelling,
therapy, intramuscular vaccination can be scheduled restlessness
shortly after such therapy is administered. Patients on Less Common: Fever, lethargy, malaise, myalgia, transient

J
anticoagulant therapy should be considered to have the injection site reactions (pain, redness, itching, burning,
same bleeding risks and treated as those with clotting small hard lump that persists for some weeks)
factor disorders. Rare: Allergic reactions including anaphylaxis, collapse,
encephalopathy, headache, hypotonic-hyporesponsive
See Diphtheria-Tetanus Toxoids (DT) under Vaccines – episodes, seizure, urticaria, peripheral neuropathy,
Bacterial Vaccines in Chapter 7: Antiinfectives for
Systemic Use for other information. Drug Interactions:
Monitor closely with:
Pregnancy Category: C Reduces therapeutic effect of the following drugs:
Other vaccines and immunoglobulins [administer at
ATC Code: J07AM51 least 4 weeks apart]

Avoid concomitant use with:

DIPHTHERIA-TETANUS Reduces therapeutic effect of the following drugs:
Rx TOXOIDS AND PERTUSSIS Anti-infectives (may interfere with the development of a
protective immune response)
VACCINE (DTP) Immunosuppressive Agents e.g. Corticosteroids
Antineoplastic (decreases antibody response)
Inj.: 0.5 mL ampule (IM)
0.5 mL pre-filled syringe (IM) Administration: For IM administration only into the
0.5 mL, 5 mL, 7.5 mL, and 10 mL vial (IM) anterolateral aspect of the thigh or the deltoid muscle.
Do NOT administer by IV or SC.
A three-component preparation of diphtheria, tetanus and
pertussis (whole-cell) vaccines whose rates of local and Shake suspension well before use. Store at 2–8°C.
systemic reactions are higher than acellular pertussis Freezing is the most common cause of vaccine damage.
vaccine. Do NOT use a defrosted vaccine unless freezing is the
recommended storage condition.
Indications: Active immunization against diphtheria,
tetanus, and pertussis Administer vaccines while patient is seated or lying down
to prevent syncope related injuries.
Contraindications: Hypersensitivity to the any component of
the formulation; severe acute neurological illness within NOT recommended for adolescents and adults.
7 days of pertussis vaccination; thrombocytopenia or any
coagulation disorders NOTE: For patients at risk of hemorrhage following IM
injection, administer by IM only if, in the opinion of the
Dose: physician familiar with the patient's bleeding risk, the
Primary immunization, by IM injection, ADULT, 0.5 mL; vaccine can be administered by this route with
CHILD 1–6 years of age, two 0.5 mL doses separated by reasonable safety.
an interval of 2 months, administer a third dose after 6–
12 months; INFANT ≥6 weeks, three 0.5 mL doses with If the patient receives anti-hemophilia or other similar
an interval of at least 4 weeks between each dose. therapy, IM vaccination can be scheduled shortly after
such therapy is administered. Patients on anticoagulant
Precautions: therapy should be considered to have the same bleeding
Whole cell pertussis component is associated with more risks and treated as those with clotting factor disorders.
frequent minor adverse effects than acellular pertussis
component.

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 ANTI-INFECTIVES FOR SYSTEMIC USE

Administer to travelers regardless of the limitations if For Wound Management, see Diphtheria-Tetanus Toxoid
time is short. (Td) under Vaccines – Bacterial Vaccines in Chapter 7:
Anti-infectives for Systemic Use for other information.
Pregnancy Category: B / C (product specific)
Adverse Drug Reactions:
ATC Code: J07AJ51 Common: Apathy, drowsiness, irritability, lethargy,
headache, fatigue, chills, skin rash, increased arm
circumference, GI disease, adenopathy, injection site
DIPHTHERIA-TETANUS reactions (erythema, pain, edema, tenderness, swelling),
Rx TOXOIDS AND ACELLULAR crying (prolonged or persistent), fever, fussiness,
myalgia, arthralgia
PERTUSSIS VACCINE (DTaP) Less Common: Anaphylaxis, angioedema, apnea, back pain,
brain disease, bronchitis, cellulitis, cough, cyanosis,
Inj.: 0.5 mL pre-filled syringe (IM) diabetes mellitus, diarrhea, encephalitis, erythema,
0.5 mL vial (IM) facial paralysis, fatigue, Guillain-Barré syndrome,
hypersensitivity reaction, headache, hypoesthesia,
A three-component preparation of diphtheria and tetanus hypotonia, hypotonic or hyporesponsive episode, IgA
toxoids, and acellular pertussis vaccine that promotes vasculitis, immune thrombocytopenia, infantile spasm,
active immunity to diphtheria, tetanus, and pertussis by injection site reaction (bruising, induration, mass,
inducing production of specific antibodies. nodule, pruritus, rash, sterile abscess, warmth),
J

intussusception, lymphadenitis, lymphadenopathy,

Indications: Active immunization against diphtheria, myalgia, myocarditis, myositis, nausea, nerve
tetanus, and pertussis compression, otalgia, paresthesia, peripheral edema
(extensive), pruritus, respiratory tract infection,
Contraindications: Hypersensitivity to diphtheria, tetanus screaming, seizure, sudden infant death syndrome,
toxoids, pertussis, or any component of the formulation; syncope, thrombocytopenia, urticaria
progressive neurologic disorder, including infantile
spasms, uncontrolled epilepsy or progressive epilepsy; Administration: For IM administration only into the
encephalopathy occurring within 7 days of anterolateral aspect of the thigh or the deltoid muscle.
administration and not attributable to another cause Do NOT administer by IV or SC.
Dose: Shake suspension well before use. Store at 2–8°C.
NOTE: Whenever possible, use the same product for all Freezing is the most common cause of vaccine damage.
doses. Interruption of recommended schedule does not Do NOT use a defrosted vaccine unless freezing is the
require starting the series over. A delay between doses recommended storage condition.
should not interfere with final immunity.
Administer vaccines while patient is seated or lying down
Primary immunization, by IM injection, CHILD and INFANT 6 to prevent syncope related injuries.
weeks to <7 years, five 0.5 mL doses administered as
follows: NOTE: For patients at risk of hemorrhage following IM
Three doses at 2, 4, and 5 months of age; may be given injection, administer by IM only if, in the opinion of the
as early as 6 weeks of age and repeated every 4–8 physician familiar with the patient's bleeding risk, the
weeks; vaccine can be administered by this route with
Fourth doses at ~15 to 20 months of age but at least 6 reasonable safety.
months after third dose; may be given as early as 12
months of age; If the patient receives antihemophilia or other similar
Fifth doses at 4–6 years of age, prior to starting school therapy, IM vaccination can be scheduled shortly after
or kindergarten; if fourth dose is given at ≥4 years of age, such therapy is administered. Patients on anticoagulant
the fifth dose may be omitted. therapy should be considered to have the same bleeding
Booster immunization, by IM injection, ADULT ≥19 years, risks and treated as those with clotting factor disorders.
0.5 mL as a single dose 5 years after last dose of tetanus
toxoid, diphtheria toxoid, and/or pertussis-containing Administer to travelers regardless of the limitations if
vaccine [NOTE: Administer a single dose to replace a time is short.
single dose of the 10 year Td booster in patients who
have not previously received Tdap or for whom vaccine See Diphtheria-Tetanus Toxoids (DT) under Vaccines –
status is not known]; Bacterial Vaccines in Chapter 7: Antiinfectives for
CHILD ≥10 years and ADOLESCENT ≤18 years, 0.5 mL as Systemic Use for other information.
a single dose 5 years after last dose of tetanus toxoid,
diphtheria toxoid, and/or pertussis-containing vaccine Pregnancy Category: C
[NOTE: Administer as a single booster dose at 11 or 12 ATC Code: J07AJ52
years of age in adolescents who have completed a
childhood DTaP vaccination series, followed by booster
doses of Td every 10 years. Adolescents who have not
received Tdap at age 11 or 12 should receive a single
dose of Tdap in place of a single Td booster dose].

290
ANTI-INFECTIVES FOR SYSTEMIC USE

HEMOPHILUS INFUENZAE Drug Interactions:

Rx TYPE B CONJUGATED Avoid concomitant use with:
Reduces therapeutic effect of Hib Vaccine:
VACCINE (Hib) Belimumab
Fingolimod [administer at least 2 weeks apart; if
Inj.: 10 micrograms/0.5 mL, 1 dose vial + 0.5 mL diluent vaccinated during fingolimod therapy, revaccinate 2–3
with tetanus protein (IM) months after fingolimod discontinuation]
10 micrograms/0.5 mL vial + 0.9% sodium chloride Immunosuppressants [Cytarabine, Liposomal]
with diphtheria CRM 197 protein (IM) [administer at least 2 weeks apart; if vaccinated during
0.5 mL vial with meningococcal protein (IM) immunosuppressant therapy, revaccinate at least 3
months after immunosuppressant discontinuation]
An inactivated bacterial vaccine that stimulates the
production of anticapsular antibodies and provides TEST INTERACTION. May interfere with urine antigen
active immunity to Haemophilus influenzae type b. detection test; antigenuria may occur up to 2 weeks
following immunization.
Indications: Active immunization for the prevention of
invasive disease caused by Haemophilus influenzae type Administration: For IM administration into the anterolateral
b (Hib) thigh or deltoid muscle. Do NOT administer into buttocks
due to potential risk of injury to sciatic nerve. Do NOT
Contraindications: Hypersensitivity to Haemophilus b inject by IV, ID, or SC.

J
polysaccharide or any component of the formulation
Shake well prior to use. Do NOT mix with other vaccines
Dose: or injections. Use different needles and syringes for each
Immunization, by IM injection, ADULT, 0.5 mL [NOTE: For injection.
adult recipients of successful hematopoietic stem cell
transplant, revaccinate with a 3-dose regimen beginning Administer while seated or lying down to prevent syncope
6–12 months after transplant, regardless of vaccination related injuries.
history; administer ≥4 weeks apart].
Pregnancy Category: C
Primary immunization, by IM injection, CHILD, 0.5 mL per
dose; number of doses for completion of Hib series ATC Code: J07AG01; J07AG53
depends on products, including some combination
formulations, see specific product monographs for
specific dosing information.
Booster immunization, by IM injection, CHILD ≥12 months, MENINGOCOCCAL
0.5 mL as a single dose. Rx (Neisseria meningitidis)
POLYSACCHARIDE VACCINE
Precautions:
Anaphylactoid or hypersensitivity reactions (immediate Inj.: 50 micrograms/0.5 mL dose (Group A + C) lyophilized
treatment, including epinephrine 1:1000 should be powder, single dose + 0.5 mL diluent syringe (IM, SC)
available during vaccine use); 50 micrograms/0.5 mL dose (Group A + C) lyophilized
Syncope (has been reported with use); powder, multi-dose (10 doses) + 5 mL diluent vial (IM,
Acute illness; SC)
Bleeding disorders (bleeding or hematoma may occur from 50 micrograms/0.5 mL dose (Serogroup A +
IM administration); Serogroup B + Serogroup W135 + Serogroup Y)
Guillain-Barré syndrome; lyophilized powder, multi-dose (10 doses) + diluent
Immunodeficiency; vial (IM, SC)
Children (apnea has occurred following vaccination in
premature infants); An inactivated bacterial vaccine that induces the formation
Pregnancy (animal reproduction studies have not been of bactericidal antibodies to meningococcal antigens.
conducted). The presence of these antibodies is strongly correlated
with immunity to meningococcal disease caused by
Adverse Drug Reactions: Neisseria meningitidis.
Common: Crying (unusual, high-pitched, prolonged),
drowsiness, fussiness, irritability, lethargy, pain, Indication: Active immunization of patients 2 years and
restlessness, seizure, skin rash, urticaria, anorexia, older to prevent invasive meningococcal disease caused
diarrhea, vomiting, thrombocytopenia, erythema, by Neisseria meningitidis
induration, pain, soreness, swelling, weakness, otitis
media, tracheitis, upper respiratory tract infection, fever Contraindication: Hypersensitivity to any component of the
Less Common: Abscess at injection site (sterile), formulation
anaphylaxis, anaphylactoid reaction, apnea,
angioedema, febrile seizures, Guillain-Barré syndrome, Dose:
hypersensitivity reaction, hypotonic / hyporesponsive Immunization, by SC injection, ADULT, ADOLESCENT, and
episode, lymphadenopathy, malaise, mass, peripheral CHILD ≥2 years, 0.5 mL per dose.
edema, pneumonia, pruritus, swelling of the injected
limb (extensive), syncope, vasodepressor syncope

291
 ANTI-INFECTIVES FOR SYSTEMIC USE

Precautions: Indications: Immunization of infants and children against

Anaphylactoid or hypersensitivity reactions (immediate Streptococcus pneumoniae infection and invasive
treatment, including epinephrine 1:1000 should be diseases caused by serotypes included in the vaccine
available during vaccine use);
Syncope (has been reported with use); Contraindication: Hypersensitivity to any component of the
Acute illness; vaccine
Meningococcal infections (not to be used to treat
meningococcal infections); Dose:
Immunodeficiency; Primary immunization, by IM injection, CHILD ≥12 months
Elderly (no specific data available; recommended only when to <6 years (previously unvaccinated), two 0.5 mL doses,
traveling to highly endemic areas); administered at least 2 months apart;
Pregnancy (animal reproduction studies have not been CHILD 7–11 months (previously unvaccinated), three 0.5
conducted); mL doses, administer first 2 doses at least 1 month
Lactation (not known if excreted in breastmilk). apart, administer the third dose after 1 year of age,
separated from the second dose by at least 2 months;
Adverse Drug Reactions: INFANT 6 weeks to 6 months,
Common: Headache, fatigue, malaise, drowsiness, three-dose primary series, three 0.5 mL doses, followed
irritability, chills, fever, rash, diarrhea, anorexia, by a booster dose (for a total of 4 doses); may administer
vomiting, injection site reactions (pain, redness, first dose as early as 6 weeks of age, but is typically given
induration, swelling), arthralgia at 2 months of age; administer second and third doses
J

Less Common: Dizziness, Guillain-Barré syndrome, at 4 and 6 months of age; administer booster dose at 12
hypersensitivity (angioedema, dyspnea, pruritus, rash, to 15 months of age; allow a minimum interval of 1
urticaria), myalgia, nausea, paresthesia, vasovagal month between each of the first 3 doses, and 6 months
syncope, weakness between third dose and booster dose;
two-dose primary series, two 0.5 mL doses, followed by
Drug Interactions: a booster dose (for a total of 3 doses); may administer
Avoid concomitant use with: first dose as early as 6 weeks of age, but is typically given
Reduces therapeutic effect of Meningococcal Vaccine: at 2 months of age; administer second dose at 4 months
Belimumab of age; administer booster dose at 11–12 months of age;
Fingolimod [administer at least 2 weeks apart; if allow a minimum interval of 2 months between the first
vaccinated during fingolimod therapy, revaccinate 2–3 2 doses, and 6 months between second dose and
months after fingolimod discontinuation] booster dose.
Immunosuppressants [Cytarabine, Liposomal]
[administer at least 2 weeks apart; if vaccinated during Precautions:
immunosuppressant therapy, revaccinate at least 3 Anaphylactoid or hypersensitivity reactions (immediate
months after immunosuppressant discontinuation] treatment, including epinephrine 1:1000 should be
available during vaccine use);
Administration: Administer by SC injection into the deltoid Apnea;
region. Do NOT administer by ID, IM, or IV. Syncope (has been reported with use);
AcUte illness;
Administer while seated or lying down to prevent syncope Bleeding disorders;
related injuries. Pneumococcal infections (not to be used to treat
pneumococcal infections);
Reconstitute using provided diluent. Shake well. Store at Immunodeficiency;
2–8oC. Do NOT freeze. Use single-dose vial immediately Pregnancy (animal reproduction studies have not been
after reconstitution. Use multidose vial within 35 days of conducted).
reconstitution. Do NOT mix with other vaccines or
injections. Use different needles and syringes for each Adverse Drug Reactions:
injection. Common: Irritability, drowsiness, fever, loss of appetite,
injection site reactions (pain, redness, swelling,
Pregnancy Category: C induration)
Less Common: Abnormal crying, allergic reactions (allergic
ATC Code: J07AH02 dermatitis, atopic dermatitis, eczema), apnea
(premature infants), diarrhea, injection site reactions
(hematoma, hemorrhage, nodule), rash, seizure (febrile
PNEUMOCOCCAL and nonfebrile), urticaria, vomiting
Rx
CONJUGATE VACCINE
Drug Interactions:
Avoid concomitant use with:
Inj.: 13 – valent, 0.5 mL single dose vial and 0.5 mL pre-
Reduces therapeutic effect of Pneumococcal Vaccine:
filled syringe, suspension for IM injection
Belimumab
Fingolimod [administer at least 2 weeksapart; if
An inactivated bacterial vaccine that promotes active
vaccinated during fingolimod therapy, revaccinate 2–3
immunization against invasive disease caused by S.
months after fingolimod discontinuation]
pneumoniae.
Immunosuppressants [Cytarabine, Liposomal]
[administer at least 2 weeks apart; if vaccinated during

292
ANTI-INFECTIVES FOR SYSTEMIC USE

immunosuppressant therapy, revaccinate at least 3 Pneumococcal vaccine-naïve, by IM injection, 0.5 mL

months after immunosuppressant discontinuation] PCV13 as a single dose, followed by PPSV23 6 to 12
months later (minimum interval of 8 weeks).
Administration: Administer by IM injection only, preferably
into the anterolateral aspect of the thigh in infants and Received previous pneumococcal polysaccharide
into the deltoid in children. Do NOT inject by IV or ID. vaccine (PPSV23), by IM injection,
Avoid SC route. Received at age <65 years, 0.5 mL PCV13 as a single
dose ≥1 year after the last dose of PPSV23, followed by
Shake well prior to use. PPSV23 at least 6 to 12 months after the PCV13 dose
and at least 5 years after the last dose of PPSV23.
Pregnancy Category: C Received at age ≥65 years, 0.5 mL PCV13 as a single
dose ≥1 year after the last dose of PPSV23; no additional
ATC Code: J07AL02 doses of PPSV23 are needed for routine vaccination.

Precautions:
PNEUMOCOCCAL Anaphylactoid or hypersensitivity reactions (immediate
Rx CONJUGATE VACCINE treatment, including epinephrine 1:1000 should be
available during vaccine use);
(13-VALENT) Fever;
Syncope (has been reported with use);

J
Inj.: 0.5 mL single dose vial and 0.5 mL, pre-filled syringe, Acute illness;
suspension for IM injection Asplenia;
Bleeding disorders;
An inactivated bacterial vaccine that promotes Chronic illness;
immunization against invasive disease caused by S. HIV;
pneumoniae capsular serotypes 1, 3, 4, 5, 6A, 6B, 7F, Pneumococcal infections (not to be used to treat
9V, 14, 18C, 19A, 19F, and 23F, all which are individually pneumococcal infections);
conjugated to CRM197 protein. Sickle cell disease;
Immunodeficiency.
Indication: Immunization against Streptococcus Elderly (antibody responses are lower in older adults >65
pneumoniae infection caused by serotypes included in years);
the vaccine Children (antibody responses are lower in preterm infants
<37 weeks gestational age);
Contraindication: Severe allergic reaction (e.g., anaphylaxis) Lactation (not known if excreted into breastmilk).
to pneumococcal vaccine, any component of the
formulation, or any diphtheria toxoid-containing vaccine Adverse Drug Reactions:
Common: Chills, drowsiness, fatigue, fever, headache,
Dose: insomnia, irritability, rash, hives, decreased appetite,
Immunization, by IM injection, ADULT, 0.5 mL as a single diarrhea, vomiting, limitation of arm motion, injection
dose. site reactions (erythema, pain, swelling, tenderness),
Primary immunization, by IM injection, CHILD and INFANT 6 arthralgia, myalgia
weeks to 15 months, four 0.5 mL doses; administer first Less Common: Abnormal crying, erythema multiforme,
dose at 8 weeks of age, may be given as early as 6 weeks febrile seizures, hypersensitivity reaction
of age; administer 3 remaining doses at 4, 6, and 12–15 (bronchospasm, dyspnea, facial edema), seizure,
months of age; recommended dosing interval is 4–8 urticaria, urticaria­like rash
weeks with minimum interval of 1 month in children <1
year of age; minimum interval between third and fourth Drug Interactions:
doses is 8 weeks. Monitor closely with:
Catch-up immunization (unvaccinated with PCV13), by IM Reduces therapeutic effect of Influenza Virus Vaccine
injection, ADOLESCENT and CHILD 6–17 years, 0.5 mL (Inactivated) [administer at least 1 month apart]
as a single dose; CHILD 24–71 months (healthy), 0.5 mL
as a single dose; CHILD 24–71 months (with underlying Avoid concomitant use with:
medical condition), two 0.5 mL doses separated by 8 Reduces therapeutic effect of PCV13 vaccine:
weeks; CHILD 12–23 months, two 0.5 mL doses Belimumab
separated by at least 8 weeks; INFANT 7–11 months, Fingolimod [administer at least 2 weeks apart; if
three 0.5 mL doses, administer first 2 doses at least 4 vaccinated during fingolimod therapy, revaccinate 2–3
weeks apart, followed by a third dose at 12 months of months after fingolimod discontinuation]
age and at least 8 weeks after the second dose. Immunosuppressants [Cytarabine, Liposomal]
[administer at least 2 weeks apart; if vaccinated during
Dose Adjustment: immunosuppressant therapy, revaccinate at least 3
Geriatric: months after immunosuppressant discontinuation]
All patients ≥65 years should receive both pneumococcal
conjugate vaccine (PCV 13) and pneumococcal Administration: Administer by IM injection into he deltoid
polysaccharide vaccine (PPSV23). muscle for toddlers, young children, and adults or lateral
midthigh in infants. Do NOT inject by IV or SC. Avoid ID
route.

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 ANTI-INFECTIVES FOR SYSTEMIC USE

Shake well prior to use. Do NOT use if a homogenous two-dose primary series, two 0.5 mL doses, followed by
white suspension does not form. Do NOT mix with other a booster dose (for a total of 3 doses); may administer
vaccines or injections. Use different needles and first dose as early as 6 weeks of age, but is typically given
syringes for each injection. at 2 months of age; administer second dose at 4 months
of age; administer booster dose at 11–12 months of age;
Administer while seated or lying down to prevent syncope allow a minimum interval of 2 months between the first
related injuries. 2 doses, and 6 months between second dose and
booster dose.
NOTE: Concurrent administration of PCV13 and PPV23 has
not been studied and is not recommended. Administration: Administer by IM injection only, preferably
For patients at risk of hemorrhage following IM injection, into the anterolateral aspect of the thigh in infants and
administer by IM only if, in the opinion of the physician into the deltoid in children. Do NOT inject by IV or ID.
familiar with the patient's bleeding risk, the vaccine can Avoid SC route.
be administered by this route with reasonable safety.
Use a fine needle (23 gauge or smaller) and apply firm Shake well prior to use.
pressure to the site (without rubbing) for at least 2
minutes. See Pneumococcal Conjugated Vaccine under Vaccines –
Bacterial Vaccines in Chapter 7: Antiinfectives for
If the patient receives anti-hemophilia or other similar Systemic Use for other information.
therapy, IM vaccination can be scheduled shortly after
J

such therapy is administered. Patients on anticoagulant Pregnancy Category: C

therapy should be considered to have the same bleeding
risks and treated as those with clotting factor disorders. ATC Code: J07AL01

Pregnancy Category: B
POLYSACCHARIDE POLYVALENT
ATC Code: J07AL02 Rx PNEUMOCOCCAL VACCINE
SOLUTION
PNEUMOCOCCAL Inj.: 25 micrograms/0.5 mL solution, 2.5 mL multi-dose
Rx
POLYVALENT VACCINE vial (IM, SC)

Inj.: 25 micrograms/0.5 mL (polysaccharide from each An inactivated bacterial vaccine that promotes active
capsular type) solution for injection, 0.5 mL pre-filled immunization against invasive disease caused by S.
syringe (IM, SC) pneumoniae.
25 micrograms/0.5 mL solution for injection, 2.5 mL
vial (IM, SC) (multidose) Indication: Active immunization for the prevention of
pneumococcal disease
An inactivated bacterial vaccine that promotes active
immunization against invasive disease caused by S. Contraindication: Hypersensitivity to any component of the
pneumoniae. vaccine

Indications: Immunization of infants and children against Dose:

Streptococcus pneumoniae infection and invasive Immunization, by IM or SC injection, ADULT, 0.5 mL.
diseases caused by serotypes included in the vaccine
Precautions:
Contraindication: Hypersensitivity to any component of the Acute illness;
vaccine Severely compromised cardiovascular or pulmonary
function;
Dose: Chronic cerebrospinal fluid leakage (may not be effective
Primary immunization, by IM injection, CHILD ≥12 months due to congenital lesions, skull fractures, or
to <6 years (previously unvaccinated), two 0.5 mL doses, neurosurgical procedures);
administered at least 2 months apart; Immunodeficiency.
CHILD 7–11 months (previously unvaccinated), three 0.5 Children (not approved for use in children <2 years).
mL doses, administer first 2 doses at least 1 month Pregnancy (animal reproduction studies have not been
apart, administer the third dose after 1 year of age, conducted);
separated from the second dose by at least 2 months; Lactation (not known if excreted into breastmilk).
INFANT 6 weeks to 6 months,
three-dose primary series, three 0.5 mL doses, followed Adverse Drug Reactions:
by a booster dose (for a total of 4 doses); may administer Common: Injection site reactions (erythema, pain, soreness,
first dose as early as 6 weeks of age, but is typically given tenderness, swelling, induration), headache, asthenia or
at 2 months of age; administer second and third doses fatigue, myalgia, chills, fever, dyspepsia, nausea, neck
at 4 and 6 months of age; administer booster dose at 12 pain, upper respiratory infection
to 15 months of age; allow a minimum interval of 1 Less Common: Pruritus, diarrhea, back pain, pharyngitis,
month between each of the first 3 doses, and 6 months cellulitis, malaise, decreased limb mobility, peripheral
between third dose and booster dose;

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ANTI-INFECTIVES FOR SYSTEMIC USE

edema, rash, vomiting, lymphadenitis,

lymphadenopathy, hemolytic anemia, thrombocytopenia, NOTE: For patients at risk of hemorrhage following IM
leukocytosis, serum sickness, anaphylactoid reactions, injection, administer by IM only if, in the opinion of the
angioneurotic edema, arthralgia, arthritis, paresthesia, physician familiar with the patient's bleeding risk, the
radiculoneuropathy, Guillain-Barré syndrome, febrile vaccine can be administered by this route with
convulsion, urticaria, erythema multiforme, increased reasonable safety. Use a fine needle (23 gauge or
serum C-reactive protein smaller) and apply firm pressure to the site (without
Rare: Ecchymosis rubbing) for at least 2 minutes.

Drug Interactions: If the patient receives anti-hemophilia or other similar

Avoid concomitant use with: therapy, intramuscular vaccination can be scheduled
Reduces therapeutic effect of Pneumococcal Vaccine: shortly after such therapy is administered. Patients on
Other Vaccines [administer at least 4 weeks apart] anticoagulant therapy should be considered to have the
same bleeding risks and treated as those with clotting
Administration: Administer by IM or SC injection only into the factor disorders.
deltoid muscle or lateral midthigh. Do NOT inject by IV or
ID. See Diphtheria-Tetanus Toxoids (DT) under Vaccines –
Bacterial Vaccines in Chapter 7: Antiinfectives for
Shake well prior to use. Systemic Use for other information.

J
Pregnancy Category: C Pregnancy Category: C

ATC Code: J07AL01 ATC Code: J07AM01

Rx TETANUS TOXOID Rx TYPHOID VACCINE

Inj.: 0.5 mL ampule (IM) Oral: live attenuated S. typhi (not less than 109) viable
10 mL vial (IM) strain, enteric-coated tablet (encapsulated)
Inj.: 25 micrograms Vi-capsular polysaccharide S. typhi in
A sterile solution of tetanus toxoid in isotonic sodium 0.5 mL pre-filled syringe (IM)
chloride solution, which is used as a booster injection
against tetanus. A bacterial vaccine containing virulent strains of Salmonella
typhi that confer immunity by the provocation of a local
Indications: Active immunization against tetanus when immune response in the intestinal tract induced by oral
combination antigen preparations are not indicated; ingestion of a live strain with subsequent aborted
tetanus prophylaxis in wound management infection.

Contraindication: Hypersensitivity to tetanus toxoid or any Indication: Active immunization against typhoid fever
component of the formulation caused by Salmonella typhi

Dose: Contraindications: Hypersensitivity to any component of the

Primary immunization, by IM injection, ADULT and CHILD ≥7 vaccine; acute febrile illness; congenital or acquired
years, 0.5 mL, administer a second dose 4–8 weeks immunodeficient state
after the first dose and a third dose at 6–12 months after
the second dose; administer a routine booster dose Dose:
every 10 years. Primary immunization, by mouth, ADULT and CHILD ≥6
years, 1 capsule on alternate days for 4 doses,
For Wound Management, see Diphtheria-Tetanus Toxoid completed at least 1 week prior to expected exposure;
(Td) under Vaccines – Bacterial Vaccines in Chapter 7: by IM injection, ADULT and CHILD ≥2 years, 0.5 mL at
Antiinfectives for Systemic Use for other information. least 2 weeks prior to expected exposure.
Reimmunization, by mouth, ADULT and CHILD ≥6 years,
Adverse Drug Reactions: repeat full course of primary immunization every 5 years;
Common: Hypotension, brachial neuritis, fever, pain, by IM injection, ADULT and CHILD ≥2 years, 0.5 mL every
malaise, nausea, injection site reactions (edema, 2 years.
induration, rash, redness, urticaria, warmth), arthralgia,
Guillain-Barré syndrome, Arthrus-type hypersensitivity Precautions:
reaction, anaphylactic reaction Anaphylactoid or hypersensitivity reactions (immediate
treatment, including epinephrine 1: 1,000 should be
Administration: For IM administration only into the available during vaccine use; syncope; acute illness;
anterolateral aspect of the thigh or the deltoid muscle. bleeding disorders, including thrombocytopenia; typhoid
Do NOT inject in the gluteal area. fever.
Pregnancy (animal reproduction studies have not been
Shake suspension well before use. Do NOT administer if conducted);
product does not form a suspension. Lactation (not known if excreted into breastmilk).

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 ANTI-INFECTIVES FOR SYSTEMIC USE

Prednisolone (Systemic); Prednisone; Triamcinolone

Adverse Drug Reactions: (Systemic) [separate administration by at least 3
Common: months]; Leflunomide [separate administration by at
[Inj.]: Malaise, headache, generalized ache, pruritus, least 3 months]
nausea, vomiting, injection site reactions (tenderness, Mercaptopurine [avoid doses >1.5 mg/kg daily]
pain, induration, erythema, swelling), muscle Methotrexate [avoid doses >0.4 mg/kg weekly]
tenderness, myalgia, fever Proguanil [separate administration by at least 10 days]
[Oral]: Headache, skin rash, abdominal pain, nausea,
diarrhea, vomiting Administration: For oral administration, swallow capsules
whole soon after placing into mouth with a cold or
Less Common: lukewarm beverage (≤37˚C/98.6˚F). Do NOT chew or
[Inj.]: Abdominal pain, anaphylaxis, angioedema, open capsule.
arthralgia, asthma, diarrhea, dizziness, flu­like
symptoms, Guillain-Barré syndrome, hypotension, To be taken 1 hour prior to a meal. Avoid alcohol 1 hour
inflammation at injection site (angioedema, urticaria), before or 2 hours after administration to prevent
intestinal perforation (jejunum), hypersensitivity disruption of the enteric coating.
reaction, loss of consciousness, lymphadenopathy,
malaise, neck pain, serum sickness, skin rash, syncope For IM administration, administer as a single 0.5 mL (25
(with and without convulsions), tremor, urticaria, micrograms) injection into the deltoid muscle. Younger
vasodilation, weakness children may also receive the dose in the anterolateral
J

[Oral]: Anaphylaxis, demyelinating disease, myalgia, thigh. Do NOT inject into the gluteal muscle. Do NOT
pain, rheumatoid arthritis, sepsis, urticaria, weakness administer by IV.

Drug Interactions: Administer while patient is seated or lying down to

Avoid concomitant use with: prevent syncope related injuries.
Increases risk of adverse or toxic effects of Typhoid Vaccine:
Azathioprine, Belimumab, Corticosteroids (Systemic), NOTE: For patients at risk of hemorrhage following IM
Dimethyl Fumarate (vaccinal infection), Fingolimod injection, administer by IM only if, in the opinion of the
(vaccinal infection) physician familiar with the patient's bleeding risk, the
Immunosuppressants, Leflunomide, Mercaptopurine, vaccine can be administered by this route with
Methotrexate reasonable safety. Use a fine needle (23 gauge or
smaller) and apply firm pressure to the site (without
Reduces diagnostic effect of Tuberculin Test [separate rubbing) for at least 2 minutes.
administration by at least 4–6 weeks]
If the patient receives anti-hemophilia or other similar
Reduces therapeutic effect of Typhoid Vaccine: therapy, intramuscular vaccination can be scheduled
Antibiotics [except Acetic Acid (Otic); Acetic Acid (Topical); shortly after such therapy is administered. Patients on
Aluminum Acetate; Azithromycin (Ophthalmic); anticoagulant therapy should be considered to have the
Aztreonam (Oral Inhalation); Bacitracin (Ophthalmic); same bleeding risks and treated as those with clotting
Bacitracin; Benzoin; Capreomycin; Ciprofloxacin factor disorders.
(Ophthalmic); Clindamycin (Topical); Dapsone (Topical);
Erythromycin; Fidaxomicin; Framycetin; Fusidic Acid; Pregnancy Category: C
Gatifloxacin; Gentamicin, Ophthalmic and Topical;
Gentian Violet; Hexachlorophene; Mafenide; ATC Code: J07AP01 (oral)
Metronidazole (Topical); Neomycin; Oxychlorosene; J07AP02 (parenteral)
Polymyxin B; Povidone-Iodine; Rifaximin; Silver Nitrate;
Silver Sulfadiazine; Sulfacetamide (Ophthalmic);
Sulfacetamide (Topical); Tobramycin (Ophthalmic) [live
attenuated Ty21a strain only; [postpone vaccination until
at least 3 days after cessation of antibacterial agents]
Azathioprine [avoid doses >3 mg/kg daily]
Corticosteroids, Systemic [avoid doses greater than an
equivalent of 2 mg/kg or 20 mg/day of prednisone for
≥2 weeks]
Dimethyl Fumarate
Fingolimod
Immune Globulins [consult full interaction monograph
for dose interval recommendations]
Immunosuppressants [except Azathioprine;
Beclomethasone (Oral Inhalation); Betamethasone
(Systemic); Budesonide (Systemic); Budesonide,
(Systemic and Oral Inhalation); Corticotropin; Cortisone;
Cytarabine (Liposomal); Deflazacort; Dexamethasone
(Systemic); Fludrocortisone; Fluticasone (Oral
Inhalation); Hydrocortisone (Systemic); Leflunomide;
Mercaptopurine; Methotrexate; Methylprednisolone;

296
ANTI-INFECTIVES FOR SYSTEMIC USE

VIRAL VACCINES conjunctivitis, otitis media, asthma, cough, nasal

congestion, nasopharyngitis, pharyngitis, rhinitis,
rhinorrhea, upper respiratory tract infection, fever,
HEPATITIS A VACCINE excessive crying
Rx
(INACTIVATED) Less Common: Anaphylaxis, angioedema, arthralgia, ataxia
(cerebellar), bronchoconstriction, croup, bronchiolitis,
Inj.: Viral antigen not less than 720 EU in 0.5 mL dehydration, dermatitis, dizziness, dysgeusia, dyspnea,
monodose vial (IM) (junior) encephalitis, erythema multiforme, eye irritation, flu­like
Viral antigen not less than 1440 EU in 1 mL symptoms, hepatitis, hyperhidrosis, otitis, Guillain-Barré
monodose vial (IM) (adult) syndrome, hypersensitivity reaction, hypertonia,
80 units/0.5 mL (GBM strain) pre-filled syringe single hypoesthesia, increased creatine kinase, increased
dose (IM) (pediatric) serum transaminases (transient), injection site reactions
160 units/0.5 mL (GBM strain) pre-filled syringe (hematoma, nodule, rash), insomnia, jaundice,
single dose (IM) (adult) lymphadenopathy, multiple sclerosis, myelitis,
neuropathy, paresthesia, photophobia, pneumonia,
An inactivated viral vaccine that induces active immunity pruritus, respiratory congestion, seizure, serum
against hepatitis A virus infection. sickness-like reaction, syncope, thrombocytopenia,
urticaria, vasculitis, vertigo, viral exanthem, wheezing
Indication: For active immunization of persons 12 months Drug Interactions:
and older against diseases caused by hepatitis A virus Avoid concomitant use with:

J
(HAV) Reduces therapeutic effect of HAV vaccine:
Belimumab
Contraindication: Immediate and/or severe allergic or Fingolimod [administer at least 2 weeks apart; if
hypersensitivity reaction to hepatitis A containing vaccinated during fingolimod therapy, revaccinate 2–3
vaccines or any component of the formulation, including months after fingolimod discontinuation]
neomycin Immunosuppressants [Cytarabine, Liposomal]
[administer at least 2 weeks apart; if vaccinated during
Dose: immunosuppressant therapy, revaccinate at least 3
Primary immunization, by IM injection, ADULT, 1 mL (50 months after immunosuppressant discontinuation]
units) with a booster dose of 1 mL (50 units) to be given
6–18 months after first dose; CHILD ≥12 months, 1 mL Administration: For IM administration into the deltoid
(50 units) at 12–23 months with a booster dose of 1 mL muscle for older children and adults or into the
(50 units) to be given 6–18 months after first dose anterolateral aspect of the thigh in infants and young
children. Do NOT administer to the gluteal region. Do
[NOTE: When used for primary immunization, administer at NOT administer by IV, ID, or SC.
least 2 weeks prior to expected exposure; when used Shake well prior to use. Discard if suspension is
prior to an international adoption, begin series when discolored, does not appear homogenous after shaking,
adoption is planned, ideally ≥2 weeks prior to expected or if there are cracks in the vial or syringe. Do NOT dilute.
arrival of adoptee].
Administer while patient is seated or lying down to
Dose Adjustment: prevent syncope related injuries.
Hepatic Impairment:
May require dose adjustment. Patients with chronic liver NOTE: For patients at risk of hemorrhage following IM
disease have lower antibody response. injection, administer by IM only if, in the opinion of the
physician familiar with the patient's bleeding risk, the
Precautions: vaccine can be administered by this route with
Anaphylactoid or hypersensitivity reactions (immediate reasonable safety. Use a fine needle (23 gauge or
treatment, including epinephrine 1:1000 should be smaller) and apply firm pressure to the site (without
available during vaccine use); rubbing) for at least 2 minutes.
Syncope (has been reported with use);
Acute illness; If the patient receives anti-hemophilia or other similar
Bleeding disorders, including thrombocytopenia; therapy, intramuscular vaccination can be scheduled
Hepatic impairment; shortly after such therapy is administered. Patients on
Immunodeficiency; anticoagulant therapy should be considered to have the
Pregnancy (animal reproduction studies have not been same bleeding risks and treated as those with clotting
conducted); factor disorders.
Lactation (not known if excreted into breastmilk).
Pregnancy Category: C
Adverse Drug Reactions:
Common: Drowsiness, headache, irritability, chills, fatigue, ATC Code: J07BC02
insomnia, malaise, skin rash, menstrual disease,
decreased appetite, abdominal pain, anorexia,
constipation, diarrhea, gastroenteritis, nausea, vomiting,
injection site reactions (erythema, soreness, warmth,
pain, swelling, tenderness, bruising, induration),
weakness, arm pain, back pain, myalgia, stiffness,

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 ANTI-INFECTIVES FOR SYSTEMIC USE

HEPATITIS B VACCINE apnea, arthritis, Bell's palsy, bronchospasm,

Rx constipation, eczema, conjunctivitis, encephalitis,
(RECOMBINANT DNA)
erythema nodosum, erythema multiforme, febrile
seizures, Guillain-Barré syndrome, herpes zoster,
Inj.: 10 micrograms/0.5 mL monodose vial (IM) (pediatric)
hypersensitivity reaction, hypoesthesia, increased
10 micrograms/0.5 mL, 5 mL (10 dose) vial (IM)
erythrocyte sedimentation rate, keratitis, lichen planus,
20 micrograms/mL monodose vial (IM) (adult) (for
limb pain, lupus-like syndrome, meningitis, migraine,
more than 10 years old)
multiple sclerosis, myasthenia, myelitis, neuritis,
20 micrograms/mL, 10 mL VIAL (10 doses/vial) adult
neuropathy, optic neuritis, palpitations, paralysis,
paresis, periarteritis nodosa, peripheral neuropathy,
N.B.: Formulations of diferent manufaturers are of equal or
petechia, purpura, radiculopathy, seizure, serum
similar immunogenicity. Follow strictly the
sickness-like reaction, Stevens-Johnson syndrome,
recommended dose of each manufacturer.
syncope, systemic lupus erythematosus, tachycardia,
thrombocytopenia, tinnitus, transverse myelitis, uveitis,
A noninfectious subunit viral vaccine, which confers active
vasculitis, visual disturbance
immunity via formation of anti-hepatitis B antibodies.
The vaccine is derived from hepatitis B surface antigen
Drug Interactions:
(HBsAg) produced through recombinant DNA techniques
Avoid concomitant use with:
from yeast cells.
Reduces therapeutic effect of HBV vaccine:
Belimumab
J

Indication: Active immunization against infection caused by

Fingolimod [administer at least 2 weeks apart; if
all known subtypes of hepatitis B virus (HBV)
vaccinated during fingolimod therapy, revaccinate 2–3
months after fingolimod discontinuation]
Contraindications: Severe allergic or hypersensitivity
Immunosuppressants [Cytarabine, Liposomal]
reaction to yeast, hepatitis B vaccine, or any component
[administer at least 2 weeks apart; if vaccinated during
of the formulation
immunosuppressant therapy, revaccinate at least 3
months after immunosuppressant discontinuation]
Dose:
Primary immunization, by IM injection, ADULT, three 1 mL
Administration: For IM administration into the deltoid
doses at 0, 1, and 6 months; ADOLESCENT, CHILD, and
muscle for adults or into the anterolateral aspect of the
INFANT, three 0.5 mL doses at 0, 1, and 6 months.
thigh in infants and young children. Do NOT administer
to the gluteal region. Do NOT administer by IV, ID, or SC.
Dose Adjustment:
Renal Impairment:
Shake well prior to withdrawal and use. Do NOT mix with
For adult pre-dialysis and dialysis patients ≥20 years,
other vaccines or injections. Use different needles and
administer 40 micrograms per dose at 0, 1, and 6
syringes for each injection.
months.
Administer while patient is seated or lying down to
prevent syncope related injuries.
Precautions:
Anaphylactoid or hypersensitivity reactions (immediate
NOTE: For patients at risk of hemorrhage following IM
treatment, including epinephrine 1:1000 should be
injection, administer by IM only if, in the opinion of the
available during vaccine use);
physician familiar with the patient's bleeding risk, the
Syncope (has been reported with use);
vaccine can be administered by this route with
Acute illness;
reasonable safety. Use a fine needle (23 gauge or
Bleeding disorders, including thrombocytopenia;
smaller) and apply firm pressure to the site (without
Multiple sclerosis;
rubbing) for at least 2 minutes.
Immunodeficiency;
Severely compromised cardiopulmonary status;
If the patient receives anti-hemophilia or other similar
Pregnancy (animal reproduction studies have not been
therapy, intramuscular vaccination can be scheduled
conducted);
shortly after such therapy is administered. Patients on
Lactation (not known if excreted into breastmilk).
anticoagulant therapy should be considered to have the
same bleeding risks and treated as those with clotting
Adverse Drug Reactions:
factor disorders.
Common: Flushing, hypotension, body pain, chills,
dizziness, drowsiness, fatigue, headache, insomnia,
Pregnancy Category: C
irritability, malaise, paresthesia, tingling sensation,
vertigo, diaphoresis, pruritus, skin rash, urticaria,
ATC Code: J07BC01
abdominal pain, anorexia, decreased appetite, diarrhea,
dyspepsia, nausea, stomach cramps, vomiting, dysuria,
lymphadenopathy, angioedema, influenza, injection site
reactions (bruising, erythema, induration, nodule,
itching, soreness, pain, swelling, tenderness, warmth),
arthralgia, back pain, myalgia, neck pain, neck stiffness,
shoulder pain, weakness, otalgia, cough, pharyngitis,
rhinitis, upper respiratory tract infection, fever
Less Common: Acute exacerbations of multiple sclerosis,
agitation, alopecia, anaphylactoid reaction, anaphylaxis,

298
ANTI-INFECTIVES FOR SYSTEMIC USE

HUMAN PAPILLOMAVIRUS pulmonary embolus, RA, acute renal failure, seizure,

Rx QUADRIVALENT (TYPE 6, 11, 16, 18) sepsis, syncope, transverse myelitis, urticaria, weakness
VACCINE (RECOMBINANT) Drug Interactions:
Avoid concomitant use with:
Inj.: 0.5 mL suspension, glass pre-filled syringe (IM) Reduces therapeutic effect of HPV vaccine:
0.5 mL glass vial Belimumab
Fingolimod [administer at least 2 weeks apart; if
An inactivated viral vaccine containing inactive human vaccinated during fingolimod therapy, revaccinate 2–3
papillomavirus (HPV) proteins HPV 6 L1, HPV 11 L1, HPV months after fingolimod discontinuation]
16 L1, and HPV 18 L1, which produce neutralizing Immunosuppressants [Cytarabine, Liposomal]
antibodies to prevent cervical cancer, cervical [administer at least 2 weeks apart; if vaccinated during
adenocarcinoma, cervical, vaginal and vulvar neoplasia, immunosuppressant therapy, revaccinate at least 3
and genital warts caused by HPV. months after immunosuppressant discontinuation]
Indications: For the prevention of cervical, vulvar, vaginal, Administration: For IM administration into the deltoid
and anal cancer caused by HPV types 16 and 18; muscle or higher anterolateral thigh area.
prevention of genital warts (condyloma acuminatum)
caused by HPV types 6 and 11; prevention of Shake well prior to use. Do NOT mix with other vaccines
precancerous or dysplastic lesions caused by HPV types or injections. Use different needles and syringes for each

J
6, 11, 16, and 18, including cervical intraepithelial injection.
neoplasia (CIN) grade 2/3 and cervical adenocarcinoma
in situ, CIN grade 1, vulvar intraepithelial neoplasia grade Administer while patient is seated or lying down to
2 and 3, vaginal intraepithelial neoplasia grade 2 and 3, prevent syncope related injuries.
and anal intraepithelial neoplasia grades 1, 2, and 3;
NOTE: For patients at risk of hemorrhage following IM
Contraindications: Hypersensitivity, including severe allergic injection, administer by IM only if, in the opinion of the
reactions to yeast (a vaccine component), or a previous physician familiar with the patient's bleeding risk, the
dose of the vaccine vaccine can be administered by this route with
reasonable safety. Use a fine needle (23 gauge or
Dose: smaller) and apply firm pressure to the site (without
Immunization, by IM injection, ADULT ≤26 years, rubbing) for at least 2 minutes.
ADOLESCENT, and CHILD ≥9 years three 0.5 mL doses
at 0, 3, and 7 months. If the patient receives anti-hemophilia or other similar
therapy, intramuscular vaccination can be scheduled
Precautions: shortly after such therapy is administered. Patients on
Anaphylactoid or hypersensitivity reactions (immediate anticoagulant therapy should be considered to have the
treatment, including epinephrine 1:1000 should be same bleeding risks and treated as those with clotting
available during vaccine use); factor disorders.
Syncope (has been reported with use);
Acute illness; Pregnancy Category: B
Bleeding disorders, including thrombocytopenia;
Human papillomavirus (HPV) infection (not for the treatment ATC Code: J07BM01
of the active disease);
Immunodeficiency;
Severely compromised cardiopulmonary status;
Pregnancy (teratogenic effects not observed in animal HUMAN PAPILLOMAVIRUS
reproduction studies); Rx VACCINE (TYPE 16 AND 18)
Lactation (not known if excreted into breastmilk). (RECOMBINANT, AS04 ADJUVANT)
Adverse Drug Reactions: Inj.: 0.5 mL suspension in a pre-filled syringe (type 1 glass)
Common: Headache, fever, dizziness, malaise, insomnia, with a plunger stopper (rubber butyl) with sterile
nausea, diarrhea, vomiting, toothache, injection site needle
reactions (pain, erythema, swelling, bruising, pruritus, 0.5 mL in 3 mL monodose type 1 glass vial
hematoma), arthralgia, myalgia, pharyngolaryngeal pain, 1 mL in 3 mL glass vial
cough, nasal congestion
Less Common: Alopecia areata, acute disseminated An inactivated viral vaccine containing human
encephalomyelitis, appendicitis, anaphylactic or papillomavirus (HPV) proteins HPV 16 L1, and HPV 18
anaphylactoid reaction, arrhythmia, arthritis, asthma, L1, which produce neutralizing antibodies to prevent
autoimmune hemolytic anemia and other autoimmune cervical cancer, cervical adenocarcinoma, and cervical
diseases, bronchospasm, cellulitis, cerebrovascular neoplasia cause by HPV.
accident, chills, DVT, fatigue, gastroenteritis, Guillain-
Barré syndrome, hypersensitivity reaction, ITP, injection Indications: Prevention of oncogenic HPV types 16 and 18,
site joint movement impairment, JIA, lymphadenopathy, including Cervical cancer, cervical intraepithelial
hyper- or hypothyroidism, motor neuron disease, neoplasia (CIN) grade 2 or higher and adenocarcinoma
pancreatitis, paralysis, pelvic inflammatory disease, in situ, and CIN grade 1, in females 9–25 years of age

299
 ANTI-INFECTIVES FOR SYSTEMIC USE

Contraindication: Severe hypersensitivity (e.g. anaphylaxis)

to papillomavirus recombinant vaccine or any Rx INFLUENZA POLYVALENT VACCINE
component of the formulation
Inj.: 0.5 mL vial + pre-filled syringe diluent (IM)
Dose: 0.5 mL suspension in a pre-filled syringe or ampule
Immunization, by IM injection, ADULT ≤25 years, (IM) (adult)
ADOLESCENT, and CHILD ≥9 years (FEMALE), three 0.5 15 micrograms/0.5 mL, 5 mL multidose glass vial
mL doses at 0, 1, and 6 months.

Adverse Drug Reactions: N.B.: Strains as recommended by WHO

Common: Fatigue, urticaria, injection site reactions (pain,
redness, swelling, pruritus), myalgia, arthralgia, A sterile, aqueous suspension of inactivated influenza virus,
nasopharyngitis, pharyngolaryngeal pain, upper which promotes immunity to seasonal influenza virus by
respiratory tract infection, influenza, pharyngitis, inducing specific antibody production.
chlamydia infection, vaginal infection
Less Common: Allergic reactions, anaphylactic or Indication: Active immunization against influenza caused by
anaphylactoid reactions, angioedema, erythema influenza virus
multiforme, syncope, vasovagal response,
lymphadenopathy NOTE: The Advisory Council on Immunization Practices
(ACIP) recommends routine annual vaccination for all
J

Administration: For IM administration into the deltoid persons ≥6 months of age who do not otherwise have
muscle. Do NOT inject by IV, SC, or ID. contraindications to the vaccine.

Shake well prior to use. Do NOT use if discolored, Contraindication: Severe allergic reactions (e.g.,
contains particulate matter, or if syringe is cracked. Do anaphylaxis) to previous doses of influenza vaccine,
NOT mix with other vaccines or injections. Use different chicken or egg protein, hydrocortisone, or any
needles and syringes for each injection. component of the formulation

Administer while patient is seated or lying down to Dose:

prevent syncope related injuries. Immunization, by IM injection, ADULT, ADOLESCENT, and
CHILD ≥9 years, 0.5 mL/dose as a single dose per
NOTE: For patients at risk of hemorrhage following IM season; CHILD 6 months to 8 years, one or two 0.5 mL
injection, administer by IM only if, in the opinion of the doses per season [NOTE: For infants and children 6
physician familiar with the patient's bleeding risk, the months to <9 years, the 2 doses need not have been
vaccine can be administered by this route with received during the same season or consecutive
reasonable safety. Use a fine needle (23 gauge or seasons].
smaller) and apply firm pressure to the site (without
rubbing) for at least 2 minutes. Precautions:
Anaphylactoid or hypersensitivity reactions (immediate
If the patient receives anti-hemophilia or other similar treatment, including epinephrine 1:1000 should be
therapy, intramuscular vaccination can be scheduled available during vaccine use);
shortly after such therapy is administered. Patients on Oculorespiratory syndrome;
anticoagulant therapy should be considered to have the Syncope (has been reported with use);
same bleeding risks and treated as those with clotting Acute illness;
factor disorders. Bleeding disorders, including thrombocytopenia;
Febrile seizures;
See Human Papillomavirus Quadrivalent (Type 6, 11, 16, Guillain-Barré Syndrome;
18) Vaccine (Recombinant) under Vaccines – Viral HIV infection;
Vaccines in Chapter 7: Antiinfectives for Systemic Use for Neurologic disorders;
other information. Immunodeficiency;
Elderly (antibody responses may be lower and decline
Pregnancy Category: B faster);
Pregnancy (has not shown to cause fetal harm when given
ATC Code: J07BM02 to pregnant women).

Adverse Drug Reactions:

Common: Chest tightness, hypertension, chills, drowsiness,
fatigue, headache, irritability, malaise, migraine,
shivering, diaphoresis, ecchymoses, abdominal pain,
anorexia, diarrhea, gastroenteritis, nausea, sore throat,
vomiting, varicella infection, injection site reactions
(bruising, erythema, hematoma, induration,
inflammation, itching, pain, rash, soreness, swelling,
tenderness), arthralgia, back pain, myalgia, bronchitis,
cough, dyspnea, nasal congestion, nasopharyngitis,
oropharyngeal pain, pharyngitis, pharyngolaryngeal pain,

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ANTI-INFECTIVES FOR SYSTEMIC USE

rhinitis, rhinorrhea, upper respiratory tract infection, same bleeding risks and treated as those with clotting
wheezing, fever factor disorders.
Less Common: Abnormal gait, anaphylactic shock,
anaphylaxis, angioedema, arthritis, asthma, Bell's palsy, Pregnancy Category: C
brachial plexopathy, brain disease, bronchospasm,
cellulitis, chest pain, confusion, constriction of the ATC Code: J07BB01 (inactivated)
pharynx, cranial nerve palsy, dizziness, dysphagia, eye J07BB03 (live attenuated)
pain, facial paralysis, febrile seizures, flu-like symptoms,
flushing, Guillain-Barré syndrome, hot flash, Henoch-
Schönlein purpura (immunoglobulin A vasculitis), INFLUENZA POLYVALENT VACCINE
hypoesthesia, pallor, hypersensitivity reaction, Rx
(SPLIT VIRION, INACTIVATED)
hypokinesia, insomnia, laryngitis, limb pain,
lymphadenopathy, maculopapular rash, microscopic
Inj.: 7.5 micrograms/0.25 mL suspension, 0.25 mL single
polyangiitis, myasthenia, myelitis, neuralgia, neuritis,
dose pre-filled syringe
ocular hyperemia, optic neuritis, paralysis, paresthesia,
pharyngeal edema, photophobia, presyncope, pruritus,
A sterile, aqueous suspension of inactivated influenza virus,
optic neuropathy, seizure, serum sickness, skin rash,
which promotes immunity to seasonal influenza virus by
Stevens-Johnson syndrome, swelling of injected limb (>1
inducing specific antibody production.
week), syncope, thrombocytopenia, transverse myelitis,
tremor, urticaria, vasculitis, vasodilatation, vesicobullous
Indication: Active immunization against influenza caused by

J
rash, voice disorder, weakness
influenza virus
Drug Interactions:
NOTE: NOT recommended for use in children <3 years.
Monitor closely with:
Reduces therapeutic effect of Influenza Vaccine:
Contraindications: Severe allergic reactions (e.g.,
Pneumococcal Conjugate Vaccine (13-valent)
anaphylaxis) to previous doses of influenza vaccine,
Venetoclax
chicken or egg protein, hydrocortisone, or any
component of the formulation; active illness with high or
Reduces therapeutic effect of Pneumococcal Conjugate
moderate temperature; acute illness
Vaccine (13-valent)
Dose:
Avoid concomitant use with:
Immunization, by IM or SC injection, ADULT and CHILD 9 to
Reduces therapeutic effect of Influenza Vaccine:
17 years, one 0.5 mL dose; CHILD <9 years, two 0.5 mL
Belimumab
doses administered at least 4 weeks apart.
Fingolimod [administer at least 2 weeks apart; if
vaccinated during fingolimod therapy, revaccinate 2–3
Adverse Drug Reactions:
months after fingolimod discontinuation]
Common: Headache, myalgia, malaise, injection site
Immunosuppressants [Cytarabine, Liposomal]
reactions (pain, swelling, redness, induration), fever,
[administer at least 2 weeks apart; if vaccinated during
shivering
immunosuppressant therapy, revaccinate at least 3
Less Common: Dizziness, diarrhea, nausea, fatigue,
months after immunosuppressant discontinuation]
injection site reactions (bruising, itching, warmth), hot
flush, lymphadenopathy, moaning, restlessness,
Administration: For IM administration into the deltoid
thrombocytopenia (transient), upper abdominal pain,
muscle for adults and older children, or into the
arthralgia
anterolateral aspect of the thigh for infants and young
Rare: Paresthesia, sleepiness, hyperhidrosis, flu-like
children. Children ≥1 year with adequate deltoid muscle
symptoms, asthenia, injection site discomfort
mass may be vaccinated in the deltoid. Do NOT inject
into the gluteal region or areas where there may be a
Administration: For IM or SC administration.
major nerve trunk.
See Influenza Polyvalent Vaccine under Vaccines – Viral
Shake well prior to use. Visually inspect for particulate
Vaccines in Chapter 7: Antiinfectives for Systemic Use for
matter and discoloration prior to administration.
other information.
NOTE: For patients at risk of hemorrhage following IM
Pregnancy Category: C
injection, administer by IM only if, in the opinion of the
physician familiar with the patient's bleeding risk, the
ATC Code: J07BB02
vaccine can be administered by this route with
reasonable safety. Use a fine needle (23 gauge or
smaller) and apply firm pressure to the site (without
rubbing) for at least 2 minutes.

If the patient receives anti-hemophilia or other similar

therapy, intramuscular vaccination can be scheduled
shortly after such therapy is administered. Patients on
anticoagulant therapy should be considered to have the

301
 ANTI-INFECTIVES FOR SYSTEMIC USE

MEASLES VACCINE history of congenital or hereditary immunodeficiency;

Rx pregnancy
(LIVE ATTENUATED)
Dose:
Inj.: Monodose vial + 0.5 mL diluent (SC)
NOTE: The minimum interval between 2 doses is 28 days.
Multi-dose vial + 5 mL diluent (SC)
Immunization, by SC injection, ADULT, one or two 0.5 mL
A live, attenuated, single-antigen vaccine propagated on
doses administered at least 28 days apart; CHILD ≥12
human diploid cells.
months, two 0.5 mL doses, first dose is recommended at
12–15 months of age; second dose is recommended at
Indication: Active immunization against measles
4–6 years of age, prior to entering kindergarten or first
grade; second dose may be administered at any time
Contraindications: Hypersensitivity to any component of the
provided 28 days have elapsed.
formulation; severe immunodeficiency; febrile states;
acute infectious diseases; leukemia; severe anemia;
Precautions:
other severe blood disorders; severe renal impairment;
Anaphylactoid or hypersensitivity reactions (immediate
decompensated heart diseases; pregnancy
treatment, including epinephrine 1:1000 should be
available during vaccine use);
Dose:
Syncope (has been reported with use);
Immunization, by SC injection, ADULT and CHILD, single 0.5
Acute illness;
J

mL dose.
CNS disorders;
Measles, Mumps and Rubella exposure;
Administration: For deep SC injection into the anterolateral
Thrombocytopenia;
aspect of the upper thigh in toddlers and deltoid muscle
Tuberculosis;
in older children.
Immunodeficiency;
Elderly (antibody responses may be lower and decline
Reconstitute only with the supplied diluent using a sterile
faster);
syringe and needle. Use reconstituted vaccine
Children (safety and efficacy of measles vaccine have not
immediately. If not used immediately, store in the dark at
been established in children <6 months of age; safety
2–8oC for no longer than 6 hours. Discard all opened
and efficacy of mumps and rubella vaccines have not
containers after 6 hours.
been established in children <12 months of age);
Pregnancy (animal reproduction studies have not been
See Measles, Mumps, and Rubella (MMR) Vaccine (Live
conducted; not known if can cause fetal harm; avoid
Attenuated) under Vaccines – Viral Vaccines in Chapter
pregnancy for 28 days after vaccination).
7: Antiinfectives for Systemic Use for other information.
Adverse Drug Reactions:
Pregnancy Category: C
Common: Syncope, vasculitis, acute disseminated
encephalomyelitis, ataxia, dizziness, brain disease,
ATC Code: J07BD01
encephalitis, Guillain-Barré syndrome, headache,
irritability, malaise, measles inclusion body encephalitis,
paresthesia, polyneuropathy, retrobulbar neuritis,
MEASLES, MUMPS, AND seizure, subacute sclerosing panencephalitis, transverse
Rx RUBELLA (MMR) VACCINE myelitis, erythema multiforme, morbilliform rash,
(LIVE ATTENUATED) pruritus, rash, Stevens-Johnson syndrome, urticaria,
diabetes mellitus, nausea, diarrhea, pancreatitis,
Inj.: Monodose vial + 0.5 mL diluent (SC) parotitis, sore throat, vomiting, epididymitis,
Multi-dose vial + 5 mL diluent (SC) leukocytosis, orchitis, purpura, anaphylactoid reaction,
thrombocytopenia, anaphylaxis, angioedema, injection
A bacterially sterile, freeze-dried preparation of live, site reactions (burning, induration, redness, stinging,
attenuated strains of measles, mumps, and rubella virus swelling, tenderness, vesiculation, wheal, flare),
that offers active immunity to disease caused by the arthropathy, myalgia, conjunctivitis, oculomotor nerve
measles, mumps, and rubella viruses. paralysis, optic neuritis, optic papillitis, retinitis, nerve
deafness, otitis media, bronchospasm, cough,
Indications: Active immunization for simultaneous pneumonia, pneumonitis, rhinitis, atypical measles,
vaccination against measles, mumps, and rubella in febrile seizures, fever, panniculitis, lymphadenopathy
patients ≥12 months of age Less Common: Aseptic meningitis

Contraindications: Hypersensitivity to measles, mumps, Drug Interactions:

and/or rubella vaccine or any component of the Avoid concomitant use with:
formulation (including neomycin); current febrile Increases risk of adverse or toxic effects of MMR Vaccine:
respiratory illness or other febrile infection; primary and Azathioprine
acquired immunodeficiency states; patients on Belimumab
immunosuppressive therapy; blood dyscrasias, Corticosteroids (Systemic)
leukemia, lymphomas, or other malignant neoplasms Dimethyl Fumarate (vaccinal infection)
affecting the bone marrow or lymphatic systems; family Fingolimod (vaccinal infection)
Immunosuppressants

302
ANTI-INFECTIVES FOR SYSTEMIC USE

Leflunomide MEASLES AND RUBELLA (MR) VACCINE

Mercaptopurine Rx
(LIVE ATTENUATED)
Methotrexate
Inj: multidose (10 doses/vial) + 5 mL diluent (SC), with
Reduces diagnostic effect of Tuberculin Test [separate vaccine vial monitor (VVM)
administration by at least 4–6 weeks]
The vaccine is prepared from the live, attenuated strains of
Reduces therapeutic effect of MMR Vaccine: Edmonston-Zagreb measles virus and Wistar RA 27/3
Azathioprine [avoid doses >3 mg/kg daily] rubella virus. Both measles and rubella viruses are
Corticosteroids (Systemic) [avoid doses greater than an propagated on human diploid cells.
equivalent of 2 mg/kg or 20 mg/day of prednisone for
≥2 weeks] Indications: Immunization against measles and rubella.
Dimethyl Fumarate
Fingolimod Contraindications: Patients receiving corticosteroids,
Immune Globulins [consult full interaction monograph immunosuppressive drugs or undergoing radiotherapy,
for dose interval recommendations] febrile states, pregnancy, acute infectious diseases,
Immunosuppressants [except Azathioprine; leukemia, severe anemia, severe blood diseases, severe
Beclomethasone (Oral Inhalation); Betamethasone renal impairment, decompensated heart diseases,
(Systemic); Budesonide (Systemic); Budesonide patients receiving gammaglobulin or blood transfusion,
(Systemic and Oral Inhalation); Corticotropin; Cortisone; or known allergies to vaccine components, and

J
Cytarabine (Liposomal); Deflazacort; Dexamethasone anaphylactic reactions to neomycin.
(Systemic); Fludrocortisone; Fluticasone (Oral
Inhalation); Hydrocortisone (Systemic); Leflunomide; Dose:
Mercaptopurine; Methotrexate; Methylprednisolone; Immunization against measles and rubella, by
Prednisolone (Systemic); Prednisone; Triamcinolone, subcutaneous injection, ADULT and CHILD, 0.5 mL.
(Systemic) [separate administration by at least 3
months] Dose Adjustment:
Leflunomide [separate administration by at least 3 No dosage adjustments provided in the manufacturer’s
months] labeling.
Mercaptopurine [avoid doses >1.5 mg/kg daily]
Methotrexate [avoid doses >0.4 mg/kg weekly] Precautions:
May cause mild pain and tenderness at the injection site.
TEST INTERACTION. Temporarily suppresses tuberculin skin
test reactivity. Adverse Drug Reactions:
Common: Fever, arthralgia, arthritis, lymphadenopathy,
Administration: For SC administration into the outer aspect myalgia, paresthesia.
of the upper arm in patients ≥12 months. Do NOT inject Less Common: Rash.
by IV. Rare: Encephalitis, thrombocytopenia, anaphylactic
reactions, urticarial, pruritus, and allergic rash.
Reconstitute vaccine using the provided diluent. Gently
agitate to mix thoroughly. Discard if powder does not Drug Interactions:
dissolve. Use immediately after reconstitution. Do NOT Immunoglobulins- risk of inactivation.
mix with other vaccines or injections. Use different
needles and syringes for each injection. Administration: The vaccine should be administered by
deep subcutaneous injection into the anterolateral
Administer while patient is seated or lying down to aspect of upper thigh in toddlers and upper arm in older
prevent syncope related injuries. children.
Store the powder at 2–8°C prior to reconstitution. Pregnancy Category: X
Protect from light. Store diluent in refrigerator or at room
temperature. Do NOT freeze diluent. Store the lyophilized ATC Code: J07BD53
vaccine between ­50 to 8˚C to maintain potency. May be
stored under refrigeration for up to 8 hours. Discard
unused portions after 8 hours.
MUMPS VACCINE
Rx
Pregnancy Category: C (LIVE ATTENUATED)

ATC Code: J07BD52 Inj.: Monodose vial + 0.5 mL diluent (SC)

A preparation of live, attenuated organisms of the Jeryl Lynn

(B level) strain of mumps virus that stimulates active
immunity to mumps infection.

Indication: Active immunization against mumps

NOTE: NOT for children <12 months old.

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 ANTI-INFECTIVES FOR SYSTEMIC USE

Contraindications: Hypersensitivity to any component of the Pregnancy Category: C

formulation (including neomycin); immunocompromised
patients; thrombocytopenia; neurodevelopment ATC Code: J07BF02
disorders (i.e., autism); tuberculosis

Dose: POLIOMYELITIS VACCINE

Primary immunization, by SC injection, CHILD and INFANT Rx
(TYPE 1, 2, 3) (INACTIVATED)
12 months to 12 years, 2 doses, administer first dose at
12–15 months of age and the second dose at 4–6 years
Inj.: 0.5 mL per dose suspension for injection, single dose
of age; the second dose may be given earlier provided at
/multi-dose vial (IM, SC)
least 28 days have elapsed since the first dose.
An inactivated viral vaccine that induces active immunity
Administration: For SC administration into the upper-outer
against poliovirus types 1, 2, and 3 infection.
triceps area or into the anterolateral thigh.
Indication: Active immunization against poliomyelitis
Administer while patient is seated or lying down to
caused by poliovirus type 1, 2, and 3.
prevent syncope related injuries.
Contraindication: Hypersensitivity to any component of the
See Measles, Mumps, and Rubella (MMR) Vaccine (Live
vaccine
Attenuated) under Vaccines – Viral Vaccines in Chapter
J

7: Antiinfectives for Systemic Use for other information.

Dose:
Immunization, by IM or SC injection, ADULT (previously
Pregnancy Category: C
unvaccinated), three 0.5 mL doses, administer 2 doses
at 1–2 month intervals and the third dose 6–12 months
ATC Code: J07BE01
later; ADULT (incompletely vaccinated), for adults with
<3 doses of OPV and/or IPV, administer at least one 0.5
mL dose; ADULT (completely vaccinated by at increased
ORAL POLIO VACCINE, risk of exposure), one 0.5 mL dose.
Rx
TRIVALENT (LIVE ATTENUATED) Primary immunization, by IM or SC injection, CHILD and
INFANT 6 weeks to 47 months, three 0.5 mL doses at 2,
Oral: 0.5 mL plastic tube and 0.5 mL vial 4, and 6–18 months of age.
1 mL vial (10 doses) and 2 mL vial (20 doses) or Booster immunization, by IM or SC injection, CHILD 4 to 6
plastic tube with vaccine vial monitor [for DOH Mass years, 0.5 mL as a single dose at least 6 months after
Immunization Program only] last dose; administer final booster dose at ≥4 years of
age, regardless of number of previous doses.
Consists of a mixture of live attenuated polio viruses of all
three serotypes. Also, Sabin vaccine. Precautions:
Anaphylactoid or hypersensitivity reactions (immediate
Indication: Active immunization of infants and children treatment, including epinephrine 1:1000 should be
against poliomyelitis available during vaccine use); syncope (has been
reported with use); acute illness; immunodeficiency.
Contraindications: Hypersensitivity to the preparation or any Elderly (boosters may be necessary since antibody titers
of its components, including neomycin; acquired or may diminish with age).
congenital immunosuppression; pregnancy (first 5 Pregnancy (animal reproduction studies have not been
months); HIV infection conducted).

Dose: Adverse Drug Reactions:

Primary immunization, by mouth, CHILD, 3 oral doses not Common: Irritability, tiredness, fever, anorexia, vomiting,
less than 4 weeks apart [NOTE: Administer a fourth dose injection site reactions (tenderness, swelling, erythema),
in endemic areas]. persistent crying
Booster immunization, by mouth, ADULT, 1 oral dose 1 year Less Common: Agitation, anaphylactic shock, allergic
after the third dose, then 1 oral dose every 5 years. reaction, anaphylaxis, hypersensitivity reactions,
arthralgia, febrile seizures, lymphadenopathy, headache,
Administration: For oral administration only. Administer 2 myalgia, paresthesia, rash, seizures, somnolence,
drops using the accompanying dropper directly into the urticaria
mouth, or on a lump of sugar or with syrup. Rare: Guillain-Barré syndrome

Store unopened containers at -20oC. After thawing, keep Drug Interactions:

refrigerated at 2–8oC for no longer than 6 months. Avoid concomitant use with:
Protect from light. Store opened containers at 0–8oC. Reduces therapeutic effect of Influenza Vaccine:
Discard unused contents at the end of the day. Belimumab
Fingolimod [administer at least 2 weeks apart; if
See Poliomyelitis Vaccine (Type 1, 2, 3) (Inactivated) under vaccinated during fingolimod therapy, revaccinate 2–3
Vaccines – Viral Vaccines in Chapter 7: Antiinfectives for months after fingolimod discontinuation]
Systemic Use for other information. Immunosuppressants [Cytarabine, Liposomal]
[administer at least 2 weeks apart; if vaccinated during

304
ANTI-INFECTIVES FOR SYSTEMIC USE

immunosuppressant therapy, revaccinate at least 3 1 year and every 5 year hence after; may administer third
months after immunosuppressant discontinuation] dose as early as day 21 if time is limited.
Pre-exposure vaccination, by IM injection, ADULT and CHILD
TEST INTERACTION. May temporarily suppress tuberculin (fully immunized within the last 5 years, with a cell
skin test sensitivity (4–6 weeks). culture rabies vaccine), two 0.5 mL doses on days 0 and
3; ADULT and CHILD (non-immunized, immunized more
Administration: For IM or SC administration into the than 5 years ago, or incomplete vaccination), five 0.5 mL
midlateral aspect of the thigh in infants and small doses on days 0, 3, 7, 14, and 28 with 20 IU/kg of body
children or in the deltoid area in adults or older children. weight human rabies immunoglobulins (RIG) or 40 IU/kg
of body weight equine RIG, administered at the same
Administer while patient is seated or lying down to time as the first injection for severe injuries [NOTE:
prevent syncope related injuries. Administer vaccine contralaterally to the RIG
administration sites];
NOTE: For patients at risk of hemorrhage following IM by ID injection, ADULT and CHILD (fully immunized within
injection, administer by IM only if, in the opinion of the the last 5 years, with a cell culture rabies vaccine), two
physician familiar with the patient's bleeding risk, the 0.1 mL doses on days 0 and 3; ADULT and CHILD (non-
vaccine can be administered by this route with immunized, immunized more than 5 years ago, or
reasonable safety. Use a fine needle (23 gauge or incomplete vaccination), one 0.1 mL dose at 2 sites on
smaller) and apply firm pressure to the site (without days 0, 3, 7, 14, and 28 with 20 IU/kg of body weight
rubbing) for at least 2 minutes. human rabies immunoglobulins (RIG) or 40 IU/kg of body

J
weight equine RIG, administered at the same time as the
If the patient receives anti-hemophilia or other similar first injection for severe injuries [NOTE: Administer
therapy, intramuscular vaccination can be scheduled vaccine contralaterally to the RIG administration sites].
shortly after such therapy is administered. Patients on
anticoagulant therapy should be considered to have the Precautions:
same bleeding risks and treated as those with clotting Anaphylactoid or hypersensitivity reactions (immediate
factor disorders. treatment, including epinephrine 1:1000 should be
available during vaccine use);
Pregnancy Category: C Syncope (has been reported with use);
Immunodeficiency;
ATC Code: J07BF03 Elderly (boosters may be necessary since antibody titers
may diminish with age).
Pregnancy (requires dose adjustment).
RABIES VACCINE – CHICK
Rx EMBRYO CELL SKILLED TASKS. May cause post-vaccination dizziness.
Avoid performing tasks, which require mental alertness,
(PURIFIED, INACTIVATED) e.g., operating machinery or driving.
Inj.: 2.5 IU/mL lyophilized powder, 1 dose vial + 1 mL Adverse Drug Reactions:
diluent (ID, IM) Common: Injection site reactions (pain, erythema, edema,
pruritus, induration), fever, shivering, malaise, asthenia,
Purified vaccine containing inactivated rabies virus headache, dizziness, arthralgia, myalgia, nausea,
cultivated in chick embryo cells. abdominal pain
Rare: Anaphylactoid reaction, urticaria, rash
Indications: Active immunization against rabies; pre-
exposure and post-exposure prevention Drug Interactions:
Monitor closely with:
NOTE: WHO recommends pre-exposure immunization of Reduces therapeutic effect of Rabies Vaccine:
individuals at high risk of contracting rabies, including Immunoglobulins
people living or traveling to enzootic areas and those at
risk due to occupational exposure, such as health and Avoid concomitant use with:
laboratory workers, animal handlers, veterinary Reduces therapeutic effect of Rabies Vaccine:
surgeons, etc. Corticosteroids (may cause failure of vaccination)
Other Immunosuppressants (may cause failure of
Contraindications: Hypersensitivity to the vaccine or any of vaccination)
its components; fever; acute illness
Administration: For IM administration into the deltoid region
Dose: in adults and children or the anterolateral thigh for
Pre-exposure vaccination, by IM injection, ADULT and children <2 years of age. Do NOT inject into the gluteal
CHILD, three 0.5 mL doses on days 0, 7, and 28, followed area because weaker levels of neutralizing antibodies
by one 0.5 mL booster dose after 1 year and every 5 year have been observed when this area is used.
hence after; may administer third dose as early as day May also administer by ID injection as an alternative into
21 if time is limited; the upper or forearm. ID route must be administered only
by ID injection, ADULT and CHILD, three 0.1 mL doses on by medical staff trained in this technique to ensure
days 0, 7, 28, followed by one 0.5 mL booster dose after vaccine is delivered by ID and NOT by SC. Use sterile

305
 ANTI-INFECTIVES FOR SYSTEMIC USE

syringe with fixed needle (insulin type). Do NOT inject by by ID injection, ADULT and CHILD (fully immunized within
IV or SC. the last 5 years, with a cell culture rabies vaccine), two
0.1 mL doses on days 0 and 3; ADULT and CHILD (non-
Thoroughly clean bite wound prior to administration. immunized, immunized more than 5 years ago, or
Immediately flush out and wash with soap or detergent incomplete vaccination), one 0.1 mL dose at 2 sites on
to eliminate rabies virus at the infection site. Thoroughly days 0, 3, 7, 14, and 28 with 20 IU/kg of body weight
remove all traces of soap then apply 70% alcohol human rabies immunoglobulins (RIG) or 40 IU/kg of body
solution, tincture or solution of iodine, or 0.1% weight equine RIG, administered at the same time as the
quaternary ammonium solution. first injection for severe injuries [NOTE: Administer
vaccine contralaterally to the RIG administration sites].
Reconstitute using the solvent provided. Shake gently to
obtain a homogenous suspension, appearing as a limpid Administration: For IM administration into the deltoid region
liquid. Immediately administer vaccine. Reconstituted in adults and children or the anterolateral thigh for
vaccine may be used for up to 8 hours provided it is children <2 years of age. Do NOT inject into the gluteal
maintained at 2–8oC. Discard unused portions after 8 area because weaker levels of neutralizing antibodies
hours. have been observed when this area is used.

Pregnancy Category: C May also administer by ID injection as an alternative into

the upper or forearm. ID route must be administered only
ATC Code: J07BG01 by medical staff trained in this technique to ensure
J

vaccine is delivered by ID and NOT by SC. Use sterile

syringe with fixed needle (insulin type). Do NOT inject by
RABIES VACCINE – VERO CELL IV or SC.
Rx
(PURIFIED)
Thoroughly clean bite wound prior to administration.
Immediately flush out and wash with soap or detergent
Inj.: 2.5 IU/0.5 mL lyophilized powder, vial + diluent (ID,
to eliminate rabies virus at the infection site. Thoroughly
IM)
remove all traces of soap then apply 70% alcohol
2.5 IU/mL suspension, 1 mL vial (IM)
solution, tincture or solution of iodine, or 0.1%
quaternary ammonium solution.
Purified vaccine containing inactivated rabies virus
cultivated in vero cells.
Reconstitute using the solvent provided. Shak gently to
obtain a homogenous suspension, appearing as a limpid
Indications: Active immunization against rabies; pre-
liquid. Immediately administer vaccine. Reconstituted
exposure and post-exposure prevention
vaccine may be used for up to 8 hours provided it is
maintained at 2–8oC. Discard unused portions after 8
NOTE: WHO recommends pre-exposure immunization of
hours.
individuals at high risk of contracting rabies, including
people living or traveling to enzootic areas and those at
See Rabies Vaccine – Chick Embryo Cell (Purified,
risk due to occupational exposure, such as health and
Inactivated) under Vaccines – Viral Vaccines in Chapter
laboratory workers, animal handlers, veterinary
7: Antiinfectives for Systemic Use for other information.
surgeons, etc.
Pregnancy Category: C
Contraindication: Hypersensitivity to the vaccine or any of its
components; fever; acute illness
ATC Code: J07BG01
Dose:
Pre-exposure vaccination, by IM injection, ADULT and
CHILD, three 0.5 mL doses on days 0, 7, and 28, followed RUBELLA VACCINE
Rx
by one 0.5 mL booster dose after 1 year and every 5 year (LIVE ATTENUATED)
hence after; may administer third dose as early as day
21 if time is limited; Inj.: Monodose vial + 0.5 mL diluent (SC)
by ID injection, ADULT and CHILD, three 0.1 mL doses on Multi-dose vial + 5 mL diluent (SC)
days 0, 7, 28, followed by one 0.5 mL booster dose after
1 year and every 5 year hence after; may administer third A preparation of live, attenuated rubella virus that
dose as early as day 21 if time is limited. stimulates active immunity to rubella infection.
Pre-exposure vaccination, by IM injection, ADULT and CHILD
(fully immunized within the last 5 years, with a cell Indication: Active immunization against rubella (German
culture rabies vaccine), two 0.5 mL doses on days 0 and measles)
3; ADULT and CHILD (non-immunized, immunized more
than 5 years ago, or incomplete vaccination), five 0.5 mL Contraindication: Hypersensitivity to any component of the
doses on days 0, 3, 7, 14, and 28 with 20 IU/kg of body formulation
weight human rabies immunoglobulins (RIG) or 40 IU/kg
of body weight equine RIG, administered at the same Dose:
time as the first injection for severe injuries [NOTE: Primary immunization, by SC injection, ADULT and
Administer vaccine contralaterally to the RIG ADOLESCENT ≥13 years, one or two 0.5 mL doses
administration sites]; administered at least 28 days apart; CHILD, two 0.5 mL

306
ANTI-INFECTIVES FOR SYSTEMIC USE

doses; administer first dose at 12–15 months of age and Acute illness;
the second dose at 4–6 years of age; second dose may HIV infection;
be given earlier provided at least 28 days have elapsed Immunodeficiency;
since the first dose and both doses are given at or after Pregnancy (avoid pregnancy for 3 months after vaccination).
12 months of age.
Adverse Drug Reactions:
Administration: For SC administration into the upper-outer Common: Injection site reactions (rash), fever, chills,
triceps area or into the anterolateral thigh. Do NOT inject disturbed sleep, fatigue, headache, irritability, malaise,
by IV. nervousness, contact dermatitis, diaper rash, varicella-
like rash, dermatitis, eczema, milliaria, pruritus, urticaria,
Reconstitute using the provided diluent and agitate the abdominal pain, xeroderma, constipation, decreased
vial. Do NOT use if the lyophilized vaccine does not appetite, diarrhea, nausea, period of tooth development,
dissolve completely. vomiting, herpes labialis, lymphadenopathy,
hypersensitivity reaction, arthralgia, myalgia, neck
Visually inspect for particulate matter and discoloration stiffness, otitis, cough, respiratory tract disease
prior to administration. Use only sterile syringes and Less Common: Anaphylactic shock, anaphylaxis,
needles that are free of preservatives, antiseptics, and angioedema, aseptic meningitis, ataxia, aplastic anemia,
detergents. Bell's palsy, cellulitis, cerebellar ataxia (acute),
cerebrovascular accident, dizziness, encephalitis,
Administer while patient is seated or lying down to erythema multiforme, facial edema, febrile seizures,

J
prevent syncope related injuries. hemiparesis (acute), Guillain-Barré syndrome, hepatitis,
herpes zoster, IgA vasculitis, impetigo, paresthesia,
necrotizing retinitis, pharyngitis, pneumonia,
See Measles, Mumps, and Rubella (MMR) Vaccine (Live pneumonitis, peripheral edema, seizure (nonfebrile),
Attenuated) under Vaccines – Viral Vaccines in Chapter Stevens-Johnson syndrome, thrombocytopenia
7: Antiinfectives for Systemic Use for other information. (including immune thrombocytopenia), transverse
myelitis, secondary skin infection, varicella
Pregnancy Category: C (disseminated or vaccine strain)

ATC Code: J07BJ01 Drug Interactions:

Avoid concomitant use with:
Increases risk of adverse or toxic effects of Varicella
VARICELLA VACCINE Vaccine:
Rx 5-ASA Derivatives (Reye's Syndrome), Azathioprine,
(LIVE ATTENUATED)
Belimumab
Corticosteroids (Systemic)
Inj.: Freeze-dried powder, not less than 2,000 PFU (OKA
Dimethyl Fumarate (vaccinal infection)
strain varicella zoster virus) monodose vial + diluent
Fingolimod (vaccinal infection), Immunosuppressants,
(0.5 mL water for injection) ampule (SC only)
Leflunomide
Mercaptopurine, Methotrexate
A live attenuated viral vaccine that offers active immunity to
Salicylates e.g. Aspirin (Reye's Syndrome)
disease caused by the varicella-zoster virus by inducing
Smallpox Vaccine, Live (skin lesions)
cell-mediated and humoral immune responses.
Reduces diagnostic effect of Tuberculin Test [separate
Indication: For the prevention of varicella in persons 12
administration by at least 4–6 weeks]
months and older
Reduces therapeutic effect of Varicella Vaccine:
Contraindications: Severe allergic or anaphylactic reaction
Acyclovir-Valacyclovir [avoid concomitant use within 14
to the vaccine, neomycin, gelatin, or any component of
days of vaccination]
the formulation; leukemia; lymphoma; other malignant
Azathioprine [avoid doses >3 mg/kg daily]
neoplasms affecting the bone marrow or lymphatic
Corticosteroids, Systemic [avoid doses greater than an
systems; HIV infection; patients on immunosuppressive
equivalent of 2 mg/kg or 20 mg/day of prednisone for
therapy; immunosuppressed or immunodeficient
≥2 weeks]
individuals; active, untreated tuberculosis; primary and
Dimethyl Fumarate
acquired immunodeficiency states; current febrile
Famciclovir [avoid concomitant use within 14 days of
illness; pregnancy
vaccination]
Fingolimod
Dose:
Immune Globulins [consult full interaction monograph
Immunization, by SC injection, ADULT, two 0.5 mL doses
for dose interval recommendations]
separated by ≥4 weeks; CHILD ≥12 months, two 0.5 mL
Immunosuppressants [except Azathioprine;
doses separated by ≥3 months.
Beclomethasone (Oral Inhalation); Betamethasone
(Systemic); Budesonide (Systemic); Budesonide
Precautions:
(Systemic and Oral Inhalation); Corticotropin; Cortisone;
Anaphylactoid or hypersensitivity reactions (immediate
Cytarabine (Liposomal); Deflazacort; Dexamethasone
treatment, including epinephrine 1:1000 should be
(Systemic); Fludrocortisone; Fluticasone (Oral
available during vaccine use);
Inhalation); Hydrocortisone (Systemic); Leflunomide;
Syncope (has been reported with use);

307
 ANTI-INFECTIVES FOR SYSTEMIC USE

Mercaptopurine; Methotrexate; Methylprednisolone; Precautions:

Prednisolone (Systemic); Prednisone; Triamcinolone Anaphylactoid or hypersensitivity reactions (immediate
(Systemic) [separate administration by at least 3 treatment, including epinephrine 1:1000 should be
months] available during vaccine use);
Leflunomide [separate administration by at least 3 Syncope (has been reported with use);
months] Acute illness;
Mercaptopurine [avoid doses >1.5 mg/kg daily] Immunodeficiency;
Methotrexate [avoid doses >0.4 mg/kg weekly] Elderly (increased incidence of serious adverse events in
patients ≥60 years of age);
Administration: For SC administration only into the outer Children (risk of encephalitis if used in infants <9 months of
aspect of upper arm or the anterolateral thigh. Do NOT age);
administer by IV or IM. Pregnancy (avoid use during pregnancy; animal
reproduction studies have not been conducted);
Administer while patient is seated or lying down to Lactation (excreted into breastmilk).
prevent syncope related injuries.
Adverse Drug Reactions:
Store the powder at ­50 to -15˚C prior to reconstitution. Common: Chills, fever, focal neurological defects,
Reconstituted vaccine may be stored under refrigeration headache, malaise, seizure, rash, urticaria, injection site
at 2–8°C for up to 72 hours. Protect from light. Store reactions (edema, erythema, hypersensitivity, mass,
diluent at 20–25°C or in refrigerator. Do NOT freeze pain, pruritus, rash, warmth), weakness, myalgia,
J

diluent. Guillain-Barré syndrome, hypersensitivity (immediate)

Rare: Vaccine-associated neurotropic disease, viscerotropic
Use the total volume of the provided diluent to disease
reconstitute vaccine. Gently agitate to mix thoroughly.
Administer within 30 minutes of preparation. Discard Drug Interactions:
reconstituted vaccine if unused within 30 minutes. Avoid concomitant use with:
Increases risk of adverse or toxic effects of Varicella
Do NOT mix with other vaccines or injections. Use Vaccine:
different needles and syringes for each injection. Azathioprine
Belimumab
Pregnancy Category: C Corticosteroids (Systemic)
Dimethyl Fumarate (vaccinal infection)
ATC Code: J07BK01 Fingolimod (vaccinal infection)
Immunosuppressants
Leflunomide
Mercaptopurine
Rx YELLOW FEVER VACCINE Methotrexate

Inj.: 1,000 DL 50 mouse min (attenuated) vial + 0.5 mL Reduces diagnostic effect of Tuberculin Test [separate
solvent syringe (IM, SC) administration by at least 4–6 weeks]

NOTE: For Bureau of Quarantine use only. Reduces therapeutic effect of Varicella Vaccine:
Azathioprine [avoid doses >3 mg/kg daily]
A live vaccine that offers active immunization against yellow Corticosteroids, Systemic [avoid doses greater than an
fever infection at an effective immune response rate of equivalent of 2 mg/kg or 20 mg/day of prednisone for
nearly 100% of patients. ≥2 weeks]
Dimethyl Fumarate, Fingolimod, Immunosuppressants
Indication: Active immunization against yellow fever virus, [except Azathioprine; Beclomethasone (Oral Inhalation);
primarily among persons traveling to or living in areas Betamethasone (Systemic); Budesonide (Systemic);
where yellow fever infection exists and laboratory Budesonide (Systemic and Oral Inhalation);
workers who may be exposed to the virus Corticotropin; Cortisone; Cytarabine (Liposomal);
Deflazacort; Dexamethasone (Systemic);
Contraindications: Acute hypersensitivity to egg or chick Fludrocortisone; Fluticasone (Oral Inhalation);
embryo protein, or any component of the formulation, Hydrocortisone (Systemic); Leflunomide;
including gelatin; infants <6 months; acute or febrile Mercaptopurine; Methotrexate; Methylprednisolone;
disease; immunosuppressed patients (e.g., HIV infection, Prednisolonen (Systemic); Prednisone; Triamcinolone
leukemia, lymphoma, thymic disease, generalized (Systemic) [separate administration by at least 3
malignancy, or immunosuppression due to drugs or months]
radiation) ; breastfeeding women Leflunomide [separate administration by at least 3
Dose: months]
Immunization, by SC injection, ADULT, ADOLESCENT, CHILD, Mercaptopurine [avoid doses >1.5 mg/kg daily]
and INFANT ≥9 months, one 0.5 mL dose ≥10 days Methotrexate [avoid doses >0.4 mg/kg weekly]
before travel.
Administration: For SC administration only. Do NOT
administer by IV or IM. If inadvertently administered by
IM, the dose does not need repeated.

308
ANTI-INFECTIVES FOR SYSTEMIC USE

Administer while patient is seated or lying down to DTP + HEMOPHILUS

prevent syncope related injuries. Rx
INFLUENZA TYPE B (Hib)
Store at 2–8°C. Reconstitute using only provided
Inj.: 0.5 mL DTP diluent in pre-filled syringe + freeze-dried
diluent. Inject diluent slowly into vial and allow to stand
10 micrograms Hib vial (IM, SC)
for 1–2 minutes. Gently swirl until a uniform suspension
forms before withdrawing dose. Avoid vigorous shaking
A combination product containing adsorbed diphtheria,
to prevent foaming of suspension. Administer within 60
tetanus, whole cell pertussis, and Haemophilus
minutes of preparation. Keep suspension refrigerated
influenzae type b vaccines.
until used. Discard reconstituted vaccine if unused
within 60 minutes.
Indication: Active immunization against diphtheria, tetanus,
pertussis, and invasive disease caused by Haemophilus
Do NOT mix with other vaccines or injections. Use
influenzae type b (Hib)
different needles and syringes for each injection.
Contraindications: Hypersensitivity to the any component of
Pregnancy Category: C
the formulation; severe acute neurological illness within
7 days of pertussis vaccination; thrombocytopenia or any
ATC Code: J07BL01
coagulation disorders

See individual monographs for Diphtheria-Tetanus Toxoids

J
BACTERIAL AND VIRAL VACCINES, and Pertussis Vaccine (DTP) and Hemophilus Influenzae
COMBINED Type B Conjugate Vaccine (Hib) under Vaccines –
Bacterial Vaccines in Chapter 7: Antiinfectives for
DTaP + HEMOPHILUS Systemic Use for other information.
Rx
INFLUENZA TYPE B (Hib)
Pregnancy Category: C
Inj.: 0.5 mL pre-filled syringe (IM)
ATC Code: J07AG52; J07AJ51
A combination product containing adsorbed diphtheria,
tetanus, acellular pertussis, and Haemophilus
influenzae type b vaccines. DTP + HEPATITIS B VACCINE
Rx
(RECOMBINANT)
Indications: Active immunization against diphtheria,
tetanus, pertussis, and invasive disease caused by Inj.: 0.5 mL vial (IM, SC)
Haemophilus influenzae type b (Hib)
A combination vaccine that promotes active immunity to
Contraindications: Hypersensitivity to any component of the diphtheria, tetanus, pertussis, and hepatitis B by
formulation; progressive neurologic disorder, including inducing production of specific antibodies and antitoxins.
infantile spasms, uncontrolled epilepsy or progressive
epilepsy; encephalopathy occurring within 7 days of Indication: Active immunization against diphtheria, tetanus,
administration and not attributable to another cause pertussis, and hepatitis B

See individual monographs for Diphtheria-Tetanus Toxoids Contraindications: Hypersensitivity to diphtheria and
and Acellular Pertussis Vaccine (DTaP) and Hemophilus tetanus toxoids, pertussis, hepatitis B, poliovirus
Influenzae Type B Conjugate Vaccine (Hib) under vaccine, or any component of the vaccine;
Vaccines – Bacterial Vaccines in Chapter 7: encephalopathy (within 7 days of a previous pertussis
Antiinfectives for Systemic Use for other information. vaccine not attributable to another identifiable cause);
progressive neurologic disorders (including infantile
Pregnancy Category: C spasms, uncontrolled epilepsy, or progressive
encephalopathy)
ATC Code: J07AG52; J07AJ52
Dose:
Primary immunization, by IM injection, CHILD <7 years and
INFANT ≥6 weeks, three 0.5 mL doses administered at
2, 4, and 6 months of age in 6–8 week intervals.

Administration: For IM administration into the anterolateral

aspect of the thigh or the deltoid muscle. Do NOT
administer by IV or SC.

Shake suspension well before use. Store at 2–8°C.

Discard if frozen. Do NOT use a defrosted vaccine. May
be stored at room temperature for up to 24 hours.

309
 ANTI-INFECTIVES FOR SYSTEMIC USE

Do NOT mix with other vaccines or injections. Use such therapy is administered. Patients on anticoagulant
different needles and syringes for each injection. therapy should be considered to have the same bleeding
risks and treated as those with clotting factor disorders.
NOTE: For patients at risk of hemorrhage following IM
injection, administer by IM only if, in the opinion of the See individual monographs for Diphtheria-Tetanus Toxoids
physician familiar with the patient's bleeding risk, the and Pertussis Vaccine (DTP) under Vaccines – Bacterial
vaccine can be administered by this route with Vaccines and Poliomyelitis Vaccine (Type 1, 2, 3)
reasonable safety. (Inactivated) under Vaccines – Viral Vaccines in Chapter
7: Antiinfectives for Systemic Use for other information.
If the patient receives anti-hemophilia or other similar
therapy, IM vaccination can be scheduled shortly after Pregnancy Category: C
such therapy is administered. Patients on anticoagulant
therapy should be considered to have the same bleeding ATC Code: J07CA02
risks and treated as those with clotting factor disorders.

See individual monographs for Diphtheria-Tetanus Toxoids

and Pertussis Vaccine (DTP) under Vaccines – Bacterial Rx DTP + IPV + Hib
Vaccines and Hepatitis B Vaccine (Recombinant DNA)
under Vaccines – Viral Vaccines in Chapter 7: Inj.: 0.5 mL pre-filled syringe (IM, SC)
Antiinfectives for Systemic Use for other information.
J

A combination vaccine that promotes active immunity to

Pregnancy Category: C diphtheria, tetanus, pertussis, poliovirus (types 1, 2 and
3) and Haemophilus influenzae type b (Hib) by inducing
ATC Code: J07CA05 production of specific antibodies and antitoxins.

Indications: Active immunization against diphtheria,

DTP + INACTIVATED POLIO tetanus, pertussis, poliovirus (type 1, 2, 3), and invasive
Rx disease caused by Haemophilus influenzae type b
VACCINE (IPV)
Inj.: 0.5 mL monodose vial (IM, SC) Contraindications: Hypersensitivity to any component of the
0.5 mL pre-filled syringe (IM, SC) vaccine; severe acute neurological illness within 7 days
of pertussis vaccination; thrombocytopenia or any
A combination vaccine that promotes active immunity to coagulation disorders
diphtheria, tetanus, pertussis, and poliovirus (types 1, 2
and 3) by inducing production of specific antibodies and Dose:
antitoxins. Immunization, by IM injection, CHILD and INFANT 6 weeks
to <5 years, four 0.5 mL doses at 2, 4, 6, and 15–18
Indications: Active immunization against diphtheria, months of age; first dose may be administered as early
tetanus, pertussis, and poliovirus as 6 weeks of age.

Contraindications: Hypersensitivity to any component of the Administration: For IM administration only into the
vaccine; severe acute neurological illness within 7 days anterolateral aspect of the thigh in children <1 year of
of pertussis vaccination; thrombocytopenia or any age or into the deltoid muscle of older children. Do NOT
coagulation disorders administer to the gluteal area or areas near a major
nerve trunk. Do NOT administer by IV or SC.
Dose:
Immunization, by IM injection, CHILD 4–6 years, 0.5 mL as Combine DTP and IPV, and gently shake suspension well
a single dose. before use. Withdraw liquid contents and inject into vial
containing Hib power. Gently swirl until a cloudy
Administration: For IM administration only into the deltoid suspension result.
muscle. Do NOT administer by ID, IV, or SC.
Store at 2–8°C. Do NOT freeze. Discard if frozen.
Shake suspension well before use. Do NOT use unless a
homogenous, turbid, white suspension forms. Discard if Do NOT mix with other vaccines or injections. Use
the suspension is discolored, or if there are cracks in the different needles and syringes for each injection.
vial or syringe.
NOTE: For patients at risk of hemorrhage following IM
Store at 2–8°C. Do NOT freeze. Discard if frozen. injection, administer by IM only if, in the opinion of the
physician familiar with the patient's bleeding risk, the
NOTE: For patients at risk of hemorrhage following IM vaccine can be administered by this route with
injection, administer by IM only if, in the opinion of the reasonable safety.
physician familiar with the patient's bleeding risk, the
vaccine can be administered by this route with If the patient receives anti-hemophilia or other similar
reasonable safety. therapy, IM vaccination can be scheduled shortly after
If the patient receives anti-hemophilia or other similar such therapy is administered. Patients on anticoagulant
therapy, IM vaccination can be scheduled shortly after

310
ANTI-INFECTIVES FOR SYSTEMIC USE

therapy should be considered to have the same bleeding

risks and treated as those with clotting factor disorders.
See individual monographs for Diphtheria-Tetanus Toxoids
and Pertussis Vaccine (DTP) and Hemophilus influenzae
Type B Conjugate Vaccine (Hib) under Vaccines –
Bacterial Vaccines and Poliomyelitis Vaccine (Type 1, 2,
3) (Inactivated) under Vaccines – Viral Vaccines in
Chapter 7: Antiinfectives for Systemic Use for other
information.

Pregnancy Category: C

ATC Code: J07CA06

DIPHTHERIA, TETANUS,
PERTUSSIS, HEPATITIS B
(RECOMBINANT), AND
Rx
HEMOPHILUS INFLUENZA

J
TYPE B (Hib) COMBINED
VACCINE
Inj.: 0.5 mL vial suspension for injection (IM)

A combination vaccine that promotes active immunity to

diphtheria, tetanus, pertussis, hepatitis B and
Haemophilus influenzae type b (Hib) by inducing
production of specific antibodies and antitoxins.

Indications: Active immunization against diphtheria,

tetanus, pertussis, hepatitis B, and invasive disease
caused by Haemophilus influenzae type b

Contraindications: Hypersensitivity to any component of the

vaccine; severe acute neurological illness within 7 days
of pertussis vaccination; thrombocytopenia or any
coagulation disorders

See individual monographs for Diphtheria-Tetanus Toxoids

and Pertussis Vaccine (DTP) and Hemophilus influenzae
Type B Conjugate Vaccine (Hib) under Vaccines –
Bacterial Vaccines and Hepatitis B Vaccine
(Recombinant DNA) under Vaccines – Viral Vaccines in
Chapter 7: Antiinfectives for Systemic Use for other
information.

Pregnancy Category: C

ATC Code: J07CA11

311
 ANTINEOPLASTIC AND IMMODULATING AGENTS

Renal impairment (e.g. hemorrhagic cystitis, pyelitis,

ANTINEOPLASTIC AND ureteritis, and hematuria; urotoxicity appears to be
IMMUNOMODULATING AGENTS dependent on dose and treatment duration; may occur
with short-term use; discontinue use when severe
hemorrhagic cystitis occurs; use with caution in patients
ANTINEOPLASTIC AGENTS with active UTI)
Elderly (watch out for signs of infections such as fever and
elevated WBC)
For antineoplastic agents, these should be administered Pregnancy (may cause fetal harm; adverse renal effects,
under the supervision of an experienced hematologist- e.g. unilateral agenesis; women of childbearing potential
oncologist in the use of cancer chemotherapeutic should avoid pregnancy for up to 1 year after completion
agents. Administer in a facility sufficient to appropriately of treatment; males with female partners who are or may
diagnose and manage complications. The dosing become pregnant should use condoms during and for at
regimen will depend on the protocol being used by the least 4 months after treatment);
institution. Lactation (excreted in breastmilk; leukopenia and
thrombocytopenia have been reported in nursing infant).
For a comprehensive information on adverse events and
dose modifications, please refer to
https://ctep.cancer.gov/protocoldevelopment/electroni
c_applications/doc/CTCAE_v5_Quick_Reference_5x7.p Rx CHLORAMBUCIL
df
Oral: 2 mg tablet
ALKYLATING AGENTS
L

A nitrogen mustard analogue that interferes with DNA

NITROGEN MUSTARD ANALOGUES replication and RNA transcription through alkylation and
crosslinking of DNAstrands producing cytotoxic effects.
General Information
Indications: Chronic lymphocytic leukemia (CLL); Hodgkin
lymphoma; non-Hodgkin’s lymphoma (NHL)
Nitrogen mustard analogues are characterized by the
presence of the bischloroethyl group. They exhibit
Contraindications: Prior (demonstrated) resistance to
anticancer activity by initially producing an aziridinium
chlorambucil
ring through intramolecular displacement of the chloride
by the amine nitrogen. The reactive aziridinium ring act
Dose:
as a DNA alklylating agent.
Chronic lymphocytic leukemia, by mouth, ADULT, 0.1 mg/kg
daily for 3–6 weeks; or 0.4 mg/kg pulsed doses
Precautions:
administered intermittently, biweekly, or monthly, then
Allergic reactions and hypersensitivity
increased by 0.1 mg/kg per dose until response or
Bone marrow suppression and immunosuppression (e.g.
toxicity is observed.
leukopenia, neutropenia, thrombocytopenia, and
Hodgkin lymphoma, by mouth, ADULT, 0.2 mg/kg daily for
anemia; may lead to serious, fatal infections, or may
3–6 weeks.
activate latent infections; may require dose reduction or
Non-Hodgkin’s lymphoma, by mouth, ADULT, 0.1-0.2 mg/kg
discontinuation of treatment)
daily for 3–6 weeks.
Wound healing impairment
Cardiotoxicity (e.g. arrhythmias, congestive heart failure,
NOTE: For adults with bone marrow lymphocytic infiltration
heart block, hemorrhagic myocarditis,
involvement or when the bone marrow is hypoplastic, the
hemopericardium, pericarditis, pericardial effusion, and
maximum dose is 0.1 mg/kg daily.
tachyarrhythmias usually with high doses associated
with transplant conditioning regimens)
Reduce initial dose if administered within 4 weeks
Fertility effects (e.g. sterility in males and females;
after full course of radiation/ myelosuppressive therapy.
amenorrhea in females; probably mutagenic and
teratogenic)
Dose Adjustment:
Gastrointestinal adverse effects (e.g. nausea and vomiting)
Geriatric:
Hyponatremia (e.g. syndrome resembling SIADH)
Initiate at the lower end of dosing range. Toxicity to
Pulmonary toxicities (e.g. pneumonitis, pulmonary fibrosis,
immunosuppressants is increased in the elderly.
pulmonary veno-occlusive disease, and ARDS)
Secondary malignancies (e.g. bladder cancer,
Renal Impairment:
myelodysplasia, acute leukemias, lymphomas, thyroid
For patients with CrCl 10–50 mL/minute, administer 75%
cancer, and sarcomas)
of dose.
Seizures (use with caution in patients with a history of
For patients with CrCl <10 mL/minute and patients
seizure disorder or head trauma);
undergoing peritoneal dialysis, administer 50% of dose.
Skin reactions (e.g, erythema multiforme, Stevens-Johnson
syndrome, toxic epidermal necrolysis).
Hepatic Impairment:
Hepatic impairment (e.g. hepatic sinusoidal obstruction
Chlorambucil is primarily metabolized in the liver. Consider
syndrome (SOS))
dose reduction.

312
ANTINEOPLASTIC AND IMMODULATING AGENTS

Precautions: Administration: May be administered as a single daily dose,

WARNING: Chlorambucil is a carcinogen in humans preferably on an empty stomach.
and can severely suppress bone marrow function.
See General Information on Nitrogen Mustard Analogues
under Antineoplastic Agents in Chapter 8: Antineoplastic
WARNING: Hazardous agent; use appropriate and Immunomodulating Agents for other information.
precautions for handling and disposal.
Pregnancy Category: D
Please see other precautions under General
ATC Code: L01AA02
Adverse Drug Reactions:
Common: Drug fever, fever, angioneurotic edema, rash,
urticaria, amenorrhea, infertility, skin hypersensitivity,
azoospermia, neutropenia, bone marrow failure Rx CYCLOPHOSPHAMIDE
(irreversible), bone marrow suppression, cystitis,
leukemia (secondary), leukopenia, lymphophenia, Inj.: 200 mg, 500 mg, and 1 g powder, vial (IV)
pancytopenia, anemia, thrombocytopenia,
hepatotoxicity, jaundice, peripheral neuropathy, A precursor nitrogen mustard analogue that acts as an
interstitial pneumonia, pulmonary fibrosis, allergic antineoplastic agent preventing cell division by
reactions, malignancies (secondary) crosslinking of DNA strands and decreasing DNA
Less Common: Diarrhea, nausea, oral ulceration, vomiting synthesis. As a prodrug, it must be metabolized in the
Rare: Agitation, ataxia, confusion, focal / generalized liver to form the active aldophosphamide. It is a cell cycle
seizure, hallucinations, erythema multiforme, Stevens-

L
phase nonspecific agent that possesses potent
Johnson syndrome, toxic epidermal necrolysis, SIADH, immunosuppressive activity.
flaccid paralysis, muscular twitching, myoclonia, tremor
Indication: Malignant diseases, including lymphomas,
Drug Interactions: leukemia, neuroblastoma, adenocarcinoma, carcinoma
Monitor closely with: of the breast and mycosis fungoides, management for
Increases risk of adverse or toxic effects of Chlorambucil: lupus in patients irresponsive to traditional therapy or
Denosumab (serious infections), Trastuzumab with kidney damage
(neutropenic effect)
Contraindications: Urinary outflow obstruction
Increases risk of adverse or toxic effects of Leflunomide
(hematologic toxicity, including pancytopenia, Dose:
agranulocytosis, and/or thrombocytopenia) Malignancy, by IV injection, ADULT, 40–50 mg/kg (400-
1800 mg/m2) in divided doses over 2–5 days, may be
Reduces diagnostic effect of Coccidioides immitis Skin Test repeated at intervals of 2-4 weeks; or 10–15 mg/kg
every 7–10 days; or 3–5 mg/kg twice weekly; or 60-120
Avoid concomitant use with: mg/m2/day (1-2.5 mg/kg/day continuous daily therapy;
Enhances therapeutic effect of Chlorambucil: 500-1500 mg/m2 IV at intervals of 2-3 weeks in
Roflumilast (immunosuppressive effect) combination with other neoplastic agents
Lupus nephritis, by IV infusion, ADULT, 50–150 mg daily as
Enhances therapeutic effect of the following drugs: a single dose.
Tofacitinib [except antirheumatic doses of Methotrexate, Malignant Diseases, CHILD, IV (intermittent therapy): 40-50
nonbiologic DMARD] (immunosuppressive effect) mg/kg (400-1800 mg/m²) divided over 2-5 days; may be
repeated at intervals of 2-4 weeks
Increases risk of adverse or toxic effects of Chlorambucil: IV (continuous daily therapy): 60-120 mg/m²/day (1-2.5
Dipyrone (agranulocytosis), Pimecrolimus, mg/kg/day)
Tacrolimus (Topical) PO (intermittent therapy): 400-1000 mg/m² divided over
4-5 days
Increases risk of adverse or toxic effects of the following PO (continuous daily therapy): 50-100 mg/m²/day
drugs: Juvenile Idiopathic Arthritis/Vasculitis, CHILD, 10 mg/kg
Clozapine (agranulocytosis), Natalizumab (concurrent IV every 2 weeks
infection), Vaccines (Live) Nephrotic Syndrome, CHILD, 2-3 mg/kg/day for up to 12
weeks when corticosteroids are unsuccessful
Reduces therapeutic effect of Chlorambucil: Systemic Lupus Erythematosus, CHILD, 500-750 mg/m²
Echinacea IV monthly; not to exceed 1 g/m²
Reduces therapeutic effect of the following drugs: Dose Adjustment:
BCG (Intravesical), Vaccines (Inactivated) [complete all Geriatric:
age-appropriate vaccinations at least 2 weeks prior to Titrate dose carefully, initiating therapy at the lowest end of
starting Chlorambucil; if vaccinated during Chlorambucil the dosage range. Adjust dose for renal function. Safety
therapy, revaccinate at least 3 months after and efficacy have not been studied.
discontinuation], Vaccines (Live) [do not administer Renal Impairment:
vaccines for at least 3 months after Chlorambucil
therapy]

313
 ANTINEOPLASTIC AND IMMODULATING AGENTS

Use with caution. Elevated levels of metabolites may occur. Increases risk of adverse or toxic effects of
Reduce dose if serum creatinine concentration >120 Cyclophosphamide:
micromoles/liter. Allopurinol (bone marrow suppression), Azathioprine
CrCl <10 mL/min, give 75% of normal dose (hepatotoxic effect), Denosumab (serious infections),
Cyclophosphamide and its metabolites are dialyzable. Filgrastim (pulmonary toxicity), Pentostatin (cardiotoxic
Differences in amount dialyzed may occur due to dialysis effect), Protease Inhibitors (neutropenia, infection,
system used. Maintain a consistent interval between mucositis), Thiazide Diuretics (granulocytopenia)
administration and dialysis.
Increases risk of adverse or toxic effects of the following
Hepatic Impairment: drugs:
Use with caution. Dose adjustment may be needed. Amiodarone (pulmonary toxicity)
Antineoplastic Agents, Anthracycline,
Give 75% of normal dose if transaminase levels are >3 Sargramostim (pulmonary toxicity)
times upper limit of normal or bilirubin is 3.1-5 mg/dl
Reduces diagnostic effect of Coccidioides immitis Skin Test
Obesity:
Maximum dose should not exceed 0.1 mg/kg daily. Avoid concomitant use with:
Enhances therapeutic effect of Cyclophosphamide:
Precautions: Roflumilast (immunosuppressive effect)
WARNING: Hazardous agent; use appropriate
precautions for handling and disposal. Enhances therapeutic effect of the following drugs:
Tofacitinib [except antirheumatic doses of Methotrexate
or nonbiologic DMARD] (immunosuppressive effect)
L

Adverse Drug Reactions:

Common: Alopecia, amenorrhea, azoospermia, gonadal
Increases metabolism of Cyclophosphamide:
suppression, oligospermia, oogenesis impaired, sterility,
CYP2B6 Inducers
abdominal pain, anorexia, diarrhea, mucositis, nausea,
vomiting, stomatitis, hemorrhagic cystitis, anemia,
Increases risk of adverse or toxic effects of
leukopenia, myelosuppression, neutropenia,
Cyclophosphamide:
neutropenic fever, thrombocytopenia, infection
Belimumab, Dipyrone (agranulocytosis, pancytopenia),
Less Common: Acute respiratory distress syndrome,
Etanercept (solid cancer development), Pimecrolimus
anaphylactic reactions, anaphylaxis, arrhythmias,
Tacrolimus, Topical
bladder or urinary fibrosis, blurred vision, cardiac
tamponade, cardiotoxicity, confusion, dizziness,
Increases risk of adverse or toxic effects of the following
dyspnea, decreased ejection fraction, erythema
drugs:
multiforme, gastrointestinal hemorrhage, hearing
Clozapine (agranulocytosis), Leflunomide (hematologic
disorders, heart block, heart failure, hematuria,
toxicity), Natalizumab (concurrent infection), Vaccines
hemopericardium, hemorrhagic colitis, hemorrhagic
(Live)
myocarditis, hemorrhagic ureteritis, hepatic sinusoidal
obstruction syndrome, hepatitis, hepatotoxicity,
Increases serum concentration of Succinylcholine
hypersensitivity reactions, hyperuricemia, hypokalemia,
hyponatremia, interstitial pneumonitis, interstitial
Reduces therapeutic effect of the following drugs:
pulmonary fibrosis, jaundice, latent infection
BCG (Intravesical), Vaccines (Inactivated) [complete all
reactivation, malaise, acute mesenteric ischemia,
age-appropriate vaccinations at least 2 weeks prior to
methemoglobinemia, multiorgan failure, myocardial
starting Cyclophosphamide; if vaccinated during
necrosis, neurotoxicity, neutrophilic eccrine hidradenitis,
Cyclophosphamide therapy, revaccinate at least 3
ovarian fibrosis, pancreatitis, pericarditis, pigmentation
months after discontinuation], Vaccines (Live) [do not
changes (skin, fingernails), pneumonia, pulmonary
administer vaccines for at least 3 months after
hypertension, pulmonary infiltrates, pulmonary veno--
Cyclophosphamide therapy]
occlusive disease, pyelonephritis, radiation recall, rash,
renal tubular necrosis, reversible posterior
Reduces therapeutic effect of Cyclophosphamide:
leukoencephalopathy syndrome, rhabdomyolysis,
Echinacea
secondary malignancy, septic shock, sepsis, SIADH,
Stevens-Johnson syndrome, testicular atrophy,
Administration: If reconstituted in normal saline (NS),
thrombocytopenia, thrombotic disorders, toxic epidermal
administer by direct IV injection, IVPB, or continuous IV
necrolysis, toxic megacolon, tumor lysis syndrome,
infusion.
weakness, wound healing impaired
Increase normal fluid intake during and for 1–2 days
after treatment to minimize bladder toxicity. Most adult
Drug Interactions:
patients will require at least 2 L of fluid intake per day.
Monitor closely with:
High-dose regimens should be accompanied by vigorous
Decreases metabolism of Cyclophosphamide:
hydration.
CYP2B6 Inhibitors
Infusion rate may vary based on protocol (refer to specific
Enhances therapeutic effect of Cyclophosphamide:
protocol for infusion rate). Administer by direct IV
Cyclosporine (immunosuppressive effect)
injection (if reconstituted in NS), IVPB, or continuous IV
Trastuzumab (neutropenic effect)
infusion.

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ANTINEOPLASTIC AND IMMODULATING AGENTS

NOTE: Cyclophosphamide is associated with a moderate to For patients with bilirubin >3 mg/dL, administer 25% of
high emetic potential depending on dose, regimen, or dose.
administration route. Antiemetics are recommended to
prevent nausea and vomiting. Obesity:
Utilize patient’s actual body weight (full weight) for
To minimize bladder toxicity, increase normal fluid intake calculation of body surface area-based or weight-based
during and for 1-2 days after cyclophosphamide dose. dosing, particularly when the intent of therapy is curative.
Most adult patients will require a fluid intake of at least If a dose reduction is utilized due to toxicity, consider
2 L daily. High-dose regimens should be accompanied by resumption of full weight-based dosing with subsequent
vigorous hydration with mesna therapy. cycles, once cause of toxicity is resolved.

See General Information on Nitrogen Mustard Analogues Precautions:

under Antineoplastic Agents in Chapter 8: Antineoplastic
and Immunomodulating Agents for other information. HIGH-ALERT MEDICATION
The Institute for Safe Medication Practices (ISMP)
Pregnancy Category: D includes this drug in the list of drug classes with a
heightened risk of causing significant patient harm
ATC Code: L01AA01 when used in error.

Rx IFOSFAMIDE WARNING: Nephrotoxicity can be severe and may

result in renal failure.

L
Inj.: 1 g and 2 g powder, vial (IV infusion)
Myelosuppression is increased with single high doses
A nitrogen mustard analogue structurally related to and decreased renal function. Severe
cyclophosphamide and is inhibitory to protein synthesis and myelosuppression may occur when administered
DNA synthesis by causing crosslinking of DNA strands in combination with other chemotherapy agents or
and by binding with nucleic acids and other intracellular radiation therapy. Antimicrobial prophylaxis may
structures. be necessary in some neutropenic patients.

Indication: Treatment of germ cell testicular cancer (third- CNS toxicities can be severe and may result in
line), lymphoma, sarcoma, solid tumors encephalopathy and death.

Contraindications: Urinary outflow obstruction; severe renal Hemorrhagic cystitis can be severe and can be
and hepatic impairment reduced by the prophylactic use of mesna.

Dose:
Testicular cancer, by IV infusion, ADULT, WARNING: Hazardous agent; use appropriate
combination chemotherapy with mesna: 1,200 mg/m2 precautions for handling and disposal.
daily for 5 days over at least 30 minutes, repeat every 3
weeks or after hematologic recovery;
VIP regimen (etoposide, mesna, cisplatin) or VeIP Adverse Drug Reactions:
regimen (vinblastine, mesna, cisplatin): 1,200 mg/m2 Common: CNS toxicity, encephalopathy, fever, alopecia,
daily for 5 days every 3 weeks for 4 cycles. metabolic acidosis, nausea, vomiting, anorexia, anemia,
Lymphoma, sarcoma, solid tumors, by IV infusion, ADULT, thrombocytopenia, phlebitis, leukopenia, neutropenic
Regimen 1: 8–12 g/m2 divided over 3–5 days, repeat fever, liver dysfunction, renal impairment, hematuria,
course every 2–4 weeks; infection, somnolence, depression, hallucinations
Regimen 2: 6 g/m2 divided over 5 days, repeat course Less Common: Abdominal pain, acute renal failure, acute
every 3 weeks; respiratory distress syndrome, acute tubular necrosis,
Regimen 3: 5–6 g/m2 (maximum, 10 g), give as a single agranulocytosis, allergic reaction, alveolitis (allergic),
24-hour infusion, repeat course every 3 to 4 weeks; amenorrhea, aminoaciduria, amnesia, anaphylactic
CHILD, 1,200 to 1,800 mg/m2/day for 3 to 5 days every 21 reaction, angina, angioedema, anuria, arrhythmia,
to 28 days. arthralgia, atrial ectopy, atrial fibrillation, atrial flutter,
asterixis, azoospermia, bladder irritation, bleeding,
Dose Adjustment: blurred vision, bone marrow failure, bradyphrenia,
Renal Impairment: bronchospasm, bradycardia, bundle branch block,
Consider dose reduction. Ifosfamide and metabolites are capillary leak syndrome, cardiac arrest, cardiogenic
excreted renally and may accumulate in patients with shock, cardiotoxicity, catatonia, cardiomyopathy, cecitis,
renal dysfunction. chest pain, chills, cholestasis, chronic renal failure,
For patients with CrCl <10 mL/min, Ifosfamide is coagulopathy, conjunctivitis, constipation, cough, colitis,
not recommended. cylindruria, cytolytic hepatitis, delirium, delusion,
Ifosfamide and metabolites are dialyzable. dermatitis, disseminated intravascular coagulation, DVT,
Hepatic Impairment: dysarthria, diarrhea, dysesthesia, dyspnea, dysuria,
Extensively hepatically metabolized to both active and echolalia, edema, decreased ejection fraction,
inactive metabolites. Use with caution. enterocolitis, enuresis, enzymuria, erythema, decreased

315
 ANTINEOPLASTIC AND IMMODULATING AGENTS

estrogen, extrapyramidal disorder, facial swelling, Increases risk of adverse or toxic effects of Ifosfamide:
Fanconi syndrome, fatigue, fecal incontinence, flushing, Allopurinol (bone marrow suppression), Busulfan
GI hemorrhage, gait disturbance, glycosuria, (hemorrhagic cystitis), Cisplatin, Denosumab (serious
granulocytopenia, growth retardation (children), hearing infections)
loss, heart failure, hemolytic uremic syndrome,
hemorrhagic cystitis, hepatic failure, hemolytic anemia, Reduces diagnostic effect of Coccidioides immitis Skin Test
hepatic sinusoidal obstruction syndrome (SOS), hepatitis
fulminant, hepatitis (viral), hepatorenal syndrome, Avoid concomitant use with:
herpes zoster, hyperhidrosis, hypoxia, hypertension, Decreases serum concentration of Ifosfamide:
hypotension, hyperpigmentation, hypersensitivity Dabrafenib
reactions, hypesthesia, ileus, hypocalcemia,
hypokalemia, hyponatremia, hypophosphatemia, Enhances therapeutic effect of Ifosfamide:
infertility, infusion site reactions, immunosuppression, Roflumilast (immunosuppressive effect)
interstitial lung disease, interstitial pneumonitis,
jaundice, increased LDH, leukoencephalopathy, limb Enhances therapeutic effect of Tofacitinib
pain, logorrhea, lymphopenia, malaise, mania, mental (immunosuppressive effect)
status change, MI, mucosal inflammation or ulceration,
methemoglobinemia, multiorgan failure, muscle Increases metabolism of Ifosfamide:
twitching, mutism, myalgia, myocardial hemorrhage, CYP2B6 Inducers
myocarditis, neuralgia, nail disorder, nephrogenic
diabetes insipidus, neutropenia, oligospermia, Increases risk of adverse or toxic effects of Ifosfamide:
osteomalacia, oliguria, ovarian failure, ovulation Dipyrone (agranulocytosis, pancytopenia),
disorder, pain, palmar-plantar erythrodysesthesia Pimecrolimus, Tacrolimus (Topical)
L

syndrome, pancreatitis, pancytopenia, paranoia, panic

attack, paresthesia, pericardial effusion, pericarditis, Increases risk of adverse or toxic effects of the following
peripheral neuropathy, petechiae, phosphaturia, drugs:
physical deterioration, pleural effusion, Pneumocystis Clozapine (agranulocytosis), Leflunomide (hematologic
jiroveci pneumonia, pneumonia, pneumonitis, toxicity such as pancytopenia, agranulocytosis, and/or
pollakiuria, polydipsia, polyneuropathy, polyuria, portal thrombocytopenia), Natalizumab (concurrent infection),
vein thrombosis, premature atrial contractions, Vaccines (Live)
progressive multifocal leukoencephalopathy, premature
menopause, proteinuria, pruritus, pulmonary edema, Reduces therapeutic effect of Ifosfamide:
pulmonary embolism, pulmonary fibrosis, pulmonary Echinacea
hypertension, abnormal QRS complex, radiation recall
dermatitis, rash, renal parenchymal damage, renal Reduces therapeutic effect of the following drugs:
tubular acidosis, respiratory failure, rickets, reversible BCG, Vaccines (Inactivated) [complete all age-
posterior leukoencephalopathy syndrome (RPLS), appropriate vaccinations at least 2 weeks prior to
seizures, rhabdomyolysis, salivation, secondary starting Ifosfamide; if vaccinated during Ifosfamide
malignancy, sepsis, septic shock, SIADH, skin necrosis, therapy, revaccinate at least 3 months after
impaired spermatogenesis, status epilepticus, Stevens- discontinuation], Vaccines (Live) [do not administer
Johnson syndrome, toxic epidermal necrolysis, vaccines for at least 3 months after Ifosfamide therapy]
stomatitis, abnormal ST-segment, supraventricular
extrasystoles, sterility, tachycardia, tinnitus, Administration: Administer IV infusion over at least 30
tubulointerstitial nephritis, tumor lysis syndrome, T-wave minutes (infusion times may vary by protocol; refer to
inversion, uremia, urticaria, vasculitis, ventricular specific protocol for infusion duration) with adequate
extrasystoles, ventricular failure, ventricular fibrillation, hydration of at least 2 L of oral or IV fluid daily.
ventricular tachycardia, vertigo, visual impairment,
wound healing impairment NOTE: Administer with mesna and hydration of at least 2 L
Severe (Potentially Fatal): Severe myelosuppression, of oral or IV fluid per day to prevent bladder toxicity.
hemorrhagic cystitis, nephrotoxicity, cardiotoxicity, coma
Associated with a moderate emetic potential.
Drug Interactions: Antiemetics are recommended to prevent nausea and
NOTE: Ifosfamide is a substrate of CYP2B6 (major), vomiting.
CYP2C19 (minor), CYP2C8 (minor), CYP2C9 (minor),
CYP3A4 (minor). See General Information on Nitrogen Mustard Analogues
under Antineoplastic Agents in Chapter 8: Antineoplastic
Monitor closely with: and Immunomodulating Agents for other information.
Decreases metabolism of Ifosfamide:
CYP2B6 Inhibitors Pregnancy Category: D

Enhances therapeutic effect of Ifosfamide: ATC Code: L01AA06

Trastuzumab (neutropenic effect)

Enhances therapeutic effect of Vitamin K Antagonists, e.g.,

Warfarin (anticoagulant effect)

316
ANTINEOPLASTIC AND IMMODULATING AGENTS

Precautions:
Rx MELPHALAN
WARNING: Hazardous agent; use appropriate
precautions for handling and disposal.
Oral: 2 mg tablet

A derivative of mechlorethamine, melphalan is an alkylating Adverse Drug Reactions:

agent that acts on both resting and rapidly dividing tumor Common: Nausea, vomiting, diarrhea, oral ulceration,
cells. It inhibits DNA and RNA syntheses and crosslinks myelosuppression, anemia, thrombocytopenia,
DNA strands. leukopenia, secondary malignancy (dose and duration
dependent)
Indications: Treatment of multiple myeloma, polycythemia Less Common: Agranulocytosis, allergic reactions, alopecia,
vera, and nonresectable epithelial ovarian carcinoma amenorrhea, bleeding (high doses), bone marrow failure
(irreversible), cardiac arrest, cardiotoxicity (high doses),
Contraindications: Resistance to prior melphalan therapy; encephalopathy, hemolytic anemia, hemorrhagic cystitis,
severe bone marrow suppression; pregnancy hepatitis, interstitial pneumonitis, infection, jaundice,
mucositis (high doses), ovarian suppression, paralytic
Dose: ileus (high doses), pruritus, pulmonary fibrosis, radiation
Multiple myeloma, remission induction treatment, by myelopathy, rash (maculopapular), renal toxicity (high
mouth, ADULT, used in combination with other doses), seizure (high doses), sepsis, SIADH, skin
chemotherapeutic agents (VMP regimen) 9mg/m2 on hypersensitivity, sterility, stomatitis, testicular
days 1 to 4 of a 28-day cycle suppression, tingling sensation, vasculitis, warmth
Palliative treatment, by mouth, ADULT, initially 6 mg once sensation
Rare: Anaphylaxis

L
daily for 2–3 weeks, followed by up to 4 weeks rest, then
2 mg daily as maintenance dose as hematologic recovery
begins; or Drug Interactions:
10 mg daily for 7–10 days, then 2 mg daily as Monitor closely with:
maintenance dose after WBC >4,000 cells/mm3 and Enhances therapeutic effect of Melphalan:
platelets >100,000 cells/mm3 for approximately 4–8 Trastuzumab (neutropenic effect)
weeks, titrate maintenance dose to hematologic
response; or 0.15 mg/kg daily for 7 days, with 2–6 Increases risk of adverse or toxic effects of Melphalan:
weeks of rest, followed by <0.05 mg/kg daily as Denosumab (serious infections)
maintenance dose as hematologic recovery begins; or
0.25 mg/kg daily for 4 days (0.2 mg/kg daily for 5 days), Increases risk of adverse or toxic effects of the following
repeat at 4– to 6–week intervals as ANC and platelet drugs:
counts return to normal; Carmustine (lung toxicity), Cyclosporine, Systemic
Usually combined with corticosteroids and rest period of (nephrotoxic effect)
up to 6 weeks to allow hematologic recovery, then repeat
the course or start maintenance treatment with 1–3 mg Reduces diagnostic effect of Coccidioides immitis Skin Test
or up to 50 micrograms/kg daily, adjust therapy to
produce moderate leucopenia (WBC count of 3,000 to Avoid concomitant use with:
3,500 cells/mm3). Enhances therapeutic effect of Melphalan:
Ovarian carcinoma, by mouth, ADULT, 0.2 mg/kg daily for 5 Roflumilast (immunosuppressive effect)
days, repeat every 4–5 weeks.
Polycythemia vera, by mouth, ADULT, 6–10 mg daily for 5– Enhances therapeutic effect of Tofacitinib
7 days; 2–4 mg daily for remission induction; (immunosuppressive effect)
maintenance dose, 2–6 mg weekly.
Increases risk of adverse or toxic effects of Melphalan:
Dose Adjustment: Dipyrone (agranulocytosis, pancytopenia), Nalidixic Acid
Geriatric: (necrotic enterocolitis in pediatric patients),
Toxicity may be increased with the elderly. Initiate therapy Pimecrolimus, Tacrolimus (Topical)
at the lower end of the dosing range.
Increases risk of adverse or toxic effects of the following
Renal Impairment: drugs:
In moderate-to-severe renal impairment, consider dose Clozapine (agranulocytosis), Leflunomide (hematologic
reduction. toxicity such as pancytopenia, agranulocytosis, and/or
In patients with multiple myeloma or ovarian thrombocytopenia), Natalizumab (concurrent infection),
adenocarcinoma, reduce dose by 50% for usual dose. Vaccines (Live)
Closely monitor patients with azotemia.
Reduces therapeutic effect of Melphalan:
Hepatic Impairment: Echinacea
Melphalan is hepatically metabolized, however, dose
adjustment does not appear to be necessary. Reduces therapeutic effect of the following drugs:
BCG (Intravesical), Vaccines (Inactivated) [complete all
age-appropriate vaccinations at least 2 weeks prior to
starting Melphalan; if vaccinated during Melphalan
therapy, revaccinate at least 3 months after

317
 ANTINEOPLASTIC AND IMMODULATING AGENTS

discontinuation], Vaccines (Live) [do not administer Extravasation (may result in tissue damage and severe
vaccines for at least 3 months after Melphalan therapy] pain)
Gastrointestinal toxicity; hepatic effects (e.g. hepatotoxicity
TEST INTERACTION. Produces a false-positive result with Coomb’s with hepatocellular necrosis and hepatic vein
test. thrombosis)
Renal and hepatic impairment (half-life is increased)
Administration: Administer on an empty stomach. Food
reduces oral absorption. Avoid excessive alcohol intake. Adverse Drug Reactions:
Common: Alopecia, nausea, vomiting, anorexia,
See General Information on Nitrogen Mustard Analogues myelosuppression, thrombocytopenia, pain on infusion,
under Antineoplastic Agents in Chapter 8: Antineoplastic leukopenia
and Immunomodulating Agents for other information. Less Common: Anaphylactic reactions, anemia, diarrhea,
eosinophilia, erythema, facial flushing, facial
Pregnancy Category: D paresthesia, flulike syndrome, hepatic necrosis, hepatic
vein occlusion, photosensitivity, rash, paresthesia, taste
ATC Code: L01AA03 alteration, urticaria

Drug Interactions:
OTHER ALKYLATING AGENTS Monitor closely with:
Decreases metabolism of Dacarbazine:
CYP1A2 Inhibitors, CYP2E1 Inhibitors
Rx DACARBAZINE
Enhances therapeutic effect of Dacarbazine:
L

Inj.: 100 mg and 200 mg powder, vial (IV, IV infusion) Trastuzumab (neutropenic effect)

A non-cell cycle specific antineoplastic that functions as an Increases risk of adverse or toxic effects of Dacarbazine:
alkylating agent after it has been activated in the liver. Denosumab (serious infections)

Indications: Treatment of metastatic melanoma; Hodgkin Increases risk of adverse or toxic effects of the following
lymphoma drugs:
Leflunomide (hematologic toxicity such as pancytopenia,
Dose: agranulocytosis, and/or thrombocytopenia), MAO
Metastatic melanoma, by IV injection, ADULT, 250 mg/m2 Inhibitors [except Linezolid, Tidezolid] (orthostatic
per dose days 1–5, every 3 weeks; or 2–4.5 mg/kg per hypotension)
day for 10 days, repeat at 4-week intervals; by IV
infusion, ADULT, 850 mg/m2 once every 3 weeks. Reduces diagnostic effect of Coccidioides immitis Skin Test
Hodgkin’s lymphoma, by IV injection, ABVD regimen, ADULT,
375 mg/m2 per dose on day 1 to be repeated every 15 Avoid concomitant use with:
days; CHILD, 150 mg/m2 for 5 days, repeat at 4-week Decreases metabolism of Dacarbazine:
intervals. CYP1A2 Inhibitors, CYP2E1 Inhibitors

Dose Adjustment: Enhances therapeutic effect of Dacarbazine:

Renal Impairment: Roflumilast (immunosuppressive effect)
Use with caution and monitor for toxicity. Consider dose
reduction as follows: Enhances therapeutic effect of Tofacitinib
CrCl 46-60 mL/min Administer 80% of dose (immunosuppressive effect)
CrCl 31-45 mL/min Administer 75% of dose Increases metabolism of Dacarbazine:
CrCl <30mL/min Administer 70% of dose CYP1A2 Inducers

Hepatic Impairment: Increases risk of adverse or toxic effects of Dacarbazine:

May cause hepatotoxicity. Use with caution and monitor Dipyrone (agranulocytosis, pancytopenia),
closely for signs of toxicity. Consider dose reduction. Pimecrolimus, Tacrolimus (Topical)
Precautions:
WARNING: Carcinogenic and/or teratogenic in Increases risk of adverse or toxic effects of the following
animals. Adverse effects have been observed in drugs:
animal studies. Clozapine (agranulocytosis), Natalizumab (concurrent
infection), Vaccines (Live)
WARNING: Hazardous agent; use appropriate
precautions for handling and disposal. Increases serum concentration of Dacarbazine:
Vemurafenib
Anaphylaxis; bone marrow suppression (leukopenia and Reduces therapeutic effect of Dacarbazine:
thrombocytopenia may be severe; may result in Echinacea
treatment delays or discontinuation)

318
ANTINEOPLASTIC AND IMMODULATING AGENTS

Reduces therapeutic effect of the following drugs: (maximum, 15 mg/dose); CHILD ≥3 years, 12 mg/dose;
BCG (Intravesical), Vaccines (Inactivated) [complete all CHILD 2 years old, 10 mg/dose; CHILD 1 year old, 8
age-appropriate vaccinations at least 2 weeks prior to mg/dose; CHILD <1 year, 6 mg/dose.
starting Dacarbazine; if vaccinated during Dacarbazine Meningeal leukemia, early intensification, CALGB 8811
therapy, revaccinate at least 3 months after regimen, by intrathecal injection, ADULT, 15 mg day 1 of
discontinuation], Vaccines (Live) [do not administer early intensification phase, repeat in 4 weeks; by IV
vaccines for at least 3 months after Dacarbazine infusion, CHILD, 1,000 mg/m2 over 24 hours in week 1
therapy] and 20 mg/m2intramuscularly on day 1 of week 2,
repeat very 2 weeks for 12 courses (use 50% dose
Administration: Administer by slow IV infusion over 30 to 60 reduction if on same day as intrathecal methotrexate); or
minutes. Rapid infusion may cause severe venous 5,000 mg/m2 over 24 hours days on 8, 22, 36, and 50
irritation. of consolidation phase with leucovorin rescue
Meningeal leukemia, CNS prophylaxis or interim
NOTE: Associated with a moderate emetic potential. maintenance phase, CALGB 8811 regimen, by
Antiemetics are recommended to prevent nausea and intrathecal injection, ADULT, 15 mg on day 1, 8, 15, 22,
vomiting. and 29; then by mouth, 20 mg/m2 day 36, 43, 50, 57,
and 64
Pregnancy Category: C Meningeal leukemia, CNS prophylaxis, by intrathecal
injection, ADULT, 12 mg on day 2 of each cycle, duration
ATC Code: L01AX04 depends on risk
Meningeal leukemia, interim maintenance, by mouth,
CHILD, 15 mg/m2 on day 0, 7, 14, 21, 28, and 35; by IV
ANTIMETABOLITES injection, CHILD, 100 mg/m2 on day 0, 10, 20, 30, and

L
40, escalate by 50 mg/m2 each dose
FOLIC ACID ANALOGUES Meningeal leukemia, maintenance, CALGB 8811 regimen,
by mouth, ADULT, 20 mg/m2 days 1, 8, 15, and 22 every
4 weeks for 24 months from diagnosis; CHILD, 20 mg/m2
Rx METHOTREXATE days 7, 14, 21, 28, 35, 42, 49, 56, 63, 70, and 77.
Meningeal leukemia, maintenance, in combination with
prednisone, vincristine, and mercaptopurine, by IV
Oral: 2.5 mg tablet (as base or sodium salt) injection, ADULT, 10 mg/m2 daily for 5 days every month
Inj.: 5 mg/mL, 3 mL vial (IM, IV) (as sodium salt) for 2 years; by IM injection, CHILD, 20 mg/m2 weekly on
25 mg/mL, 2 mL ampule/vial (IM, IV, Intrathecal) (as day 1 of weeks 25–130
base) Meningeal leukemia, dose-intensive regimen, in
25 mg/mL, 2 mL and 20 mL vial (IM, IV, Intrathecal) combination with cytarabine, alternates with Hyper-
(as sodium salt, preservative-free) CVAD, by IV injection, ADULT, 200 mg/m2 over 2 hours,
100 mg/mL, 10 mL vial (as base) followed by 800 mg/m2 over 24 hours beginning on day
100 mg/mL, 10 mL vial (IM, IV, intrathecal) (as 1, followed by leucovorin rescue of even numbered
sodium salt, preservative-free) cycles
Breast cancer, in combination with cyclophosphamide and
An antimetabolite antineoplastic that acts as an antagonist fluorouracil, by IV injection, ADULT, 40 mg/m2 on days 1
of folic acid. Methotrexate competitively inhibits the and 8 every 4 weeks for 6–12 cycles; ADULT>60 years,
enzyme dihydrofolatereductase and prevents the 30 mg/m2 on days 1 and 8 every 4 weeks for up to 12
formation of tetrahydrofolate, subsequently inhibiting cycles
the formation of DNA and RNA. It is most active against Choriocarcinoma, chorioadenoma, gestational
cells in the S phase of the cell cycle. trophoblastic diseases, by mouth or IM injection, ADULT,
15–30 mg daily for a 5-day course, may repeat for 3–5
Indications: Therapy of acute lymphoblastic leukemia (ALL); courses; by IV infusion, ADULT, 100 mg/m2 over 30
prophylaxis and treatment of ALL meningeal leukemia; minutes followed by 200 mg/m2 IV over 12 hours, with
treatment of trophoblastic neoplasms (gestational leucovorin 24 hours after the start of methotrexate,
choriocarcinoma, chorioadenoma destruens and administer second course if hCG levels plateau for 3
hydatidiform mole); breast cancer; head and neck cancer consecutive weeks
(epidermoid); cutaneous T-cell lymphoma (advanced Head and neck cancer, advanced, by IV injection, ADULT, 40
mycosis fungoides); lung cancer (squamous cell and mg/m2 once weekly until disease progression or
small cell); advanced non-Hodgkin’s lymphomas (NHL); unacceptable toxicity.
osteosarcoma Non-Hodgkin’s lymphoma, CODOX­M/IVAC regimen, cycles
1 and 3 of CODOX­M, alternating with IVAC, by IV
Contraindications: Breastfeeding injection, ADULT >65 years, 100 mg/m2 over 1 hour on
day 10, followed by 900 mg/m2 over 23 hours with
Dose: leucovorin rescue; ADULT ≤65 years, 300 mg/m2 over 1
Acute Lymphoblastic Leukemia, maintenance phase of hour on day 10, followed by 2700 mg/m2 over 23 hours
treatment, typically in combination with mercaptopurine, with leucovorin rescue.
by mouth, ADULT 20 mg/m2 weekly. Non-Hodgkin’s lymphoma, hyper-CVAD alternating with
Meningeal leukemia, prophylaxis and treatment, by high-dose methotrexate or cytarabine regimen, by IV
intrathecal injection, ADULT, 12 mg every 2–7 days, injection, ADULT, 1000 mg/m2 over 24 hours on day 1
continue for 1 dose beyond CSF cell count normalization during even courses (days 2, 4, 6, and 8) of 21-day

319
 ANTINEOPLASTIC AND IMMODULATING AGENTS

treatment cycles; by IV bolus, ADULT, 200 mg/m2 on day

1 followed by IV infusion of 800 mg/m2 over 24 hours Errors have occurred (some resulting in death) when
during even courses (days 2, 4, 6, and 8) of 21-day methotrexate was administered as a “daily” dose
treatment cycles, with leucovorin rescue. instead of a “weekly” dose intended for some
T-cell lymphoma, early stages, by mouth or IM injection, indications.
ADULT, 5–50 mg once weekly or 15 to 37.5 mg twice
weekly; by mouth, 25 mg once weekly, may increase to Do NOT use methotrexate formulations and/or
50 mg once weekly; by IV injection, CHILD, 15 mg/m2 on diluents containing preservatives for intrathecal or
day 0, 7, 14, 21, 28, and 35; for low-dose therapy, 40 high-dose methotrexate therapy.
mg/m2 on day 2; for high-dose therapy, 500 mg/m2 over
30 minutes followed by 4,500 mg/m2 over 23.5 hours Methotrexate-induced lung disease, including acute
on day 22 with leucovorin rescue. or chronic interstitial pneumonitis, is a potentially
Osteosarcoma, MAP regimen, by IV injection, ADULT ≤30 dangerous lesion, which may occur acutely at any
years, 12 g/m2 over 4 hours, followed by leucovorin time during therapy and may require interruption
rescue for 4 doses during induction (before surgery) at of treatment and careful investigation.
weeks 3, 4, 8, and 9, and for 8 doses during
maintenance (after surgery) at weeks 15, 16, 20, 21, 25, Potentially fatal opportunistic infections, specially
26, 30, and 31, in combination with doxorubicin and Pneumocystis carinii and Pneumocystis jirovecii
cisplatin (maximum dose, 20 g); CHILD, 12 mg/m2 of pneumonia, may occur.
methotrexate at weeks 0, 1, 5, 6, 13, 14, 18, 19, 23, 24,
37, 38 followed by leucovorin 15 mg PO every six hours
for 10 doses. Surgery follows with doxorubicin and Concurrent administration with NSAIDs may cause
cisplatin. severe bone marrow suppression, aplastic
L

anemia, and GI toxicity; do not administer NSAIDS

Dose Adjustment: prior to or during high-dose methotrexate therapy.
Geriatric:
Reduce recommended doses when initiating therapy due to
possible decreased metabolism, reduced renal function, WARNING: Hazardous agent; use appropriate
and presence of interacting diseases and drugs, as well precautions for handling and disposal.
as decreased
CSF volume and turnover. Use caution and monitor closely Chronic leukoencephalopathy; chemical arachnoiditis; Bone
due to increased risk of toxicity. marrow suppression (e.g. anemia, leukopenia, or
thrombocytopenia)
Renal Impairment: CNS effects (e.g. seizures, dizziness, fatigue)
For patients with CrCl 46–60 mL/minute, administer 65% Dermatologic toxicity (e.g. TEN, Stevens-Johnson syndrome,
of the dose. exfoliative dermatitis, skin necrosis, and erythema
For patients with CrCl 31–45 mL/minute and patients on multiforme)
intermittent hemodialysis or continuous renal Gastrointestinal toxicity (e.g. hemorrhagic enteritis or death
replacement therapy (CRRT), administer 50% of the from intestinal perforation); peptic ulcer disease and
dose. ulcerative colitis (diarrhea and stomatitis may occur);
For patients with CrCl <30 mL/minute, avoid use. hepatotoxicity (e.g. acute and potentially fatal chronic
hepatotoxicity, fibrosis, cirrhosis)
Renal Impairment in Children: Renal impairment (may cause acute renal failure with high
For patients with CrCl 10–50 mL/minute/1.73 m2 and doses; monitor renal function and methotrexate levels
patients on continuous renal replacement therapy closely)
(CRRT), administer 50% of the dose. Pneumonitis; Malignant lymphomas; Tumor lysis syndrome;
For patients with CrCl <10 mL/minute/1.73 m2 andpatients Fertility effects (e.g. oligospermia, menstrual
on intermittent hemodialysis or continuous ambulatory dysfunction)
peritoneal dialysis (CAPD), administer 30% of the dose. Radiotherapy (concomitant use with radiotherapy may
increase the risk of soft tissue necrosis and
Hepatic Impairment: osteonecrosis)
Use with caution in patients with impaired hepatic function Elderly (increased risk for toxicity)
or preexisting hepatic damage. Pregnancy (may cause fetal death and/or congenital
For patients with bilirubin 3.1–5 mg/dL or transaminases anomalies; low birth weight and developmental delay);
>3 times ULN, administer 75% of the dose. lactation (low amounts of methotrexate are excreted into
For patients with bilirubin >5 mg/dL, avoid use. breastmilk)
Precautions: SKILLED TASKS. May impair ability to perform tasks, which
WARNING: Methotrexate should be used only by require mental alertness, like driving or operating
health care providers whose knowledge and machinery.
experience include the use of antimetabolite
therapy and only in life-threatening neoplastic Adverse Drug Reactions:
diseases due to the possibility of serious toxic, NOTE: Adverse reactions vary by route and dosage.
potentially fatal reactions. Serious and fatal Common: Arterial thrombosis, cerebral thrombosis, chest
toxicities have occurred at all dose levels. pain, deep vein thrombosis, hypotension, pericardial
effusion, pericarditis, pulmonary embolism, retinal

320
ANTINEOPLASTIC AND IMMODULATING AGENTS

thrombosis, thrombophlebitis, vasculitis, chills, Avoid concomitant use with:

dizziness, headache, abnormal cranial sensation, brain Enhances therapeutic effect of Methotrexate:
disease, chemical arachnoiditis, cognitive dysfunction, Roflumilast (immunosuppressive effect)
drowsiness, fatigue, leukoencephalopathy, malaise,
mood changes, neurological signs and symptoms (high Increases risk of adverse or toxic effects of Methotrexate:
doses), severe neurotoxicity, alopecia, speech Acitretin (hepatotoxic effect), Cyclosporine, Systemic
disturbance, skin photosensitivity, skin rash, acne (nausea, vomiting, oral ulcers, hepatotoxicity and/or
vulgaris, dermal ulcer, diaphoresis, skin abnormalities nephrotoxicity), Dipyrone (agranulocytosis,
related to radiation recall, ecchymoses, erythematous pancytopenia), Foscarnet (nephrotoxic effect),
rash, erythema multiforme, furunculosis, Pimecrolimus, Sulfonamide derivatives, Tacrolimus
hyperpigmentation, hypopigmentation, exfoliative (Topical), Trimethoprim
dermatitis, skin necrosis, Stevens-Johnson syndrome,
toxic epidermal necrolysis, urticaria, telangiectasia, Increases risk of adverse or toxic effects of the following
decreased libido, diabetes mellitus, gynecomastia, drugs:
menstrual disease, diarrhea, nausea, vomiting, Clozapine (agranulocytosis), Cyclosporine, Systemic
stomatitis, abdominal distress, anorexia, aphthous (nephrotoxicity), Dipyrone (agranulocytosis,
stomatitis, enteritis, GI hemorrhage, gingivitis, pancytopenia), Natalizumab (concurrent infection),
hematemesis, intestinal perforation, melena, azotemia, Vaccines (Live)
cystitis, defective oogenesis, defective spermatogenesis,
impotence, dysuria, infertility, oligospermia, pancreatitis, Increases serum concentration of Methotrexate:
proteinuria, severe renal disease, vaginal discharge, Cyclosporine (Systemic), Dexketoprofen [avoid
hematuria, leukopenia (WBC <3000/mm3), concomitant administration with 15 mg methotrexate
agranulocytosis, anemia, bone marrow depression weekly or more], Loop Diuretics e.g. Furosemide,

L
(nadir, 7–10 days), aplastic anemia, decreased NSAIDS, Probenecid, Salicylates e.g. Aspirin
hematocrit, eosinophilia, hypogammaglobulinemia,
gastric ulcer, lymphoma, lymphoproliferative disorder, Increases serum concentration of the following drugs:
lymphadenopathy, neutropenia, non-Hodgkin’s Cyclosporine (Systemic), Loop Diuretics e.g., Furosemide
lymphoma, tumor lysis syndrome, cirrhosis (chronic use),
hepatic failure, hepatic fibrosis (chronic use), Reduces therapeutic effect of the following drugs:
hepatotoxicity, hepatitis (acute), cryptococcosis, BCG (Intravesical), Loop Diuretics e.g. Furosemide,
anaphylactoid reaction, cytomegalovirus disease, herpes Vaccines (Inactivated) [complete all age-appropriate
simplex infection, herpes zoster, histoplasmosis, vaccinations at least 2 weeks prior to starting
infection, Pneumocystis jiroveci pneumonia, vaccinia Methotrexate; if vaccinated during Methotrexate
(disseminated), arthralgia, myalgia, myelopathy therapy, revaccinate at least 3 months after
(subacute), osteonecrosis (with radiotherapy), discontinuation], Vaccines (Live) [do not use
osteoporosis, stress fracture, blurred vision, concomitantly with high-dose Methotrexate (≥0.4 mg/kg
conjunctivitis, eye pain, visual disturbance, tinnitus, per week)]
renal failure, chronic obstructive pulmonary disease,
cough, epistaxis, pharyngitis, pneumonia, pulmonary Reduces therapeutic effect of Methotrexate:
alveolitis, pulmonary disease, pulmonary fibrosis, Echinacea
respiratory failure, upper respiratory tract infection,
fever, nodule, tissue necrosis Reduces absorption of Methotrexate:
Milk-rich Foods
Drug Interactions:
Monitor closely with: Administration:
Enhances therapeutic effect of Methotrexate: For oral administration, administer without regard to
Trastuzumab (neutropenic effect) food. This is the preferred route for low doses.

Enhances therapeutic effect of Tofacitinib For IV administration, administer as slow IV push at a

(immunosuppressive effect) rate of 10 mg/minute, as bolus injection, or as 24-hour
continuous infusion. The route and rate of administration
Increases risk of adverse or toxic effects of Methotrexate: depends on indication and/or protocol.
Systemic (hepatotoxicity), Denosumab (serious
infections), Leflunomide (pancytopenia and/or For intrathecal administration, do NOT prepare during
hepatotoxicity), Sulfasalazine (hepatotoxicity) the preparation of any other agents. After preparation,
store in an isolated location or container clearly marked
Increases risk of adverse or toxic effects of Tegafur with a label "intrathecal" use only. Administer only with
other medications intended for administration into the
Reduces absorption of Methotrexate: central nervous system.
Bile Acid Sequestrants
NOTE: Optimal intrathecal chemotherapy dosing should be
Reduces diagnostic effect of Coccidioides immitis Skin Test based on age rather than on body surface area (BSA) as
CSF volume correlates with age and not to BSA.

321
 ANTINEOPLASTIC AND IMMODULATING AGENTS

Doses ≥250 mg/m2 (≥12 g/m2in children) are Administer at the low end of the dosing range or increase
associated with moderate emetic potential. Antiemetics dosing interval to every 36–48 hours to avoid
may be recommended to prevent nausea and vomiting. accumulation.

Doses >500 mg/m2 require leucovorin calcium rescue. Renal Impairment in Children:
Doses between 100–500 mg/m2 may require leucovorin For CrCl ≤50 mL/minute/1.73 m2, pediatric patients
calcium rescue. receiving hemodialysis, continuous ambulatory
peritoneal dialysis (CAPD), or continuous renal
Monitoring High Dose Methotrexate Treatment replacement therapy (CRRT), administer every 48 hours.
Some renal adverse effects may be minimized with
Plasma MTX levels should also be monitored closely to hydration and prophylactic anti-hyperuricemic therapy.
detect any delay in MTX clearance. Depending on the
treatment protocol, plasma MTX assays may be Hepatic impairment:
appropriate at 24, 48, and 72 hours after the start of Administer at the low end of the dosing range with close
MTX infusion. Other protocols may require serum MTX monitoring for toxicity.
measurements at 36 hours (i.e. 12 hours after the end
of a 24-hour infusion) or at 42 hours from the start. NUDT15 Genetic Variation:
Importantly, leucovorin or folinic acid doses are adjusted For patients homozygous for either TPMT or NUDT15
based on plasma MTX drug levels, and other supportive- enzyme defect (or heterozygous for both), dose reduction
care measures such as hydration and alkalinization can of ≥50% may be required.
be fine-tuned to ensure adequate urine output.
TPMT Deficiency:
Pregnancy Category: X For patients with homozygous TPMT deficiency, i.e. little or
L

no TPMT activity, reduce initial dose of mercaptopurine

ATC Code: L01BA01; L04AX03 to 10%, with further adjustments based on the
occurrence of myelotoxicity.
For patients with heterozygous TPMT deficiency, i.e. low or
PURINE ANALOGUES intermediate TPMT activity, usual dose may be tolerated
but reduce dose as necessary.

Rx MERCAPTOPURINE Concomitant use of Allopurinol:

Administer 25–33% of the usual dose to avoid severe
myelotoxicity.
Oral: 50 mg tablet
Precautions:
A purine antagonist that acts as a false metabolite in DNA
and RNA syntheses, thereby inhibiting these processes. WARNING: Discontinued temporarily at the first sign
It is most active against cells in the S phase of the cell of an unexpected abnormally large or rapid
cycle. decrease in any of the formed elements of the
blood that is not attributable to disease or another
Indication: First-line maintenance therapy in conjunction drug. Decrease dose or discontinue use according
with methotrexate for the maintenance of drug-induced to severity and rapidity of hematologic effects.
remission in adults and pediatric patients with acute
lymphocytic leukemia (ALL)
Discontinue permanently if deterioration of liver
Contraindications: Patients whose disease showed prior function tests, jaundice, hepatomegaly, anorexia
resistance to mercaptopurine with tenderness in the right hypochondrion, or
other evidence of toxic hepatitis or biliary stasis
Dose: occurs, until the exact etiology is determined.
Acute lymphocytic leukemia, maintenance, by mouth,
ADULT and CHILD, 50 – 75 mg/m2 once daily in Avoid using the terms “6-mercaptopurine” or “6-
conjunction with methotrexate (evening schedule MP” as use of these terms has been associated
recommended), continue based on blood counts. with six-fold overdoses.
Depending upon the protocol used based on risk
stratification in acute lymphoblastic leukemia, dose in
maintenance phase for children varies between 50–75 WARNING: Hazardous agent. Use appropriate
mg/m2 orally. precautions for handling and disposal.

Dose Adjustment:
Geriatric: Hematologic effects (e.g. anemia, leukemia,
Initiate treatment at the low end of dosing range due to thrombocytopenia, or any combination of; consider bone
renal decline with age. marrow examination to distinguish between leukemia
progression, resistance to therapy, or marrow hypoplasia
Renal Impairment: induced by mercaptopurine).
Hepatic effects (hepatotoxicity manifested by rapid-onset
jaundice, cholestasis, ascites, hepatic encephalopathy,
elevated hepatic enzyme concentrations, possibly fatal

322
ANTINEOPLASTIC AND IMMODULATING AGENTS

hepatic necrosis, severe fibrosis, anorexia, diarrhea; Reduces therapeutic effect of the following drugs:
monitor hepatic function weekly with initiation, then BCG (Intravesical), Vaccines (live virus vaccines may
monthly, or more frequently as needed). progress to infection)
Immunosuppression (lethargy and confusion following
infection; common signs of infection, e.g. fever and Administration: Administer preferably on an empty stomach,
leukocytosis may not occur). 1 hour before or 2 hours after meals.
Malignancies and lymphoproliferative disorders
(hepatosplenic T-cell lymphoma has been reported). Pregnancy Category: D
Elderly (increased risk of toxicity).
ATC Code: L01BB02
Adverse Drug Reactions:
Common: Anorexia, bone marrow depression (onset: 7-10
days; nadir: 14 days; recovery: 21 days), diarrhea, PYRIMIDINE ANALOGUES
hyperbilirubinemia, hyperpigmentation, hyperuricemia,
malaise, nausea (minimal), oral lesion, pancreatitis, skin
rash, urticaria, vomiting Rx CAPECITABINE
Frequency Not Defined: Alopecia, anemia, ascites,
cholestasis, granulocytopenia, hemorrhage, hepatic
encephalopathy, hepatic fibrosis, hepatic injury, drug Oral: 150 mg and 500 mg tablet
fever, hepatomegaly, hepatosplenic T-cell lymphomas,
hepatotoxicity, hepatic necrosis, immunosuppression, Metabolized in the liver to form a fluorinated pyrimidine
intrahepatic cholestasis, infection, jaundice, leukopenia, antimetabolite that inhibits the enzyme thymidylate
lymphocytopenia, metastases, mucostasis, renal toxicity, synthetase, subsequently preventing DNA and RNA

L
neutropenia, oligospermia, pulmonary fibrosis, sprue- syntheses.
like symptoms, stomach pain, thrombocytopenia, toxic
hepatitis, ulcerative bowel lesion, uricosuria Indications: Palliative treatment of metastatic breast cancer
in patients resistant to paclitaxel and not candidates for
Drug Interactions: further anthracycline therapy; (in combination with
Monitor closely with: docetaxel) treatment of metastatic breast cancer in
Enhances therapeutic effect of Mercaptopurine: patients that failed to respond to or have relapsed
Sulfamethoxazole (myelosuppressive effect), following anthracycline chemotherapy; adjuvant therapy
Trastuzumab (neutropenic effect), Trimethoprim for patients with stage III (Dukes’ C) colon cancer after
(myelosuppressive effect) complete resection of the primary tumor; first-line
treatment of metastatic colorectal cancer
Increases risk of adverse or toxic effects of Mercaptopurine:
5-ASA Derivatives, e.g. Mesalamine, Olsalazine, Contraindications: Severe renal impairment (CrCl <30
Sulfasalazine (hematologic toxicity), Denosumab mL/minute)
(serious infections), Doxorubicin (hepatotoxicity)
Dose:
Reduces diagnostic effect of Coccidioides immitis Skin Test Breast cancer, metastatic, by mouth, ADULT, alone or in
combination with docetaxel, 1,250 mg/m2 twice daily for
Reduces therapeutic effect of Vitamin K Antagonists, e.g. 2 weeks, every 21 days
Warfarin (anticoagulant effect) Colorectal cancer, metastatic, by mouth, ADULT, 1,250
mg/m2 twice daily for 2 weeks, every 21 days.
Avoid concomitant use with: Dukes’ C colon cancer, adjuvant therapy, by mouth, ADULT,
Enhances therapeutic effect of Mercaptopurine: 1,250 mg/m2 twice daily for 2 weeks, every 21 days, for
Azathioprine (profound myelosuppression), Roflumilast a total duration of 24 weeks (8 cycles of 2 weeks drug
(immunosuppressive effect), Tofacitinib administration and 1-week rest period).
(immunosuppressive effect)
Dose Adjustment:
Increases risk of adverse or toxic effects of Mercaptopurine: Renal Impairment:
Dipyrone (agranulocytosis, pancytopenia), For CrCl 30–50 mL/minute, administer 75% of dose.
Pimecrolimus, Tacrolimus (Topical) For CrCl <30 mL/minute, use is contraindicated.

Increases risk of adverse or toxic effects of the following Obesity:

drugs: Use actual body weight (full weight) for calculation of BSA-
Clozapine (agranulocytosis), Leflunomide (hematologic based or weight-based dosing, especially if the intent of
toxicity such as pancytopenia, agranulocytosis, and/or therapy is curative.
thrombocytopenia), Natalizumab (concurrent infection) If dose reduction is done due to toxicity, consider
resumption of full weight-based dosing with subsequent
Increases serum concentration of Mercaptopurine by cycles, especially if cause of toxicity is resolved.
inhibiting its metabolism:
Allopurinol, Febuxostat

Reduces therapeutic effect of Mercaptopurine:

Echinacea

323
 ANTINEOPLASTIC AND IMMODULATING AGENTS

North American descent: Elderly (increased risk for adverse events; may experience
Initiate at 1,000 mg/m2 twice daily for 2 weeks, every 21 a greater incidence of grade 3 or 4 adverse events, e.g.,
days. Increased incidence of capecitabine toxicities, diarrhea, hand-and-foot syndrome, nausea, vomiting; at
particularly hand-and-foot syndrome. higher risk for dehydration).

Dihydropyrimidine Dehydrodeganase (DPD) Mutations: Adverse Drug Reactions:

May require therapy interruption or permanent Common: Abdominal distention, abdominal pain, abnormal
discontinuation. Partial, total, or near total absence of gait, abnormal hepatic function tests, alopecia, anemia,
DPD are at an increased risk for acute early-onset toxicity angina pectoris, anorexia, ataxia, arthralgia, atrial
(potentially severe, life-threatening, or fatal), which may fibrillation, back pain, bradycardia, brain disease,
include mucositis or stomatitis, diarrhea, neutropenia, cardiac arrest, cardiac arrhythmia, cardiomyopathy,
and neurotoxicity. cardiac failure, chest mass, chest pain, collapse,
conjunctivitis, constipation, cough, decreased appetite,
Toxicity: dehydration, depression, dermal ulcer, dermatitis,
Monitor closely for toxicity and adjust dose as needed. diarrhea, dizziness, drug-induced hypersensitivity,
Doses reduced should not be increased later on. dysarthria, dysgeusia, ECG changes, dyspepsia,
For combination therapy, monitor and adjust doses for dysphagia, dysphasia, eye irritation, dyspnea, edema,
docetaxel as well. epistaxis, equilibrium disturbance, erythema,
If treatment delay is required for either capecitabine or extrasystoles, fatigue, fever, flu-like symptoms, GI
docetaxel, withhold both agents until appropriate. hemorrhage, GI motility disorder, GI inflammation,
headache, granulocytopenia, hemoptysis, hemorrhage,
Precautions: hot flash, hoarseness, hyperbilirubinemia, immune
thrombocytopenia, hypokalemia, hypomagnesemia,
L

WARNING: May increase the anticoagulant effects of

warfarin. Bleeding events, including death, have increased thirst, insomnia, intestinal obstruction,
occurred with concomitant use. An increased risk of irritability, keratoconjunctivitis, ischemic heart disease,
coagulopathy is correlated with a cancer diagnosis laryngitis, lethargy, lymphedema, limb pain,
and age >60 years. Monitor PT and INR frequently lymphocytopenia, mood changes, myalgia, myasthenia,
and adjust anticoagulant dose accordingly. myocardial infarction, nail disease, nausea, necrotizing
In patients with colorectal cancer, treatment with enterocolitis, neutropenia, palmar-plantar
capecitabine immediately following 6 weeks of erythrodysesthesia, paresthesia, oral discomfort,
fluorouracil/leucovorin (FU/LV) therapy has been pericardial effusion, peripheral sensory neuropathy,
associated with an increased incidence of grade ≥3 pharyngeal disease, pain, pruritus, rectal pain, sedation,
toxicity, when compared to patients receiving the skin discoloration, skin rash, stomatitis,
reverse sequence, capecitabine (two 3­week thrombocytopenia, toxic dilation of intestine, tremor,
courses) followed by FU/LV. sore throat, upper abdominal pain, venous thrombosis,
ventricular premature contractions, vertigo, viral
infection, visual disturbance, vomiting, weakness, weight
WARNING: Hazardous agent; use appropriate
gain
precautions for handling and disposal.
Less Common: Acute renal failure, arthritis, ascites,
asthma, blood coagulation disorder, bronchitis, bone
Bone marrow suppression (use with caution, dose reduction marrow depression, bronchopneumonia, bronchospasm,
may be required; not recommended in patients with cerebrovascular accident, flu-like symptoms, cachexia,
baseline platelets <100,000/mm3 and/or neutrophils cholestatic hepatitis, confusion, cutaneous lupus
<1,500/mm3) erythematosus, diaphoresis, ecchymoses, esophagitis,
Cardiotoxicity (e.g. myocardial infarction, ischemia, angina, fibrosis, fungal infection, gastric ulcer, gastroenteritis, GI
dysrhythmias, cardiac arrest, cardiac failure, sudden perforation, hepatic failure, hepatic fibrosis,
death, cardiomyopathy, ECG changes) hypertension, hypotension, hepatitis, hypersensitivity,
Dermatologic toxicity (e.g. SJS, TEN); (permanently jaundice, keratitis, lacrimal stenosis,
discontinue use if severe dermatologic or leukoencephalopathy, loss of consciousness,
mucocutaneous reaction occurs). leukopenia, nocturia, ostealgia, pancytopenia, phlebitis
Gastrointestinal toxicity (NEC, severe prolonged diarrhea, (venous), photophobia, myocarditis, pneumonia,
dehydration); (antidiarrheal therapy, e.g. loperamide is pulmonary embolism, radiation recall phenomenon,
recommended; adequately hydrate prior to initiation of renal insufficiency, respiratory distress, sepsis, SJS, TEN,
treatment) syncope, tachycardia
Hand-and-foot syndrome (numbness, dysesthesia or
paresthesia, tingling, painless or painful swelling, Drug Interactions:
erythema, desquamation, blistering, and severe pain Monitor closely with:
may occur). Enhances therapeutic effect of Capecitabine:
Hepatotoxicity (grade 3 and 4 hyperbilirubinemia, Trastuzumab (neutropenic effect)
transaminase, alkaline phosphatase elevations may
occur; use with caution in mild-to-moderate hepatic Increases risk of adverse or toxic effects of Capecitabine:
impairment due to liver metastases). Denosumab (serious infections), Leucovorin Calcium-
Renal toxicity (dehydration may occur and result in possibly Levo-leucovorin
fatal acute renal failure; use with caution in mild-to-
moderate renal impairment). Reduces diagnostic effect of Coccidioides immitis Skin Test

324
ANTINEOPLASTIC AND IMMODULATING AGENTS

Avoid concomitant use with: 100 mg/m2 daily for 7 days, in combination with
Decreases metabolism of Capecitabine: daunorubicin, doxorubicin, idarubicin, or mitoxantrone;
CYP2C9 Substrates ADULT<60 years, 200 mg/m2 daily for 7 days, in
combination with daunorubicin.
Enhances therapeutic effect of Capecitabine: CHILD, standard AML induction therapy in children
Roflumilast (immunosuppressive effect), Tofacitinib comprises 3 days of anthracycline (e.g. daunorubicin,
(immunosuppressive effect) idarubicin or mitoxantrone) and 7-10 days of cytarabine
(100 – 200 mg/m2). CNS prophylaxis, by intrathecal
Increases risk of adverse or toxic effects of Capecitabine: injection, doses are age-adjusted: age 1 – 1.9 yrs 30 mg,
Dipyrone (agranulocytosispancytopenia), Pimecrolimus, age 2 to 2.9 yrs 50 mg, more than 3 yrs 70 mg.
Tacrolimus (Topical) Acute myeloid leukemia, consolidation, by IV infusion,
ADULT, HiDAc regimen, standard dose of 3 g/m2 over 2
Increases risk of adverse or toxic effects of the following hours every 12 hours on days 1, 3, and 5 of a 21 to 28
drugs: day regimen for 4 cycles
Clozapine (agranulocytosis), Leflunomide (hematologic Meningeal leukemia, by intrathecal injection, 30 mg/m2
toxicity such as pancytopenia, agranulocytosis, and/or every 4 days, range of 5–75 mg/m2 once daily for 4 days
thrombocytopenia), Natalizumab (concurrent infection) or once every 4 days until CNS findings normalize,
followed by 1 additional treatment.
Increases serum concentration of Capecitabine: Consolidation chemotherapy for AML in remission (High
Gimeracil [active metabolite, fluoruracil] Dose Cytarabine), 1 - 3 g/m2 12 hourly in 500 mL sodium
chloride 0.9 % intravenous infusion over 4 hours
Increases serum concentration of the following drugs: (frequency and number of doses will depend upon the
Diclofenac (Systemic), Fosphenytoin, Phenytoin, Vitamin protocol in use)

L
K antagonists, e.g. Warfarin *This course should be given once blood counts have
recovered to: Neutrophils >1x109/L and Platelets
Reduces therapeutic effect of Capecitabine: >100x109/L.
Echinacea
Dose Adjustment:
Reduces therapeutic effect of the following drugs: Renal Impairment:
BCG (Intravesical), Vaccines (live virus vaccines may May be at a higher risk of CNS toxicities, especially if on
progress to infection) high-dose cytarabine (1–3 g/m2).
For CrCl 46–60 mL/minute, administer 60% of dose.
Administration: Swallow tablets whole. Do NOT cut or crush For CrCl 31–45 mL/minute, administer 50% of dose.
tablets. Administer with water, within 30 minutes after a For CrCl <30 mL/minute, use alternative drug.
meal. Usually given in 2 divided doses, 12 hours apart.
Hepatic Impairment:
Pregnancy Category: D May be at a higher risk of CNS toxicities.
For transaminases or if bilirubin >2 mg/dL, administer 50%
ATC Code: L01BC06 of dose. May increase subsequent doses in the absence
of toxicities.

Obesity:
Rx CYTARABINE Use actual body weight (full weight) for calculation of BSA-
based or weight-based dosing, especially if the intent of
therapy is curative.
Inj.: 20 mg/mL solution, 5 mL ampule (IM, SC, intrathecal)
If dose reduction is done due to toxicity, consider
100 mg/mL solution for injection, 1 mL, 5 mL, and 10
resumption of full weight-based dosing with subsequent
mL ampule/vial
cycles, especially if cause of toxicity is resolved.
A pyrimidine analogue that inhibits the enzyme DNA
Precautions:
polymerase resulting in decreased DNA synthesis and
repair. It is specific for cells in the S phase of the cell WARNING: Should be administered under the
cycle. supervision of an experienced cancer
chemotherapy physician. Induction treatment
Indications: Remission induction in acute myeloid leukemia should be in a facility with sufficient laboratory and
(AML); treatment of acute lymphocytic leukemia (ALL); supportive resources that can handle its potential
treatment of chronic myeloid leukemia (CML); toxicities
prophylaxis and treatment of meningeal leukemia

Dose:
Acute myeloid leukemia, remission induction, by continuous
IV infusion, 100 mg/m2 daily for 7 days; or
200 mg/m2 daily (as 100 mg/m2 over 12 hours every 12
hours) for 7 days.
Acute myeloid leukemia, remission induction, by continuous
IV infusion, ADULT, 7 + 3 regimens, may administer a
second induction course if needed; or

325
 ANTINEOPLASTIC AND IMMODULATING AGENTS

retention, urticaria, reversible posterior

High-dose regimens (1–3 g/m2) have been leukoencephalopathy syndrome (RPLS)
associated with GI, CNS, pulmonary, ocular
toxicities, and cardiomyopathy. GI toxicities may Associated with high-dose cytarabine: Alopecia (complete),
present as nausea, vomiting, diarrhea, abdominal cardiomegaly, cerebellar toxicity, coma, cardiomyopathy
pain, oral ulcerations and hepatic dysfunction. (combination with cyclophosphamide), corneal toxicity,
CNS toxicity may present as acute cerebellar GI ulcer, desquamation, hemorrhagic conjunctivitis,
toxicity with or without cerebral impairment, hyperbilirubinemia, liver abscess, liver damage,
personality changes, seizure and/or coma. High necrotizing colitis, neurotoxicity (up to 55% in renal
doses (>18 g/m2 per cycle) and age >50 years also impairment), pancreatitis, peripheral neuropathy (motor
increase the risk for cerebellar toxicity. Ocular and sensory), peritonitis, personality change,
toxicities may present as reversible corneal toxicity pneumatosis cystoides intestinalis, pulmonary edema,
or hemorrhagic conjunctivitis. rash (severe), sepsis, somnolence, syndrome of sudden
respiratory distress
May cause myelosuppression, characterized by
leukopenia, thrombocytopenia and anemia. Associated with intrathecal administration: Accessory nerve
paralysis, aphonia, blindness (with concurrent systemic
Cytarabine (conventional) is not the same with chemotherapy and cranial irradiation), cough, diplopia,
cytarabine (liposomal). dysphagia, fever, hoarseness, nausea, necrotizing
leukoencephalopathy (concurrent cranial irradiation,
intrathecal methotrexate, and intrathecal
WARNING: Hazardous agent; use appropriate hydrocortisone), neurotoxicity, paraplegia, vomiting
precautions for handling and disposal.
L

Drug Interactions:
Bone marrow suppression (monitor blood counts frequently; Monitor closely with:
monitor bone marrow frequently once blasts are no Enhances therapeutic effect of Cytarabine:
longer apparent in peripheral blood; monitor for signs of Trastuzumab (neutropenic effect)
infection, neutropenia fever, or bleeding); pancreatitis;
tumor lysis syndrome (may occur, with subsequent Increases risk of adverse or toxic effects of Cytarabine:
hyperuricemia). Denosumab (serious infections), Cyclophosphamide
Cytarabine syndrome (fever, myalgia, bone pain, occasional (fatal cardiomyopathy)
chest pain, maculopapular rash, conjunctivitis, and
malaise may occur); hypersensitivity (rarely causes Reduces diagnostic effect of Coccidioides immitis Skin Test
anaphylaxis resulting in acute cardiopulmonary arrest).
Sudden respiratory distress syndrome (severe dyspnea, Avoid concomitant use with:
Enhances therapeutic effect of Cytarabine:
refractory hypoxia, diffuse pulmonary infiltrates, possibly
Tofacitinib (immunosuppressive effect)
fatal respiratory failure, progressing to pulmonary
edema and cardiomegaly, have been reported in high-
Increases risk of adverse or toxic effects of Cytarabine:
dose cytarabine).
Dipyrone (agranulocytosis, pancytopenia), Tacrolimus
Adverse Drug Reactions: (Topical)
Common: Anal inflammation, anal ulceration, anemia,
anorexia, bleeding, hepatic dysfunction, fever, diarrhea, Increases risk of adverse or toxic effects of the following
megaloblastosis, nausea, leukopenia, mucositis, drugs:
myelosuppression, neutropenia (onset: 1–7 days; nadir Clozapine (agranulocytosis), Leflunomide (hematologic
[biphasic]: 7–9 days and at 15–24 days; recovery toxicity such as pancytopenia, agranulocytosis, and/or
[biphasic]: 9–12 days and at 24–34 days), decreased thrombocytopenia), Natalizumab (concurrent infection)
reticulocytes, thrombocytopenia (onset: 5 days; nadir:
12–15 days; recovery 15–25 days), thrombophlebitis, Reduces therapeutic effect of Cytarabine:
rash, vomiting Echinacea
Less Common: Abdominal pain, acute respiratory distress
syndrome, allergic edema, alopecia, anaphylaxis, Reduces therapeutic effect of the following drugs:
angina, aseptic meningitis, bowel necrosis, BCG (Intravesical), Flucytosine, Vaccines (live virus
cardiopulmonary arrest (acute), cerebral dysfunction, vaccines may progress to infection)
chest pain, conjunctivitis, cytarabine syndrome (bone
pain, dizziness, dyspnea, esophageal ulceration, Administration:
esophagitis, fever, headache, hepatic sinusoidal For continuous IV infusion, reconstitute standard dose
with bacteriostatic water for injection, then further dilute
obstruction syndrome, hyperuricemia, injection site
in 0.9% NaCl or D5W. This is the preferred route for AML
cellulitis, injection site pain or inflammation (SC
therapy (100–200 mg/m2 daily).
injection), interstitial pneumonitis, jaundice, rash,
malaise, myalgia, neural toxicity, neuritis, pancreatitis,
exanthematous pustulosis, paralysis (intrathecal and IV For intrathecal injection, administer doses immediately
combination therapy), pericarditis, renal dysfunction, after preparation due to absence of preservatives.
pruritus, sepsis, rhabdomyolysis, skin freckling, skin Reconstitute with preservative free sodium chloride
0.9%. May be further diluted to preferred final volume
ulceration, sore throat, toxic megacolon, urinary

326
ANTINEOPLASTIC AND IMMODULATING AGENTS

with Elliott's B solution, sodium chloride 0.9% or lactated Dihydropyrimidine Dehydrodeganase (DPD) Mutations:
Ringer’s. Genetic absence of DPD has been associated with
Do NOT prepare intrathecal medications during the prolonged clearance and increased toxicity, e.g.
preparation of other agents. diarrhea, neutropenia, neurotoxicity.

NOTE: Optimal intrathecal chemotherapy dosing should be Precautions:

based on age rather than on BSA as CSF volume WARNING: Discontinue treatment for stomatitis or
correlates with age. esophagopharyngitis, rapidly falling WBC count,
leukopenia (WBC <3,500/mm3), intractable
Doses >1,000 mg/m2 (>200 mg/m2 in children) are vomiting, diarrhea, frequent bowel movements, GI
associated with a moderate emetic potential. Doses at ulcer or bleeding, watery stools, thrombocytopenia
3,000 mg/m2 have a high emetic potential in children. (platelets <100,000/mm3), hemorrhage, or MI.
Antiemetics are recommended to prevent nausea and
To be administered only by or under the supervision of
vomiting.
an experienced cancer chemotherapy physician who
is well versed in the use of potent antimetabolites.
Pregnancy Category: D
Hospitalize patients during the initial course of
therapy due to the possibility of severe toxic
ATC Code: L01BC01
reactions.

WARNING: Hazardous agent. Use appropriate

Rx FLUOROURACIL precautions for handling and disposal.

L
Inj.: 50 mg/mL, 10 mL ampule / vial (IV, IV infusion) Hand-and-foot syndrome (tingling sensation, pain,
symmetrical swelling, erythema, tenderness,
A pyrimidine analogue antimetabolite that intercalates with desquamation may occur).
RNA and inhibits thymidylate synthetase, subsequently
interfering with DNA synthesis and results to tumor cell Adverse Drug Reactions: Agranulocytosis, acute cerebellar
cytotoxicity. syndrome, alopecia, anaphylaxis, anemia,angina,
anorexia, arrhythmia, bleeding, confusion, dermatitis,
Indications: Treatment of breast cancer, colon cancer, rectal diarrhea, disorientation, epistaxis, esophagopharyngitis,
cancer, pancreatic cancer, and stomach (gastric) cancer euphoria, dry skin, fissuring, generalized allergic
reactions, headache, heart failure, lacrimal duct
Contraindications: Poor nutritional states; depressed bone stenosis, lacrimation, MI, leukopenia (nadir: days 9–14;
marrow function; potentially serious infections recovery by day 30), mesenteric ischemia (acute),
Dose: myocardial ischemia, nail changes (nail loss), palmar-
ADULTS, for various cancer protocols: plantar erythrodysesthesia syndrome, nausea,
• 500 mg/m2 on Days 1-5, OR nystagmus, pancytopenia, photophobia,
• 450-600 mg/m2 weekly, OR photosensitivity, sloughing, pruritic maculopapular rash,
• 400 mg/m2 IV bolus on Day 1, then 1200 mg/m2/day x stomatitis, Stevens-Johnson syndrome, stroke,
2 days continuous infusion every 2 weeks thrombocytopenia, thrombophlebitis, toxic epidermal
necrolysis, ulceration, vasospasm, vein pigmentation,
Dose Adjustment: visual changes, ventricular ectopy, vomiting
Renal Impairment:
Use with extreme caution. Drug Interactions:
For patients with CrCl <50 mL/minute or on continuous Monitor closely with:
renal replacement therapy (CRRT), dose adjustment is Enhances therapeutic effect of Fluorouracil:
not necessary. Leucovorin Calcium-Levo-leucovorin,
For patients undergoing hemodialysis, administer 50% of Trastuzumab (neutropenic effect)
standard dose following hemodialysis.
Increases risk of adverse or toxic effects of Fluorouracil:
Hepatic Impairment: Denosumab (serious infections), Leucovorin Calcium-
Use with extreme caution. Levo-leucovorin
Administer <50% of dose, then increase if toxicity does not
occur. Reduces diagnostic effect of Coccidioides immitis Skin Test
For patients with bilirubin >5 mg/dL, avoid use.
Avoid concomitant use with:
Obesity: Enhances therapeutic effect of Fluorouracil:
Use actual body weight (full weight) for calculation of BSA- Roflumilast, Tofacitinib (immunosuppressive effect)
based or weight-based dosing, especially if the intent of
therapy is curative. Increases risk of adverse or toxic effects of Fluorouracil:
If dose reduction is done due to toxicity, consider Dipyrone (agranulocytosis, pancytopenia),
resumption of full weight-based dosing with subsequent Pimecrolimus, Tacrolimus (Topical)
cycles, especially if cause of toxicity is resolved.
Increases risk of adverse or toxic effects of the following
drugs:

327
 ANTINEOPLASTIC AND IMMODULATING AGENTS

Clozapine (agranulocytosis), Leflunomide (hematologic NOTE: NOT indicated for use with concurrent radiation
toxicity such as pancytopenia, agranulocytosis, and/or therapy.
thrombocytopenia), Natalizumab (concurrent infection)
Dose Adjustment:
Increases serum concentration of the following drugs: Renal Impairment:
CYP2C9 Substrates, Diclofenac (Systemic), Use with caution in patients with pre-existing renal
Fosphenytoin, Phenytoin, Vitamin K Antagonists, e.g., dysfunction. Discontinue if severe renal toxicity or
Warfarin hemolytic uremic syndrome (HUS) occur during
treatment.
Reduces therapeutic effect of Fluorouracil: For mild-to-severe renal impairment, dose adjustment is not
Echinacea necessary.
For patients with ESRD on hemodialysis, initiate
Reduces therapeutic effect of the following drugs: hemodialysis 6–12 hours after gemcitabine infusion.
BCG (Intravesical), Vaccines (live virus vaccines may
progress to infection) Hepatic Impairment:
Use with caution. Discontinue if severe hepatotoxicity
Administration: May be administered by IV push, IV bolus, or occurs during treatment.
continuous IV infusion. For elevated transaminases with normal bilirubin, dose
adjustment is not necessary.
Avoid extravasation. Consider increasing dietary intake For serum bilirubin >1.6 mg/dL, initiate at 800 mg/m2, may
of thiamine in patients taking this drug. escalate dose if tolerated.

Pregnancy Category: D Obesity:

L

Use actual body weight (full weight) for calculation of BSA-

ATC Code: L01BC02 based or weight-based dosing, especially if the intent of
therapy is curative.
If dose reduction is done due to toxicity, consider
resumption of full weight-based dosing with subsequent
Rx GEMCITABINE cycles, especially if cause of toxicity is resolved.

Inj.: 200 mg and 1 g (as hydrochloride), vial (IV infusion) Precautions:

WARNING: Has radio-sensitizing activity when used
A pyrimidine antimetabolite that inhibits DNA polymerase concomitantly with radiation therapy or ≤7 days apart
and ribonucleotide reductase subsequently inhibiting and may cause radiation recall when administered
DNA synthesis. >7 days apart. Radiation toxicity, including tissue
Indications: First-line treatment of metastatic breast cancer, injury, severe mucositis, esophagitis, or pneumonitis,
in combination with paclitaxel after failure of adjunct has been reported.
chemotherapy with an anthracycline (unless WARNING: Hazardous agent. Use appropriate
contraindicated); first-line treatment of inoperable, precautions for handling and disposal.
locally advanced or metastatic (stage IIIA, IIIB, or IV) Non-
small cell lung cancer (NSCLC), in combination with
Bone marrow suppression (e.g. neutropenia,
cisplatin; treatment of advanced ovarian cancer, in
thrombocytopenia, anemia); capillary leak syndrome
combination with carboplatin that has relapsed at least
(discontinue if capillary leak syndrome occurs).
6 months following completion of platinum based
Hemolytic uremic syndrome (may lead to renal failure and
chemotherapy; first-line treatment of locally advanced or
dialysis, including fatalities; elevation of bilirubin or LDH,
metastatic pancreatic adenocarcinoma (nonresectable
reticulocytosis, severe thrombocytopenia, and/or renal
stage II, III, or stage IV)
failure; discontinue if HUS or severe renal impairment
occurs).
Dose:
Hepatotoxicity (may lead to liver failure and death; use in
Breast cancer, metastatic, by IV infusion, ADULT, in
patients with hepatic impairment or hepatic metastases
combination with paclitaxel, 1,250 mg/m2 over 30
may worsen hepatic impairment; monitor hepatic
minutes on days 1 and 8, repeat cycle every 21 days.
function at baseline and periodically during treatment).
NSCLC, locally advanced or metastatic, by IV infusion,
Posterior reversible encephalopathy syndrome (blindness,
ADULT, in combination with cisplatin, 1,000 mg/m2 over
confusion, headache, hypertension, lethargy, seizure,
30 minutes days 1, 8, and 15, repeat cycle every 28
and other visual and neurologic disturbances may occur;
days; or
discontinue if posterior reversible encephalopathy
in combination with cisplatin, 1,250 mg/m2 over 30
diagnosis confirmed).
minutes on days 1 and 8, repeat cycle every 21 days.
Pulmonary toxicity (ARDS, interstitial pneumonitis,
Ovarian cancer, advanced, by IV infusion, ADULT, in
pulmonary edema, pulmonary fibrosis; may lead to
combination with carboplatin, 1,000 mg/m2 over 30
possibly fatal respiratory failure despite discontinuation;
minutes days 1 and 8, repeat cycle every 21 days.
discontinue if unexplained dyspnea or other evidence of
Pancreatic cancer, locally advanced or metastatic, by IV
pulmonary toxicity occurs).
infusion, ADULT, 1,000 mg/m2 over 30 minutes once
Infusion duration >60 minutes and administration
weekly for 7 weeks followed by 1-week rest, then once
frequency more than once weekly have been shown to
weekly for 3 weeks out of every 4 weeks.
increase toxicity.

328
ANTINEOPLASTIC AND IMMODULATING AGENTS

Adverse Drug Reactions: Pregnancy Category: D

Common: Alopecia, anemia, bronchospasm, diarrhea,
drowsiness, dyspnea, edema, fever, flu-like symptoms, ATC Code: L01BC05
hematuria, hemorrhage, vomiting, paresthesia, skin
rash, peripheral edema, proteinuria, stomatitis,
thrombocytopenia
Less Common: ARDS, anaphylactoid reaction, anorexia, Rx TEGAFUR + URACIL
arthralgia, bullous skin disease, capillary leak syndrome,
cardiac arrhythmia, cardiac failure, cellulitis, Oral: 100 mg + 224 mg capsule
cerebrovascular accident, desquamation, digital
vasculitis, constipation, gangrene of skin or other tissue, Tegafur is a prodrug of fluorouracil. Uracil is an inhibitor of
hemolytic uremic syndrome, hepatic veno-occlusive thee nzyme dihydropyrimidine dehydrogenase, which is
disease, hepatic failure, hypertension, hypocalcemia, MI, responsible for the degradation of fluorouracil.
hypotension, interstitial pneumonitis, neuropathy,
petechiae, pruritus, pulmonary edema, pulmonary Indications: First-line treatment for metastatic colorectal
fibrosis, radiation recall phenomenon, renal failure, cancer, in combination with leucovorin calcium;
respiratory failure, reversible posterior treatment of head and neck, gastric, colorectal,
leukoencephalopathy syndrome, sepsis, hepatocellular, hepatobiliary, lung, pancreatic, breast,
supraventricular cardiac arrhythmia, thrombotic bladder, and uterine or cervical cancers
thrombocytopenic purpura
Rare: Hepatotoxicity Contraindications: Women who are or may become
pregnant; breastfeeding; infants, children, or
Drug Interactions:

L
adolescents; severe hepatic impairment; evidence of
Monitor closely with: bone marrow suppression from prior radiation therapy or
Enhances therapeutic effect of Gemcitabine: prior chemotherapy; known deficiency of hepatic
Trastuzumab (neutropenic effect) CYP2A6; known or suspected dihydropyrimidine
dehydrogenase (DPD) deficiency; concurrent or recent
Enhances therapeutic effect of Warfarin (anticoagulant treatment with DPD inhibitors; concurrent use, or within
effect) 7 days of tegafur + gimeracil + oteracil

Increases risk of adverse or toxic effects of Gemcitabine: Dose:

Denosumab (serious infections) Colorectal cancer, metastatic, by mouth, ADULT, in
combination with oral leucovorin calcium 300 mg/m2
Reduces diagnostic effect of Coccidioides immitis Skin Test tegafur + 672 mg/m2 uracil daily in 3 divided doses, or
every 8 hours on days 1 through 28 every 35 days, begin
Avoid concomitant use with: subsequent cycles after a 7-day break.
Enhances therapeutic effect of Gemcitabine: Head and neck, gastric, colorectal, hepatocellular,
Roflumilast (immunosuppressive effect) hepatobiliary, pancreatic, lung, breast, and bladder
cancer, by mouth, ADULT, 300–600 mg tegafur
Enhances therapeutic effect of Tofacitinib component daily in 2–3 divided doses.
(immunosuppressive effect) Uterine or cervical cancers, by mouth, ADULT, 600 mg
tegafur component daily in 2–3 divided doses.
Increases risk of adverse or toxic effects of Gemcitabine:
Dipyrone (agranulocytosis, pancytopenia), Dose based on BSA, number of tegafur + uracil (UFT)
Pimecrolimus, Tacrolimus (Topical) capsules required:

Increases risk of adverse or toxic effects of the following

UFT Daily Schedule
drugs:
BSA capsules
Bleomycin (pulmonary toxicity), Clozapine Morning Noon Evening
daily
(agranulocytosis), Leflunomide (hematologic toxicity
such as pancytopenia, agranulocytosis, and/or <1.17 3 1 1 1
thrombocytopenia), Natalizumab (concurrent infection) 1.17–
4 2 1 1
1.49
Reduces therapeutic effect of Gemcitabine:
1.5–1.83 5 2 2 1
Echinacea
>1.83 6 2 2 2
Reduces therapeutic effect of the following drugs: Dose Adjustment:
BCG (Intravesical), Vaccines (live virus vaccines may Obesity:
progress to infection) Use actual body weight (full weight) for calculation of BSA-
based or weight-based dosing, especially if the intent of
Administration: Administer IV infusion over 30 minutes. therapy is curative.
Infusion duration >60 minutes and frequency more than If dose reduction is done due to toxicity, consider
once weekly have been shown to increase toxicity. resumption of full weight-based dosing with subsequent
cycles, especially if cause of toxicity is resolved.
Avoid extravasation.

329
 ANTINEOPLASTIC AND IMMODULATING AGENTS

Dihydropyrimidine dehydrodeganase (DPD) mutations: speech disturbance, SJS, urinary incontinence, urinary
Genetic DPD deficiency of has been associated with retention, urticaria
prolonged clearance and increased and potentially fatal
toxicity, e.g., diarrhea, neutropenia, neurotoxicity. Drug Interactions:
Monitor closely with:
Precautions: Enhances therapeutic effect of Tegafur + Uracil:
Trastuzumab (neutropenic effect)
WARNING: Hazardous agent. Use appropriate
precautions for handling and disposal. Increases risk of adverse or toxic effects of Tegafur + Uracil:
Denosumab (serious infections), Leucovorin Calcium-
Bone marrow suppression (e.g. anemia, leukopenia, Levo-leucovorin, Methotrexate
neutropenia, thrombocytopenia; may require dosage
modification; monitor blood counts as necessary) Reduces diagnostic effect of Coccidioides immitis Skin Test
Cardiovascular effects (e.g. myocardial infarction, ischemia,
angina; use with caution in patients with history of Avoid concomitant use with:
significant cardiac disease) Decreases serum concentration of Tegafur + Uracil:
Gastrointestinal toxicity (e.g. milddiarrhea, nausea, Moderate and Strong [active metabolites of tegafur]
vomiting, anorexia, stomatitis, and abdominal pain; (inhibits conversion of tegafur to 5-fluorouracil)
withhold treatment for grade 2 or higher diarrhea)
Hepatotoxicity (e.g. fatal fulminant hepatitis, hepatic Enhances therapeutic effect of Tegafur + Uracil:
cirrhosis; long-term administration may lead to cirrhosis Roflumilast (immunosuppressive effect)
without remarkable increase in transaminases;
discontinue if prolonged prothrombin time or decreased Enhances therapeutic effect of Tofacitinib
L

albumin occurs). (immunosuppressive effect)

Fertility effects (both men and women of childbearing
potential should use effective contraception during and Increases risk of adverse or toxic effects of Tegafur + Uracil:
for 3 months following cessation of treatment; may Dipyrone (agranulocytosis, pancytopenia),
cause irreversible infertility). Pimecrolimus, Tacrolimus (Topical)
Pregnancy (may cause fetal harm)
Increases risk of adverse or toxic effects of the following
Adverse Drug Reactions: drugs:
Common: Abdominal pain, ageusia, alopecia, anemia, Clozapine (agranulocytosis), Leflunomide (hematologic
anorexia, arthralgia, back pain, blood coagulation toxicity such as pancytopenia, agranulocytosis, and/or
disorder, cachexia, candidiasis, chills, confusion, thrombocytopenia), Natalizumab (concurrent infection)
conjunctivitis, constipation, cough, deep vein
thrombophlebitis, dehydration, depression, diaphoresis, Increases serum concentration of Tegafur + Uracil:
diarrhea (may be dose limiting), dizziness, drowsiness, Gimeracil [active metabolites of tegafur, specifically
dysgeusia, dyspepsia, dyspnea, eructation, exfoliative fluorouracil]
dermatitis, febrile neutropenia, fever, flatulence,
headache, insomnia, intestinal obstruction, lacrimation, Increases serum concentration of the following drugs:
leukopenia, malaise, mucositis, myalgia, nail disease, Diclofenac (Systemic), Fosphenytoin, Phenytoin, Vitamin
nausea and vomiting, neutropenia (may be dose K Antagonists, e.g., Warfarin
limiting), pain, paresthesia, pharyngitis, pruritus, skin
discoloration, skin photosensitivity, skin rash, peripheral Reduces therapeutic effect of Tegafur + Uracil:
edema, stomatitis, thrombocytopenia, weakness, weight Allopurinol, Echinacea
loss, xeroderma, xerostomia
Less Common: Abnormal gait, acute myelocytic leukemia Reduces therapeutic effect of the following drugs:
(including promyelocytic), acute pancreatitis, acute renal BCG (Intravesical), Vaccines (live virus vaccines may
failure, agranulocytosis, altered sense of smell, amnesia, progress to infection)
angina pectoris, anosmia, cardiac arrest, cardiac
arrhythmia, ascites, cardiac failure, dermatological Administration: To be taken at least 1 hour before or 1 hour
reaction (including blistering, dermatitis), chest pain, after meals.
duodenal ulcer, disseminated intravascular coagulation,
enteritis, enterocolitis, fatigue, extrapyramidal reaction, NOTE: Do not make up doses that are withheld during the
fulminant hepatitis, gastric ulcer, gastritis, hematuria, 28 days of consecutive treatment. If tegafur and uracil
hemolytic anemia, hepatic cirrhosis, hepatic failure, treatment is withheld, leucovorin calcium should also be
hepatic fibrosis, hepatitis, hypoesthesia, ileitis, impaired withheld. Do NOT reduce leucovorin calcium dose if
consciousness, increased susceptibility to infection, tegafur and uracil dose is reduced.
intestinal perforation, ischemic colitis, jaundice,
impotence, leukoencephalopathy, lupus erythematous- Pregnancy Category: X
like rash (discoid), movement disorder, myelodysplastic
syndrome, MI, multi-organ failure, nephrotic syndrome, ATC Code: L01BC53
palmar-plantar erythrodysesthesia, pneumonia,
pancytopenia, paralysis (extremities), paralytic ileus,
pulmonary embolism, renal insufficiency, sepsis, shock,

330
ANTINEOPLASTIC AND IMMODULATING AGENTS

PLANT ALKALOIDS AND

Should be administered under the supervision of an
OTHER NATURAL PRODUCTS experienced cancer chemotherapy physician,
experienced in vinblastine administration.
VINCA ALKALOIDS

WARNING: Hazardous agent. Use appropriate

Rx VINBLASTINE precautions for handling and disposal.

Inj.: 10 mg powder for reconstitution (as sulfate), vial (IV)

Bone marrow suppression (e.g. leukopenia,
1 mg/mL (as sulfate), 10 mL vial (IV)
granulocytopenia, thrombocytopenia, anemia may
occur; monitor for infections if WBC <2,000/mm3;
It inhibits microtubule formation and arrests division,
leukopenia may be more pronounced in cachectic
specifically for cells in the M and S phases of the cell
patients, patients with skin ulcerations)
cycle.
Ischemic heart disease
Pulmonary toxicity (e.g. acute shortness of breath, severe
Indications: Treatment of Hodgkin’s lymphoma; lymphocytic
bronchospasm).
lymphoma; histiocytic lymphoma; mycosis fungoides;
Gastrointestinal toxicity (stomatitis may occur; may be
testicular cancer; Kaposi’s sarcoma; Langerhans Cell
disabling but is usually reversible)
Histiocytosis (LCH)
Hepatic impairment (use with caution; toxicity may be
increased).
Contraindications: Significant granulocytopenia, unless as a
Neurotoxicity (e.g. seizures, severe permanent CNS
result of a condition being treated; bacterial infection

L
damage; seizures, CNS damage has occurred with
higher then recommended doses and/or when
Dose:
administered more frequently than recommended).
NOTE: Determine dose frequency and duration based on
indication, concomitant combination chemotherapy and
Adverse Drug Reactions:
hematologic response.
Common: Alopecia, bone pain, constipation, hypertension,
jaw pain, leukopenia or granulocytopenia (nadir, 5–10
Hodgkin’s lymphoma, lymphocytic lymphoma, histiocytic
days; recovery, 7–14 days; dose-limiting toxicity),
lymphoma, mycosis fungoides, testicular cancer,
malaise, myelosuppression, tumor pain
Kaposi’s sarcoma, or Langerhans Histiocytosis (LCH), by
Less Common: Abdominal pain, anemia, angina, anorexia,
IV infusion, ADULT, 3.7 mg/m2, adjust dose every 7 days
aspermia, auditory damage, bronchospasm, cellulitis
based on WBC response up to 5.5 mg/m2 for the second
(with extravasation), cerebrovascular accident, coronary
dose, 7.4 mg/m2 for the third dose; 9.25 mg/m2 for the
ischemia, deafness, deep tendon reflex loss, depression,
fourth dose, and 11.1 mg/m2 for the fifth dose; do not
dermatitis, diarrhea, dizziness, dyspnea, ECG
administer more frequently than every 7 days; usual
abnormalities, GI bleeding, headache, hemolytic uremic
dose range, 5.5–7.4 mg/m2 every 7 days (maximum
syndrome, hemorrhagic enterocolitis, ileus, irritation,
dose, 18.5 mg/m2), goal of dose adjustment is to reduce
limb ischemia, metallic taste, MI, myalgia, myocardial
WBC count to ~3,000/mm3.
ischemia, nausea (mild), neurotoxicity (>24 hours),
Hodgkin’s lymphoma, by IV infusion, CHILD, initially 6
nystagmus, paresthesia, peripheral neuritis, paralytic
mg/m2, do not administer more frequently than every 7
ileus, pharyngitis, phlebitis (with extravasation),
days.
photosensitivity (rare), radiation recall, rash, Raynaud's
Langerhans Histiocytosis or (LCH), by IV infusion, CHILD,
phenomenon, rectal bleeding, seizure, skin blistering,
initially 6.5 mg/m2, do not administer more frequently
stomatitis, SIADH, thrombocytopenia (recovery within a
than every 7 days.
few days), thrombotic thrombocytopenic purpura, toxic
Testicular cancer, by IV infusion, CHILD, initially 3 mg/m2,
megacolon, urinary retention, vertigo, vestibular
do not administer more frequently than every 7 days.
damage, vomiting (mild), weakness
Dose Adjustment:
Hepatic Impairment:
Drug Interactions:
For serum bilirubin >3 mg/dL, administer 50% of dose.
Monitor closely with:
Enhances therapeutic effect of Vinblastine:
Obesity:
Trastuzumab (neutropenic effect)
Use actual body weight (full weight) for calculation of BSA-
based or weight-based dosing, especially if the intent of
Increases risk of adverse or toxic effects of Vinblastine:
therapy is curative.
Denosumab (serious infections)
If dose reduction is done due to toxicity, consider
resumption of full weight-based dosing with subsequent
Increases risk of adverse or toxic effects of the following
cycles, especially if cause of toxicity is resolved.
drugs:
MAO Inhibitors [except Linezolid, Tedizolid] (orthostatic
Precautions:
hypotension), Mitomycin (Systemic) (pulmonary toxicity)
WARNING: For IV use only. Fatal if given by other
routes. Reduces diagnostic effect of Coccidioides immitis Skin Test

Avoid concomitant use with:

331
 ANTINEOPLASTIC AND IMMODULATING AGENTS

Decreases serum concentration of Vinblastine:

Dabrafenib, Mitotane, Sofosbuvir Rx VINCRISTINE

Decreases serum concentration of the following drugs: Inj.: 1 mg/mL (as sulfate), 1 mL and 2 mL vial (IV)
Afatinib, Dabigatran Etexilate, Doxorubicin
(Conventional), Ledipasvir, Linagliptin It inhibits microtubule formation and arrests division,
specifically for cells in the M and S phases of the cell
Enhances therapeutic effect of Vinblastine: cycle.
Roflumilast (immunosuppressive effect)
Indications: Treatment of acute lymphocytic leukemia (ALL),
Enhances therapeutic effect of Tofacitinib acute myeloid leukemia (AML), chronic myelogenous
(immunosuppressive effect) leukemia (CML), Hodgkin’s lymphoma, non-Hodgkin’s
lymphomas, Wilms' tumor, neuroblastoma, small cell
Increases risk of adverse or toxic effects of Vinblastine: lung cancer, and rhabdomyosarcoma
Dipyrone (agranulocytosis, pancytopenia),
Pimecrolimus, Posaconazole, Tacrolimus (Topical), Contraindication: Demyelinating form of Charcot-Marie-
Voriconazole Tooth syndrome

Increases risk of adverse or toxic effects of the following Dose:

drugs: NOTE: Dosing and frequency may vary by protocol and/or
Clozapine (agranulocytosis), Leflunomide (hematologic treatment phase. Cap doses at a maximum of 2
toxicity such as pancytopenia, agranulocytosis, and/or mg/dose.
thrombocytopenia), Natalizumab (concurrent infection)
L

Cancer chemotherapy, by IV infusion, ADULT, 1.4 mg/m2 per

Increases serum concentration of Vinblastine: dose, frequency may vary based on protocol; CHILD ≤10
Fusidic Acid (Systemic), Lopinavir, Macrolide Antibiotics, kg, 0.05 mg/kg per dose once weekly; CHILD >10 kg, 1.5
e.g. Erythromycin, Clarithromycin [except Azithromycin, – 2.0 mg/m2 per dose, frequency may vary based on
systemic, Fidaxomicin], Mifepristone, Posaconazole, protocol. Maximum allowable dose is 2 mg.
Ritonavir, Tolterodine

Reduces therapeutic effect of Vinblastine: Dose Adjustment:

Echinacea Hepatic Impairment:
For serum bilirubin >3 mg/dL, administer 50% of dose.
Reduces therapeutic effect of the following drugs:
BCG (Intravesical), Vaccines (live virus vaccines may Obesity:
progress to infection) Use actual body weight (full weight) for calculation of BSA-
based or weight-based dosing, especially if the intent of
Administration: For IV use only. A short IV infusion in a 25– therapy is curative.
50 mL mini-bag is preferred. If not possible, administer If dose reduction is done due to toxicity, consider
undiluted as a 1-minute infusion into a free flowing IV line resumption of full weight-based dosing with subsequent
to prevent venous irritation or extravasation. cycles, especially if cause of toxicity is resolved.

Local injection of hyaluronidase and the application of Precautions:

moderate heat to the area of leakage help disperse the WARNING: For IV use only. Fatal if given by other
drug and are thought to minimize discomfort and the routes.
possibility of cellulitis.
Should be administered under the supervision of
an experienced cancer chemotherapy physician,
NOTE: Extravasation may cause significant irritation. If
experienced in vinblastine administration.
extravasation occurs, discontinue immediately and
initiate appropriate extravasation management,
including local injection of hyaluronidase and moderate WARNING: Hazardous agent. Use appropriate
heat application to the affected area. Use a separate precautions for handling and disposal.
vein to administer any remaining portion of the dose.
Gastrointestinal effects (e.g. constipation, paralytic ileus,
Prolonged administration times (≥30 to 60 minutes) intestinal necrosis and/or perforation; responds to high
and/or increased administration volumes may increase enemas and laxatives).
the risk of vein irritation and extravasation. Hepatic impairment (e.g. hepatic sinusoidal obstruction
syndrome, characterized by bilirubin >1.4 mg/dL,
Pregnancy Category: D unexpected weight gain, ascites, hepatomegaly, or
unexplained right upper quadrant pain).
ATC Code: L01CA01 Neurotoxicity (alterations in mental status such as
depression, confusion, or insomnia may occur; use with
caution in patients with pre-existing neuromuscular
disease and/or with concomitant neurotoxic agents).
Pulmonary toxicity (e.g. acute shortness of breath, severe
bronchospasm, or progressive dyspnea; use caution in

332
ANTINEOPLASTIC AND IMMODULATING AGENTS

patients with preexisting pulmonary disease; Macrolide Antibiotics, e.g. Erythromycin, Clarithromycin
permanently discontinue if pulmonary dysfunction [except Azithromycin, systemic], Mifepristone,
occurs) Posaconazole, Ritonavir
Uric acid nephropathy
Elderly (may cause or exacerbate syndrome of Increases risk of adverse or toxic effects of Vincristine:
inappropriate antidiuretic hormone secretion or Itraconazole, Pimecrolimus, Posaconazole, Tacrolimus
hyponatremia; monitor sodium closely); children (Topical), Voriconazole
(increased risk of developing hepatic impairment in
children <3 years of age). Increases risk of adverse or toxic effects of the following
drugs:
Adverse Drug Reactions: Leflunomide (hematologic toxicity such as pancytopenia,
Common and Less Common: Abdominal cramps, abdominal agranulocytosis, and/or thrombocytopenia),
pain, acute uric acid nephropathy, alopecia, anemia Natalizumab (concurrent infection)
(mild), anorexia, ataxia, back pain, bladder atony, bone
pain, bronchospasm, coma, cortical blindness Reduces therapeutic effect of Vincristine:
(transient), cranial nerve dysfunction (e.g., extraocular Echinacea
muscle impairment, auditory damage, laryngeal muscle
impairment, paresis, vestibular damage, vocal cord Reduces therapeutic effect of the following drugs:
paralysis), constipation, deafness, deep tendon reflex BCG (Intravesical), Vaccines (live virus vaccines may
loss, paralysis, diarrhea, difficulty walking, dizziness, progress to infection)
dyspnea, dysuria, edema, fever, foot drop, gait changes,
headache, hemolytic uremic syndrome, hepatic Administration: For IV use only. A short 5– to 10– minute IV
sinusoidal obstruction syndrome, intestinal necrosis, infusion in a 25–50 mL mini-bag is preferred. If not

L
hypertension or hypotension, hyperuricemia, intestinal possible, administer as a slow 1-minute IV push.
perforation, jaw pain, leukopenia (mild), limb pain, MI, Administer concomitantly with prophylactic bowel
motor difficulties, muscle wasting, myalgia, myocardial management regimen to minimize GI adverse effects.
ischemia, nausea, neuropathic pain, neurotoxicity (dose-
related), nystagmus, optic atrophy with blindness, oral NOTE: Extravasation may cause significant irritation. If
ulcers, paralysis, paralytic ileus, paresthesia, parotid extravasation occurs, discontinue immediately and
pain, peripheral neuropathy, pharyngeal pain, polyuria, initiate appropriate extravasation management,
rash, seizure, sensorimotor dysfunction, sensory loss, including local injection of hyaluronidase and moderate
thrombocytopenia (mild), thrombotic thrombocytopenic heat application to the affected area. Use a separate
purpura, phlebitis, vertigo, tissue irritation or necrosis (if vein to administer any remaining portion of the dose.
infiltrated), urinary retention, vomiting, weight loss
Rare: Allergic reactions, anaphylaxis, hypersensitivity, Pregnancy Category: D
SIADH
ATC Code: L01CA02
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect of Vincristine: PODOPHYLLOTOXIN DERIVATIVES
Trastuzumab (neutropenic effect)

Increases risk of adverse or toxic effects of Vincristine: Rx ETOPOSIDE

Denosumab (serious infections), Teniposide (neurotoxic
effect)
Inj.: 100 mg vial (IV)
Increases risk of adverse or toxic effects of the following
20 mg/mL powder, 10 mL vial (IV)
drugs:
20 mg/mL, 5 mL ampule / vial (IV)
MAO Inhibitors [except Linezolid, Tedizolid] (orthostatic
hypotension),
A topoisomerase II inhibitor that arrests cells in the late S or
Mitomycin, Systemic (pulmonary toxicity)
early G2 phase of cell division.
Reduces diagnostic effect of Coccidioides immitis Skin Test
Indications: Treatment of small cell lung cancer (SCLC; first-
and second-line) ; treatment of non-small cell lung
Avoid concomitant use with:
cancer (NSCLC); treatment of non-Hodgkin’s lymphomas
Decreases serum concentration of Vincristine:
(first-line) ; treatment of testicular cancer (first-line);
Dabrafenib, Mitotane
Hemophagocytic Lymphohistiocytosis (HLH); Childhood
solid malignancies (e.g. Retinoblastoma,
Enhances therapeutic effect of Vincristine:
Neuroblastoma)
Roflumilast (immunosuppressive effect)
Contraindications: Hypersensitivity to etoposide or any
Enhances therapeutic effect of Tofacitinib
component of the formulation; severe leukopenia or
(immunosuppressive effect)
thrombocytopenia; severe hepaticimpairment; severe
renal impairment
Increases serum concentration of Vincristine:
Fusidic Acid (Systemic), Itraconazole, Lopinavir,

333
 ANTINEOPLASTIC AND IMMODULATING AGENTS

Dose:
Non-Hodgkin’s lymphoma (in combination with other WARNING: Hazardous agent. Use appropriate
agents), NSCLC (alone or in combination), SCLC (first-line precautions for handling and disposal.
in combination; second-line alone or in combination),
testicular cancer (in combination), by IV infusion, ADULT, Hypersensitivity reaction (anaphylactic-like reactions
50–100 mg/m2 daily for 5 days, administer doses >200 manifested by chills, fever, tachycardia, bronchospasm,
mg in 2 divided doses. dyspnea, and hypotension may occur; facial or tongue
Hemophagocytic Lymphohistiocytosis, Acute myeloid swelling, coughing, chest tightness, cyanosis,
leukemia, CHILD under 3 yrs, 3.3 mg/kg/day IV infusion laryngospasm, diaphoresis, hypertension, back pain,
for 4 days; CHILD above 3 yrs, 100 mg/m2/d IV infusion loss of consciousness, and flushing); hypotension (may
for 4 days. occur due to rapid administration).
Secondary malignancies (secondary acute leukemias); low
Dose Adjustment: serum albumin (at an increased risk for toxicities).
Renal Impairment: Elderly (may be more likely to develop severe
For CrCl >50 mL/minute, dose adjustment is not required. myelosuppression and/or GI effects); children (at an
For CrCl 15–50 mL/minute, administer 75% of dose. increased risk of anaphylactic-like reactions when used
For CrCl <15 mL/minute, consider further dose reductions. at concentrations higher than recommended).
No data available.
Infants, children, and adolescents: Adverse Drug Reactions:
GFR >50 ml/min/1.73 m2: no dosage adjustment Common: Abdominal pain, alopecia, anaphylactic-like
GFR 10-50 ml/min/ 1.73 m2: administer 75% of dose reaction, anorexia, diarrhea, hepatic toxicity, anemia,
GFR < 10 ml/min/1.73 m2: administer 50% of dose hypotension (infusion-related), nausea, vomiting,
leukopenia (nadir, 7–14 days; recovery, by day 20),
L

Hepatic Impairment: peripheral neuropathy, stomatitis, thrombocytopenia

For mild-to-moderate impairment, no recommended dose (nadir, 9–16 days; recovery, by day 20)
adjustment. Less Common: Amenorrhea, back pain, blindness
For severe impairment, use is contraindicated. (transient; cortical), constipation, cyanosis, cough,
Infants, children, and adolescents: diaphoresis, dysphagia, erythema, esophagitis,
Bilirubin 1.5-3 mg/dL or AST > 3 times ULN: administer 50% extravasation (induration; necrosis), facial swelling,
of dose fatigue, fever, hyperpigmentation, hypersensitivity,
Bilirubin > 3mg/dL: administer 25% of dose or consider hypersensitivity-associated apnea, interstitial
avoiding dose pneumonitis, laryngospasm, maculopapular rash,
metabolic acidosis, MI, malaise, mucositis, myocardial
Obesity: ischemia, optic neuritis, ovarian failure, perivasculitis,
Use actual body weight (full weight) for calculation of BSA- pruritus, pulmonary fibrosis, radiation-recall dermatitis,
based dosing. Use adjusted body weight 25% (ABW25) rash, reversible posterior leukoencephalopathy
for weight-based (mg/kg) dosing for hematopoietic stem syndrome (RPLS), seizure, Stevens-Johnson syndrome,
cell transplant conditioning regimens in adults. tongue swelling, somnolence, toxic epidermal necrolysis,
ABW25: toxic megacolon, urticaria, vasospasm, weakness
Adjusted wt (kg) = Ideal body weight (kg) + 0.25 [actual Associated with higher doses: Alopecia, ethanol
wt (kg) –ideal body weight (kg)] intoxication, hepatitis, hypotension (infusion-related),
If dose reduction is done due to toxicity, consider metabolic acidosis, nausea and vomiting (severe),
resumption of full weight-based dosing with subsequent secondary malignancy, mucositis, skin lesions
cycles, especially if cause of toxicity is resolved. (resembling Stevens-Johnson syndrome)

Toxicity: Drug Interactions:

If hypersensitivity reaction occurs, interrupt infusion. Monitor closely with:
For severe non-hematologic adverse reactions, reduce dose Enhances therapeutic effect of Etoposide:
or discontinue treatment. Trastuzumab (neutropenic effect)
If WBC 2,000–3,000/mm3 or platelets 75,000–
100,000/mm3, reduce dose by 50%. Enhances therapeutic effect of Vitamin K Antagonists [e.g.
If ANC <500/mm3 or platelets <50,000/mm3, withhold Warfarin (anticoagulant effect)]
treatment until recovery.
Increases risk of adverse or toxic effects of Etoposide:
Precautions: Denosumab (serious infections)

WARNING: Should be administered under the Reduces diagnostic effect of Coccidioides immitis Skin Test
supervision of a qualified healthcare provider,
experienced in the use of cancer Avoid concomitant use with:
chemotherapeutic agents. Decreases metabolism of Etoposide:
Cyclosporine (Systemic), CYP3A4 Inhibitors
Severe myelosuppression, with resulting infection
or bleeding, may occur. Decreases serum concentration of Etoposide:
Dabrafenib, Mitotane,

Enhances therapeutic effect of Etoposide:

334
ANTINEOPLASTIC AND IMMODULATING AGENTS

Roflumilast (immunosuppressive effect) Indications: Treatment of locally advanced or metastatic

breast cancer (adjuvant treatment of operable node-
Enhances therapeutic effect of Tofacitinib positive); treatment of advanced gastric
(immunosuppressive effect) adenocarcinoma; treatment of recurrent and/or
metastatic squamous cell head and neck cancer;
Increases risk of adverse or toxic effects of Etoposide: treatment of locally advanced or metastatic NSCLC;
Dipyrone (agranulocytosis, pancytopenia), treatment of metastatic ovarian cancer following failure
Pimecrolimus, Tacrolimus (Topical) of first-lineor subsequent chemotherapy; treatment of
hormone refractory, metastatic prostate cancer
Increases risk of adverse or toxic effects of the following
drugs: Contraindications: Hypersensitivity to other medications
Clozapine (agranulocytosis), Leflunomide (hematologic containing polysorbate 80; neutrophil count
toxicity such as pancytopenia, agranulocytosis, and/or <1,500/mm3, severe hepatic impairment; pregnancy;
thrombocytopenia), Natalizumab (concurrent infection) breastfeeding

Increases serum concentration of Etoposide: Dose:

Fusidic Acid (Systemic), Mifepristone Breast cancer, locally advanced or metastatic, by IV
infusion, ADULT, as combination therapy, 75 mg/m2
Reduces therapeutic effect of the following drugs: every 3 weeks;
BCG (Intravesical), Vaccines (live virus vaccines may as a single agent, 100 mg/m2 every 3 weeks.
progress to infection) Breast cancer, operable, node-positive, adjuvant treatment,
by IV infusion, ADULT, in combination with doxorubicin
Administration: For IV infusion, administer diluted over 30– and cyclophosphamide, 75 mg/m2 every 3 weeks for 6

L
60 minutes to prevent occurrence of hypotension. courses.
Gastric adenocarcinoma, by IV infusion, ADULT, in
Do NOT administer by IV push, by IM or SC. combination with cisplatin and fluorouracil, 75 mg/m2
Avoid extravasation. every 3 weeks.
Locally advanced or metastatic NSCLC, metastatic ovarian
NOTE: Extravasation may cause significant irritation. Tissue cancer, recurrent and/or metastatic head and neck
irritation and inflammation have occurred following cancer, by IV infusion, ADULT, as combination therapy,
extravasation. 75 mg/m2 every 3 weeks; as a single agent, 100 mg/m2
every 3 weeks.
Concentrations >0.4 mg/mL may form precipitate within Metastatic prostate cancer, hormone-refractory, by IV
a few minutes. For large doses, where dilution to ≤0.4 infusion, ADULT, in combination with prednisone or
mg/mL is not feasible, consider slow infusion of the prednisolone, 75 mg/m2 every 3 weeks.
undiluted drug through a running normal saline, dextrose
or saline and dextrose infusion, or use etoposide
phosphate. An inline filter may be used to address the Dose Adjustment:
risk for precipitation. Etoposide solutions of 0.1–0.4 Hepatic Impairment:
mg/mL may be filtered through a 0.22 micron filter. If total bilirubin is greater than the ULN, or if AST and/or ALT
>1.5 times ULN concomitant with alkaline phosphatase
Pregnancy Category: D >2.5 times ULN, use is not recommended.
Specific for gastric or head and neck cancer:
ATC Code: L01CB01 AST/ALT >2.5 to ≤5 times ULN and alkaline phosphatase
≤2.5 times ULN, administer 80% of dose.
AST/ALT >1.5 to ≤5 times ULN and alkaline phosphatase
TAXANES >2.5 to ≤5 times ULN, administer 80% of dose.
AST/ALT >5 times ULN and /or alkaline phosphatase >5
times ULN, discontinue use.
Rx DOCETAXEL
Obesity:
Use actual body weight (full weight) for calculation of BSA-
Inj.: 10 mg/mL solution for infusion, 2 mL and 8 mL vial
based or weight-based dosing, especially if the intent of
(IV)
therapy is curative.
20 mg/0.5 mL (anhydrous), 0.5 mL vial (IV infusion)
If dose reduction is done due to toxicity, consider
20 mg/mL concentrate for solution (as trihydrate), 1
resumption of full weight-based dosing with subsequent
mL (IV infusion)
cycles, especially if cause of toxicity is resolved.
40 mg/mL (anhydrous), 2 mL vial (IV infusion)
80 mg/4 mL concentrate for solution (as trihydrate),
Precautions:
4 mL (IV infusion)
WARNING: Patients with abnormal liver function, those
A taxane derivative that inhibits DNA, RNA, and protein receiving higher doses, and patients with NSCLC and
synthesis by preventing the depolymerization of a history of prior treatment with platinum derivatives
microtubules during cell division, specifically during the who receive single-agent docetaxel at a dose of 100
M phase. mg/m2 are at higher risk for treatment-related
mortality.

335
 ANTINEOPLASTIC AND IMMODULATING AGENTS

ventricular ejection fraction, dermatological reaction,

Avoid use in patients with bilirubin exceeding upper limit diarrhea, dysgeusia, epiphora (associated with
of normal (ULN) or AST and/or ALT >1.5 times ULN in canalicular stenosis), febrile neutropenia (dose-
conjunction with alkaline phosphatase >2.5 times dependent), fever, fluid retention (dose-dependent),
ULN. Patients with isolated transaminase elevations hypotension, infection (dose-dependent), infusion site
>1.5 times ULN at an increased risk of neutropenic reactions (including hyperpigmentation, inflammation,
fever, although no increased incidence of toxic death. redness, dryness, phlebitis, extravasation, swelling of the
vein), leukopenia, myalgia, nail disease, nausea,
Do NOT give to patients with neutrophil counts of neuromuscular reaction, neutropenia (dose-dependent),
<1,500 cells/mm3. Perform frequent blood cell peripheral motor neuropathy (mainly distal extremity
counts to monitor occurrence of neutropenia. weakness), pulmonary reaction, stomatitis,
thrombocytopenia (dose-dependent), vomiting,
weakness
Do NOT administer to patients with a history of severe Less Common: Abdominal pain, acute myelocytic leukemia,
hypersensitivity to docetaxel or polysorbate 80. acute respiratory distress, anorexia, anaphylactic shock,
Severe hypersensitivity reactions, characterized by ascites, atrial fibrillation, atrial flutter, AV block,
generalized rash or erythema, hypotension, bronchospasm, cardiac arrhythmia, cardiac failure,
bronchospasms, or anaphylaxis may occur and may cardiac tamponade, bradycardia, chest pain, chest
be fatal. tightness, colitis, confusion, conjunctivitis, constipation,
cystoid macular edema, deepvein thrombosis,
Severe fluid retention, characterized by pleural effusion, dehydration, disease of the lacrimal apparatus (duct
ascites, peripheral edema, dyspnea at rest, cardiac obstruction), disseminated intravascular coagulation,
tamponade, generalized edema, and weight gain, drug fever, duodenal ulcer, ECG abnormality, dyspnea,
L

has been reported. erythema multiforme, esophagitis, gastrointestinal

hemorrhage, GI obstruction, GI perforation, hearing loss,
hemorrhagic diathesis, hepatitis, hypertension,
WARNING: Hazardous agent. Use appropriate hyponatremia, intestinalobstruction, interstitial
precautions for handling and disposal. pulmonary disease, ischemic colitis, ischemic heart
disease, loss of consciousness (transient), lymphedema
Bone marrow suppression (neutropenia may occur; (peripheral), multiorgan failure, lacrimation,
neutropenia is the dose limiting toxicity; platelets should myelodysplastic syndrome, pain, myocardial infarction,
be >100,000/mm3 prior to treatment; patients with neutropenic enterocolitis, ototoxicity, palmar-plantar
increased liver function tests may experience more erythrodysesthesia, pericardial effusion, pleural
episodes of neutropenia with more frequent severe effusion, pneumonia, pneumonitis, pulmonary
infections); edema,pulmonary embolism, pulmonary fibrosis,
Cutaneous reactions (e.g. erythema with edema and pruritus, radiation pneumonitis, radiation recall
desquamation) phenomenon, renal failure, renal insufficiency,
Fluid retention (may begin as lower extremity peripheral respiratory failure, skin changes (scleroderma-like),
edema and become generalized; weight gain may be seizure, sepsis, sinus tachycardia, SJS, subacute
around 2 kg; administer corticosteroid, starting 1 day cutaneous lupus erythematosus, syncope, tachycardia,
prior to administration, to reduce the incidence and thrombophlebitis, TEN, unstable angina pectoris, visual
severity of fluid retention). disturbance (transient)
Hepatic impairment (increased risk of grade 4 neutropenia,
infections, stomatitis, severe thrombocytopenia, skin Drug Interactions:
toxicity, or toxic death). Monitor closely with:
Hypersensitivity reactions (severe reactions occur; minor Enhances therapeutic effect of Docetaxel:
reactions include flushing or localized skin reactions; Trastuzumab (neutropenic effect)
discontinue for severe reactions; administer
corticosteroid, starting 1 day prior to administration, to Increases risk of adverse or toxic effects of Docetaxel:
prevent or reduce the severity ofhypersensitivity Denosumab (serious infections)
reactions)
Neurosensory symptoms (e.g. paresthesia, dysesthesia, Reduces diagnostic effect of Coccidioides immitis Skin Test
neuropathic pain; reversal of symptoms may be delayed
after discontinuation). Avoid concomitant use with:
Ocular adverse effects (cystoid macular edema may occur; Decreases metabolism of Docetaxel:
promptly administer a comprehensive ophthalmic exam Antifungal Agents, Azole Derivatives, Systemic [except
if vision impairment occurs; majority experience tearing Fluconazole]
which subsided after therapy completion)
Secondary malignancies (treatment-related AML or Decreases serum concentration of Docetaxel:
myelodysplasia) Dabrafenib, Mitotane
Weakness (fatigue or weakness may occur; weakness may
be severe, lasting for a few days up to several weeks). Enhances therapeutic effect of Docetaxel:
Platinum Derivatives [e.g., Cisplatin, Carboplatin,
Adverse Drug Reactions: Oxaliplatin (myelosuppressive effect)], Roflumilast
Common: Alopecia, anemia (dose-dependent), arthralgia, (immunosuppressive effect)
CNS toxicity (including neuropathy), decreased left

336
ANTINEOPLASTIC AND IMMODULATING AGENTS

Enhances therapeutic effect of Tofacitinib

(immunosuppressive effect) Rx PACLITAXEL

Increases risk of adverse or toxic effects of the following Inj.: 6 mg/mL, 5 mL, 16.7 mL, 17 mL, 25 mL, and 43.4
drugs: mL vial (IV, IV infusion)
Antineoplastic Agents [Anthracycline, Systemic (e.g.,
Doxorubicin, Epirubicin, Idarubicin)], Clozapine A taxane derivative that stabilizes microtubule formation
(agranulocytosis), Dipyrone (agranulocytosis, which interferes with the late G2 phase of cell division.
pancytopenia), Leflunomide (hematologic toxicity such
as pancytopenia, agranulocytosis, and/or Indications: Adjuvant treatment of node-positive breast
thrombocytopenia), Natalizumab (concurrent infection) cancer; treatment of metastatic breast cancer after
failure of combination chemotherapy or relapse within 6
Increases risk of adverse or toxic effects of Docetaxel: months of adjuvant chemotherapy (prior therapy should
Pimecrolimus, Tacrolimus (Topical) have included an anthracycline); second-line treatment
of AIDS-related Kaposi’s sarcoma (KS); first-line
Increases serum concentration of Docetaxel: treatment of non-small cell lung cancer (in combination
Dronedarone, Fusidic Acid (Systemic), Mifepristone, with cisplatin) in patients who are notcandidates for
potentially curative surgery and/or radiation therapy;
Reduces therapeutic effect of Docetaxel: subsequent therapy for treatment of advanced ovarian
Echinacea cancer; first-linetherapy of ovarian cancer (in
combination with cisplatin)
Reduces therapeutic effect of the following drugs:
BCG (Intravesical), Vaccines (live virus vaccines may

L
Contraindications: Hypersensitivity to paclitaxel, polyoxyl 35
progress to infection) or polyoxyethylated castor oil, or any component of the
formulation; treatment of solid tumors in patients with
Administration: Dilute with NS or D5W to a final baseline neutrophil counts <1,500/mm3; treatment of
concentration of 0.3-0.74 mg/mL, and prepare in a glass Kaposi’s sarcoma inpatients with baseline neutrophil
bottle, polypropylene, or polyolefin plastic bag to prevent counts <1,000/mm3
leaching of plasticizers. Non-PVC tubing must be used.
Dose:
Preparation instructions may vary by manufacturer, refer to Breast cancer, adjuvant treatment, by IV infusion, ADULT,
specific prescribing information. 175 mg/m2 over 3 hours every 3 weeks for 4 cycles,
following an anthracycline-containing regimen.
NOTE: Extravasation may cause significant irritation. Ensure Breast cancer, metastatic or relapsed, by IV infusion,
proper needle or catheter placement prior to and during ADULT, 175 mg/m2 over 3 hours every 3 weeks; 80
infusion. If extravasation occurs, discontinue mg/m2/IV Day 1 weekly.
immediately and initiate appropriate extravasation Non-small cell lung cancer, by IV infusion, ADULT, in
management, including local injection of hyaluronidase combination with cisplatin, 135 mg/m2 over 24 hours
and moderate heat application to the affected area. Use every 3 weeks.
a separate vein to administer any remaining portion of Ovarian cancer, advanced, previously treated, by IV infusion,
the dose. ADULT, 135 or 175 mg/m2 over 3 hours every 3 weeks.
Ovarian cancer, advanced, previously untreated, by IV
Some preparations contain alcohol, which may affect the infusion, ADULT, in combination with cisplatin, 175
CNS and cause symptoms of alcohol intoxication. mg/m2 over 3 hours every 3 weeks; or 135 mg/m2 over
24 hours administered every 3 weeks.
Pre-medicate with corticosteroids for 3 days, beginning 1 Kaposi’s sarcoma, AIDS related, by IV infusion, ADULT, 135
day prior to docetaxel administration, to reduce the mg/m2 over 3 hours every 3 weeks or 100 mg/m2 over
severity of hypersensitivity reactions and fluid retention. 3 hours every 2 weeks (due to dose-related toxicity; use
100 mg/m2 dose only for patients with lower
Patients being treated for prostate cancer with performance status).
concurrent prednisone should be premedicated with oral
dexamethasone at 12 hours, 3 hours, and 1 hour prior Dose Adjustment:
to docetaxel administration. Hepatic Impairment:
NOTE: Recommendations are for the first course of therapy
Pregnancy Category: D where the usual dose is 135 mg/m2 (over 24 hours) or
175 mg/m2 (over 3 hours).
ATC Code: L01CD02 Dosing in subsequent courses should be based upon
individual tolerance.

24-hour infusion:
If transaminases <2 times upper limit of normal (ULN) and
bilirubin level ≤1.5 mg/dL, administer 135 mg/m2.
If transaminases 2 to <10 times ULN and bilirubin level ≤1.5
mg/dL, administer 100 mg/m2.
If transaminases <10 times ULN and bilirubin level 1.6 to
7.5 mg/dL, administer 50 mg/m2.

337
 ANTINEOPLASTIC AND IMMODULATING AGENTS

If transaminases ≥10 times ULN or bilirubin level >7.5 Peripheral neuropathy (commonly occurs; patients with
mg/dL, avoid use. preexisting neuropathies may be at a higher risk).
Elderly (at an increased risk of toxicity, including severe
3-hour infusion: neutropenia, neuropathy, and cardiovascular events).
If transaminases <10 times ULN and bilirubin level ≤1.25
times ULN, administer 175 mg/m2. Adverse Drug Reactions:
If transaminases <10 times ULN and bilirubin level 1.26 to Common: Abdominal pain (with intraperitoneal paclitaxel),
2 times ULN, administer 135 mg/m2. increased alkaline phosphatase, alopecia, anemia,
If transaminases <10 times ULN and bilirubin level 2.01 to arthralgia or myalgia, bleeding, bradycardia, diarrhea,
5 times ULN, administer 90 mg/m2. dyspnea, abnormal ECG, edema, febrile neutropenia,
If transaminases ≥10 times ULN or bilirubin level >5 times flushing, hypersensitivity reaction, hypertension,
ULN, avoid use. hypotension, infection, injection site reaction (erythema,
tenderness, skin discoloration, swelling), leukopenia,
Obesity: mucositis, nail changes, nausea, vomiting, neutropenia,
Use actual body weight (full weight) for calculation of BSA- peripheral neuropathy, rhythm abnormalities, rash,
based or weight-based dosing, especially if the intent of stomatitis (at doses >390 mg/m2), syncope,
therapy is curative. thrombocytopenia, tachycardia, weakness, venous
If dose reduction is done due to toxicity, consider thrombosis
resumption of full weight-based dosing with subsequent Less Common: Anaphylaxis, arrhythmia, ataxia, atrial
cycles, especially if cause of toxicity is resolved. fibrillation, AV block, back pain, cardiac conduction
abnormalities, cellulitis, CHF, chills, conjunctivitis,
Immunosuppression (in advanced HIV) or Toxicity: enterocolitis, extravasation recall, dehydration, hepatic
NOTE: Reduce the dexamethasone premedication dose to 10 mg and encephalopathy, hepaticnecrosis, induration, intestinal
L

initiate G-CSF treatment as clinically indicated. obstruction, intestinal perforation, interstitial

pneumonia, increased lacrimation, maculopapular rash,
For severe peripheral neuropathy or severe neutropenia
ischemic colitis, malaise, MI, myocardial ischemia,
(neutrophil <500/mm3for ≥7 days), reduce dose by 20%.
necrotic changes and ulceration following extravasation,
For neutrophil <1000 cells/mm3 or platelet neuroencephalopathy, neutropenic enterocolitis,
<100,000/mm3, do not administer paclitaxel. neutropenic typhlitis, ototoxicity (tinnitus; hearing loss),
pancreatitis, paralytic ileus, phlebitis, pneumonitis,
Precautions: pruritus, pulmonary embolism, pulmonary fibrosis,
WARNING: Should be administered under the radiation recall, radiation pneumonitis, renal
supervision of an experienced cancer insufficiency, seizure, skin edema (diffuse), skin
chemotherapy physician, experienced in the use of exfoliation, scleroderma exacerbation, skin fibrosis, skin
cancerchemotherapeutic agents. Administer in a necrosis, skin sclerosis,skin thickening, SJS, TEN
facility sufficient to appropriately diagnose and ventricular tachycardia (asymptomatic), supraventricular
manage complications. tachycardia, visual disturbances (scintillating scotomata)
Severe bone marrow suppression, primarily
neutropenia, with resulting infection or bleeding, Drug Interactions:
may occur. Do NOT administer if baseline Monitor closely with:
neutrophil count is <1,500/mm3 for solid tumors Increases risk of adverse or toxic effects of Paclitaxel:
or <1,000/mm3 for AIDS-related Kaposi’s Denosumab (serious infections)
sarcoma.
Anaphylaxis and severe hypersensitivity reactions Increases risk of adverse or toxic effects of Vinorelbine
have occurred in 2–4% of patients in clinical (neurotoxic effect)
studies. Some reactions have been fatal. If severe
hypersensitivity occurs, STOP INFUSION AND DO Reduces diagnostic effect of Coccidioides immitis Skin Test
NOT RECHALLENGE.
Avoid concomitant use with:
Decreases metabolism of Doxorubicin (Conventional)
WARNING: Hazardous agent. Use appropriate
precautions for handling and disposal. Decreases serum concentration of Paclitaxel:
Dabrafenib, Mitotane
Bone marrow suppression (usually in the form of
neutropenia; dose-dependent; dose-limiting toxicity) Decreases serum concentration of Aripiprazole
Cardiovascular effects (e.g. infusion-related hypotension,
bradycardia, and/or hypertension; rare but severe Enhances therapeutic effect of Paclitaxel:
conduction abnormalities). Platinum Derivatives [e.g., Cisplatin, Carboplatin,
Injection-site reactions (e.g. skin discoloration, tenderness, Oxaliplatin (myelosuppressive effect)], Roflumilast
erythema, or swelling; more severe reactions, e.g. (immunosuppressive effect)
phlebitis, cellulitis, skin exfoliation, necrosis, fibrosis,
induration; skin reactions may occur despite Enhances therapeutic effect of Tofacitinib
administering through a different IV site); (immunosuppressive effect)
Hypersensitivity reactions (e.g. flushing, skin reactions,
dyspnea, hypotension, or tachycardia);

338
ANTINEOPLASTIC AND IMMODULATING AGENTS

Increases risk of adverse or toxic effects of Paclitaxel: adjunctive) of locally recurrent orlocoregional solid
Dipyrone (agranulocytosis, pancytopenia), tumors (sarcomas, carcinomas, and adenocarcinomas)
Pimecrolimus, Sorafenib, Tacrolimus (Topical)
Contraindications: Patients with concurrent or recent
Increases risk of adverse or toxic effects of the following chickenpox or herpes zoster
drugs:
Antineoplastic Agents [Anthracycline, Systemic (e.g., Dose:
Doxorubicin, Epirubicin, Idarubicin)], Clozapine NOTE: Dose intensity per 2-week cycle should not exceed 15
(agranulocytosis), Leflunomide (hematologic toxicity micrograms/kg daily for 5 days or 400–600
such as pancytopenia, agranulocytosis, and/or micrograms/m2 daily for 5 days.
thrombocytopenia), Natalizumab (concurrent infection)
Calculate dose for obese or edematous adult patients
Increases serum concentration of Paclitaxel: based on BSA to relate dosage to lean body mass.
Atazanavir, Fusidic Acid (Systemic), Mifepristone
Associated with a high emetic potential. Antiemetics are
Reduces therapeutic effect of Paclitaxel: recommended to prevent nausea and vomiting.
Echinacea
Testicular cancer, metastatic, by slow IV push, ADULT, in
Reduces therapeutic effect of the following drugs: combination with cyclophosphamide, bleomycin,
BCG (Intravesical), Vaccines (live virus vaccines may cisplatin, and vinblastine, 1,000 micrograms/m2 on day
progress to infection) 1.

Administration: Administer by IV infusion over 3 or 24 hours, Gestational trophoblastic neoplasm, by slow IV push,

L
depending on indication or protocol, through a ADULT, 12 microgams/kg daily for 5 days;
0.22micronin-linefilter and polyethylene-lined (non-PVC) in combination with etoposide, methotrexate, leucovorin,
administration set. vincristine, cyclophosphamide, and cisplatin, 500
micrograms/dose on days 1 and 2.
Pre-medicate with corticosteroids, diphenhydramine,
and H2 antagonists prior to infusion. Wilms’ tumor, Ewing’s sarcoma, rhabdomyosarcoma, by
slow IV push, ADULT and CHILD>6 months, in various
NOTE: Pre-medication with dexamethasone (20 mg orally or combination regimens and schedules, 15
IV at 12 and 6 hours before the dose; reduce to 10 mg micrograms/kg daily for 5 days.
with advanced HIV disease), diphenhydramine (50 mg IV
30 to 60 minutes prior to the dose), and cimetidine 300 Regional perfusion, by IV injection, ADULT,
mg, famotidine 20 mg, or ranitidine 50 mg (IV 30 to 60 lower extremity or pelvis, 50 micrograms/kg;
minutes prior to the dose) is recommended. upper extremity, 35 micrograms/kg;
[NOTE: Doses and techniques may vary by institution.
Irritant with vesicant-like properties. Avoid extravasation. Obese patients and patients with prior chemotherapy or
Ensure proper needle or catheter position prior to radiation therapy may require lower doses. Regional
administration. perfusion therapy may result in local limb edema, soft
tissue damage, and possible venous thrombosis.
Pregnancy Category: D Dactinomycin leakage into systemic circulation may
result in hematologic toxicity, infection, impaired wound
ATC Code: L01CD01 healing, and mucositis.]

Dose Adjustment:
CYTOTOXIC ANTIBIOTICS Renal Impairment
AND RELATED SUBSTANCES Based onthe amount of urinary excretion, dose adjustment
may not be necessary.
ACTINOMYCINES Hepatic Impairment:
For mild impairment, no dose adjustments provided.
Rx DACTINOMYCIN (ACTINOMYCIN D) For moderate-to-severe impairment, consider dose
reduction.
For patients with hyperbilirubinemia, reduce doses by 33–
Inj.: 500 micrograms powder, vial (IV) 50%.

An actinomycine derivative that binds to guanine portions of Obesity:

the DNA to intercalate between base pairs and inhibit Use actual body weight (full weight) for calculation of BSA-
DNA, RNA, and protein synthesis. based or weight-based dosing, especially if the intent of
therapy is curative.
Indications: Treatment of Wilms' tumor, childhood If dose reduction is done due to toxicity, consider
rhabdomyosarcoma, metastatic testicular tumors (non- resumption of full weight-based dosing with subsequent
seminomatous), Ewing's sarcoma, and gestational cycles, especially if cause of toxicity is resolved.
trophoblastic neoplasm; regional perfusion (palliative or
Radiation Therapy Recipients:

339
 ANTINEOPLASTIC AND IMMODULATING AGENTS

Use with caution in patients who have received radiation thrombocytopenia, thrombocytopenia (immune-
therapy. Reduce doses in patients receiving concomitant mediated), tissue necrosis, toxic epidermal necrolysis,
radiation therapy. Avoid dactinomycin use within ulceration (following extravasation), vomiting
2months of radiation treatment for right-sided Wilms'
tumor. Drug Interactions:
Monitor closely with:
Precautions: Enhances therapeutic effect of Dactinomycin:
WARNING: Should be administered under the Trastuzumab (neutropenic effect)
supervision of an experienced cancer
chemotherapy physician, experienced in the use of Increases risk of adverse or toxic effects of Dactinomycin:
cancer chemotherapeutic agents. Administer in a Denosumab (serious infections)
facility sufficient to appropriately diagnose and
manage complications. Reduces diagnostic effect of Coccidioides immitis Skin Test

WARNING: Highly toxic. Use caution in handling Avoid concomitant use with:
andadministration of both powder and solution. Enhances therapeutic effect of Dactinomycin:
Review special handling procedures and follow Roflumilast (immunosuppressive effect)
diligently to minimize toxic effects of dactinomycin,
e.g., mutagenicity, teratogenicity, carcinogenicity, Enhances therapeutic effect of Tofacitinib
corrosivity. (immunosuppressive effect)

Increases risk of adverse or toxic effects of Dactinomycin:

Secondary malignancies (second primary tumors may Dipyrone (agranulocytosis, pancytopenia),
L

occur; long-term observation of cancer survivors is Pimecrolimus, Tacrolimus (Topical)

recommended due to increased risk following radiation
and chemotherapy treatment). Increases risk of adverse or toxic effects of the following
Toxic effects (e.g. severe myelosuppression, diarrhea or, drugs:
stomatitis; discontinue treatment if toxic effects occur) Clozapine (agranulocytosis), Leflunomide (hematologic
Hepatotoxicity (e.g. hepatic sinusoidal obstruction toxicity such as pancytopenia, agranulocytosis, and/or
syndrome / SOS, characterized by bilirubin >1.4 mg/dL, thrombocytopenia), Natalizumab (concurrent infection)
unexpected weight gain, ascites, hepatomegaly, and
unexplained right upper quadrant pain) Reduces therapeutic effect of Dactinomycin:
Concurrent radiation therapy (potentiates the effects of Echinacea
radiation therapy; may result in increased toxicity, e.g.,
GI toxicity, myelosuppression, severe oropharyngeal Reduces therapeutic effect of the following drugs:
mucositis; may reactivate erythema from prior radiation BCG (Intravesical), Vaccines (live virus vaccines may
therapy; may increase the risk of hepatotoxicity) progress to infection)
Extravasation (extravasation during IV use causes severe
damage to soft tissues; has rarely led to contracture of Administration: For IV administration only. Do NOT
the arms). administer by IM or SC.
Elderly (may be associated with an increased risk of
myelosuppression) Administer by slow IV push or by IV infusion over 10–
Children (avoid use in infants <6 months of age due to a 15minutes. Do NOT filter with cellulose ester membrane
more frequent occurrence of toxic effects; risk of fatal filters.
hepatic sinusoidal obstruction syndrome (SOS) is
increased in children <4 years). Avoid inhalation of vapors or contact with skin, mucous
Pregnancy (avoid exposure during pregnancy). membrane, or eyes.
Adverse Drug Reactions: Abdominal pain, acne, alopecia NOTE: Avoid extravasation. Vesicant and extremely
(reversible), anaphylactoid reaction, agranulocytosis, corrosive to soft tissue. Ensure proper needle or catheter
anemia, anorexia, aplastic anemia, ascites, bilirubin position prior to and during administration.
increased, cheilitis, diarrhea, dysphagia, edema,
epidermolysis, erythema, erythema multiforme, Associated with a high emetic potential. Antiemetics are
esophagitis, fatigue, febrile neutropenia, fever, GI recommended to prevent nausea and vomiting.
ulceration, growth retardation, hepatic failure, hepatitis,
hepatic sinusoidal obstruction syndrome (SOS), Pregnancy Category: D
hepatomegaly, hepatopathy thrombocytopenia
syndrome, hepatotoxicity, abnormal liver function test, ATC Code: L01DA01
hyperuricemia, hypocalcemia, increased pigmentation,
infection, lethargy, leukopenia, myalgia,
myelosuppression, pain, malaise, mucositis, nausea,
neutropenia, or erythema of previously irradiated skin;
skin eruptions, pancytopenia, pharyngitis, proctitis,
pneumonitis, abnormal renal function, sepsis (including
neutropenic sepsis), sloughing, Stevens-Johnson
syndrome, reticulocytopenia, stomatitis,

340
ANTINEOPLASTIC AND IMMODULATING AGENTS

ANTHRACYCLINES AND Obesity:

RELATED SUBSTANCES Use actual body weight (full weight) for calculation of BSA-
based or weight-based dosing, especially if the intent of
therapy is curative.
Rx DOXORUBICIN If dose reduction is done due to toxicity, consider
resumption of full weight-based dosing with subsequent
cycles, especially if cause of toxicity is resolved.
Inj.: 10 mg and 50 mg powder (as hydrochloride), vial (IV)
2 mg/mL (as hydrochloride), 5 mL and 25 mL vial (IV) Inadequate Marrow Reserve:
Consider lower doses due to advanced age, prior treatment,
An anthracycline that inhibits DNA and RNA synthesis by or neoplastic marrow infiltration. Cumulative doses
intercalating with DNA and by inhibiting DNA repair above 550 mg/m2 are associated with an increased risk
through topoisomerase II inhibition. of cardiomyopathy. Discontinue in patients who develop
signs or symptoms of cardiomyopathy.
Indications: Adjuvant therapy in women with evidence of
axillary lymph node involvement following resection of Precautions:
primary breast cancer; treatment of acute lymphoblastic
leukemia, acute myeloid leukemia,Wilms’ tumor, WARNING: Should be administered under the
neuroblastoma, soft tissue and bone sarcomas, breast supervision of an experienced cancer
cancer, ovarian cancer, thyroid carcinoma, transitional chemotherapy physician, experienced in the use of
cell bladder carcinoma, gastric carcinoma, Hodgkin’s cancerchemotherapeutic agents. Administer in a
lymphoma, non-Hodgkin’s lymphoma, and bronchogenic facility sufficient to appropriately diagnose and
carcinoma in which thesmall cell histologic type is the manage complications.

L
most responsive compared with other cell types
The risk for myocardial toxicity increases with
Contraindications: Hypersensitivity to doxorubicin, other cumulative exposure and with concomitant
anthracyclines, e.g., daunorubicin, epirubicin, idarubicin, cardiotoxic therapy. The incidence of irreversible
anthracenediones, e.g., mitoxantrone, or any component myocardial toxicity increases as the total
of the formulation; severe myocardial insufficiency; cumulative (lifetime) doses approach 300–500
recent MI (within 4–6 weeks); severe arrhythmia; mg/m2 (with an every-3-week regimen). Assess left
previous therapy with high cumulative doses of ventricular ejection fraction (LVEF) with either an
doxorubicin, daunorubicin, idarubicin, or other echocardiogram or MUGA scan before, during, and
anthracyclines, e.g., epirubicin, and anthracenediones, after therapy. Increase frequency of assessments
e.g., mitoxantrone; severe persistent drug-induced as the cumulative dose exceeds 300 mg/m2.
myelosuppression or baseline neutrophil count Secondary acute myelogenous leukemia (AML) and
<1500/mm3; severe hepatic impairment, i.e., Child-Pugh myelodysplastic syndrome (MDS) have been
class C or bilirubin >5 mg/dL; G6PD deficiency reported following treatment.
Dose: May cause severe myelosuppression, which may
Breast cancer, by IV push, ADULT, in combination with result in serious infection, septic shock,
cyclophosphamide, 50-60 mg/m2 on day 1 of a 14 or 21- transfusion requirements, hospitalization, and
day cycle for 4-6 cycles. death. May cause hemolytic anemia with G6PD
Metastatic solid tumors, leukemia, or lymphoma, by IV push, deficiency.
ADULT, as single-agent, 60–75 mg/m2 every 21 days;
in combination therapy, 40–75 mg/m2 every 21 to 28
days. WARNING: Hazardous agent. Use appropriate precautions for
handling and disposal.
Acute lymphoblastic leukemia, acute myeloid leukemia,
Wilms’ tumor. Ewing’s sarcoma, osteosarcoma, and soft
tissue sarcoma, CHILD: Always consult institutional Bone marrow suppression (e.g. leukopenia, neutropenia,
protocols. Maximum cumulative dose in children in 450 anemia, thrombocytopenia; monitor blood counts at
mg/m2. Lifetime cumulative dose above 550 mg/m2 are baseline and regularly during therapy).
associated with an increased risk of cardiotoxicity. Cardiotoxicity (delayed cardiotoxicity, sub-acute effects,
e.g., pericarditis or myocarditis, early toxicity, e.g.,
Dose Adjustment: tachyarrhythmias, sinus tachycardia, premature
Hepatic Impairment: ventricular contractions, ventricular tachycardia, or
Reduce doses in patients with impaired hepatic function. bradycardia, and ECG changes; dose-limiting, delayed
For transaminases 2–3 times Upper Limit of Normal (ULN), toxicity may occur late in treatment or months to years
administer 75% of dose. after therapy; total cumulative dose should be taken into
For transaminases >3 times ULN or serum bilirubin 1.2 to 3 account before treating with other anthracyclinesor
mg/dL, administer 50% of dose. anthracenediones, cardiotoxic agents, or irradiation of
For serum bilirubin 3.1–5 mg/dL, administer 25% of dose. chest; irreversible cardiotoxicity may occur at any dose
In severe hepatic impairment, i.e., Child-Pugh class C or level).
bilirubin >5 mg/dL, use is contraindicated. Fertility impairment (e.g. damage to spermatozoa and
testicular tissue, oligospermia, azoospermia, or loss of
fertility may occur in men; infertility, amenorrhea,
premature menopause may occur in women of
reproductive potential).

341
 ANTINEOPLASTIC AND IMMODULATING AGENTS

Secondary malignancy (may occur within 1-3 years of Enhances therapeutic effect of Doxorubicin:
treatment) Roflumilast (immunosuppressive effect)
Tumor lysis syndrome (tumor lysis syndrome or
hyperuricemia; urinary alkalinization and anti- Enhances therapeutic effect of Tofacitinib
hyperuricemic prophylaxis may be required; monitor (immunosuppressive effect)
electrolytes, renal function, and hydration status).
Concurrent radiation therapy (radiation recall may occur; Increases risk of adverse or toxic effects of Doxorubicin:
may increase radiation-induced toxicity to the Dipyrone (agranulocytosis, pancytopenia),
myocardium, mucosa, skin, and liver). Pimecrolimus, Tacrolimus (Topical), Trastuzumab
Extravasation (extravasation during IV use causes severe (cardiotoxic effects)
local tissue damage leading to tissue injury, blistering,
ulceration, and necrosis may occur, requiring wide Increases risk of adverse or toxic effects of the following
excision of the affected area and skin grafting). drugs:
Children (at an increased risk for developing delayed Clozapine (agranulocytosis), Leflunomide (hematologic
cardiotoxicity;may contribute to prepubertal growth toxicity such as pancytopenia, agranulocytosis, and/or
failure in children; may also contribute to gonadal thrombocytopenia), Natalizumab (concurrent infection),
impairment, usually temporary; radiation recall Taxane Derivatives (e.g. Paclitaxel, Docetaxel),
pneumonitis has been reported in children receiving Zidovudine
concomitant dactinomycin and doxorubicin).
Increases serum concentration of Doxorubicin:
Adverse Drug Reactions: Abiraterone Acetate, Cyclosporine, CYP2D6 Inhibitors
Common: Abdominal pain, acute cardiotoxicity (AV block, (Moderate), CYP2D6 Inhibitors (Strong), Fusidic Acid
bradycardia, bundle branch block, ECG abnormalities, (Systemic), Mifepristone, P-glycoprotein / ABCB1
L

extrasystoles (atrial orventricular), sinus tachycardia, ST- Inhibitors,

T wave changes, SVT, VT, tachyarrhythmia), alopecia,
amenorrhea, anemia, anorexia, colon necrosis, Reduces therapeutic effect of Doxorubicin:
dehydration, delayed cardiotoxicity (decreased LVEF, Dexrazoxane, Echinacea
CHF, myocarditis, pericarditis), diarrhea, fluid
discoloration (saliva, sweat, tears, urine), GI ulceration, Reduces therapeutic effect of the following drugs:
hyperuricemia, infertility (may be temporary), itching, BCG (Intravesical), Stavudine, Vaccines (immune
leukopenia or neutropenia, malaise, mucositis, nausea, response; live virus vaccines may progress to infection),
photosensitivity, radiation recall, rash, skin “flare” at Zidovudine
injection site, thrombocytopenia, urticaria, vomiting,
weakness Administration: For IV administration only. Administer IV
Less Common: Anaphylaxis, azoospermia, bilirubin push over at least 3–10 minutes or by continuous IV
increased, chills, coma (in combination with cisplatin or infusion via a central venous line. Rate of administration
vincristine), conjunctivitis, fever, gonadal impairment varies by protocol, refer to individual protocol for details.
(children), growth failure (prepubertal), hepatitis,
hyperpigmentation (nail, skin, oral mucosa), keratitis, Do NOT administer by IM or SC.
lacrimation, myelodysplastic syndrome, neutropenic
fever, infection, neutropenic typhlitis, oligospermia, Protect from light until completionof infusion. Avoid
onycholysis, phlebosclerosis, radiation recall contact with alkaline solutions.
pneumonitis (children), secondary acute myelogenous
leukemia, seizure (in combination with cisplatin or Monitor for local erythematous streaking along vein
vincristine), sepsis, shock, systemic hypersensitivity and/or facial flushing, which indicates rapid infusion
(including urticaria, pruritus, angioedema, dysphagia, rate. Decrease rate if this occurs.
and dyspnea), SJS, TEN, urticaria
NOTE: Avoid extravasation. Ensure proper needle or
Drug Interactions: catheter position prior to and during administration. If
Monitor closely with: extravasation occurs, discontinue infusion immediately
Increases risk of adverse or toxic effects of Doxorubicin: and apply ice to the affected area.
Bevacizumab (cardiotoxic effect), Cyclophosphamide
(cardiotoxic effect), Denosumab (serious infections) Associated with a high emetic potential. Antiemetics are
recommended to prevent nausea and vomiting.
Increases risk of adverse or toxic effects of Mercaptopurine
(hepatotoxic effect)
Pregnancy Category: D
Reduces diagnostic effect of Coccidioides immitis Skin Test
ATC Code: L01DB01
Avoid concomitant use with:
Decreases metabolism of Doxorubicin:
Taxane Derivatives [e.g., Paclitaxel (except Docetaxel)]

Decreases serum concentration of Doxorubicin:

Dabrafenib, Mitotane, P-glycoprotein / ABCB1 Inducers,

342
ANTINEOPLASTIC AND IMMODULATING AGENTS

Reduce day 1 dose in subsequent cycles to 75% of

Rx EPIRUBICIN previous day 1 dose if patient experiences nadir platelet
counts <50,000/mm3, ANC <250/mm3, neutropenic
Inj.: 10 mg and 50 mg powder (as hydrochloride), vial (IV) fever, or grade 3/4 nonhematologic toxicity during the
previous cycle.
Inhibits DNA and RNA synthesis by intercalating between For CEF-120 regimen, reduce day 8 dose to 75% of day 1
DNA base pairs and disrupting topoisomerase II repair. It dose if platelet counts are 75,000 to 100,000/mm3 and
also inhibits DNA helicase. ANC is 1000 to1499/mm3; omit day 8 dose if platelets
are <75,000/mm3, ANC <1000/mm3, or grade 3/4
Indications: Adjuvant therapy component for primary breast nonhematologic toxicity.
cancer in patients with evidence of axillary node
involvement following tumor resection Precautions:
WARNING: Should be administered under the
Contraindications: Hypersensitivity to epirubicin, other supervision of an experienced cancer chemotherapy
anthracyclines, anthracenediones, or any component of physician. Administer in a facility sufficient to
the formulation; cardiomyopathy and/or heart failure; appropriately diagnose and manage complications.
recent myocardial infarction, severe arrhythmias;
Severe myelosuppression may occur.
previous treatment with anthracyclines
Secondary acute myeloid leukemia (AML) has been
Dose: reported.
Breast cancer, adjuvant treatment, by slow IV push, ADULT, Cardiac toxicity, including fatal CHF, may occur either
100–120 mg/m2 per 3– or 4–week treatment cycle as during therapy or months to years after termination

L
follows: of therapy. In the adjuvant treatment of breast
in combination with cyclophosphamide and fluorouracil cancer, the maximum cumulative dose is 720
(CEF-120 regimen), 60 mg/m2 on days 1 and 8 every 28 mg/m2. The risk of developing CHF increases rapidly
days for 6 cycles; or with increasing total cumulative doses >900 mg/m2.
in combination with cyclophosphamide and fluorouracil Children may be at increased risk for developing
(FEC-100 regimen), 100 mg/m2 on day 1 every 21 days acute and delayed cardiotoxicity.
for 6 cycles.
Patients receiving 120 mg/m2 per cycle as part of
combination therapy (CEF-120 regimen) should also
Dose Adjustment: receive prophylactic antibiotic therapy with
Geriatric: sulfamethoxazole/trimethoprim or a fluoroquinolone.
Plasma clearance in elderly female patients was reduced by Lower starting doses may be necessary for heavily
35%. Monitor toxicity and adjusting subsequent dosage pretreated patients, patients with preexisting
in elderly patients with great care, particularly females myelosuppression, or with bone marrow involvement.
>70 years of age. Maximum lifetime dose is 900 mg/m2.
Renal Impairment: Prophylactic antibiotics should be administered with
In severe renal impairment (serum creatinine >5 mg/dL), the CDF-120 regimen.
lower doses. May have radiosensitizing activity. Radiation recall
(inflammatory) has been reported. Use with caution
Hepatic Impairment: in radiation recipients.
Reduce doses in with impaired hepatic function.
In bilirubin 1.2–3 mg/dL or AST 2–4 times the upper limit Patients should recover from acute toxicities
of normal, administer 50% of recommended starting (stomatitis, myelosuppression, infections) prior to
dose. initiating treatment. Assess baseline labs (blood
In bilirubin >3 mg/dL or AST >4 times the upper limit of counts, bilirubin, ALT, AST, serum creatinine) and
normal, administer 25% of recommended starting dose. cardiac function (LVEF).
In severe impairment, use is not recommended.
WARNING: Hazardous agent; use appropriate
Obesity: precautions for handling and disposal.
Use actual body weight (full weight) for calculation of BSA-
based or weight-based dosing, especially if the intent of Bone marrow suppression (e.g. leukopenia,
therapy is curative. thrombocytopenia, anemia; myelosuppression may
If dose reduction is done due to toxicity, consider result in severe neutropenia and severe infection,
resumption of full weight-based dosing with subsequent needing supportive care)
cycles, especially if cause of toxicity is resolved. Thromboembolic events (e.g. thrombophlebitis,
thromboembolic phenomena, including pulmonary
Toxicity: embolism).
In heavily-treated patients and patients with preexisting Hepatic impairment (evaluate hepatic function at baseline
bone marrow depression or neoplastic bone marrow and during treatment; predominantly hepatically
infiltration, consider lower starting doses of 75–90 eliminated; impaired function may lead to increased
mg/m2. exposure and toxicity); renal impairment (evaluate renal
Delay day 1 dose of subsequent cycles until platelets are function at baseline and during treatment).
≥100,000/mm3, ANC ≥1500/mm3, and nonhematologic Myocardial toxicity (e.g. tachyarrhythmias, sinus
toxicities have recovered to ≤grade 1. tachycardia, premature ventricular contractions,

343
 ANTINEOPLASTIC AND IMMODULATING AGENTS

ventricular tachycardia, bradycardia, ECG changes; Reduces therapeutic effect of Epirubicin:

cardiotoxicity is dose-limiting; risk increases with Echinacea
cumulative dose, but irreversible cardiotoxicity may
occur at any level; regularly monitor LVEF and Reduces therapeutic effect of the following drugs:
discontinue at first sign of impairment). BCG (Intravesical), Vaccines (immune response; live
Secondary malignancy (latency period for secondary virus vaccines may progress to infection)
leukemias may be as short as 1–3 years);
Tumor lysis syndrome (monitor serum uric acid, potassium, Administration:
calcium, phosphate, and serum creatinine after initial For IV administration, infuse over 15–20 minutes or slow
administration; hydration and anti-hyperuricemic IV push. If lower doses due to dose reduction are
prophylaxis may minimize potential TLS complications). administered, reduce infusion time proportionally. Do
NOT infuse over <3 minutes.
Adverse Drug Reactions:
Common: Alopecia, amenorrhea, anemia, anorexia, Infuse into a free-flowing IV solution (NS or D5W). Avoid
conjunctivitis, diarrhea, fever, HF, hot flashes, infection, the use of veins over joints or inextremities with
injection site reactions, leukopenia, lethargy, mucositis, compromised venous or lymphatic drainage.
nausea, decreased LVEF, vomiting, neutropenia,
neutropenic fever, rash, skin changes, thrombocytopenia Do NOT administer by IM or SC route.
Less Common: Abdominal pain, acute lymphoid leukemia,
acute myelogenous leukemia, AV block, anaphylaxis, NOTE: Avoid extravasation. Ensure proper needle or
arterial embolism, ascites, arrhythmia, bradycardia, catheter position prior to and during administration. If
bundle-branch block, cardiomyopathy, chills, extravasation occurs, discontinue infusion immediately
dehydration, dyspnea, ECG abnormalities, erythema, and apply ice to the affected area.
L

esophagitis, flushing, GI burning sensation, GI erosions

or ulcerations, GI pain, GI bleeding, hepatomegaly, Injection into a small vein or repeated administration in
hyperpigmentation (oral mucosa, nails, skin), the same vein may result in venous sclerosis.
hypersensitivity, hyperuricemia, myelodysplastic
syndrome, myocarditis, neutropenic typhlitis, phlebitis, Associated with a high emetic potential. Antiemetics are
pneumonia, premature menopause, premature recommended to prevent nausea and vomiting.
ventricular contractions, pulmonary edema, pulmonary
embolism, photosensitivity, radiation recall, sepsis, Pregnancy Category: D
shock, sinus tachycardia, stomatitis, ST wave changes,
tachyarrhythmias, thromboembolism, thrombophlebitis, ATC Code: L01DB03
toxic megacolon, urticaria, urine discoloration (red),
ventricular tachycardia

Drug Interactions: Rx IDARUBICIN

Monitor closely with:
Increases risk of adverse or toxic effects of Epirubicin:
Inj.: 5 mg powder (as hydrochloride), vial (IV)
Bevacizumab (cardiotoxic effect), Cyclophosphamide
(cardiotoxic effect), Denosumab (serious infections)
Inhibits DNA and RNA synthesis by intercalating between
DNA base pairs and disrupting topoisomerase II repair.
Reduces diagnostic effect of Coccidioides immitis Skin Test
Indications: Treatment of acute myeloid leukemia (AML) in
Avoid concomitant use with:
combination with other approved chemotherapy agents
Enhances therapeutic effect of Epirubicin:
Roflumilast (immunosuppressive effect)
Contraindications: Hypersensitivity to idarubicin, other
anthracyclines, anthracenediones, or any component of
Enhances therapeutic effect of the following drugs:
the formulation; bilirubin >5 mg/dL
Tofacitinib (immunosuppressive effect)
Increases risk of adverse or toxic effects of Epirubicin:
Dose:
Dipyrone (agranulocytosis; pancytopenia),
AML, induction, by slow IV injection, ADULT, 12 mg/m2 IV
Pimecrolimus, Tacrolimus (Topical), Taxane Derivatives
everyday over 10-15 minutes for 3 days with
(e.g. Paclitaxel, Docetaxel), Trastuzumab (cardiotoxic
concomitant cytarabine; CHILD, 12 mg/m2 for 3 days in
effects)
combination with cytarabine and etoposide.
AML, consoldation, ADULT, 10-12mg/m2/day IV for 2 days.
Increases risk of adverse or toxic effects of the following
AML Protocol (including Down Syndrome), CHILD, 5 to 8
drugs:
mg/m2 four-hour IV infusion (depending upon phase of
Clozapine (agranulocytosis), Leflunomide (hematologic
treatment).
toxicity such as pancytopenia, agranulocytosis, and/or
thrombocytopenia), Natalizumab (concurrent infection)
Dose Adjustment:
Renal Impairment:
Increases serum concentration of Epirubicin:
Reduce doses.
Cimetidine
ADULT
In CrCl 10–50 mL/minute, administer 75% of dose.

344
ANTINEOPLASTIC AND IMMODULATING AGENTS

In CrCl <10 mL/minute, administer 50% of dose. Adverse Drug Reactions:

Common: Alopecia, CHF (dose-related), diarrhea,
INFANT, CHILD, and ADOLESCENT discoloration of urine (darker yellow), headache,
In GFR ≤50 mL/minute/1.73 m2, and in patients myelosuppression, nausea, peripheral neuropathy,
receiving intermittent hemodialysis, peritoneal dialysis, radiation recall, seizure, skin rash, stomatitis, transient
or continuous renal replacement therapy, administer ECG abnormalities (SVT, ST wave changes, atrial or
75% of dose. ventricular extrasystoles), GI hemorrhage, urticaria,
vomiting
Hepatic Impairment: Less Common: Cardiomyopathy, hyperuricemia,
Reduce doses in impaired hepatic function. myocarditis, neutropenic typhlitis
In bilirubin 2.6–5 mg/dL, administer 50% of dose.
In bilirubin >5 mg/dL, avoid use. Drug Interactions:
Monitor closely with:
Impaired Bone Marrow Function: Increases risk of adverse or toxic effects of Idarubicin:
Lower doses of 60–75 mg/m2 are recommended. Bevacizumab (cardiotoxic effect), Cyclophosphamide
(cardiotoxic effect), Denosumab (serious infections)
Toxicity:
If patients experience severe mucositis during the first Reduces diagnostic effect of Coccidioides immitis Skin Test
induction cycle, delay administration of the second cycle
until mucositis has resolved. Consider reducing the dose Avoid concomitant use with:
by 25%. Enhances therapeutic effect of Idarubicin:
Roflumilast (immunosuppressive effect)
Precautions:

L
Enhances therapeutic effect of Tofacitinib
WARNING: Should be administered under the (immunosuppressive effect)
supervision of an experienced cancer chemotherapy
physician. Administer in a facility sufficient to Increases risk of adverse or toxic effects of Idarubicin:
appropriately diagnose and manage complications. Dipyrone (agranulocytosis; pancytopenia),
Pimecrolimus, Tacrolimus (Topical), Taxane Derivatives
Severe myelosuppression may occur. (e.g. Paclitaxel, Docetaxel), Trastuzumab (cardiotoxic
effects)

Systemic infections should be controlled prior to Increases risk of adverse or toxic effects of the following
initiation of treatment. drugs:
Clozapine (agranulocytosis), Leflunomide (hematologic
May cause myocardial toxicity. May lead to heart toxicity such as pancytopenia, agranulocytosis, and/or
failure. Cardiotoxicity is more common in patients thrombocytopenia), Natalizumab (concurrent infection)
who have previously received anthracyclines (e.g.
doxorubicin, epirubicin) or have preexisting cardiac Reduces therapeutic effect of Idarubicin:
disease. Echinacea

Patients >60 years who were undergoing induction Reduces therapeutic effect of the following drugs:
therapy experienced heart failure, serious BCG (Intravesical), Vaccines (immune response; live
arrhythmias, chest pain, MI, and asymptomatic virus vaccines may progress to infection)
declines in LVEF more frequently than younger
patients. Administration: For IV administration only. Administer
through a slow injection over 10–15 minutes into a
rapidly flowing IV solution of NS or D5W. Refer to
WARNING: Hazardous agent; use appropriate individual protocols for infusion rate details.
precautions for handling and disposal.
NOT for IM or SC administration.
Bone marrow suppression (e.g. neutropenia, NOTE: Avoid extravasation. Ensure proper needle or
thrombocytopenia; risk of infection and bleeding; catheter position prior to and during administration. If
monitor blood counts frequently). extravasation occurs, discontinue infusion immediately
Hyperuricemia (rapid lysis of leukemic cells may lead to and apply ice to the affected area.
hyperuricemia; ensure adequate hydration; consider use
of anti-hyperuricemic prophylaxis). Associated with a high emetic potential. Antiemetics are
Myocardial toxicity (e.g. potentially fatal heart failure, recommended to prevent nausea and vomiting.
cardiomyopathies, or acute arrhythmias, which may be
life-threatening; risk of myocardial toxicity increased in
patients with concomitant or prior mediastinal or Pregnancy Category: D
pericardial irradiation, anemia, bone marrow depression,
infections, leukemic pericarditis, or myocarditis). ATC Code: L01DB06

345
 ANTINEOPLASTIC AND IMMODULATING AGENTS

Toxicity:
Rx MITOXANTRONE AML:
In severe or life-threatening nonhematologic toxicity,
Inj.: 2 mg/mL solution, 5 mL and 10 mL withhold treatment until toxicity resolves.

A cell-cycle nonspecific agent that intercalates into DNA and Hepatocellular cancer, lymphoma, or breast cancer
inhibits DNA topoisomerase II to inhibit DNA and RNA (metastatic):
synthesis. In WBC nadir >1,500/mm3 or platelet nadir >50,000/mm3,
and recovery ≤21 days, repeat previous dose or increase
Indications: Initial treatment of acute myelogenous dose by 2mg/m2 if myelosuppression is inadequate.
leukemias; treatment of advanced hormone-refractory In WBC nadir >1,500/mm3 or platelet nadir >50,000/mm3,
prostate cancer; treatment of metastatic breast cancer, and recovery >21 days, withhold treatment until recovery
relapsed leukemia, lymphoma, and hepatocellular then resume at previous dose.
carcinoma In WBC nadir <1,500/mm3 or platelet nadir <50,000/mm3,
withhold treatment until recovery then decrease
Contraindications: Prior substantial anthracycline exposure previous dose by 2 mg/m2.
and abnormal cardiac function prior to initiation of In WBC nadir <1,000/mm3 or platelet nadir <25,000/mm3,
mitoxantrone therapy; presence of withhold treatment until recovery then decrease
severemyelosuppression due to prior chemoand/or previous dose by 4 mg/m2.
radiotherapy; severe hepatic impairment; intrathecal
administration Precautions:

WARNING: Should be administered under the

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Dose:
Acute leukemia, relapsed, induction, by slow IV infusion, supervision of an experienced cancer
ADULT, 12 mg/m2 once daily for 5 consecutive days, may chemotherapy physician. Administer in a facility
repeat once if needed. sufficient to appropriately diagnose and manage
Acute myeloid leukemia (AML), induction, by slow IV complications.
infusion, ADULT, 12mg/m2/day IV on days 1-3 with
cytarabine 100mg/m2/day IV continuous infusion on Administer only if baseline neutrophil count
days 1-7. May be given with etoposide. Second induction <1,500 cells/mm3 (except in AML). Monitor blood
with same doses of mitoxantrone for 2 days and counts and monitor for infection due to
cytarabine for 5 days may be given if incomplete neutropenia.
antileukemic response and no severe nonhematologic
toxicity in first induction. AML, consolidation, ADULT, in Use increases the risk of developing secondary
combination with cytarabine, 12 mg/m2 once daily for 2 acute myeloid leukemia (AML).
days, repeat in 4 weeks; CHILD, 10 mg/m2 in
combination with high dose cytarabine Congestive heart failure, potentially fatal, may
Breast cancer, metastatic or lymphoma, initial, by slow IV occur during therapy or months to years after
infusion, ADULT, 14 mg/m2 every 21 days, reduce to ≤12 termination of therapy. Cardiotoxicity risk
mg/m2 for myelosuppression due to previous treatment increases with cumulative dose. Assess all
or for poor general health; reduce to 10–12mg/m2 when patients for cardiac signs and symptoms by
used in combination with other agents. history, physical examination, and ECG. Evaluate
Hepatocellular cancer, initial, by slow IV infusion, ADULT, 14 all patients for baseline quantitative evaluation of
mg/m2 every 21 days; reduce initial dose to ≤12 mg/m2 left ventricular ejection fraction.
for myelosuppression due to previous treatment or for
poor general health.
Patients >60 years who were undergoing induction
Prostate cancer, advanced, hormone-refractory, by IV
therapy experienced heart failure, serious
infusion, ADULT, in combination with corticosteroids,
arrhythmias, chest pain, MI, and asymptomatic
12–14mg/m2 every 3 weeks.
declines in LVEF more frequently than younger
patients.
Dose Adjustment:
Hepatic Impairment:
In mild-to-moderate impairment, consider dose
WARNING: Hazardous agent; use appropriate
adjustments and monitor closely.
precautions for handling and disposal.
Obesity:
Use actual body weight (full weight) for calculation of BSA- Bone marrow suppression (use is not recommended in
based or weight-based dosing, especially if the intent of patients with pre-existing myelosuppression from prior
therapy is curative. chemotherapy unless expected benefit outweighs risk)
If dose reduction is done due to toxicity, consider Hyperuricemia (caused by rapid lysis of tumor cells)
resumption of full weight-based dosing with subsequent Secondary malignancy (e.g. excessive bruising, bleeding,
cycles, especially if cause of toxicity is resolved. recurrent infections, which may be symptoms of
secondary malignancy; acute promyelocytic leukemia;
risk for secondary leukemia is increased in patients who
are heavily pretreated, with higher doses, and with
combination chemotherapy).

346
ANTINEOPLASTIC AND IMMODULATING AGENTS

Elderly (decreased clearance; use with caution). Reduces therapeutic effect of the following drugs:
BCG (Intravesical), Vaccines (immune response; live
Adverse Drug Reactions: virus vaccines may progress to infection)
Common: Abdominal pain, abnormal urine, alkaline
phosphatase increased, alopecia, amenorrhea, anemia Administration: For IV administration only. Dilute in at least
or decreased hemoglobin, anorexia, anxiety, aphthosis, 50mL of NS or D5W. Administer via a free-flowing IV, as
arrhythmia, arthralgia, back pain, bleeding, blurred a short IV infusion over 5–15 minutes or continuous IV
vision, cardiac function changes, chills, conjunctivitis, infusion over 24 hours. Do NOT infuse over <3 to 5
CHF, constipation, cough, increasedcreatinine, minutes. Must be diluted prior to use.
cutaneous mycosis, depression, diaphoresis, diarrhea,
dyspepsia, dyspnea, ECG changes, edema, fatigue, Do NOT administer by SC, IM, or intraarterial injection. Do
fever, fungal infection, granulocytopenia, headache, NOT administer intrathecally to prevent serious
hematuria, hemorrhage, hyperglycemia, hypertension, permanent neurologic damage.
pain, LVEF decreased, hypocalcemia, hypokalemia,
hyponatremia, impotence, infection, ischemia, jaundice, NOTE: Avoid extravasation. Ensure proper needle or
leukopenia, lymhopenia, menorrhagia, menstrual catheter position prior to and during administration. If
disorder, mucositis, myalgia, nail bed changes, nausea, extravasation occurs, discontinue infusion immediately
neutropenia, neutropenic petechiae or bruising, and apply ice to the affected area.
pharyngitis, pneumonia, proteinuria, renal failure,
rhinitis, secondary acute leukemias (including AML and Associated with a high emetic potential. Antiemetics are
APL), fever, seizure, sepsis, sinusitis, skin infection, recommended to prevent nausea and vomiting.
sterility, stomatitis, systemic infection,
thrombocytopenia, upper respiratory tract infection, May cause urine, saliva, tears, and sweat to turn blue-

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urinary tract infection, vomiting, weakness, weight gain green for 24 hours post-infusion; whites of eyes may
or loss have blue-green tinge.
Less Common: Allergic reaction, anaphylactoid reactions,
anaphylaxis, chest pain, dehydration, extravasation at Pregnancy Category: D
injection site (erythema, pain, burning, skin
discoloration, swelling, or tissue necrosis), interstitial ATC Code: L01DB07
pneumonitis, hypotension, hyperuricemia, phlebitis at
the infusion site, rash, sclera discoloration (blue),
tachycardia, urine discoloration (blue-green), urticaria
OTHER CYTOTOXIC ANTIBIOTICS
Drug Interactions:
Monitor closely with: Rx BLEOMYCIN
Enhances therapeutic effect of Mitoxantrone:
Trastuzumab (neutropenic effect)
Inj.: 15 IU powder (as sulfate), ampule / vial (IM, IV)
Increases risk of adverse or toxic effects of Mitoxantrone:
Denosumab (serious infections) Inhibits synthesis of DNA by binding to DNA leading to single
and double-strand breaks. It also inhibits RNA and
Reduces diagnostic effect of Coccidioides immitis Skin Test protein synthesis.

Avoid concomitant use with: Indications: Treatment of squamous cell carcinomas of the
Enhances therapeutic effect of Mitoxantrone: head and neck; Hodgkin’s Lymphoma; extracranial germ
Roflumilast (immunosuppressive effect) cell tumors; sclerosing agent for malignant pleural
effusion; treatment of testicular cancer
Enhances therapeutic effect of Tofacitinib
(immunosuppressive effect) Dose:
NOTE: Doses below expressed as USP units; 1 USP unit = 1 mg (by
potency) = 1,000 international units.
Increases risk of adverse or toxic effects of Mitoxantrone:
Dipyrone (agranulocytosis; pancytopenia), Squamous cell carcinomas, by IM or IV injection, 10-15 x
Pimecrolimus, Tacrolimus (Topical) 103 IU/m2 body surface area (BSA), once or twice a week,
at intervals of 3-4 weeks up to a lifetime cumulative dose
Increases risk of adverse or toxic effects of the following of 360 x 103 IU; by IV infusion, 10-15 x 103 IU/m2/day
drugs: for 6-24 hours on 4 to 7 consecutive days, at intervals of
Clozapine (agranulocytosis), Leflunomide (hematologic 3-4 week.
toxicity such as pancytopenia, agranulocytosis, and/or
thrombocytopenia), Natalizumab (concurrent infection) Lymphoma, test dose, by IM, IV, or SC injection, 1–2 units
before the first 1–2 doses; monitor vital signs every 15
Increases serum concentration of Mitoxantrone: minutes; wait a minimum of 1 hour before administering
Cyclosporine (Systemic) remainder of dose; if no acute reaction occurs, follow
regular dosing schedule [NOTE: Test doses may not be
Reduces therapeutic effect of Mitoxantrone: predictive of a reaction and/or may produce false-negative
Echinacea results].

347
 ANTINEOPLASTIC AND IMMODULATING AGENTS

Malignant pleural infusion, by intrapleural route, 60 units as reactions (hypotension, confusion, fever, chills, and
a single instillation, mixed in 50–100 mL of NS. wheezing), cough, bilateral pulmonary infiltrates,
Extracranial germ cell tumors (yolk sac tumor, anorexia, dyspnea, erythema, diffuse scleroderma,
choriocarcinoma, embryonal carcinoma), CHILD, 15 hypoxia (potentially fatal), pain at the tumor site,
units/m2 on day 1 in combination with cisplatin and hyperpigmentation, idiosyncratic reactions,
etoposide. hyperkeratosis, induration, mucositis, nailbed changes,
Hodgkin’s Lymphoma, CHILD, 10 units/m2 in combination onycholysis, rash, peeling of the skin (hands and feet),
with various chemotherapy regimen. phlebitis, pruritus, skin thickening, pulmonary fibrosis,
rales, stomatitis, striae, tachypnea, vesiculation, weight
Dose Adjustment: loss
Renal Impairment: Less Common: Angioedema, cerebrovascular accident,
In CrCl 40–50mL/minute, administer 70% of dose. cerebral arteritis, chest pain, coronary artery disease,
In CrCl 30–40mL/minute, administer 60% of dose. flagellate hyperpigmentation, MI, hepatotoxicity,
In CrCl 20–30mL/minute, administer 55% of dose. malaise, myocardial ischemia, nausea, pericarditis,
In CrCl 10–20mL/minute, administer 45% ofdose. Raynaud’s phenomenon, renal toxicity, scleroderma-like
In CrCl 5–10mL/minute, administer 40% of dose. skin changes, SJS, TEN, thrombotic microangiopathy,
vomiting
Obesity: Rare: Myelosuppression
Consider use of fixed doses, independent of body weight or
BSA, due to toxicity concerns.
Toxicity: Drug Interactions:
If pulmonary changes occur, discontinue until determined Monitor closely with:
not to be drug-related. Enhances therapeutic effect of Bleomycin:
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If the pulmonary diffusion capacity for carbon monoxide Trastuzumab (neutropenic effect)
(DLCO) is <30–35% of baseline, discontinue treatment.
Increases risk of adverse or toxic effects of Bleomycin:
Precautions: Denosumab (serious infections), Filgrastim (pulmonary
toxicity)
WARNING: Should be administered under the
supervision of an experienced cancer chemotherapy
Reduces diagnostic effect of Coccidioides immitis Skin Test
physician. Administer in a facility sufficient to
appropriately diagnose and manage complications.
Avoid concomitant use with:
Occurrence of pulmonary fibrosis is the most severe Enhances therapeutic effect of Bleomycin:
toxicity. It commonly presents as pneumonitis, Roflumilast (immunosuppressive effect)
occasionally progressing to pulmonary fibrosis. Risk
is higher in elderly patients, glomerular filtration rate Enhances therapeutic effect of Tofacitinib
<80 mL/minute advanced disease, or patients (immunosuppressive effect)
receiving >400 units total lifetime dose or >300 units
cumulative dose. Risk is also increased in surgery Increases risk of adverse or toxic effects of Bleomycin:
patients receiving O2. Gemcitabine (pulmonary toxicity), Pimecrolimus,
Tacrolimus (Topical)
A severe idiosyncratic reaction consisting of
hypotension, mental confusion, fever, chills, and Increases risk of adverse or toxic effects of the following
wheezing has been reported. drugs:
Leflunomide (hematologic toxicity such as pancytopenia,
agranulocytosis, and/or thrombocytopenia),
WARNING: Hazardous agent; use appropriate precautions for Natalizumab (concurrent infection)
handling and disposal.
Reduces therapeutic effect of Bleomycin:
Echinacea
Hepatotoxicity; Renal toxicity
Pulmonary toxicity (e.g. bronchiolitis obliterans and Reduces therapeutic effect of the following drugs:
organizing pneumonia, eosinophilic hypersensitivity, and BCG (Intravesical), Vaccines (immune response; live
interstitial pneumonitis, progressing to pulmonary virus vaccines may progress to infection)
fibrosis)
Idiosyncratic reaction (since reactions usually occur after Administration: For IV injections, administer slowly over 10
first or second dose, careful monitoring is essential after minutes.
these doses)
Elderly (at greater risk of pulmonary toxicity); children (has For IM or SC administration, may cause pain at injection
been associated with a higher incidence of pulmonary site.
toxicity).
Pregnancy Category: D
Adverse Drug Reactions:
Common: Acute febrile reactions, acute or chronic ATC Code: L01DC01
interstitial pneumonitis, alopecia, anaphylactoid-like

348
ANTINEOPLASTIC AND IMMODULATING AGENTS

OTHER ANTINEOPLASTIC AGENTS Renal Impairment:

Dose determination with Calvert formula uses GFR and,
PLATINUM COMPOUNDS therefore, inherently adjusts for renal dysfunction.
For baseline CrCl 41–59 mL/minute, initiate at 250 mg/m2
and adjust subsequent doses based on bone marrow
Rx CARBOPLATIN toxicity.
For baseline CrCl 16–40 mL/minute, initiate at 200 mg/m2
and adjust subsequent doses based on bone marrow
Inj.: 150 mg and 450 mg powder, vial (IV) toxicity.
10 mg/mL, 15 mL and 45 mL vial (IV) In hemodialysis, administer on a non-dialysis day,
hemodialysis should occur between 12–24 hours after
A platinum compound alkylating agent, which covalently administration. Calculate dose as follows:
binds to DNA, interfering with DNA function by producing
interstrand DNA crosslinks. Carboplatin dose (mg) = Target AUC x 25

Indications: Initial treatment of advanced ovarian cancer in Bone Marrow Suppression:

combination with other established chemotherapy Reduce dose. Delay cycles until WBC and platelet counts
agents; palliative treatment of recurrent ovarian cancer have recovered.
after prior chemotherapy. Childhood solid malignancy:
neuroblastoma, retinoblastoma; relapsed Non-Hodgkin’s Toxicity:
lymphoma (NHL); recurrent soft tissue sarcomas If platelets <50,000 cells/mm3 or ANC <500 cells/mm3,
administer 75% of dose.
Contraindications: History of severe allergic reaction to

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carboplatin, cisplatin, other platinum-containing Precautions:
formulations, mannitol, or any component of the
formulation; severe bone marrow depression; significant WARNING: Should be administered under the
bleeding supervision of an experienced cancer chemotherapy
physician. Administer in a facility sufficient to
Dose: appropriately diagnose and manage complications.
NOTE: Doses for adults are commonly calculated by the
target AUC using the Calvert formula, where
WARNING: Hazardous agent; use appropriate
Total dose (mg) = Target AUC x (GFR + 25) precautions for handling and disposal.

If estimating glomerular filtration rate (GFR) instead of a

Bone marrow suppression (increased risk with prior
measured GFR, consider capping estimated GFR at a
myelosuppressive therapy, renal dysfunction);
maximum of 125 mL/minute to avoid potential toxicity.
neurotoxicity
Ovarian cancer, advanced, by IV infusion, ADULT, as a single Hypersensitivity or anaphylactoid reactions (risk increased
agent, 360 mg/m2 every 4 weeks; in combination with in patients previously exposed to platinum therapy;
cyclophosphamide 300 mg/m2 every 4 weeks; as a consider skin testing or desensitization protocols).
single agent in previously-treated patients, target AUC 4– Liver function abnormalities (may be caused by high doses
6. of >4 times the recommended dose)
Neuroblastoma, induction and post induction, CHILD, 500 Ototoxicity (may occur when given together with
mg/m2/d for 2 days on 1 cycle. aminoglycosides; long-term audiology monitoring is
Retinoblastoma, CHILD < 36 months, 18.6 mg/kg/dose recommended)
(single dose each cycle); CHILD > 36 months, 560 Renal toxicity (limited unless given together with
mg/m2/dose (single dose each cycle). aminoglycosides)
Recurrent soft tissue sarcoma, CHILD, 150 mg/m2/d as 3h Vision loss (reported with higher than recommended doses;
IV infusion for 2 days. usually reversible weeks after discontinuation)
Elderly (increased incidence of peripheral neuropathy and
Dose Adjustment: severe thrombocytopenia; increased incidence of
Geriatric: neurotoxicity; considered inappropriate for elderly use)
Calculate dose based on Calvert formula: Children (children <6 months are at an increased risk of
ototoxicity)
Total dose (mg) = Target AUC x (GFR + 25)
Adverse Drug Reactions:
Obesity: Common: Abdominal pain, alopecia, anemia, pain, bleeding
Consider dosing based on GFR. GFR should not exceed 125 complications, constipation, decreased creatinine
mL/minute. clearance, bone marrow depression (dose related; dose
Use actual body weight (full weight) for calculation of BSA- limiting), dysgeusia, hemorrhage, hypersensitivity,
based dosing for hematopoietic stem cell transplant hypocalcemia, hypokalemia, hypomagnesemia,
conditioning regimens in adults. hyponatremia, diarrhea, infection, leukopenia,
mucositis, nausea, neurotoxicity, neutropenia,
ototoxicity, peripheral neuropathy, stomatitis,
thrombocytopenia, visual disturbance, vomiting,
weakness

349
 ANTINEOPLASTIC AND IMMODULATING AGENTS

Less Common: Anaphylaxis, bronchospasm, cardiac failure, platinum derivatives to limit myelosuppression and to
cerebrovascular accident, dehydration, anorexia, enhance efficacy.
embolism, febrile neutropenia, erythema, hemolytic
anemia (acute), HUS, hypertension, hypotension, Pregnancy Category: D
injection site reaction (pain, redness, swelling), limb
ischemia (acute), malaise, metastases, pruritus, skin ATC Code: L01XA02
rash, tissue necrosis (associated with extravasation),
urticaria, vision loss

Drug Interactions: Rx CISPLATIN

Monitor closely with:
Enhances therapeutic effect of Carboplatin: Inj.: 1 mg/mL, 10 mLand 50 mL vial (IV)
Trastuzumab (neutropenic effect)
A platinum compound that inhibits DNA synthesis by the
Increases risk of adverse or toxic effects of Carboplatin: formation of DNA crosslinks.
Denosumab (serious infections), Aminoglycosides [e.g.
Streptomycin, Amikacin (ototoxic effect)] Indications: Treatment of advanced bladder cancer
(transitional cell) in patients who are no longer
Reduces diagnostic effect of Coccidioides immitis Skin Test candidates for local therapy including surgery and/or
radiation therapy; treatment of metastatic ovarian
Avoid concomitant use with: cancer in patients who have previously received
Enhances therapeutic effect of Carboplatin: appropriate surgery and/or radiation therapy; for
Roflumilast (immunosuppressive effect)
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refractory tumors in patients who have not previously

received cisplatin; treatment of metastatic testicular
Enhances therapeutic effect of the following drugs: cancer in patients who have previously received
Taxane Derivatives [e.g. Paclitaxel, Docetaxel appropriate surgery and/or radiation therapy; Childhood
(myelosuppressive effect)], Tofacitinib solid malignancies: Hodgkin’s Lymphoma (HD); Brain
(immunosuppressive effect) tumors; neuroblastoma; malignant bone tumors;
hepatoblastoma; germ cell tumor (GCT).
Increases risk of adverse or toxic effects of Carboplatin:
Dipyrone (agranulocytosis; pancytopenia), Contraindications: Preexisting renal impairment;
Pimecrolimus, Sorafenib, Tacrolimus (Topical) myelosuppression; hearing impairment
Increases risk of adverse or toxic effects of the following Dose:
drugs: Bladder cancer, advanced, by slow IV infusion, ADULT, 50–
Clozapine (agranulocytosis), Leflunomide (hematologic 70 mg/m2 every 3–4 weeks; or 50 mg/m2 every 4 weeks
toxicity such as pancytopenia, agranulocytosis, and/or in heavily pretreated patients.
thrombocytopenia), Natalizumab (concurrent infection), Ovarian cancer, metastatic, by slow IV infusion, ADULT, 100
Topotecan mg/m2 every 4 weeks.
Germ Cell Tumors, CHILD, 20 mg/m2 IV as a single dose
Reduces therapeutic effect of Carboplatin: once daily for 5 days with bleomycin and etoposide (PEB
Echinacea regimen); repeat every 3 weeks; Refer to institutional
protocols for other dosing regimen for CNS tumors,
Reduces therapeutic effect of the following drugs: neuroblastoma, hepatoblastoma.
BCG (Intravesical), Vaccines (immune response; live Hodgkin’s Lymphoma, CHILD, 90 mg/m2 as IV infusion for
virus vaccines may progress to infection) 6h (single dose per cycle)
Germinoma, CHILD, 20 mg/m2/d for 5 days
Administration: For IV administration. Infuse over 15–60 Neuroblastoma, induction, CHILD, 40 mg/m2/d for 5 days
minutes. Some protocols may require infusions up to 24 on 2 cycles; post induction, 40 mg/m2/d for 5 days on 1
hours. cycle
Osteosarcoma, CHILD, 60 mg/m2/d for 2 days
Do NOT use needles or IV administration sets that Hepatoblastoma, low risk (PRETEXT I, II), CHILD < 10 kg, 3.3
contain aluminum during preparation or administration. mg/kg/d; CHILD > 10 kg, 100 mg/m2/d;
Aluminumcan react with carboplatin resulting in Hepatoblastoma, high risk (PRETEXT III, IV), CHILD, 80
precipitate formation and loss of potency. mg/m2/d for Day 1 then 70 mg/m2/d on succeeding
days
NOTE: Avoid extravasation. Ensure proper needle or
catheter position prior to and during administration. If
extravasation occurs, discontinue infusion immediately Dose Adjustment:
and apply ice to the affected area. Renal Impairment:
Associated with a high emetic potential. Antiemetics are If serum creatinine is >1.5 mg/dL and/or BUN is >25
mg/dL, do not repeat course.
recommended to prevent nausea and vomiting.

When administered as sequential infusions, with taxane

derivaties, administer taxane derivatives before

350
ANTINEOPLASTIC AND IMMODULATING AGENTS

Obesity: Elderly (may be more susceptible to nephrotoxicity and

Use actual body weight (full weight) for calculation of BSA- peripheral neuropathy; considered potentially
based or weight-based dosing, especially if the intent of inappropriate for elderly)
therapy is curative.
If dose reduction is done due to toxicity, consider Adverse Drug Reactions:
resumption of full weight-based dosing with subsequent Common: Anemia, local irritation, leukopenia (dose related),
cycles, especially if cause of toxicity is resolved. nausea, nephrotoxicity (acute renal failure and chronic
renal insufficiency), neurotoxicity, peripheral neuropathy
Precautions: (dose and duration dependent), ototoxicity,
thrombocytopenia, vomiting
WARNING: Should be administered under the Less Common: Alopecia (mild), anaphylaxis, aortic
supervision of an experienced cancer thrombosis, autonomic neuropathy, bradycardia,
chemotherapy physician, experienced in the use of bronchoconstriction, cardiac arrhythmia, cardiac failure,
cancerchemotherapeutic agents.Administer in a ageusia, cerebrovascular accident, cerebral arteritis,
facility sufficient to appropriately diagnose and dehydration, diarrhea, extravasation, heart block,
manage complications. hemolytic anemia (acute), hypercholesterolemia,
hemolytic-uremic syndrome, hyperuricemia,
Doses >100 mg/m2/cycle (once every 3–4 weeks) hypomagnesemia, hypocalcemia, hypokalemia,
are rare. Verify with prescriber prior to hyponatremia, skin rash, hiccups, hypophosphatemia,
administration. At the approved dose, cisplatin hypotension, increased serum amylase, ischemic heart
should not be administered more frequently than disease, leukoencephalopathy, Lhermitte's sign,
once every 3–4 weeks. myocardial infarction, neutropenic enterocolitis, optic
neuritis, pancreatitis, papilledema, SIADH, peripheral

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Exercise caution to avoid inadvertent overdose due ischemia (acute), phlebitis, reversible posterior
to potential sound-alike/look-alike confusion leukoencephalopathy syndrome, vision loss, seizure,
between cisplatin and carboplatin or prescribing tachycardia, tetany, thrombotic thrombocytopenic
practices that fail to differentiate daily doses from purpura, vision color changes
the total dose per cycle.
Drug Interactions:
Monitor closely with:
Associated with severe cumulative renal toxicity, as Enhances therapeutic effect of Cisplatin:
well as dose-related myelosuppression, nausea, Trastuzumab (neutropenic effect)
and vomiting.
Increases risk of adverse or toxic effects of Cisplatin:
Anaphylactic-like reactions have occurred. Facial Denosumab (serious infections), Loop Diuretics [e.g.
edema, bronchoconstriction, tachycardia, and Furosemide (nephrotoxiceffect)]
hypotension may occur within minutes of
administration. Epinephrine, corticosteroids, and Increases risk of adverse or toxic effects of the following
antihistamines have been effectively employed to drugs:
alleviate symptoms. Aminoglycosides [e.g., Streptomycin
(nephrotoxiceffect)], Vinorelbine (granulocytopenia)
Significant ototoxicity. Manifests as tinnitus or loss of Reduces diagnostic effect of Coccidioides immitis Skin Test
high frequency hearing, and occasionally
deafness. May be more pronounced in children. Reduces therapeutic effect of Cisplatin:
Alpha-Lipoic Acid

WARNING: Hazardous agent. Use appropriate Avoid concomitant use with:

precautions for handling and disposal. Enhances therapeutic effect of Cisplatin:
Roflumilast (immunosuppressive effect)
Gastrointestinal events (e.g. nausea, vomiting, diarrhea;
dose-related); hyperuricemia (more pronounced with Enhances therapeutic effect of the following drugs:
doses >50 mg/m2; consider anti-hyperuricemic therapy). Taxane Derivatives [e.g. Paclitaxel, Docetaxel
Neurotoxicity (severe, possibly irreversible neuropathies (myelosuppressive effect)], Tofacitinib
e.g. stocking-glove paresthesias, areflexia, loss of (immunosuppressive effect)
proprioception or vibratory sensation, seizures, loss of
motor function, loss of taste, leukoencephalopathy, Increases risk of adverse or toxic effects of Cisplatin:
posterior reversible leukoencephalopathy syndrome) Dipyrone (agranulocytosis; pancytopenia),
Ototoxicity (cumulative; may be severe; audiometric testing Pimecrolimus, Tacrolimus (Topical)
should be performed at baseline, prior to each dose, and
several years after discontinuing therapy) Increases risk of adverse or toxic effects of the following
Renal toxicity (monitor serum creatinine, BUN, creatinine drugs:
clearance, and serum electrolytes closely) Clozapine (agranulocytosis), Leflunomide (hematologic
Secondary malignancies toxicity such as pancytopenia, agranulocytosis, and/or
thrombocytopenia), Natalizumab (concurrent infection),
Topotecan

351
 ANTINEOPLASTIC AND IMMODULATING AGENTS

Reduces therapeutic effect of Cisplatin: Obesity:

Echinacea Use actual body weight (full weight) for calculation of BSA-
based or weight-based dosing, especially if the intent of
Reduces therapeutic effect of the following drugs: therapy is curative.
BCG (Intravesical), Vaccines (immune response; live If dose reduction is done due to toxicity, consider
virus vaccines may progress to infection) resumption of full weight-based dosing with subsequent
cycles, especially if cause of toxicity is resolved.
Administration: For IV administration, infuse over 6–8
hours. Do NOTadminister as a rapid IV injection. Toxicity:
Neurosensory events:
Hydrate with 1–2 L of fluid prior to administration. For persistent grade 2 neurosensory events lasting >7 days,
Adequate post hydration and urinary output (>100 consider withholding oxaliplatin despite dose reduction:
mL/hour) should be maintained for 24 hours after In stage III colon cancer, reduce dose to 75 mg/m2.
administration. Monitor serum electrolytes, particularly In advanced colorectal cancer, reduce dose to 65
magnesium and potassium, and replace as needed mg/m2.
during and after therapy.
For persistent grade 3 neurosensory events lasting >7 days:
Do NOT use needles or IV administration sets that In stage III colon cancer, discontinue use.
contain aluminum during preparation or administration. In advanced colorectal cancer, reduce dose to 65
Aluminumcan react with carboplatin resulting in mg/m2; if not resolved prior to the next cycle, discontinue
precipitate formation and loss of potency. use.

NOTE: Avoid extravasation. Ensure proper needle or For persistent grade 4 neurosensory events:
L

catheter position prior to and during administration. If In advanced colorectal cancer, discontinue use.
extravasation occurs, discontinue infusion immediately
and apply ice to the affected area. Gastrointestinal toxicity (grade 3/4):
In stage III colon cancer, delay next dose until recovery
Associated with a high emetic potential. Antiemetics are from toxicity, then reduce dose to 75 mg/m2.
recommended to prevent nausea and vomiting. In advanced colorectal cancer, delay next dose until
recovery from toxicity, then reduce dose to 65 mg/m2.
Pregnancy Category: D
Hematologic toxicity (grade 3/4 neutropenia, grade 3/4
ATC Code: L01XA01 thrombocytopenia, or febrile neutropenia,):
In stage III colon cancer, delay next dose until neutrophils
recover to ≥1,500/mm3 and platelets to ≥75,000/mm3,
then reduce dose to 75 mg/m2.
Rx OXALIPLATIN In advanced colorectal cancer, delay next dose until
neutrophils recover to ≥1,500/mm3 and platelets to
≥75,000/mm3, then reduce dose to 65 mg/m2.
Inj.: 50 mg powder, vial (IV infusion)
5 mg/mL concentrate solution, 10 mL and 20 mLvial
Precautions:
(IV infusion)
WARNING: Anaphylactic-like reactions have been
A platinum derivative that acts as an alkylating agent. It reported and may occur within minutes of
forms DNA cross links to inhibit DNA replication. administration. Epinephrine, corticosteroids, and
antihistamines have been employed to alleviate
Indications: Adjuvant treatment of stage III colon cancer symptoms of anaphylaxis.
after complete resectionof primary tumor; treatment of
advanced colorectal cancer
WARNING: Hazardous agent. Use appropriate
Contraindications: Pregnancy; breastfeeding; severe renal
precautions for handling and disposal.
impairment

Dose: Hypersensitivity or anaphylactoid reactions (e.g. pruritus,

Advanced colorectal cancer, by IV infusion, ADULT, in bronchospasm, erythema, hypotension, rash, urticaria,
combination with fluorouracil and leucovorin, 85 mg/m2 flushing, diaphoresis, diarrhea, chest pain, shortness of
every 2 weeks until disease progression or breath, disorientation, or syncope may occur; grade 3 or
unacceptable toxicity; in combination with Capecitabine, 4 hypersensitivity)
130 mg/m2 every 3 weeks. Neuropathy (e.g. acute, reversible, peripheral sensory
Stage III colon cancer, adjuvant, by IV infusion, ADULT, in neuropathy which may interfere with daily activities (e.g.,
combination with fluorouracil and leucovorin, 85 mg/m2 writing, buttoning, swallowing; cold-triggered neuropathy
every 2 weeks for 6 months (12 cycles); in combination commonly recurs with subsequent doses and may last
with Capecitabine, 130 mg/m2 every 3 weeks. up to 7 days after administration).
Hepatotoxicity (e.g. hepatitis and hepatic failure); Renal
Dose Adjustment: impairment
Renal Impairment:
In CrCl <30 mL/minute, reduce dose to 65 mg/m2.

352
ANTINEOPLASTIC AND IMMODULATING AGENTS

Pulmonary fibrosis (withhold treatment for unexplained Taxane Derivatives [e.g. Paclitaxel, Docetaxel
pulmonary symptoms until interstitial lung disease or (myelosuppressive effect)], Tofacitinib
pulmonary fibrosis are excluded) (immunosuppressive effect)
Reversible posterior leukoencephalopathy syndrome (e.g.
headache, mental status changes, seizure, blurred Increases risk of adverse or toxic effects of Oxaliplatin:
vision, blindness, other vision changes) Dipyrone (agranulocytosis; pancytopenia),
Elderly (more sensitive to adverse events, particularly Pimecrolimus, Tacrolimus (Topical)
diarrhea, dehydration, hypokalemia, leukopenia, fatigue,
and syncope) Increases risk of adverse or toxic effects of the following
drugs:
Adverse Drug Reactions: Clozapine (agranulocytosis), Leflunomide (hematologic
Common :Abdominal pain, abnormal lacrimation, alopecia, toxicity such as pancytopenia, agranulocytosis, and/or
anemia, anorexia, arthralgia, back pain, constipation, thrombocytopenia), Natalizumab (concurrent infection),
cough, dehydration, diarrhea, dizziness, dysgeusia, Topotecan
dyspepsia, dysphagia, dyspnea, dysuria, edema,
epistaxis, fatigue, fever, flatulence, flushing, chest pain, Reduces therapeutic effect of Oxaliplatin:
GERD, headache, hiccups, hypersensitivity reaction, Echinacea
hypokalemia, injection site reaction (redness, swelling,
pain), insomnia, leukopenia, mucositis, neutropenia, Reduces therapeutic effect of the following drugs:
nausea, palmar-plantar erythrodysesthesia, peripheral BCG (Intravesical), Vaccines (immune response; live
edema, peripheral neuropathy (dose limiting), virus vaccines may progress to infection)
pharyngitis, pain, pharyngolaryngeal dysesthesia,
rhinitis, rigors, skin rash, stomatitis, thrombocytopenia, Administration: Administer as IV infusion over 2 hours.

L
thromboembolism, upper respiratory tract infection, Longer infusion time (6 hours) may mitigate acute
vomiting toxicities (e.g., pharyngolaryngeal dysesthesia). Extend
Less Common: Abnormal gait, acute renal failure, infusion time to 6 hours for acute toxicities.
anaphylaxis,anaphylactic shock, anaphylactoid reaction,
angioedema, aphonia, blepharoptosis, cerebral Do NOT use needles or IV administration sets that
hemorrhage, colitis, cranialnerve palsy, decreased deep contain aluminum during preparation or administration.
tendon reflex, deafness, decreased visual acuity, Aluminum can react with carboplatin resulting in
diplopia, dysarthria, eosinophilic precipitate formation and loss of potency.
pneumonitis,fasciculations, febrile neutropenia,
hematuria, hemolysis, hemolytic anemia Avoid mucositis prophylaxis with ice chips to prevent
(immunoallergic), ataxia, hemolytic- exacerbation of acute neurological symptoms associated
uremicsyndrome,hemorrhage, hepatic failure, hepatic with exposure to coldtemperatures, or consumption of
sinusoidal obstruction syndrome, hepatitis, cold food or beverages during or within hours of
hepatotoxicity, hypomagnesemia, hypoxia, hypertension, administration.
idiopathic noncirrhotic portal hypertension (nodular
regenerative hyperplasia)I , infusion related reaction NOTE: Avoid extravasation. Ensure proper needle or
(extravasation), interstitial pulmonary disease, intestinal catheter position prior to and during administration. If
obstruction, laryngospasm, Lhermittes' sign, interstitial extravasation occurs, discontinue infusion immediately
nephritis (acute), metabolic acidosis, myoclonus, and apply ice to the affected area.
neutropenic enterocolitis, neutropenic infection (sepsis),
optic neuritis, pancreatitis, muscle spasm, purpura, Associated with a high emetic potential. Antiemetics are
rectal hemorrhage, renal tubular necrosis, reversible recommended to prevent nausea and vomiting.
posterior leukoencephalopathy syndrome, seizure,
rhabdomyolysis, sepsis, temporary vision loss, Do NOT prepare using a chloride-containing solution
thrombocytopenia (immunoallergic), trigeminal such as NaCl. Flush infusion line with D5W prior to, and
neuralgia, visual field loss, voice disorder following, administration of concomitant medications via
same IV line.
Drug Interactions:
Monitor closely with: When used in combination with a fluoropyrimidine (e.g.,
Enhances therapeutic effect of Oxaliplatin:
fluorouracil), infuse oxaliplatin first.
Trastuzumab (neutropenic effect)
Pregnancy Category: D
Increases risk of adverse or toxic effects of Oxaliplatin:
Denosumab (serious infections) ATC Code: L01XA03
Reduces diagnostic effect of Coccidioides immitis Skin Test

Avoid concomitant use with:

Enhances therapeutic effect of Oxaliplatin:
Roflumilast (immunosuppressive effect)

Enhances therapeutic effect of the following drugs:

353
 ANTINEOPLASTIC AND IMMODULATING AGENTS

MONOCLONAL ANTIBODIES NHL, by slow IV infusion, ADULT, in combination with

ibritumomab, 250 mg/m2 IV day 1, repeat in 7–9 days
with ibritumomab.
Rx RITUXIMAB NHL, CD20-positive, mature B-cell lymphoma, Diffuse Large
B-Cell Lymphoma, CHILDREN and ADOLESCENTS, 375
mg/m2 prior to consolidation therapy (frequency and
Inj.: 10 mg/mL, 10 mL and 50 mL vial (IV)
number of doses depend upon treatment protocol).
Microscopic polyangiitis (MPA), by slow IV infusion, ADULT,
A monoclonal antibody directed against the CD20 antigen
in combination with methylprednisolone IV for 1–3 days
on B lymphocytes. It binds to the antigen to initiate killing
followed by daily prednisone, 375 mg/m2 once weekly
of B-cells, delaying the progression of structural damage.
for 4 doses.
Pemphigus vulgaris, moderate-to-severe, Initial: 1000 mg IV
Indications: Treatment of CD20-positive non-Hodgkin’s
once then repeat dose in 2 weeks used in combination
lymphomas (NHL); treatment of CD20-positive chronic
with tapering course of glucocorticoids; Maintenance:
lymphocytic leukemia (CLL); treatment of
500 mg at month 12 and every 6 months thereafter or
granulomatosis with polyangiitis (GPA; Wegener’s
based on clinical evaluation; Treatment relapse: 1000
granulomatosis); treatment of microscopic polyangiitis
mg IV and consider resuming or increasing glucocorticoid
(MPA)
dose based on clinical evaluation.
Rheumatoid Arthritis, rituximab only, 1000 mg IV infusion
Contraindications: Type 1 hypersensitivity or anaphylactic
(not to exceed 1000 mg/dose), repeat after 2 weeks (2
reaction to murine proteins, Chinese Hamster Ovary
infusions separated by 2 weeks is 1 course). Repeat
(CHO) cell proteins, or any component of the formulation;
course every 24 weeks or based on clinical evaluation
current or a history of progressive multifocal
(but no sooner than 16 weeks); use in combination with
L

leukoencephalopathy (PML)
methotrexate.
Dose:
Precautions:
CLL, by slow IV infusion, ADULT, in combination with
fludarabine and cyclophosphamide, 375 mg/m2 the day WARNING: Can result in serious, including fatal,
prior to fludarabine / cyclophosphamide in cycle 1, then infusion reactions. Deaths within 24 hours of
500mg/m2 on day 1 (every 28 days) of cycles 2–6. infusion have been reported. Carefully monitor
Fludarabine dose: 25 mg/m2 IV per day for 3 days, patients during infusions. Discontinue when severe
Cyclophosphamide dose: 250 mg/IV per day for 3 days. reactions occur and administer medical treatment
Granulomatosis with polyangiitis, by slow IV infusion, for grade 3 or 4 infusion reactions.
ADULT, in combination with methylprednisolone IV for 1–
3 days followed by daily prednisone, 375 mg/m2 once
weekly for 4 doses. Severe, sometimes fatal, mucocutaneous reactions
Non-Hodgkin’s lymphoma (NHL), low-grade or follicular (e.g., paraneoplastic pemphigus, Stevens-Johnson
CD20-positive, B-cell, previously untreated, by slow IV syndrome, lichenoid dermatitis, toxic epidermal
infusion, ADULT, 375 mg/m2 once weekly for 4 or 8 necrolysis, vesiculobullous dermatitis) have been
doses. May give IV formulation at first cycle, followed by reported.
subcutaneous formulation injected at a fixed dose of
1400mg per cycle for up to 8 cycles. As maintenance for Hepatitis B virus (HBV) reactivation can occur, in
previously untreated follicular lymphoma who have some cases resulting in fulminant hepatitis,
responded to induction treatment, 1400mg hepatic failure, and death. Screen all patients for
subcutaneously once every 2 months (starting 2 months HBV infection by measuring HBsAg and anti-HBc
after the last dose of induction therapy) until disease before treatment initiation. Monitor patients during
progression or a maximum period of 2 years. and after treatment. Discontinue in the event of
NHL, low-grade or follicular CD20-positive, B-cell, relapsed/ HBV reactivation.
refractory, by slow IV infusion, ADULT, 375 mg/m2 once
weekly for 4 or 8 doses. May give IV formulation at first JC virus infection resulting in progressive multifocal
cycle, followed by subcutaneous formulation injected at leukoencephalopathy (PML) and death can occur.
a fixed dose of 1400 mg per cycle for up to 8 cycles. As
maintenance for relapsed/ refractory follicular
lymphoma who have responded to induction treatment, WARNING: Hazardous agent. Use appropriate
1400 mg subcutaneously once every 3 months (starting precautions for handling and disposal.
3 months after the last dose of induction therapy) until
disease progression or a maximum period of 2 years. Bowel obstruction or perforation (e.g. abdominal pain,
NHL, diffuse large B-cell, in combination with CHOP therapy. bowel obstruction, perforation; complaints of abdominal
Rituximab given by slow IV infusion, 375 mg/m2, pain or repeated vomiting should be evaluated,
followed by rituximab subcutaneous formulation injected especially if early in the treatment course)
at a fixed dose of 1400 mg per cycle in total of 8 cycles. Cardiovascular disease (use with caution; discontinue if
NHL, CD20-positive, B-cell, non-progressing, low-grade, serious cardiac arrhythmia occurs); respiratory disease
after 6–8 cycles of first line CVP, by slow IV infusion, (use with caution in patients)
ADULT, 375 mg/m2, once weekly for 4 doses every 6 Hepatitis B virus reactivation (monitor patients for clinical
months for a maximum of 16 doses. and laboratory signs of hepatitis or HBV during and
several months after treatment; reactivation may occur
even in those with previously resolved HBV infection, and

354
ANTINEOPLASTIC AND IMMODULATING AGENTS

up to 24 months after therapy discontinuation; use with fulminant hepatitis, gastrointestinal perforation,
caution in those with evidence of prior HBV infection) hemolytic anemia, hepatic failure, hepatitis, hepatitis B
Infections (serious and potentially fatal bacterial, fungal, reactivation, hypogammaglobulinemia (prolonged), optic
and either new or reactivated viral infections may occur neuritis, interstitial pneumonitis, hyperviscosity
during treatment and after; monitor immunoglobulin syndrome (Waldenström’s macroglobulinemia), hypoxia,
levels as necessary; discontinue in patients who develop laryngeal edema, lichenoid dermatitis, lupus-like
other serious infections and initiate appropriate anti- syndrome, marrow hypoplasia, mucositis,
infectivetreatment; use is not recommended in active mucocutaneous reaction, pleuritis, neutropenia,
infection) pancytopenia (prolonged), pure red cell aplasia,
Infusion reactions (e.g. hypotension, angioedema, paraneoplastic pemphigus, renal toxicity, pneumonia,
bronchospasm, hypoxia, urticaria, pulmonary infiltrates, pneumonitis, polyarticular arthritis, polymyositis,
ARDS, myocardial infarction, ventricular fibrillation, posterior reversible encephalopathy syndrome (PRES),
cardiogenic shock, or anaphylaxis; closely monitor progressive multifocal leukoencephalopathy (PML),
patients with history of prior cardiopulmonary reactions, serum sickness, Stevens-Johnson syndrome, toxic
with preexisting cardiac or pulmonary conditions, or with epidermal necrolysis, reversible posterior
high numbers of circulating malignant cells, i.e., leukoencephalopathy syndrome (RPLS),
>25,000/mm3; perform cardiacmonitoring during and supraventriculararrhythmia, systemic vasculitis,
after the infusion in patients who develop clinically tuberculosis reactivation, tumor lysis syndrome, uveitis,
significant arrhythmias or who have a history of ventricular fibrillation, vasculitis withrash, ventricular
arrhythmia or angina; mild-to-moderate infusion-related tachycardia, vesiculobullous dermatitis, viral reactivation
reactions, e.g., chills, fever, or rigors, occur frequently (JC virus, cytomegalovirus, herpes simplex virus,
and are typically managed through slowing or parvovirus B19, varicella zoster virus, West Nile virus, and
interrupting the infusion; due to the potential for hepatitis C), wheezing

L
hypotension, consider withholding antihypertensives 12
hours prior to treatment) Drug Interactions:
Mucocutaneous reactions (discontinue in severe Monitor closely with:
mucocutaneous skin reactions); progressive multifocal Enhances therapeutic effect of Rituximab:
leukoencephalopathy (e.g. confusion or disorientation, Trastuzumab (neutropenic effect)
motor weakness or hemiparesis, altered vision or
speech, and poor motor coordination; promptly evaluate Increases risk of adverse or toxic effects of Rituximab:
patients with neurological changes; discontinue in Denosumab (serious infections)
patients who develop PML; consider reduction or
discontinuation of concurrent chemotherapy Reduces diagnostic effect of Coccidioides immitis Skin Test
orimmunosuppressants)
Renal toxicity (may be fatal; discontinue with increasing Avoid concomitant use with:
serum creatinine or oliguria); Enhances therapeutic effect of Rituximab:
Tumor lysis syndrome (may lead to acute renal failure Roflumilast (immunosuppressive effect)
requiring dialysis, may be fatal; hyperkalemia,
hypocalcemia, hyperuricemia, and/or Enhances therapeutic effect of Certolizumab Pegol
hyperphosphatemia may occur; correct electrolyte (immunosuppressive effect)
abnormalities; monitor renal function and hydration
status). Increases risk of adverse or toxic effects of the following
Elderly (use with caution; at higher risk of cardiac and drugs:
pulmonary adverse events). Abatacept, Balimumab, Clozapine (agranulocytosis),
Leflunomide (hematologic toxicity such as pancytopenia,
Adverse Drug Reactions: agranulocytosis, and/or thrombocytopenia),
Common: Abdominal pain, anemia, angioedema, anxiety, Natalizumab (concurrent infection), Tofacitinib
arthralgia, bronchospasm, back pain, chills, cough,
cytopenias (may be prolonged), diarrhea, dizziness, Increases risk of adverse or toxic effects of Rituximab:
dyspepsia, dyspnea, dyspnea, epistaxis, fatigue, Antihypertensives (hypotensive effect), Dipyrone
flushing, headache, positive human antichimeric (agranulocytosis; pancytopenia), Pimecrolimus,
antibody (HACA), fever, hyperglycemia, hypertension, Tacrolimus (Topical)
hypotension, infection, infusion-related reactions
(decreases with subsequent infusions), night sweats, Reduces therapeutic effect of Rituximab:
insomnia, increased LDH, leukopenia, lymphopenia, Echinacea
migraine, muscle spasm, myalgia, nausea, neuropathy,
neutropenia, neutropenic fever, paresthesia, peripheral Reduces therapeutic effect of the following drugs:
edema, pruritus, rash, rhinitis, sinusitis, throat irritation, BCG (Intravesical), Vaccines (immune response; live
pain, thrombocytopenia, upper respiratory tract virus vaccines may progress to infection)
infection, urticaria, vomiting, weakness, weight gain
Less Common: Acute renal failure, anaphylactoid reaction Administration:
or anaphylaxis, angina, aplastic anemia, arrhythmia, Refer to institutional guideline on administration, if available.
bowel obstruction or perforation, ARDS, bronchiolitis
obliterans, cardiac failure, MI, cardiogenic shock, For IV infusion only.
disease progression (Kaposi’s sarcoma), For initial IV infusion, start at a rate of 50 mg/hour. If
encephalomyelitis, fatal infusion-related reactions, there is no reaction, increase the rate by 50 mg/hour

355
 ANTINEOPLASTIC AND IMMODULATING AGENTS

increments every 30 minutes, to a maximum rate of 400 Indications: Treatment of HER-2 overexpressing node
mg/hour. positive or node negative (estrogen receptor or
progesterone receptor negative or with 1 high risk
For subsequent IV infusions, feature) in early stage breast cancer, alone or in
Standard infusion rate: combination
If patient tolerated initial infusion, start at 100 mg/hour.
If there is no reaction, increase the rate by 100 mg/hour Contraindication: Hypersensitivity to trastuzumab, Chinese
increments every 30 minutes, to a maximum rate of 400 hamster ovary (CHO) cell proteins, or any component of
mg/hour. the formulation

Accelerated infusion rate (90 minutes): Dose:

For patients with previously untreated follicular NHL and HER2+ early stage breast cancer, adjunct treatment, by IV
diffuse large B-cell NHL who are receiving a infusion, ADULT,
corticosteroid concurrently, with a circulating lymphocyte in combination with paclitaxel or docetaxel, initially 4
count <5000/mm3, or have no significant cardiovascular mg/kg as loading dose, infused over 90 minutes,
disease, after tolerance has been established (no grade followed by 2 mg/kg maintenance dose, infused over 30
3 or 4 infusion-related event) at the recommended minutes weekly for total of 12 weeks, followed 1 week
infusion rate in cycle 1, a rapid infusion rate may be used later, after completion of concurrent chemotherapy, by 6
beginning with cycle 2. Administer dose over 90 minutes, mg/kg infused over 30–90 minutes every 3 weeks for
with 20% of the dose administered over the first 30 total therapy duration of 52 weeks;
minutes and the remaining 80% is given over 60 in combination with docetaxel and carboplatin, initially 4
minutes, after the daily corticosteroid, acetaminophen, mg/kg as loading dose, infused over 90 minutes,
and diphenhydramine. If the 90-minute infusion in cycle followed by 2 mg/kg maintenance dose, infused over 30
L

2 is tolerated, the same rate may be used for the minutes weekly for total of 18 weeks, followed 1 week
remainder of the treatment regimen (through cycles 6 or later, after completion of concurrent chemotherapy, by 6
8). mg/kg infused over 30–90 minutes every 3 weeks for
total therapy duration of 52 weeks;
Do NOT administer by IV push or bolus. If a reaction following completion of multi-modality anthracycline-
occurs, slow or stop the infusion. Once reaction abates, based chemotherapy, initially 8 mg/kg, as loading dose,
restart infusion at 50% of the previous rate. Discontinue infused over 90 minutes, followed by 6 mg/kg
infusion in the event of serious or life-threatening cardiac maintenance dose, infused over 30–90 minutes every 3
arrhythmias. weeks for total therapy duration of 52 weeks.

NOTE: Pretreatment with acetaminophen and an Dose Adjustment:

antihistamine is recommended. Cardiotoxicity:
For LVEF ≥16% decrease from baseline or LVEF below
Anti-hyperuricemic therapy and aggressive hydration are normal limits and ≥10% decrease from baseline,
recommended for patients with a high tumor burden or withhold treatment for at least 4 weeks and repeat LVEF
lymphocytes >25,000/mm3. every 4 weeks. Resume treatment if LVEF returns to
normal limits within 4–8 weeks and remains at ≤15%
In patients with CLL, Pneumocystis jirovecii pneumonia decrease from baseline value. Discontinue permanently
(PCP) and antiherpetic viral prophylaxis is recommended for persistent (>8 weeks) LVEF decline or for >3 incidents
during treatment (and for up to 12 months following of treatment interruptions for cardiomyopathy.
treatment).
Infusion-related events:
In granulomatosis with polyangiitis (GPA) and If mild-moderate infusion reactions occur, decrease
microscopic polyangiitis (MPA), PCP prophylaxis is infusion rate.
recommended during and for 6 months after treatment. If dyspnea or clinically significant hypotension occurs,
interrupt infusion.
Pregnancy Category: C If severe or life-threatening infusion reactions occur,
discontinue.
ATC Code: L01XC02
Precautions:
WARNING: Associated with symptomatic and
Rx TRASTUZUMAB asymptomatic reductions in left ventricular
ejection fraction (LVEF) and heart failure. Incidence
and severity were highest in concurrent use with
Inj.: 150 mg lyophilized powder (IV infusion) anthracycline-containing chemotherapy regimens.
600 mg/5 mL (120 mg/mL) solution for injection, 5 Evaluate left ventricular function in all patients
mL vial (SC) prior to and during treatment.
A monoclonal antibody which binds to the extracellular Infusion reactions, including fatalities, have been
domain of the human epidermal growth factor receptor associated with use. Discontinue for anaphylaxis or
2 protein (HER-2). It mediates antibody-dependent angioedema. Interrupt infusion for dyspnea or
cellular cytotoxicity by inhibiting proliferation of cells significant hypotension.
which over express HER-2 protein.

356
ANTINEOPLASTIC AND IMMODULATING AGENTS

(membranous, focal and fibrillary), coma,

May cause serious pulmonary toxicity, including glomerulopathy, hematemesis, hemorrhage,
dyspnea, hypoxia, interstitial pneumonitis, hemorrhagic cystitis, hepatic failure, hepatic injury,
pulmonary infiltrates, pleural effusion, hepatitis, herpes zoster, hiccups, hypoprothrombinemia,
noncardiogenic pulmonary edema, pulmonary hydrocephalus, hydronephrosis, hypercalcemia,
insufficiency, acute respiratory distress syndrome hypervolemia, hypotension, hypothyroidism, hypoxia,
[ARDS], and/or pulmonary fibrosis. Discontinue for intestinal obstruction, interstitial pneumonitis, jaundice,
ARDS or interstitial pneumonitis. laryngeal edema, laryngitis, lethargy, leukemia (acute),
limb pain, lymphangitis, madarosis, mania, mastalgia,
Conventional trastuzumab and ado-trastuzumab meningitis, musculoskeletal pain, myopathy,
emtansine are different products and are NOT neutropenia, neutropenic sepsis, nephrotic syndrome,
interchangeable. oligohydramnios, onychoclasis, osteonecrosis,
pancreatitis, paresis, oxygen desaturation,
pancytopenia, paroxysmal nocturnal dyspnea,
WARNING: Hazardous agent. Use appropriate pathological fracture, pericardial effusion, pericarditis,
precautions for handling and disposal. pleural effusion, pneumonitis, shock, pulmonary edema
(noncardiogenic), pulmonary fibrosis, pulmonary
hypertension, pneumothorax, renal failure, pulmonary
Cardiomyopathy (e.g. arrhythmias, hypertension, mural infiltrates, pyelonephritis, radiation injury, respiratory
thrombus formation, stroke, cardiac death may occur; distress, respiratory failure, seizure, sepsis, syncope,
observe extreme caution in patients with pre-existing stomatitis, thrombosis (including mural), urticaria,
cardiac disease or dysfunction; monitor cardiac function vertigo, thyroiditis (autoimmune), ventricular
closely; consider discontinuation in clinically significant dysfunction, wheezing

L
reduction in LVEF during therapy; withhold treatment for
≥16% decrease from pretreatment levels or LVEF below Drug Interactions:
normal limits and ≥10% decrease from baseline) Monitor closely with:
Infusion reactions (e.g. fever, chills, nausea, vomiting, pain, Enhances therapeutic effect of Immunosuppressants
headache, dizziness, dyspnea, hypotension, rash, (neutropenic effect)
weakness)
Renal toxicity (e.g. nephrotic syndrome with evidence of Avoid concomitant use with:
glomerulopathy; complications may include volume Increases risk of adverse or toxic effects of the following
overload and HD) drugs:
Pulmonary toxicity (use caution; pulmonary events may Anthracycline {Systemic (cardiotoxic effect) [avoid
occur during or within 24 hours of administration) anthracycline therapy for up to 7 months after
Pregnancy (can result in oligohydramnios and discontinuation of trastuzumab]}, Belimumab
oligohydramnios sequence manifesting as pulmonary
hypoplasia, skeletal abnormalities, and neonatal death) Administration: For IV infusion. Infuse loading doses over 90
minutes and maintenance doses over 30 minutes, if
Adverse Drug Reactions: tolerated.
Common: Abdominal pain, accidental injury, acne vulgaris,
anemia, anorexia, arthralgia, back pain, arrhythmia, Do NOT administer by IV push or by rapid bolus. Do NOT
cardiac failure, chills, constipation, decreased left extend treatment beyond 1 year.
ventricular ejection fraction, depression, diarrhea,
dizziness, dyspepsia, cough, dyspnea, edema, epistaxis, Do NOT administer with D5W. Do NOT mix with any other
fever, flu-like symptoms, headache, herpes simplex medications.
infection, hypersensitivity reaction, hypertension,
infection, influenza, infusion related reaction (chills, Observe patients closely during the infusion for fever,
fever), insomnia, leukopenia, muscle spasm, myalgia, chills, or other infusion-related symptoms.
nasopharyngitis, nausea, neuropathy, ostealgia, nail
disease, pain, palpitations, paresthesia, peripheral NOTE: Pretreatment with acetaminophen and an
edema, pharyngitis, peripheral neuritis, antihistamine is recommended for managing infusion-
pharyngolaryngeal pain, pruritus, skin rash, rhinitis, related events.
sinusitis, tachycardia, upper respiratory tract infection, MISSED DOSE.
urinary tract infection, vomiting, weakness If a dose is missed by ≤1 week, administer usual
Less Common: Abnormality in thinking, amblyopia, adult maintenance dose as soon as possible. Do NOT wait until
respiratory distress syndrome, apnea, anaphylactic next planned cycle. Administer subsequent maintenance
shock, anaphylactoid reaction, anaphylaxis, doses 7 or 21 days later based on patient’s maintenance
angioedema, ascites, asthma, ataxia, blood coagulation dose or schedule.
disorder, bradycardia, bronchitis, bronchospasm,
cardiogenic shock, cardiomyopathy, cellulitis, cerebral If a dose is missed by >1 week, administer a reloading
edema, cerebrovascular accident, cerebrovascular dose or 4 mg/kg if on a weekly schedule, or 8 mg/kg if
disease, cardiac arrest, chest discomfort, colitis, on an every-3-week schedule, followed by the usual
confusion, cystitis, deafness, dermal ulcer, dermatitis, maintenance dose administered 7 or 21 days later
dysuria, erysipelas, esophageal ulcer, febrile based on patient’s maintenance dose or schedule.
neutropenia, focal segmental glomerulosclerosis,
gastritis, gastroenteritis, glomerulonephritis Pregnancy Category: D

357
 ANTINEOPLASTIC AND IMMODULATING AGENTS

ATC Code: L01XC03 interactions, consider mutational analysis; switch to 2nd

line TKI and evaluate for allo-HSCT
Ph+ CML, chronic phase, newly diagnosed, by mouth,
PROTEIN KINASE INHIBITORS ADOLESCENT and CHILD ≥1 year, starting dose is:
Chronic Phase: 260 - 300 mg/m2 (maximum absolute dose
400 mg)
Rx IMATINIB Accelerated Phase: 400 mg/m2 (maximum absolute dose
600 mg)
Blastic Crisis: 500 mg/m2 (maximum absolute dose 800
Oral: 100 mg and 400 mg tablet (as mesilate)
mg)
Ph+ ALL, newly diagnosed or relapsed or refractory, by
A protein kinase inhibitor that inhibits BCR-ABL kinase, as
mouth, ADULT, 600-800 mg once daily, alone or in
well as the c-KIT kinase 234 and the platelet-derived
growth factor receptor (PDGFR) kinase. combination with steroids ± chemotherapy
Ph+ ALL, newly diagnosed, induction, by mouth, ADULT, 600
Indications: Treatment of newly diagnosed, relapsed, or mg once daily;
refractory Philadelphia chromosome–positive (Ph+) ADOLESCENT and CHILD ≥1 year, in combination with
acute lymphoblasticleukemia (ALL) in adults; treatment chemotherapy, 340 mg/m2 daily (maximum, 600 mg
of newly diagnosed Ph+ ALL in children; treatment of daily).
aggressive systemic mastocytosis without D816V c-Kit GIST, adjuvant treatment following complete resection, by
mutation (or c-Kit mutational status unknown) in adults; mouth, ADULT, 400 mg once daily for 3 years.
treatment of Ph+ chronic myeloid leukemia (CML) in GIST, unresectable and/or metastatic malignant, by mouth,
chronic phase (newly diagnosed) in adults andchildren; ADULT, 400 mg once daily; may be increased up to 800
mg daily (400 mg twice daily), if tolerated, for disease
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treatment of Ph+ CML in blast crisis, accelerated phase,

or chronic phase after failure of interferon-alfa therapy; progression.
treatment with unresectable, recurrent, and/or Aggressive systemic mastocytosis with eosinophilia, by
metastatic dermatofibrosarcoma protuberans (DFSP) in mouth, ADULT, initially 100 mg once daily, titrate up to a
adults; treatment of Kit (CD117)-positive unresectable maximum of 400 mg once daily, if tolerated for
and/or metastatic malignant gastrointestinal stromal insufficient response to lower dose.
tumors (GIST); adjuvant treatment of Kit (CD117)– ASM without D816V c-Kit mutation or c-Kit mutation status
positive GIST following complete gross resection; unknown, by mouth, ADULT, 400 mg once daily.
treatment of hypereosinophilic syndrome (HES) and/or DFSP, by mouth, ADULT, 400 mg twice daily.
chroniceosinophilic leukemia (CEL) in adult patients who HES and/or CEL, by mouth, ADULT, 400 mg once daily.
have the FIP1L1–platelet-derived growth factor (PDGF) HES/CEL with FIP1L1-PDGFRα fusion kinase, by mouth,
receptor alpha fusion kinase (mutational analysis or ADULT, initially 100 mg once daily, titrate up to a
fluorescent in situ hybridization [FISH] demonstration of maximum of 400 mg once daily, if tolerated, for
CHIC2 allele deletion) and for patients with HES and/or insufficient response to lower dose.
CEL who are FIP1L1-PDGF receptor alpha fusion kinase MDS/MPD, by mouth, ADULT, 400 mg once daily.
negative or unknown; treatment of myelodysplastic
syndrome/myeloproliferative diseases (MDS/MPD) Dose Adjustment:
associated with PDGF receptor gene rearrangements in Renal Impairment:
adults In CrCl 40–59 mL/minute, maximum dose is 600 mg.
In CrCl 20–39 mL/minute, decrease starting dose by 50%.
Dose: Increase doses as tolerated. The maximum dose is 400
For patients with CML, during treatment with TKI, mg.
quantitative reverse-transcriptase polymerase chain In CrCl <20 mL/minute, 100 mg daily has been tolerated.
reaction (qRT-PCR) for BCR-ABL monitoring should be
done every 3 months until a major molecular response Hepatic Impairment:
(MMR) is achieved, then every 3-6 months. Karyotyping In mild-to-moderate impairment, an initial dose of 400 mg
(Chromosomal Band Analysis, CBA of marrow cells) may once daily is the minimum effective dose.
also be used at 3, 6, and 12 months until a complete In severe impairment, initiate at 200 mg once daily, may
cytogenetic response (CCyR) is achieved, then every 12 increase up to 300 mg once daily in the absence of
months. Once CCyR is achieved, peripheral blood FISH severe toxicity. Decrease dose with unacceptable
for BCR-ABL may be used. toxicity.
Ph+ CML, chronic phase, by mouth, ADULT, 400 mg once During therapy:
daily, if BCR-ABL by qRT-PCR is >10% or CBA shows > If elevations of bilirubin >3 times ULN or transaminases
35% Ph+ cells at 3 months, evaluate compliance to >5 times ULN occur, withhold treatment until bilirubin
therapy and drug interactions, consider mutational <1.5 times ULN and transaminases <2.5 times ULN.
analysis; switch to 2nd line TKI and evaluate for allo- Resume treatment at a reduced doseas follows:
HSCT.
Ph+ CML, accelerated phase or blast crisis, by mouth, CURRENT REDUCED
DOSE DOSE
ADULT 800 mg daily (400 mg twice daily), must be
evaluated for allo-HSCT at diagnosis; for blast phase, 300 mg
400 mg daily
daily
consider lineage-directed chemotherapy + TKI; if BCR- ADULT
400 mg
ABL by qRT-PCR is >10% or CBA shows > 35% Ph+ cells 600 mg daily
daily
at 3 months, evaluate compliance to therapy and drug

358
ANTINEOPLASTIC AND IMMODULATING AGENTS

800 mg daily
600 mg Hemorrhage (e.g. severe hemorrhage, grades 3 and 4,
daily including GI hemorrhage and tumor hemorrhage;
260 incidence is higher in patients with GIST; gastric antral
CHILD ≥1 year 340 mg/m2
mg/m2
ADOLESCENT daily
daily
vascular ectasia; monitor for GI symptoms with
treatment initiation)
NOTE: Consider the initial severity of hepatotoxicity
Hepatotoxicity (fatal hepatic failure and severe hepatic
when deciding to resume treatment.
injury requiring liver transplantation; use with caution in
patients with hepatic impairment; monitor liver function
Hematologic Toxicity:
prior to initiation and monthly or as needed thereafter);
In chronic phase CML, initiate at 400 mg daily in adults or
renal impairment (use with caution)
340 mg/m2 daily in children. In accelerated phase or
Thyroid disease (e.g. hypothyroidism; monitor thyroid
blast crisisCML or Ph+ ALL, adjust dose as follows;
function; consider doubling levothyroxine doses upon
ADULT (ANC <500/mm3 and/or platelets <10,000/mm3,
initiation of imatinib)
unrelated to leukemia), if initial dose is 600 mg daily,
Tumor lysis syndrome (increased risk in high tumor burden
reduce dose to 400 mg daily; if cytopenia persists for an
or high proliferation rate; monitor closely).
additional 2 weeks, further reduce dose to 300 mg daily;
Children (e.g. growth retardation in prepubertal children;
if cytopenia persists for 4 weeks, withhold treatment
growth velocity restored during puberty)
until ANC ≥1,000/mm3 and platelets ≥20,000/mm3,
then resume treatment at 300 mg daily.
SKILLED TASKS. May impair ability to perform tasks, which
In ASM, MDS/MPD, and HES/CEL, initiate at 400mg daily.
require mental alertness, like driving or operating
In GIST, initiate at 400 mg daily or 400–600 mg daily. If ANC
machinery.
<1,000/mm3 and/orplatelets <50,000/mm3, withhold
until ANC ≥1,500/mm3 and platelets ≥75,000/mm3.
Adverse Drug Reactions:

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Resume treatment at original starting dose. For recurrent
Common: Abdominal distention, abdominal pain, alopecia,
neutropenia and/or thrombocytopenia, withhold until
anemia, anorexia, anxiety, arthralgia, back pain, blurred
recovery, and reinstitute treatment at a reduced dose as
vision, cardiac failure, cerebral hemorrhage, chest pain,
follows:
chills, conjunctival hemorrhage, conjunctivitis,
INITIAL REDUCED
constipation, cough, decreased appetite, depression,
DOSE DOSE
dermatitis, diaphoresis, diarrhea, dizziness, dyspepsia,
400 mg 300 mg dyspnea, edema, dry eyes, eosinophilia, epistaxis,
daily daily erythema, eyelid edema, facial edema, fatigue, febrile
ADULT
600 mg 400 mg neutropenia, fever, flatulence, flu-like symptoms, fluid
daily daily retention, flushing, gastritis, gastroenteritis, GERD, GI
CHILD ≥1 year 340 mg/m2 260 mg/m2 hemorrhage, headache, hemorrhage, hyperglycemia,
ADOLESCENT daily daily hyperkalemia, hypertension, hypocalcemia,
hypoesthesia, hypokalemia, hypophosphatemia,
Precautions: hypotension, hypoxia, hypoproteinemia, increased
WARNING: Hazardous agent; use appropriate lacrimation, infection, influenza, insomnia, joint swelling,
precautions for handling and disposal. leukopenia, limb pain, lymphocytopenia,
musculoskeletal pain, muscle cramps, myalgia, nail
disease, nasopharyngitis, nausea, neutropenia,
Bone marrow suppression (e.g. anemia, neutropenia,
oropharyngeal pain, night sweats, ostealgia, palpitations,
thrombocytopenia; usually occurs within first several
pancytopenia, pain, paresthesia, periorbital edema,
months of treatment; monitor blood counts weekly for
peripheral neuropathy, pharyngitis, pharyngolaryngeal
the first month, biweekly for the second month, and
pain, pleural effusion, pneumonia, pneumonitis, pruritus,
asclinically necessary thereafter)
purpura, rhinitis, rigors, sinusitis, skin photosensitivity,
Cardiovascular effects (e.g. severe heart failure and left
stomatitis, taste disorder, skin rash, thrombocytopenia,
ventricular dysfunction; usually occurs in patients with
upper respiratory tract infection, vomiting, weakness,
comorbidities and/or risk factors; also reported in
weight gain, weight loss, xeroderma, xerostomia
hypereosinophilic syndrome and cardiac involvement) Less Common: Actinic keratosis, acute generalized
Dermatologic reactions (e.g. severe bullous dermatologic exanthematous pustulosis, anaphylactic shock,
reactions, erythema multiforme, SJS and DRESS; if anginapectoris, angioedema, aplastic anemia, arthritis,
symptoms of DRESS occur, interrupt therapy and ascites, atrial fibrillation, avascular necrosis of bones,
consider permanently discontinuing) blepharitis, bullous rash, cardiac arrest, cardiac
CNS effects (e.g. dizziness, blurred vision, somnolence) arrhythmia, cardiac tamponade, cataract, cellulitis,
Fluid retention or edema (occasionally serious and may lead cerebral edema, cardiogenic shock, cheilitis,
to significant complications, including pleural effusion, coldextremities, colitis, confusion, decreased libido,
pericardial effusion, pulmonary edema, and ascites; use decreased linear skeletal growth rate (children), DRESS
withcaution in patients where fluid accumulation may be syndrome, dehydration, diverticulitis, dysphagia,
poorly tolerated, such as in cardiovascular disease and drowsiness, dyschromia, embolism, eructation,
pulmonary disease) erythema multiforme, esophagitis, exfoliative dermatitis,
Gastric surgery (imatinib exposure may be reduced in folliculitis, fungal infection, gastric ulcer, GI obstruction,
patients who have had gastric surgery, e.g. bypass, GI perforation, glaucoma, gout, gynecomastia, hearing
major gastrectomy, or resection; monitor imatinib trough loss, hematemesis, hematoma, hematuria, hepatic
concentrations); GI toxicity (e.g GI irritation, GI failure, hepatic necrosis, hepatitis, hepatotoxicity,
perforation) hemolytic anemia, herpes simplex infection, herpes

359
 ANTINEOPLASTIC AND IMMODULATING AGENTS

zoster, hypercalcemia, hypersensitivity angiitis, Increases serum concentration of the following drugs:
hypermenorrhea, hyperuricemia, IgA vasculitis, Avanafil, Budesonide (Systemic, Oral Inhalation, Topical),
hypomagnesemia, hyponatremia, inflammatory Cilostazol, Colchicine, Dapoxetine, Domperidone,
boweldisease, hypothyroidism, increased intracranial Doxorubicin (Conventional), Eletriptan, Eplerenone,
pressure, interstitial pneumonitis, interstitial pulmonary Everolimus, Fentanyl, Ibrutinib, Ivabradine, Ivacaftor,
disease, intestinal obstruction, jaundice, left ventricular Olaparib, Pazopanib, Pimozide, Ranolazine, Simeprevir,
dysfunction, lichen planus, lower respiratory tract Tolvaptan, Topotecan, Ulipristal, Zopiclone
infection, lymphadenopathy, macular edema, melena,
memory impairment, menstrual disease, MI, migraine, Reduces therapeutic effect of Imatinib:
myopathy, onychoclasis, optic neuritis, oral mucosa Echinacea (immunosuppressive effects)
ulcer, osteonecrosis (hip), palmar-plantar
erythrodysesthesia, pleuritic chest pain, ovarian Reduces therapeutic effect of the following drugs:
cyst(hemorrhagic), papilledema, pericarditis, BCG, (Intravesical), Fludarabine (myelosuppressive
pancreatitis, petechia, psoriasis, pulmonary fibrosis, effect), Vaccines (live virus vaccines may progress to
pulmonary hemorrhage, polyuria,pulmonary infection)
hypertension, Raynaud's phenomenon, renal failure,
respiratoryfailure, restless leg syndrome, retinal Administration: Administered with a meal and a large glass
hemorrhage, rhabdomyolysis, ruptured corpus luteal of water to minimize irritation.
cyst, sciatica, scrotal edema, seizure, sepsis, sexual
disorder, subconjunctival hemorrhage, subdural Do NOT crush or chew tablets due to bitter taste. Tablets
hematoma, Stevens-Johnson syndrome, tumor lysis may be dispersed in water or apple juice (~50 mL for 100
syndrome, Sweet’s syndrome, syncope, tachycardia, mg tablet and ~200 mL for 400 mg tablet). Stir until
telangiectasia (gastric antral), thrombocythemia, dissolved and administer immediately.
L

thrombosis, tinnitus, TEN, tremor, tumor hemorrhage

(GIST), urinary tract infection, urticaria, vertigo, vesicular In adults, doses ≤600 mg may be given once daily. 800
eruption, vitreous hemorrhage mg dose should be administered in 2 divided doses.
Dosing in children may be once or twice daily for CML and
Drug Interactions: once daily for Ph+ALL.
Monitor closely with: For daily dosing ≥800 mg, use 400 mg tablets to reduce
Decreases metabolism of the following drugs: iron exposure.
Simvastatin
Avoid grapefruit juice.
Enhances therapeutic effect of Imatinib:
Trastuzumab (neutropenic effect) NOTE: Associated with moderate emetic potential.
Antiemetics may be recommended to prevent nausea
Reduces diagnostic effect of Coccidioides immitis Skin Test and vomiting.

Increases risk of adverse or toxic effects of Imatinib: Pregnancy Category: D

Denosumab (serious infections), Lansoprazole
(dermatologic adverse effect), Paracetamol (hepatotoxic ATC Code: L01XE01
effect), Propacetamol (hepatotoxic effect)

Avoid concomitant use with: OTHER ANTINEOPLASTIC AGENTS

Deceases metabolism of the following drugs
Warfarin
Rx ASPARAGINASE
Decreases serum concentration of Imatinib:
Dabrafenib, Dexamethasone (Systemic), Ibuprofen,
Mitotane, Rifamycin Derivatives, e.g. Rifampicin, Inj.: 10,000 IU lyophilized powder, vial (IV)
Rifabutin, Rifaximin
An enzyme that hydrolyzes L-asparagine in leukemic cells to
Enhances therapeutic effect of Imatinib: ammonia and L-aspartic acid, leading to depletion of
Roflumilast (immunosuppressive effect) asparagine. Asparagine depletion in leukemic cells leads
to inhibition of protein synthesis and apoptosis.
Enhances therapeutic effect of the following drugs:
Tofacitinib (immunosuppressive effect), Warfarin Indication: Treatment of acute lymphoblastic leukemia (ALL)
(anticoagulant effect)
Contraindications: Hepatic insufficiency; pancreatitis;
Increases risk of adverse or toxic effects of Imatinib: pregnancy; breastfeeding; recent yellow fever
Dipyrone (agranulocytosis; pancytopenia), vaccination; concurrent administration with phenytoin;
Pimecrolimus, Tacrolimus hypersensitivity to asparaginase

Increases risk of adverse or toxic effects of the following Dose:

drugs: NOTE: Dose, frequency, number of doses, and start date
Clozapine (agranulocytosis), Leflunomide (hematologic may vary by protocol and treatment phase.
toxicity), Natalizumab, Oxycodone

360
ANTINEOPLASTIC AND IMMODULATING AGENTS

ALL, daily administration, by IV infusion, 200–1,000 and/or development of a pancreatic pseudocyst; avoid
units/kg daily for 28 consecutive days; continue alcohol use).
induction therapy for an additional 14 days if not Tumor lysis syndrome (monitor, consider anti-hyperuricemic
inremission or begin maintenance therapy if in therapy, hydration and urinary alkalization).
remission; Elderly (increased risk of thrombosis); children (at an
ALL, intermittent administration, by IV infusion, 400 increased risk of allergic reactions).
units/kg on Monday and Wednesday and 600 units/kg
on Friday; repeat for 4 weeks; continue induction therapy Adverse Drug Reactions:
for an additional 2 weeks if not in remission or begin Common and Less Common: Abdominal pain, acute
maintenance therapy if in remission. pancreatitis (may be fatal), allergic reactions (including
ALL, induction phase, CHILDREN AND ADOLESCENTS, anaphylactic shock, anaphylaxis, bronchospasm,
6,000 units/m2 3x weekly for 9 doses. edema, hypotension, laryngeal edema, skin rash,
urticaria), antithrombin III deficiency, amenorrhea,
Precautions: azoospermia, blood coagulation disorder (change in
hemostatic function), bone marrow depression, CNS
WARNING: Should be administered under the
disease (including delusion, disorientation, mild
supervision of an experienced cancer
depression, personality disorder, Parkinsonian-like
chemotherapy physician. Administer in a facility
syndrome, seizure), cerebral hemorrhage,
sufficient to appropriately diagnose and manage
cerebrovascular accident (hemorrhagic stroke and
complications.
thrombotic stroke), cerebrovascular hemorrhage,
cholestatic injury, decreased clotting factors (factors VII,
Allergic reactions may occur during therapy, VIII, IX, and X), fever, decreased glucose tolerance,
particularly in patients with known hypersensitivity diarrhea (infrequent), hepatic injury, hepatoxicity (rarely

L
to other forms of L-asparaginase. fatal), hyperammonemia (with clinical signs of metabolic
encephalopathy, e.g., impaired consciousness with
Adverse effects on liver function may be observed, coma, confusion, stupor), hyperbilirubinemia, decreased
including exacerbation of preexisting liver plasminogen, hypercholesterolemia, hyperglycemia,
impairment. hypertriglyceridemia, hypoalbuminemia,
hypocholesterolemia, hypofibrinogenemia,
hyperuricemia jaundice, liver steatosis, nausea
WARNING: Hazardous agent. Use appropriate (frequent; rarely severe), prolonged partial
precautions for handling and disposal. thromboplastin time, or prothrombin time, renal failure,
respiratory distress (with retrosternal pressure),
septicemia, thrombosis (including cerebral thrombosis),
Allergic reactions (immediate treatment for hypersensitivity
vomiting (frequent; rarely severe), weight loss
reactions should be available during administration; may
Rare: Intestinal perforation
exhibit cross-sensitivity between E. coli asparaginase,
asparaginase (Erwinia), or pegaspargase).
Drug Interactions:
Coagulopathy (increased prothrombin time, partial
Monitor closely with:
thromboplastin time, hypofibrinogenemia,
Increases serum concentration of Dexamethasone
cerebrovascular thrombosis, and hemorrhage may
(Systemic)
occur; monitor coagulation parameters at baseline and
periodically during and after therapy); thrombotic events
Administration:
(serious thrombosis, including sagittal sinus thrombosis
L-asparaginase can be administered intravenously (IV),
may occur)
subcutaneously (SC) or intramuscularly (IM). Refer to
Hepatotoxicity (monitor liver function tests at least weekly
institutional guidelines for administration, if available.
during therapy)
Hyperammonemia (may induce excessive ammonia
For IV administration, infuse over at least 30 minutes
production; monitor for signs of metabolic
through the side arm of a NS or D5W infusion.
encephalopathy, e.g., confusion, stupor, coma);
hyperglycemia (may cause hyperglycemia or glucose
For IM route, L-asparaginase can be (1) dissolved with
intolerance, which may be irreversible, and diabetic
Lidocaine (Refer to institutional guideline for more
ketoacidosis; monitor blood glucose as clinically
information); OR (2) reconstituted (10,000 IU vial) with
necessary)
1-2 mL sterile water; limit volume of single injection site
Neurotoxicity (posterior reversible encephalopathy
to 2 mL; if volume of dose exceeds 2 mL, use multiple
syndromehas been observed and may manifest as
injection sites.
altered mental status, hypertension, seizures,
headache, or visual disturbances).
Observe patients for 1 hour after administration. Have
Pancreatitis (may cause serious and possibly fulminant or
epinephrine, diphenhydramine, and hydrocortisone at
fatal pancreatitis (signs/symptoms: vomiting, severe
the bedside. A physician should be readily accessible.
abdominal pain); promptly evaluate patients with
abdominal pain; may consider continuing therapy for
May administer corticosteroids 1–2 days prior to initiating
asymptomatic chemical pancreatitis (amylase or lipase
reinduction therapy to prevent hypersensitivity reaction.
>3 times ULN) or only radiologic abnormalities; monitor
closely for rising amylase and/or lipase levels;
Pregnancy Category:X
discontinue permanently for clinical pancreatitis with
amylase/lipase elevation >3 times ULN for >3 days

361
 ANTINEOPLASTIC AND IMMODULATING AGENTS

ATC Code: L01XX02 hemoglobin, total leukocyte count, platelet count at least
once a week; address severe anemia with whole blood
replacement prior to treatment; during treatment,
address anemia with whole blood replacement without
Rx HYDROXYUREA interrupting hydroxyurea therapy; megaloblastic
erythropoiesis is self-limiting and may occur without
Oral: 500 mg capsule anemia; may delay plasma iron clearance and reduce
iron utilization of RBC).
Inhibitor of ribonucleotide reductase, which causes Dermatologic toxicity (e.g. vasculitic ulcerations, gangrene;
inhibition of DNA synthesis. discontinue treatment if cutaneous vasculitic toxicity
occurs in myeloproliferative disorders); mucositis (may
Indications: Treatment of acute blastic and chronic phases occur in combination therapy); post-radiation erythema.
of chronic myelogenous leukemia (CML); management of Gastric distress (e.g. nausea, vomiting, anorexia; may be
myeloproliferative neoplasms (e.g. essential controlled by temporary interruption); hepatotoxicity
thrombocythemia, polycythemia vera, primary (fatal hepatotoxicity has occurred in concomitant use of
myelofibrosis, hypereosinophilia, β-thalassemia); antiretroviral agents, particularly didanosine with or
cytoreduction in hyperleukocytosis secondary to acute without stavudine); pancreatitis (fatal pancreatitis has
leukemia; treatment of sickle cell and thalassemic crisis occurred in concomitant use of antiretroviral agents,
particularly didanosine with or without stavudine); renal
Contraindications: Marked bone marrow depression (i.e., dysfunction (use with caution).
leukopenia with <2,500 WBC/mm3 or thrombocytopenia Elderly (more sensitive to adverse effects).
<100,000/mm3); severe anemia
Adverse Drug Reactions:
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Dose: NOTE: Combining hydroxyurea with radiation therapy with

NOTE: All doses should be based on patient’s actual or ideal may increase the incidence and severity of its side
weight, whichever is less. effects.

CML, as initial therapy and for control of hyperleukocytosis Common: Bone marrow depression (leukopenia, anemia,
in AML - 20-30 mg/kg/day; depending on the height of thrombocytopenia), drowsiness (large doses), renal
the WBC count, up to 6 g/day; may require higher doses tubular function impairment (temporary)
at extremely high total WBC count. Reduce dose to 1 to Less Common: Abnormal bromsulphalein (BSP) retention,
2g/day when total WBC count reaches 20 x 109/L; in chills, dermatological reactions (maculopapular rash,
CML, continue therapy until tyrosine kinase inhibitor facial erythema), fever, GI symptoms (stomatitis,
(TKI) therapy is started; blood cell counts must be anorexia, nausea, vomiting, diarrhea, constipation),
monitored closely if used together with TKIs; in AML, malaise
discontinue once definitive chemotherapy is started; Rare: Alopecia, dysuria, neurological disturbances
hold therapy for leukopenia or thrombocytopenia, (headache, dizziness, disorientation, convulsion,
recheck after 3 days and resume if WBC and platelet hallucination)
counts normalize.
Head and neck carcinoma, by mouth, ADULT, 80 mg/kg Drug Interactions:
single dose every third day; begin administration at least Pancreatitis, hepatotoxicity, and peripheral neuropathy
7 days prior to radiation therapy and continue during and have occurred when hydroxyurea was administered
after radiation; administer radiation therapy at maximum concomitantly with antiretroviral drugs, including
dose. didanosine and stavudine
Solid tumors, intermittent therapy, by mouth, ADULT, 80
mg/kg single dose every third day; Concomitant use with a live virus vaccine may potentiate the
Solid tumors, continuous therapy, by mouth, ADULT, 20–30 replication of the vaccine virus and/or may increase the
mg/kg daily single dose; CHILDREN/ADOLESCENTS, 20– adverse reactions of the vaccine virus and result in
30 mg/kg orally. severe infections
Polycythemia vera, essential thrombocythemia, primary
myelofibrosis (cellular phase), by mouth, ADULT, 15 Interference with uric acid, urea, or lactic acid assays may
mg/kg once daily. Titrate to control platelets & maintain falsely elevate results in patients treated with
WBC count. hydroxyurea
β-thalassemia intermedia, CHILD, starting dose of 10 mg/kg
/day with dose escalation of 3-5 mg/kg/day every 8 Administration: Taken orally.
weeks to maximal tolerated dose. Not to exceed 20
mg/kg/day. Capsule contents may be emptied into a glass of water
and taken immediately. Some inert material used as a
Precautions: vehicle in the capsule may not dissolve and may float on
the surface.
WARNING: Hazardous agent. Use appropriate
precautions for handling and disposal. Pregnancy Category: D

Bone marrow suppression (e.g. leukopenia, ATC Code: L01XX05

thrombocytopenia, or anemia; monitor blood status
before and periodically during treatment; determine

362
ANTINEOPLASTIC AND IMMODULATING AGENTS

Obesity:
Rx IRINOTECAN Use actual body weight (full weight) for calculation of BSA-
based or weight-based dosing, especially if the intent of
Inj.: 40 mg/2 mL concentrate (as hydrochloride), vial (IV therapy is curative.
infusion) If dose reduction is done due to toxicity, consider
100 mg/5 mL concentrate (as hydrochloride), vial (IV resumption of full weight-based dosing with subsequent
infusion) cycles, especially if cause of toxicity is resolved.

Irinotecan and its active metabolite bind reversibly to Precautions:

topoisomerase I-DNA complex, preventing relegation of WARNING: Early and late forms of diarrhea may occur.
the cleaved DNA strand. This results in the accumulation Early diarrhea may be accompanied by cholinergic
of cleavable complexes and double-strand DNA breaks, symptoms that may be prevented or ameliorated
causing cell death consistent with S-phase cell cycle by atropine. Late diarrhea can be life-threatening
specificity, leading to termination of cellular replication. and should be treated promptly with loperamide.
Monitor patients with diarrhea and give fluid and
Indication: Treatment of metastatic carcinoma of the colon electrolytes as needed. Institute antibiotic therapy
or rectum if patients develop ileus, fever, or severe
neutropenia. Interrupt irinotecan and reduce
Dose: subsequent doses if severe diarrhea occurs.
NOTE: Consider reducing the starting dose by 1 dose level
Severe myelosuppression may occur.
for prior pelvic or abdominal radiotherapy, performance
status of 2, or known homozygosity for UGT1A1*28
WARNING: Hazardous agent. Use appropriate

L
allele. Subsequent dose adjustments should be based
on individual tolerance. precautions for handling and disposal.

Colorectal cancer, metastatic, weekly-regimen, by IV Bone marrow suppression (severe neutropenia, followed by
infusion, ADULT, 125 mg/m2 over 90 minutes on days 1, death due to sepsis has been reported; withhold therapy
8, 15, and 22 of a 6-week treatment cycle, may adjust temporarily if neutropenic fever occurs or if the absolute
upward to 150mg/m2 if tolerated; adjusted dose level 1, neutrophil count is <1,000/mm3); thromboembolism
100 mg/m2; adjusted dose level 2, 75 mg/m2; further (thromboembolic events have been reported).
adjust to 50 mg/m2 in decrements of 25 to 50 mg/m2, if Hypersensitivity reactions (severe hypersensitivity reactions
needed. (including anaphylaxis) have occurred; discontinue
Colorectal cancer, metastatic, single-agent therapy or once- therapy if hypersensitivity occurs).
every-3-week regimen, by IV infusion, ADULT, 350 mg/m2 Pulmonary toxicity (fatal cases of interstitial pulmonary
over 90 minutes, once every 3 weeks; adjusted dose disease-like events have been reported; monitor for
level 1, 300 mg/m2; adjusted dose level 2, 250 mg/m2; respiratory symptoms before and during treatment;
further adjust to 200 mg/m2 in decrements of 25 to 50 promptly evaluate progressive changes in baseline
mg/m2, if needed. pulmonary symptoms or any new-onset pulmonary
Colorectal cancer, metastatic, six-week (42-day) cycle, symptoms).
regimen 1, by IV infusion, ADULT, in combination with Renal toxicity (renal impairment and acute renal failure
bolus fluorouracil and leucovorin (administer leucovorin have been reported; use with caution; use has not been
immediately following irinotecan and fluorouracil studied; not recommended in patients undergoing
immediately following leucovorin), 125 mg/m2 over 90 dialysis).
minutes on days 1, 8, 15, and 22; adjusted dose level 1,
100 mg/m2; adjusted dose level 2, 75 mg/m2; further Adverse Drug Reactions:
adjust if needed in decrements of ~20%. Common: Abdominal fullness, abdominal pain, alkaline
regimen 2, by IV infusion, ADULT, in combination with phosphatase increased, alopecia, anemia, anorexia,
fluorouracil bolus or infusion and leucovorin infusion ascites, back pain, cholinergic toxicity (including rhinitis,
(administer leucovorin immediately following irinotecan increased salivation, miosis, lacrimation, diaphoresis,
and fluorouracil immediately following leucovorin), 180 flushing, intestinal hyperperistalsis), chills, confusion,
mg/m2 over 90 minutes on days 1, 15, and 29; adjusted constipation, cramps, dehydration, diaphoresis, diarrhea
dose level 1:150 mg/m2; adjusted dose level 2:120 (early and late), dizziness, dyspepsia, dyspnea, cough,
mg/m2; further adjust if needed in decrements of ~20%. edema, fever, flatulence, headache, hemorrhage,
hypotension, infection, insomnia, jaundice, leukopenia,
Dose Adjustment: mucositis, neutropenia, neutropenic fever, neutropenic
Geriatric: infection, pain, nausea, pneumonia, rash, rhinitis,
For every 3-week dosing colorectal cancer schedule, initiate somnolence, stomatitis, thrombocytopenia,
at 300 mg/m2 per dose for patients ≥70 years. thromboembolic events, vasodilation, vomiting,
weakness, weight loss
Hepatic Impairment: Less Common: Anaphylactoid reaction, anaphylaxis, angina,
In bilirubin >ULN to ≤2 mg/dL, consider reducing initial dose arterial thrombosis, bradycardia, cardiac arrest,
bone dose level. In bilirubin >2 mg/dL, use is not bleeding, cerebrovascular accident, circulatory failure,
recommended. colitis, deep thrombophlebitis, dysarthria, dysrhythmia,
embolus, GI bleeding, GI obstruction, hepatomegaly,
hiccups, ileus, hyperglycemia, hypersensitivity,
hyponatremia, interstitial pulmonary disease (IPD),

363
 ANTINEOPLASTIC AND IMMODULATING AGENTS

intestinal perforation, ischemic colitis, lymphocytopenia, Consider premedication of atropine 0.25–1 mg IV or SC

megacolon, MI, muscle cramps, myocardial ischemia, for cholinergic symptoms or early-onset diarrhea.
neutropenic typhlitis, pancreatitis, paresthesia,
peripheral vascular disorder, pulmonary toxicity The recommended regimen to manage late diarrhea is
(dyspnea, fever, reticulonodular infiltrates on chest x- loperamide 4 mg orally at onset, followed by 2 mg every
ray), pulmonary embolus, renal failure (acute), renal 2 hours (or 4 mg every 4 hours at night) until 12 hours
impairment, syncope, thrombosis, typhlitis, ulcerative have passed without a bowel movement. If diarrhea
colitis, thrombocytopenia (immune mediated), recurs, repeat administration. Do NOT use loperamide
thrombophlebitis, ulceration, vertigo for more than 48 consecutive hours.

Drug Interactions: Pregnancy Category: D

Monitor closely with:
Enhances therapeutic effect of Irinotecan: ATC Code: L01XX19
Trastuzumab (neutropenic effect)

Increases risk of adverse or toxic effects of Irinotecan: ADJUNCTS TO ANTINEOPLASTIC

Bevacizumab, Denosumab (serious infections) CHEMOTHERAPY
Reduces diagnostic effect of Coccidioides immitis Skin Test
CALCIUM FOLINATE (LEUCOVORIN
Rx
Avoid concomitant use with: CALCIUM, FOLINIC ACID)
Decreases serum concentration of Irinotecan:
Dabrafenib Inj.: 10 mg/mL, 5 mL ampule/vial (IM, IV)
L

50 mg vial (IM, IV)

Enhances therapeutic effect of Irinotecan:
Roflumilast (immunosuppressive effect) A reduced form of folic acid that supplies the necessary co-
factor blocked by methotrexate. It actively competes with
Enhances therapeutic effect of Tofacitinib methotrexate for transport sites, displaces methotrexate
(immunosuppressive effect) from intracellular binding sites, and restores active folate
stores required for DNA/RNA synthesis. Leucovorin
Increases risk of adverse or toxic effects of Irinotecan: stabilizes the binding of 5-dUMP and thymidylate
Dipyrone (agranulocytosis; pancytopenia), synthetase, enhancing the activity of fluorouracil.
Pimecrolimus, Tacrolimus (Topical)
Indications: Rescue agent after high-dose methotrexate
Increases risk of adverse or toxic effects of the following treatment; to diminish toxicity and counteract the effects
drugs: of impaired methotrexate elimination and of inadvertent
Clozapine (agranulocytosis), Leflunomide (hematologic overdosage of folic acid antagonists; treatment of
toxicity), Natalizumab (concurrent infection) megaloblastic anemias due to folic acid deficiency when
oral therapy is not feasible; palliative treatment of
Increases serum concentration of Irinotecan: advanced colorectal cancer
Fusidic Acid (Systemic), Gemfibrozil, Grapefruit Juice,
Mifepristone, UGT1A1 Inhibitors Contraindication: Pernicious anemia and other
megaloblastic anemias secondary to vitamin B12-
Reduces therapeutic effect of Irinotecan: deficiency
Conivaptan, Echinacea (immunosuppressive effects)
Dose:
Reduces therapeutic effect of the following drugs: Colorectal cancer, by IV injection, ADULT, in combination
BCG (Intravesical), Vaccines (live virus vaccines may with fluorouracil, 200 mg/m2 daily over at least 3
progress to infection) minutes for 5 days every 4 weeks for 2 cycles, then every
4–5 weeks or 20 mg/m2 daily for 5 days every 4 weeks
Administration: Administer by IV infusion, usually over 90 for 2 cycles, then every 4–5 weeks.
minutes. Folate-deficient megaloblastic anemia, by IM or IV injection,
ADULT, ≤1 mg once daily.
NOTE: Avoid extravasation. Ensure proper needle or High-dosemethotrexate-rescue, initial, by IM or IV injection,
catheter position prior to and during administration. If ADULT, 15 mg (~10 mg/m2); start 24 hours after
extravasation occurs, flush the external site with sterile beginning methotrexate infusion; continue every 6 hours
water and apply ice to the affected area. for 10 doses, until methotrexate level is <0.05
micromolar; adjust dose as follows:
Associated with moderate emetic potential. Antiemetics normal methotrexate elimination (serum methotrexate
are recommended to prevent nausea and vomiting. level ~10 micromolar at 24 hours after administration, 1
Premedication with dexamethasone and a 5-HT3 blocker micromolar at 48 hours, and <0.2 micromolar at 72
is recommended 30 minutes prior to administration. hours),15 mg every 6 hours for 60 hours (10 doses)
Prochlorperazine may be considered for subsequent use, beginning 24 hours after the start of methotrexate
if needed. infusion;
delayed late methotrexate elimination (serum
methotrexate level remaining >0.2 micromolar at 72

364
ANTINEOPLASTIC AND IMMODULATING AGENTS

hours and >0.05 micromolar at 96 hours after Avoid concomitant use with:
administration), continue leucovorin calcium 15 mg Reduces therapeutic effect of the following drugs:
every 6 hours until methotrexate level is <0.05 Raltitrexed, Trimethoprim
micromolar;
delayed early methotrexate elimination and/or acute Administration: Administer by IV or IM routeas a rescue after
renal injury (serum methotrexate level ≥50 micromolar folate antagonists. Administer by IM injection, IV push, or
at 24 hours, or ≥5 micromolar at 48 hours, or a doubling by IV infusion or 15 minutes to 2 hours.
of serum creatinine level at 24 hours after methotrexate
administration), 150 mg every 3 hours until Do NOT administer intrathecally.
methotrexate level is <1 micromolar, then 15 mg every 3
hours until methotrexate level is <0.05 micromolar. Do NOT administer IV solutions at a rate >160
CHILD, starting dose is 10 mg/m2 every 6 hours to start 24- mg/minute due to calcium content.
36 hours after start of methotrexate infusion, continue
until serum levels drop below 0.1 micromolar. NOTE: Do NOT administered concurrently with
Leucovorin dose should be increased dramatically at methotrexate. It is commonly initiated 24 hours after the
100 mg/m2 every 3 hours when serum methotrexate start of methotrexate. Toxicity to normal tissues may be
levels are elevated above 5 micromolar at 42 hours after irreversible if leucovorin is not initiated by ~40 hours
the start of methotrexate infusion. after the start of methotrexate.
Methotrexate overdose, inadvertent, begin as soon as
possible after overdose, by IM, or IV injection, ADULT, 10 Fluorouracil is usually given after, or at the midpoint, of
mg/m2 every 6 hours until methotrexate level is < 0.01 leucovorin infusion by IV bolus injection or short IV
micromolar; if serum creatinine is increased more than infusion over 10–120 minutes. Other administration
50% above baseline 24 hours after methotrexate schedules have been used; refer to individual protocols.

L
administration, if 24-hour methotrexate level is >5
micromolar, or if 48-hour methotrexate level is >0.9 Pregnancy Category: C
micromolar, increase leucovorin dose to 100 mg/m2 IV
every 3 hours until the methotrexate level is <0.01 ATC Code: Not available
micromolar. [NOTE: Monitor methotrexate serum
concentrations to determine dose and duration of
leucovorin therapy. Do NOT wait for the results of a MESNA (SODIUM-2-
Rx
methotrexate level before initiating leucovorin. Adjust MERCAPTOETHANE SULPHONATE)
leucovorin dose once methotrexate level is known. Dose
may need to be increased or administration prolonged in Inj.: 100 mg/mL, 4 mL ampule (IV)
situations where methotrexate excretion may be
delayed, e.g., ascites, pleural effusion, renal Mesna provides a free thiol group which binds to and
insufficiency, inadequate hydration.] inactivates acrolein, the urotoxic metabolite of
ifosfamide and cyclophosphamide.
Precautions:
WARNING: Hazardous agent. Use appropriate Indication: Preventive agent for
precautions for handling and disposal. cyclophosphamide/ifosfamide-induced hemorrhagic
cystitis
Renal impairment (excreted renally; risk for toxicities may
be increased). Contraindication: NOT indicated to reduce the risk of
Seizures (seizures or syncope have been rarely reported; hematuria due to other conditions such as
reported in patients with cancer receiving leucovorin, thrombocytopenia
usually in association with fluoropyrimidine
administration, and most commonly in patients with CNS Dose:
metastases or other predisposing factors). Prevention of cyclophosphamide and ifosfamide-induced
hemorrhagic cystitis, standard dose ifosfamide, by IV
Adverse Drug Reactions: Allergic reactions, anaphylactoid bolus, ADULT, 20% of ifosfamide dose given for 3 doses
reactions, erythema, pruritus, rash, thrombocytosis, at hour 0, at hour 4, and at hour 8 after ifosfamide (total
urticaria, wheezing daily mesna dose is 60% of the ifosfamide dose); CHILD,
intravenous injection for 15-30 minutes at 20% of the
Drug Interactions: simultaneously administered
Monitor closely with: cyclophosphamide/ifosfamide on a weight for weight
Enhances therapeutic effect of the following drugs: basis (w/w). The same dose is repeated after 4 and 8
Fluorouracil (Systemic) (anticancer effects), Tegafur hours. The total dose of mesna is 60% (w/w) of
(anticancer effects) cyclophosphamide/ifosfamide dose. This is repeated on
each occasion that the cytotoxic agents are used.
Increases risk of adverse or toxic effects of the following
drugs: NOTE: Repeat mesna dosing schedule each day ifosfamide
Capecitabine, Fluorouracil (Systemic and Topical), is received. Adjust mesna dose based on ifosfamide
Tegafur dose to maintain the mesna-to-ifosfamide ratio.

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 ANTINEOPLASTIC AND IMMODULATING AGENTS

Precautions:
ENDOCRINE THERAPY
WARNING: Hazardous agent. Use appropriate
precautions for handling and disposal.
HORMONES AND RELATED AGENTS
Anaphylaxis or hypersensitivity reactions (watch out for
fever, hypotension, tachycardia, acute renal impairment, PROGESTOGENS
hypoxia, respiratory distress, urticaria, angioedema,
signs of disseminated intravascular coagulation,
hematologic abnormalities, nausea, vomiting, arthralgia; Rx MEGESTROL
monitor for signs or symptoms of reactions; may require
discontinuation).
Dermatologic toxicity (e.g. rash, pruritus, urticaria, Oral: 40 mg and 160 mg tablet (as acetate)
erythema, burning sensation, angioedema, periorbital
edema, flushing, and stomatitis; reactions consistent A progestogen structurally related to progesterone with anti-
with SJS or TEN have been reported). estrogenic properties that disrupt estrogen receptor
Hematuria (monitor urine for hematuria; severe hematuria cycle. It is an antineoplastic progestin thought to act
despite utilization of mesna may require ifosfamide dose through an anti-leutenizing effect mediated via the
reduction or discontinuation; examine morning urine pituitary.
specimen for hematuria prior to ifosfamide or
cyclophosphamide treatment). Indications: Breast cancer; endometrial cancer
Ifosfamide or cyclophosphamide toxicities (intended for the
prevention of hemorrhagic cystitis and will not prevent or Dose:
L

alleviate other toxicities associated with ifosfamide or Breast cancer, advanced, by mouth, ADULT, 160 mg per day
cyclophosphamide). in divided doses of 40 mg given 4 times daily for at least
2 months.
Adverse Drug Reactions: Endometrial cancer, advanced, by mouth, ADULT, 40 to 320
Common: Anorexia, arthralgia, conjunctivitis, back pain, mg daily in divided doses for at least 2 months.
constipation, cough, diarrhea, dizziness, fever,
flatulence, flu-like syndrome, flushing, headache, Dose Adjustment:
hyperesthesia, rash, injection site reactions, nausea, Geriatric:
pharyngitis, rhinitis, rigors, somnolence, vomiting Use with caution. Avoid use in elderly.
Less Common: Allergic reaction, anaphylactic reaction,
hypersensitivity, hypertension, injection site erythema, Renal Impairment:
hypotension, injection site pain, limb pain, malaise, Use with caution. Urinary excretion is substantial.
myalgia, platelets decreased, ST-segment increased,
tachycardia, tachypnea Precautions:
WARNING: Hazardous agent. Use appropriate
Drug Interactions: No information found precautions for handling and disposal.

TEST INTERACTIONS. Adrenal suppression (may suppress hypothalamic-pituitary-

May produce false-positive results for urinary ketones adrenal axis with chronic use); Cushing syndrome
with nitroprusside-based urine tests, including dipstick (associated with long-term use).
tests AIDS-related cachexia; diabetes (new-onset diabetes
May produce falsely low creatinine kinase levels by mellitus or exacerbation of pre-existing diabetes;
interfering with enzymatic creatinine kinase activity associated with long-term use); thromboembolism (use
tests, which use thiol compounds with caution).
May produce false-positive results for ascorbic acid with Elderly (increased risk of thrombosis and possibly death);
Tillman’s reagent-based urine screening tests for children (safety and efficacy have not been established).
ascorbic acid Females (may cause vaginal bleeding or discharge).
Pregnancy (may cause fetal harm); lactation (excreted in
Administration: Administer as an IV bolus. Refer to specific breastmilk; discontinue breastfeeding while receiving
protocol for administration rate or details. megestrol).

Maintain adequate hydration and urinary output during Adverse Drug Reactions:
ifosfamide treatment. Common: Hypertension, cardiomyopathy, chest pain,
edema, palpitations, headache, pain, insomnia,
Pregnancy Category: B abnormality in thinking, confusion, convulsions,
peripheral edema, depression, hypoesthesia,
ATC Code: Not available neuropathy, paresthesia, skin rash, alopecia,
dermatological disease, diaphoresis, pruritus,
vesicobullous dermatitis, decreased libido, albuminuria,
gynecomastia, increased lactate dehydrogenase,
diarrhea, flatulence, vomiting, hyperglycemia, nausea,
dyspepsia, abdominal pain, constipation, oral moniliasis,
sialorrhea, xerostomia, impotence, urinary incontinence,
urinary tract infection, breakthrough bleeding, urinary

366
ANTINEOPLASTIC AND IMMODULATING AGENTS

frequency, sarcoma, hepatomegaly, candidiasis, herpes Dose:

virus infection, weakness, leukopenia, amblyopia, Prostate cancer, advanced, by SC implant, ADULT (male), for
dyspnea, pharyngitis, cough, pulmonary disorder, 28-day implants, 3.6 mg every 28 days; for 12-week
pneumonia, fever implants, 10.8 mg every 12 weeks.
Less Common: Cardiac failure, lethargy, malaise, mood Prostate cancer, stage B2 to C, by SC implant, ADULT (male),
changes, adrenocortical insufficiency, amenorrhea, in combination with an antiandrogen and radiotherapy,
Cushing’s syndrome, carpal tunnel syndrome, diabetes for combination 28-day or 12-week implants, 3.6 mg,
mellitus, hot flash, HPA-axis suppression, hypercalcemia, then 10.8 mg after 28 days (initiate therapy 8 weeks
weight gain, tumor flare, hyperventilation, prior to radiotherapy); for 28-day implant (alternate
thromboembolic phenomena dosing), 3.6 mg repeated every 28 days for 4 doses
(initiate therapy 8 weeks prior to radiotherapy).
Drug Interactions: Breast cancer, advanced, by SC implant, ADULT (female),
Monitor closely with: 3.6 mg every 28 days.
Enhances therapeutic effect of C1 Inhibitors Endometriosis, by SC implant, ADULT (female), 3.6 mg every
28 days for 6 months.
Reduces therapeutic effect of the following drugs: Endometrial thinning, by SC implant, ADULT (female), 3.6
Antidiabetic Agents, Choline C11 mg every 28 days for 1 or 2 doses.

Avoid concomitant use with: Precautions:

Increases serum concentration of Dofetilide WARNING: Hazardous agent. Use appropriate
precautions for handling and disposal.
Reduces diagnostic effect of Indium111 Capromab
Pendetide

L
Cervical resistance (may be increased; use with caution)
Decreased bone density (may be irreversible);
Reduces therapeutic effect of Megestrol: Hypercalcemia
Ulipristal [avoid progestins within 5 days of stopping Hyperglycemia (may manifest as diabetes or worsening of
ulipristal] preexisting diabetes);
Hypersensitivity
Injection site injury (may manifest as pain, hematoma,
Reduces therapeutic effect of the following drugs: hemorrhage, or hemorrhagic shock)
Anticoagulants, Ulipristal [avoid progestins within 5 days Pituitary apoplexy (may present as sudden headache,
of stopping ulipristal] vomiting, visual or mental status changes, or
cardiovascular collapse; immediate medical attention
Administration: To be taken with food. Swallow tablet whole. required)
Do NOT crush, break, or chew. Tumor flare (may result in worsening of disease signs and
symptoms during first few weeks of treatment; spinal
Pregnancy Category: D cord compression and urinary tract obstruction have
been reported).
ATC Code: L02AB01 Cardiovascular disease (increased risk for myocardial
infarction (MI), sudden cardiac death, and stroke have
been reported; may cause prolongation of QT / QTc
GONADOTROPIN-RELEASING HORMONE interval; correct electrolytes prior to initiation).
ANALOGUES Obesity (may result in decreased AUC when using 3-month
implant); underweight.
Women of childbearing potential (may result in effects on
Rx GOSERELIN reproductive function due to anti-gonadotropic
properties).
Inj.: 3.6 mg depot solution (as acetate), pre-filled syringe
(SC) Adverse Drug Reactions:
10.8 mg depot solution (as acetate), pre-filled syringe Common: Vasodilatation, peripheral edema, headache,
(SC) emotional lability, depression, pain, dyspareunia,
insomnia, diaphoresis, acne vulgaris, seborrhea, hot
A synthetic analogue of gonadotropin-releasing hormone, flash, decreased or increased libido, abdominal pain,
which causes an initial increase in luteinizing hormone vaginitis, breast atrophy or hypertrophy, sexual disorder,
(LH) and follicle stimulating hormone (FSH). Chronic decrease in erectile frequency, pelvic symptoms,
administration of goserelin results in a sustained genitourinary signs and symptoms, tumor flare, infection,
suppression of pituitary gonadotropins, causing serum decreased bone mineral density, weakness, edema,
testosterone to fall to levels comparable to surgical hypertension, cardiac failure, cardiac arrhythmia,
castration. cerebrovascular accident, peripheral vascular disease,
varicose veins, chest pain, myocardial infarction,
Indications: Management of prostate cancer; breast cancer palpitations, tachycardia, lethargy, migraine, malaise,
(advanced); endometriosis; endometrial thinning dizziness, chills, anxiety, nervousness, voice disorder,
abnormality in thinking, drowsiness, paresthesia, skin
rash, hair disease, pruritus, alopecia, skin discoloration,
xeroderma, gynecomastia, gout, hyperglycemia, weight
gain, anorexia, gastric ulcer, constipation, diarrhea,

367
 ANTINEOPLASTIC AND IMMODULATING AGENTS

vomiting, increased appetite, dyspepsia, flatulence,

xerostomia, pelvic pain, mastalgia, uterine hemorrhage, Rx LEUPRORELINE (LEUPRORELIN)
vulvovaginitis, breast swelling, urinary tract obstruction,
urinary tract infection, urinary frequency, vaginal Inj.: 1.88 mg powder (as acetate), single-dose vial with
hemorrhage, anemia, bruise, hemorrhage, syringe (IM, SC)
hypersensitivity reaction, sepsis, application site 3.75 mg powder (as acetate), single-dose vial with
reaction, myalgia, leg cramps, hypertonia, arthralgia, syringe (IM, SC)
arthropathy, amblyopia, dry eye syndrome, renal 11.25 mg powder (as acetate), depot solution, vial +
insufficiency, upper respiratory tract infection, chronic syringe (IM, SC)
obstructive pulmonary disease, flu-like symptoms, 3.75 mg/2 mL (as acetate), vial with syringe (IM, SC)
pharyngitis, sinusitis, bronchitis, cough, epistaxis,
rhinitis, fever An analogue of gonadorelin with similar properties, is used
Less Common: Anaphylaxis, bone fracture, convulsions, for the suppression ofgonadal sex hormone production
deep vein thrombosis, diabetes mellitus, hypercalcemia, in the treatment of malignant neoplasms of the prostate.
hypotension, injection site reaction, osteoporosis,
ovarian cyst, ovarian hyperstimulation syndrome, Indications: Endometriosis; prostate cancer; uterine
pituitary apoplexy, hyperlipidemia, pituitary neoplasm, leiomyomata (fibroids)
pulmonary embolism, psychotic reaction, transient
ischemic attacks Contraindications: Women who are or may become
pregnant, breast‐feeding, undiagnosed abnormal
Drug Interactions: vaginal bleeding
Monitor closely with: Dose:
Reduces therapeutic effect of the following drugs:
L

Prostate cancer, advanced, by IM or SC depot injection,

Antidiabetic Agents, Choline C11 ADULT, administer 3.75 mg once a month or 11.25 mg
every 3 months.
Avoid concomitant use with: Endometriosis; uterine leiomyomata (fibroids), by IM or SC
Enhances QTc-prolonging effect of Goserelin: depot injection, ADULT, administer 3.75 mg once a
Ivabradine, Mefepristone, QTc-prolonging Agents month or 11.25 mg every 3 months, for up to 6 months.
(Highest and Moderate Risk)
Dose Adjustment:
Reduces diagnostic effect of Indium111 Capromab Renal and Hepatic Impairment:
Pendetide Use with caution. No studies have been conducted.

Reduces therapeutic effect of the following drugs: Precautions:

Corifollitropin Alfa
WARNING: Hazardous agent. Use appropriate
precautions for handling and disposal.
Administration: Administer by SC injection.
Cardiovascular diseases (may increase risk for
Insert needle at a 30- to 45-degree angle into the
cardiovascular disease; sudden cardiac death and
anterior abdominal wall below the navel line. Use caution
stroke have been reported among men; may prolong the
while injecting into the anterior abdominal wall due to the
QT / QTc interval)
proximity of underlying inferior epigastric artery and its
Decreased bone density (use with caution in patients with
branches.
additional risk factors for bone loss);
Endometriosis (may exacerbate endometriosis or uterine
Goserelin is an implant. Do NOT attempt to eliminate air
leiomyomata)
bubbles prior to injection to prevent displacing the
Hyperglycemia (diabetes and/or worsening of glycemic
implant.
control have been reported in men).
Pituitary apoplexy (may present as sudden headache,
Do NOT attempt to aspirate prior to injection. If a large
vomiting, visual or mental status changes, and
vessel is penetrated, blood will be visualized in the
infrequently cardiovascular collapse; immediate medical
syringe chamber. If this occurs, withdraw needle and
attention required);
inject elsewhere with a new syringe.
Prostate cancer (may increase risk for cardiovascular
disease, diabetes, insulin resistance, obesity, alterations
Do NOT penetrate muscle or peritoneum. Implant may be
in lipids, and fractures).
detected by ultrasound if removal is required. Monitor for
Psychiatric illness (use with caution; alteration in mood,
signs or symptoms of abdominal hemorrhage. Use extra
memory impairment, and depression have been
care when administering to patents with a low BMI
associated with use)
and/or to patients receiving full dose anticoagulation.
Seizures
Spinal cord compression (monitor closely for weakness and
Pregnancy Category: X (endometriosis, endometrial
paresthesia in first few weeks of therapy)
thinning); D (advanced breast cancer)
Tumor flare
Urinary tract obstruction (monitor closely for urinary tract
ATC Code: L02AE03
obstruction and hematuria in first few weeks of therapy).

368
ANTINEOPLASTIC AND IMMODULATING AGENTS

Adverse Drug Reactions: Drug Interactions:

Common: Edema, headache, pain, depression, insomnia, Monitor closely with:
fatigue, dizziness, allergic skin reaction, hot flash, weight Reduces therapeutic effect of the following drugs:
changes, hyperlipidemia, decreased libido, nausea and Antidiabetic Agents, Choline C11
vomiting, gastrointestinal disease, change in bowel
habits, vaginitis, testicular atrophy, genitourinary Avoid concomitant use with:
complaint, burning sensation at injection site, weakness, Enhances QTc-prolonging effect of Leuproreline:
arthropathy, flu-like symptoms, respiratory tract disease Hydroxychloroquine, Promazine, QTc-prolonging Agents
Less Common: Angina pectoris, atrial fibrillation, (Highest and Moderate Risk)
bradycardia, cardiac arrhythmia, cardiac failure, deep
thrombophlebitis, hypertension or hypotension, Administration:
palpitations, vasodilation, syncope, tachycardia, For IM administration, administer as a single injection to
nervousness, paresthesia, anxiety, agitation, confusion, the gluteal area, anterior thigh, or deltoid. Rotate
delusions, dementia, emotional lability, mood changes, injection site periodically.
neuropathy, paralysis, seizure, ostealgia, headache,
pain, acne vulgaris, alopecia, diaphoresis, cellulitis, hair For SC administration, rotate injection site. Choose site
disease, pruritus, seborrhea, skin rash, dehydration, with adequate SC tissue but without excessive pigment,
gynecomastia, hyperglycemia, menstrual disorder, nodules, lesions, or hair (e.g., upper or mid‐abdomen,
hyperphosphatemia,, peptic ulcer, hirsutism, anorexia, upper buttocks). Avoid areas with brawny or fibrous
GI hemorrhage, dysphagia, eructation, intestinal tissues or areas that may be compressed or rubbed (e.g.,
obstruction, constipation, gastroenteritis, gastric ulcer, belt or waistband). Administer within 30 minutes of
diarrhea, mastalgia, impotence, balanitis, breast preparation.
hypertrophy, lactation, penile disease, testicular disease,

L
urinary incontinence, urinary tract infection, nocturia, Pregnancy Category: X
testicular pain, dysuria, bladder spasm, erectile
dysfunction, hematuria, urinary retention, urinary ATC Code: L02AE02
urgency, bruise, eosinophilia, myalgia, leukopenia,
ecchymoses, lymphadenopathy, neoplasm, anemia,
hepatomegaly, hypersensitivity reaction, pathological HORMONE ANTAGONISTS AND RELATED AGENTS
fracture, infection, neuromuscular disease, arthralgia,
altered urine specific gravity, fever, polyuria, ANTI-ESTROGENS
emphysema, epistaxis, hemoptysis, increased bronchial
secretions, pleural effusion, pulmonary edema, dyspnea,
cough, weight gain, vaginal discharge, vaginal Rx TAMOXIFEN
hemorrhage, vaginitis, injection site reaction
Rare: Abnormal gait, abscess at injection site, alopecia,
anaphylaxis, anaphylactoid reaction, arthralgia, asthma, Oral: 10 mg and 20 mg tablet (as citrate)
body odor, bone fracture (spine), bradycardia,
cerebrovascular accident, cervix disease, constipation, A triphenylethylene-derivative, non-steroidal estrogen
convulsions, coronary artery disease, cough, decreased agonist antagonist. It competitively binds to estrogen
appetite, decreased visual acuity, decreased white blood receptors on tumors and other tissue targets, producing
cell count, depression, diabetes mellitus, dizziness, a nuclear complex that decreases DNA synthesis and
drowsiness, dysmenorrhea, dyspepsia, dysphagia, inhibits estrogen effects.
epistaxis, excessive crying, feminization, fever,
fibromyalgia syndrome, flu‐like symptoms, gingivitis, Indications: Adjunct in the treatment of breast cancer after
goiter, growth suppression, gynecomastia, hemoptysis, primary treatment with surgery and radiation; reduce risk
hepatic injury, hepatotoxicity, hirsutism, hepatic of invasive breast cancer in women with ductal
insufficiency, hyperhidrosis, hyperkinesia, limb pain, carcinoma in situ (DCIS) after surgery and radiation and
hypersensitivity reaction, hypertension, hyperuricemia, in women at high risk
hypokalemia, increased appetite, induration at injection
site, infection, interstitial pulmonary disease, Contraindications: Concurrent warfarin therapy; history of
lacrimation, leucocytosis, musculoskeletal pain, deep vein thrombosis or pulmonary embolism
leukoderma, myalgia, myocardial infarction, myopathy,
nausea, nervousness, obesity, pallor, osteopenia, Dose:
paralysis, penile swelling, peripheral edema, peripheral Breast cancer, treatment adjunct, by mouth, ADULT
neuropathy, personality disorder, pharyngitis, pituitary (premenopausal women), 20 mg once daily for 5 years.
apoplexy, precocious puberty, prolonged QT interval, Breast cancer, treatment adjunct, by mouth, ADULT
prostate pain, pulmonary embolism, pulmonary (postmenopausal women), 20 mg once daily for 2-3
infiltrates, purpura, retroperitoneal fibrosis, rhinitis, years, followed by an aromatase inhibitor to complete 5
seizure, sinusitis, skin photosensitivity, skin striae, years;
suicidal ideation, syncope, tenosynovitis, for extended therapy, 20 mg once daily for 4.5 to 6 years,
thrombocytopenia, transient ischemic attacks, urinary followed by aromatase inhibitor for 5 years.
incontinence, vomiting, weakness Breast cancer, early (ER-positive), by mouth, ADULT, 20 mg
once daily for 10 years.

369
 ANTINEOPLASTIC AND IMMODULATING AGENTS

Breast cancer, metastatic, by mouth, ADULT (male and lymphedema, infection or sepsis, diaphoresis, neoplasm,
female), 20–40 mg daily; doses >20 mg should be given allergic reaction
in 2 divided doses. Less Common: Cholestasis, corneal changes,
Breast cancer, ductal carcinoma in situ (DCIS), by mouth, endometriosis, endometrial cancer, endometrial
ADULT (female), 20 mg once daily for 5 years. hyperplasia, endometrial polyps, fatty liver, hepatic
Endometrial carcinoma, recurrent, metastatic, or high-risk, necrosis, hepatitis, hypercalcemia, lightheadedness,
by mouth, ADULT, 20 mg once daily for 5 years. phlebitis, pruritus vulvae, pulmonary embolism, retinal
vein thrombosis, retinopathy, second primary tumours,
Dose Adjustment: stroke, superficial phlebitis, taste disturbances, tumour
Hepatic Impairment: pain, local disease flare, uterine fibroids, vaginal
Use with caution. No studies have been conducted. dryness, angioedema, bullous pemphigoid, erythema
multiforme, hypersensitivity reactions, impotence
Precautions: (males), interstitial pneumonitis, loss of libido (males),
pancreatitis, SJS, visual color perception changes
WARNING: Hazardous agent. Use appropriate
precautions for handling and disposal. Drug Interactions:
Monitor closely with:
Use for breast cancer risk reduction is associated Enhances QTc-prolonging effect of Tamoxifen:
with an increased incidence of uterine or QTc-prolonging Agents (Moderate Risk)
endometrial cancers (some fatal). Monitor and
promptly evaluate abnormal vaginal bleeding. Avoid concomitant use with:
Decreases metabolism of Tamoxifen:
L

Bone marrow suppression (e.g. thrombocytopenia and/or Grapefruit Juice

leukopenia)
Gynecological effects (e.g. endometrial hyperplasia, polyps, Decreases serum concentration of Tamoxifen:
endometriosis, uterine fibroids, ovarian cysts; Dabrafenib, Mitotane
amenorrhea, and menstrual irregularities have been
reported) Decreases serum concentration of Anastrozole
Hepatotoxicity Enhances QTc-prolonging effect of Tamoxifen:
Ocular effects (e.g. decreased visual acuity, retinal vein QTc-prolonging Agents (Highest Risk)
thrombosis, retinopathy, corneal changes, color
perception changes and increased incidence of Increases metabolism of Tamoxifen:
cataracts) Rifamycin Derivatives e.g. Rifampicin
Thromboembolic events (increased risk)
Bone mineral density (may be associated with an increased Increases serum concentration of Tamoxifen:
risk of fractures) Abiraterone, Conivaptan, Fusidic Acid (Systemic),
Hyperlipidemia Idelalisib, Mifepristone
Metastatic breast cancer (local disease flare and increased
bone and tumor pain may occur; may be associated with Increases serum concentration of the following drugs:
(good) tumor response; discontinue if severe). Amodiaquine, Colchicine (may increase distribution of
Children (safety and efficacy have not been established for colchicine into certain tissues, e.g., brain), Dabigatran
treatment longer than 1 year). Etexilate, Doxorubicin (Conventional), Pazopanib,
Pregnancy (vaginal bleeding, birth defects, and fetal loss Silodosin, Topotecan, Vincristine (Liposomal), Vitamin K
have been reported); lactation (not known if excreted in Antagonists, e.g., Warfarin
breast milk; may inhibit lactation).
Reduces therapeutic effect of Tamoxifen:
Adverse Drug Reactions: SSRIs e.g. Fluoxetine
Common: Vasodilation, flushing, hypertension, peripheral
edema, chest pain, venous thrombotic events, Administration: May be taken with or without meals.
cardiovascular ischemia, angina, deep venous
thrombus, MI, mood changes, edema, depression, Pregnancy Category: D
insomnia, dizziness, headache, anxiety, fatigue, skin
ATC Code: L02BA01
changes, rash, alopecia, hot flashes, fluid retention,
altered menses, pain, amenorrhea, oligomenorrhea,
breast pain, breast neoplasm, hypercholesterolemia,
weight loss, weight gain, menstrual disorder, nausea,
vomiting, abdominal pain, constipation, diarrhea,
dyspepsia, abdominal cramps, anorexia, vaginal
discharge, urinary tract infection, leukorrhea, vaginal
bleeding, vaginal hemorrhage, vaginitis, vulvovaginitis,
ovarian cyst, thrombocytopenia, anemia, weakness,
arthritis, arthralgia, back pain, bone pain, osteoporosis,
arthrosis, joint disorder, flu-like syndrome, fracture,
myalgia, paresthesia, muskoskeletal pain, cataract, cyst,
pharyngitis, cough, dyspnea, bronchitis, sinusitis,

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ANTINEOPLASTIC AND IMMODULATING AGENTS

ANTI-ANDROGENS abscess, xerostomia, urinary tract infection, impotence,

difficulty in micturition, urinary retention, dysuria, urinary
urgency, urinary incontinence, gastrointestinal
Rx BICALUTAMIDE carcinoma, rectal hemorrhage, skin carcinoma, herpes
zoster, sepsis, ostealgia, arthritis, leg cramps, myalgia,
neck pain, pathological fracture, cataract, polyuria,
Oral: 50 mg and 150 mg tablet / FC tablet
hydronephrosis, increased blood urea nitrogen and
serum creatinine, cough, pharyngitis, flu-like symptoms,
A non-steroidal anti-androgen that acts as an androgen
bronchitis, asthma, epistaxis, sinusitis, pneumonia,
receptor inhibitor. It competes with dihydrotestosterone
rhinitis, cyst, fever
and testosterone to prevent stimulation of cell growth in
Less Common: Decreased glucose tolerance, hepatic
prostate cancer.
failure, hepatitis, hepatotoxicity, hypersensitivity,
interstitial pneumonitis, interstitial pulmonary disease,
Indication: Metastatic prostate cancer
pulmonary fibrosis
Contraindications: Women
Drug Interactions:
Monitor closely with:
Dose:
Reduces therapeutic effect of Choline C11
Prostate cancer, metastatic, by mouth, ADULT, in
combination with an LNRH analogue, 50 mg once daily.
Increases risk of adverse or toxic effects of the following
drugs:
Dose Adjustment:
Aminolevulinic Acid (photosensitizing effect), Porfimer
Hepatic Impairment:
(photosensitizing effect), Verteporfin (photosensitizing

L
Use with caution in moderate-to-severe hepatic impairment.
effect)
Clearance may be delayed in severe impairment.
Avoid concomitant use with:
Precautions:
Increases serum concentration of the following drugs:
WARNING: Hazardous agent. Use appropriate Astemizole, Cisapride, Pimozide, Terfenadine
precautions for handling and disposal.
Reduces diagnostic effect of Indium111 Capromab
Pendetide
Cardiovascular disease (may increase the risk of
cardiovascular disease; may cause QT/QTc prolongation; Administration: May be taken with or without food. Doses
correct electrolytes prior to initiation; consider periodic should be taken at the same time each day, either in the
electrolyte and ECG monitoring) morning or in the evening.
Decreased bone mineral density (associated with prolonged
use; increased risk of osteoporosis and fracture) Treatment for metastatic cancer should be started
Diabetes (loss of glycemic control and decrease in glucose concomitantly with an LHRH analogue.
tolerance has been reported).
Gynecomastia Pregnancy Category: X
Anemia (may occur with testosterone suppression; monitor
CBC periodically) ATC Code: L02BB03
Hepatotoxicity
Hypersensitivity (e.g. angioneuretic edema and urticaria);
interstitial lung disease; fertility (may lead to
spermatogenesis inhibition; may impair male fertility) Rx CYPROTERONE
Pregnancy (may affect fetal development).
Anti-androgen withdrawal symptom (discontinue use Oral: 50 mg tablet (as acetate)
immediately if disease worsens).
Children (safety and efficacy have not been established). A progestogen with antiandrogenic, anti-gonadotropic, and
progestin-like activity. It blocks the binding of
Adverse Drug Reactions: dihydrotestosterone (DHT) to prostatic cancer cells and
Common: Peripheral edema, pain, hot flash, gynecomastia, exerts negative feedback to hypothalamic-pituitary axis
constipation, nausea, diarrhea, abdominal pain, by inhibiting luteinizing hormone (LH) secretion leading
mastalgia, pelvic pain, hematuria, nocturia, anemia, to decreased testosterone production.
infection, back pain, weakness, dyspnea, chest pain,
hypertension, angina pectoris, cardiac arrest, cardiac Indication: Palliative treatment of advanced prostate cancer
failure, coronary artery disease, edema, myocardial
infarction, syncope, dizziness, paresthesia, headache, Contraindications: Liver disease or hepatic dysfunction;
insomnia, myasthenia gravis, anxiety, chills, confusion, Dubin-Johnson syndrome; Rotor syndrome; previous or
drowsiness, hypertonia, nervousness, neuropathy, existing liver tumors (not due to metastases from
depression, skin rash, diaphoresis, alopecia, pruritus, prostate cancer); presence or history of meningioma;
xeroderma, weight loss, hyperglycemia, weight gain, wasting diseases; severe chronic depression; existing
decreased libido, dehydration, gout, thromboembolic processes; use in women
hypercholesterolemia, dyspepsia, anorexia, flatulence,
vomiting, dysphagia, hernia, melena, periodontal

371
 ANTINEOPLASTIC AND IMMODULATING AGENTS

Dose: malaise, meningioma (chronic use), personality disorder,

Prostate cancer, advanced, palliative treatment, by mouth, psychotic depression, pyrexia, restlessness, vascular
ADULT, 200–300 mg daily in 2–3 divided doses headache, vasovagal reactions, dry skin (sebum
(maximum dose, 300 mg daily); following orchiectomy, reduction), eczema, erythema nodosum, exfoliative
reduce dose to 100–200 mg daily. dermatitis, hirsutism, skin discoloration,
maculopapuplar rash, patchy loss of body hair,
Dose Adjustment: photosensitivity, pruritus, rash scleroderma, urticarial,
Renal Impairment: adrenal suppression (dose-related), fatigue, benign
Use with caution. No studies have been conducted, nodular breast hyperplasia, diabetes mellitus,
however, 33% is excreted renally. galactorrhea, gynecomastia, hypercalcemia,
hypernatremia, impotence, inhibition of
Precautions: spermatogenesis, decreased libido, negative nitrogen
WARNING: Hazardous agent. Use appropriate balance, hot flashes, constipation, diarrhea, dyspepsia,
precautions for handling and disposal. glossitis, nausea, pancreatitis, vomiting, weight gain or
loss, bladder carcinoma, crystalluria, urinary frequency,
Cardiovascular disease (use with caution in conditions that enlarged uterine fibroids, uterine hemorrhage, anemia,
may be aggravated by fluid retention, or cardiovascular increased fibrinogen, haemolytic anemia, hemorrhage,
disease) hypochromic anemia, leukopenia, leucocytosis,
Respiratory effects (shortness of breath was observed in normocytic anemia, anorexia, decreased PT,
doses 300 mg daily; use with caution in pulmonary thrombocytopenia, ascites, cholestatic jaundice,
dysfunction). cirrhosis, hepatic carcinoma, hepatic coma, hepatic
CNS depression (lassitude, weakness, and fatigue may dysfunction (dose-related), hepatitis, hepatic failure,
hepatic necrosis, hepatomegaly, hepatoma, injection
L

occur during the first few weeks of treatment);

Depression (associated with an increased incidence of site reaction, myasthenia, abnormal gait, renal failure,
depression, particularly early in the initial 6–8 weeks of weakness, abnormal accommodation, abnormal vision,
therapy). blindness, optic neuritis, optic atrophy, retinal vascular
Diabetes (use with caution; may cause alterations in disorder, retinal vein thrombosis, hematuria,
glucose metabolism; may require adjustments in osteoporosis, asthma, cough, dyspnea, hyperventilation,
diabetes medications); gynecomastia (hyperplasia of the pulmonary oil microembolism, pulmonary embolism,
breast has been reported); thromboembolism (may pulmonary fibrosis, allergic reaction, diaphoresis
increase risk).
Hepatotoxicity (usually develops after a few weeks to Drug Interactions:
several months of treatment initiation; monitor hepatic Monitor closely with:
function; discontinue in hepatic injury); lipid effects (may Enhances absorption of Aripiprazole
increase HDL-cholesterol and triglycerides; may
decrease LDL-cholesterol). Enhances therapeutic effect of C1 Inhibitors (thrombogenic
Fertility (in males, reduced sperm count and volume of effect)
ejaculate, and production of abnormal spermatozoa has
been reported; reversible upon discontinuation Reduces therapeutic effect of the following drugs:
oftherapy); carcinogenesis (benign and malignant Antidiabetic Agents, Choline C11
hepatic tumors have been observed; rule out presence
of tumor in severe upper abdominal discomfort, hepatic Avoid concomitant use with:
enlargement, or intra-abdominal hemorrhage). Decreases serum concentration of Cyproterone:
Adrenocortical function suppression (reported with use; Dabrafenib, Mitotane
monitor adrenal function periodically during therapy);
antiandrogen withdrawal syndrome (may promote Increases risk of adverse or toxic effects of Cyproterone:
prostate cancer growth; discontinue therapy Stiripentol
immediately with increasing prostate specific antigen
(PSA) levels; monitor for 6–8 weeks for withdrawal Increases serum concentration of Cyproterone:
response prior to initiating alternative treatment); Conivaptan, Fusidic Acid (Systemic), Idelalisib,
orchiectomy (may lower 5-year survival rate). Mifepristone
Anemia (hypochromic anemia has been observed; monitor
CBC regularly); meningioma formation (reported with Increases serum concentration of the following drugs:
chronic therapy (years) at doses >25 mg daily). Amodiaquine, HMG-CoA Reductase Inhibitors e.g.,
Pregnancy (effect on fertilization or embryo formation is Simvastatin
unknown).
Reduces diagnostic effect of Indium111 Capromab
SKILLED TASKS. May impair ability to perform tasks, which Pendetide
require mental alertness, like driving or operating
machinery. Reduces therapeutic effect of Cyproterone:
Ethyl Alcohol (interferes with antiandrogenic effect of
Adverse Drug Reactions:Edema, heart failure, hypotension, cyproterone), GnRH Agonist (lowers 5-year survival rate),
phlebitis, shock, stroke, syncope, tachycardia, Ulipristal
thrombosis (DVT), embolus, MI, superficial venous
thrombosis, aphasia, chills, coma, depression, dizziness, Reduces therapeutic effect of the following drugs:
encephalopathy, headache, hemiplegia, lassitude, Anticoagulants, Ulipristal

372
ANTINEOPLASTIC AND IMMODULATING AGENTS

Administration: To be taken after meals, with liquids. jaundice, macrocytic anemia, MI, malignant neoplasm of
Administer tablets at the same time each day. Tablets breast (male), skin methemoglobinemia, oligospermia,
may be divided into equal halves. pulmonary embolism, photosensitivity, thrombophlebitis,
sulf-hemoglobinemia, urine discoloration (amber, yellow-
Pregnancy Category: D green)

ATC Code: Not available Drug Interactions:

Monitor closely with:
Increases risk of adverse or toxic effects
(methemoglobinemia) of Flutamide:
Rx FLUTAMIDE Dapsone (Topical), Nitric Oxide, Prilocaine, Sodium
Nitrite
Oral: 250 mg tablet
Reduces therapeutic effect of Choline C11
A nonsteroidal antiandrogen that inhibits androgen uptake
and/or inhibits binding of androgen in target tissues. Avoid concomitant use with:
Indication: Prostate cancer Decreases serum concentration of Flutamide:
Dabrafenib, Mitotane
Contraindications: Severe hepatic impairment
Enhances therapeutic effect of Warfarin
Dose:
Prostate cancer, metastatic, by mouth, ADULT, 250 mg Increases serum concentration of Flutamide:
Conivaptan, Fusidic Acid (Systemic), Idelalisib,

L
given 3 times daily (every 8 hours), preferably at least 3
days before gonadorelin analogue treatment. Mifepristone, Stiripentol, Tizanidine [if concomitant use
cannot be avoided, initiate tizanidine at 2 mg and
Precautions: increase in 24 mg increments based on patient
response], Vemurafenib
WARNING: Hazardous agent. Use appropriate
precautions for handling and disposal. Reduces diagnostic effect of Indium111 Capromab
Pendetide
Hospitalization and death (rare) due to liver failure
have been reported. Use is not recommended in Administration: May be administered with or without food.
patients with ALT values greater than 2 times ULN.
Pregnancy Category: D
Gynecomastia (may occur when administered in
combination with medical castration) ATC Code: L02BB01
Hepatic impairment (e.g. elevated serum transaminase
levels, jaundice, hepatic encephalopathy, and acute
hepatic failure; hepatotoxicity is reversible; monitor AROMATASE INHIBITORS
serum transaminase levels periodically).
Cardiovascular disease (may increase risk of cardiovascular
disease) Rx LETROZOLE
Hemoglobin M disease (increased risk of toxicities
associated with aniline exposure). Oral: 2.5 mg tablet / FC tablet
Glucose-6-phosphate dehydrogenase (G6PD) deficiency
and smoking (increased risk of toxicities associated with A nonsteroidal competitive inhibitor of the aromatase
aniline exposure) enzyme which catalyzes the conversion of androgens to
Women (should not be used in women, particularly for non- estrogens. Inhibition of the enzyme leads to significant
serious or nonlife-threatening conditions). reduction in plasma estrogen.
Pregnancy (may cause fetal harm); lactation (no information
available; use is not recommended). Indication: Adjuvant treatment of postmenopausal,
hormone-receptor positive early stage breast cancer
Adverse Drug Reactions:
Common: Edema, hypertension, anxiety, confusion, Contraindications: Women of child-bearing potential
depression, dizziness, drowsiness, headache, insomnia,
nervousness, skin rash, ecchymoses, pruritus,hot flash, Dose:
decreased libido, increased lactate dehydrogenase, NOTE: American Society of Clinical Oncology (ASCO)
gynecomastia, diarrhea, vomiting, nausea, proctitis, guidelines for Adjuvant Endocrine Therapy of Hormone
anorexia, tumor flare, constipation, dyspepsia, increased Receptor‐Positive Breast Cancer recommend a
appetite, impotence, cystitis, breast tenderness, gastric maximum duration of 5 years of aromatase inhibitor
distress, hematuria, rectal hemorrhage, anemia, therapy for postmenopausal women. Aromatase
anemia, leukopenia, thrombocytopenia, herpes zoster, inhibitors may be combined with tamoxifen for up to 10
weakness years of endocrine therapy.
Less Common: Cholestatic jaundice, hemolytic anemia,
hepatic encephalopathy, hepatic failure, hepatic
necrosis, hepatitis, hypersensitivity pneumonitis,

373
 ANTINEOPLASTIC AND IMMODULATING AGENTS

Breast cancer, advanced (first-line or second-line Increases serum concentration of the following drugs:
treatment), by mouth, ADULT, 2.5 mg once daily; Artesunate, CYP2A6 Substrates
continue until tumor progression.
Breast cancer, early, adjuvant treatment, by mouth, ADULT, Administration: May be taken with or without food.
2.5 mg once daily for a planned duration of 5 years;
discontinue if relapse occurs. Pregnancy Category: X
Breast cancer, early, extended adjuvant treatment, by
mouth, ADULT, 2.5 mg once daily for a planned duration ATC Code: L02BG04
of 5 years after 5 years of tamoxifen; discontinue if
relapse occurs.

Dose Adjustment: IMMUNOSTIMULANTS

Renal Impairment:
Use with caution. Dose adjustments have not been studied
for patients with CrCl <10 mL/minute. COLONY STIMULATING FACTORS

Hepatic Impairment:
Use with caution. Dose adjustment is recommended in
Rx FILGRASTIM (G-CSF)
patients with cirrhosis or severe hepatic dysfunction.
For patients with severe impairment (Child-Pugh class C) Inj.: 150 micrograms/0.6 mL vial (IV, SC)
and cirrhosis, administer 2.5 mg every other day. Effect 300 micrograms/0.5 mL solution, pre-filled syringe
has not been determined in non-cirrhotic patients with (IV, SC)
elevated bilirubin. 300 micrograms/mL vial (IV, SC)
L

300 micrograms/1.2 mL vial (IV, SC)

Precautions:
WARNING: Hazardous agent. Use appropriate A granulocyte colony stimulating factor (G-CSF) produced by
precautions for handling and disposal. recombinant DNA technology. It stimulates the
production, maturation, and activation of neutrophils.
CNS depression (may cause dizziness, fatigue, and
somnolence) Indications: To decrease the incidence of infection
Decreased bone mineral density (may cause decrease in (neutropenic fever) in patients with non-myeloid
bone mineral density) malignancies receiving myelosuppressive chemotherapy
Increased cholesterol (may increase total serum associated with a significant incidence of severe
cholesterol; monitor cholesterol panel). neutropenia with fever; to reduce the time to neutrophil
recovery and the duration of fever following induction or
SKILLED TASKS. May impair ability to perform tasks, which require consolidation chemotherapy in adults with acute myeloid
mental alertness, like driving or operating machinery. leukemia (AML); to reduce the duration of neutropenia
and neutropenia-related events in patients with non-
Adverse Drug Reactions: myeloid malignancies receiving myeloablative
Common: Edema, chest pain, hypertension, chest wall pain, chemotherapy followed by marrow transplantation; to
thromboembolism, angina pectoris, myocardial increase survival in patients acutely exposed to
infarction, transient ischemic attacks, headache, myelosuppressive doses of radiation; for mobilization of
dizziness, fatigue, insomnia, pain, cerebrovascular peripheral blood progenitor cells (PBPCs) for collection
accident, anxiety, depression, drowsiness, diaphoresis, by leukapheresis in autologous or allogeneic
night sweats, skin rash, alopecia, pruritus, hematopoietic cell transplantation; long-term
hypercholesterolemia, weight gain or loss, hot flash, administration to reduce the incidence and duration of
hypercalcemia, nausea, constipation, diarrhea, vomiting, neutropenic complications in symptomatic patients with
abdominal pain, anorexia, dyspepsia, mastalgia, urinary congenital, cyclic, or idiopathic neutropenia.
tract infection, vaginal dryness, vaginal hemorrhage,
vaginal irritation, metastases, infection, viral infection, Contraindication: History of serious allergic reactions to
influenza, weakness, decreased bone mineral density, human granulocyte colony-stimulating factors, such as
arthralgia, arthritis, ostealgia, back pain, osteoporosis, filgrastim or pegfilgrastim, or any component of the
bone fracture, limb pain, myalgia, cataract, renal formulation
disease, dyspnea, cough, pleural effusion
Less Common: Anaphylaxis, angioedema, arterial Dose:
thrombosis, cardiac failure, carpal tunnel syndrome, Myelosuppressive chemotherapy recipient with non-myeloid
endometrial carcinoma, endometrial hyperplasia, malignancies, by SC injection or IV infusion, ADULT/
erythema multiforme, hepatitis, leukopenia, memory CHILD/ ADOLESCENT, 5 micrograms/kg per day, may
impairment, stomatitis, tachycardia, tenosynovitis increase by 5 micrograms/kg for each chemotherapy
(trigger finger), thrombocytopenia, TEN cycle according to the duration and severity of the
neutropenia; continue for up to 14 days until the
Drug Interactions: absolute neutrophil count (ANC) reaches 10,000/mm3;
Avoid concomitant use with: discontinue if the ANC surpasses 10,000/mm3 after the
Decreases serum concentration of the following drugs: expected chemotherapy-induced neutrophil nadir.
Artesunate, Tegafur AML following induction or consolidation chemotherapy, by
SC injection or IV infusion, ADULT/ CHILD/ ADOLESCENT,

374
ANTINEOPLASTIC AND IMMODULATING AGENTS

5 micrograms/kg per day, may increase by 5 symptomatically with antihistamines, steroids,

micrograms/kg (for each chemotherapy cycle) according bronchodilators, or epinephrine; reactions may recur
to the duration and severity of the neutropenia; continue within days after initial allergy management has been
for up to 14 days until the absolute neutrophil count stopped; permanently discontinue in serious allergic
(ANC) reaches 10,000/mm3; discontinue if the ANC reactions).
surpasses 10,000/mm3 after the expected Alveolar hemorrhage (pulmonary infiltrates, hemoptysis
chemotherapy-induced neutrophil nadir. may occur; resolved upon discontinuation)
Bone marrow transplantation, by IV infusion, ADULT, 10 Respiratory distress syndrome
micrograms/kg per day, ≥24 hours after chemotherapy Capillary leak syndrome (hypoalbuminemia, hypotension,
and ≥24 hours after bone marrow infusion; adjust the edema, or hemoconcentration may occur; may vary in
dose according to the duration and severity of frequency and severity; may be life-threatening if
neutropenia; treatment is delayed)
If ANC >1,000/mm3 for 3 consecutive days, reduce dose Cutaneous vasculitis (generally occurs in patients with
to 5 micrograms/kg per day; severe chronic neutropenia on chronic therapy; withhold
If ANC remains >1,000/mm3 for 3 more consecutive treatment if cutaneous vasculitis occurs)
days, discontinue; Hematologic effects (excessive leukocytosis or
If ANC decreases to <1,000/mm3, resume at 5 thrombocytopenia may occur; discontinue when
micrograms/kg per day; absolute neutrophil count (ANC) exceeds 10,000/mm3
If ANC decreases to <1,000/mm3 during the 5 after the ANC nadir has occurred; monitor CBC twice
micrograms/kg per day dose, increase dose to 10 weekly during therapy; monitor platelet counts)
micrograms/kg per day and follow the above steps. Severe chronic neutropenia (myelodysplastic syndrome
Hematopoietic radiation injury syndrome, by SC injection, (MDS) and acute myeloid leukemia (AML) have been
ADULT, 10 micrograms/kg once daily; begin as soon as reported)

L
possible after suspected or confirmed radiation doses Sickle cell disorders (may precipitate severe sickle cell
>2 gray (Gy) and continue until ANC remains crises, some fatal; discontinue in patients undergoing
>1,000/mm3 for 3 consecutive CBCs or ANC exceeds sickle cell crisis)
10,000/mm3 after the radiation-induced nadir. [NOTE: Nephrotoxicity (glomerulonephritis, resulting in azotemia,
Initiate within 24 hours of exposure of a dose ≥2 Gy hematuria, or proteinuria may occur; if
and/or significant decrease in absolute lymphocyte glomerulonephritis is suspected, evaluate for cause).
count, or for anticipated neutropenia <500/mm3 for ≥7 Splenic rupture (if upper abdominal pain, left upper
days.] quadrant pain, or shoulder tip pain occurs, withhold
Peripheral blood progenitor cell collection and therapy, by treatment and evaluate for enlarged spleen or splenic
SC injection, ADULT, 10 micrograms/kg daily, usually for rupture).
6–7 days with apheresis occurring on days 5, 6, and 7;
begin at least 4 days before the first apheresis and Adverse Drug Reactions:
continue until the last apheresis; discontinue for WBC Common: Alopecia, anemia, antibody development,
>100,000/mm3. arthralgia, back pain, cardiac arrhythmia, chest pain,
Severe chronic neutropenia, congenital, by SC injection, dizziness, dyspnea, epistaxis, erythema, cough, fatigue,
ADULT/ADOLESCENT/ CHILD/INFANT 7 months & older, fever, headache, hypertension, hypoesthesia, increased
initially 6 micrograms/kg per day in 2 divided doses; lactate dehydrogenase and uric acid (mild-to-moderate;
adjust dose based on ANC and clinical response; mean reversible), leukocytosis, limb pain, maculopapular rash,
dose is 6 micrograms/kg daily; musculoskeletal pain, MI, muscle spam, nausea,
Severe chronic neutropenia, idiopathic, by SC injection, ostealgia (dose and cycle related), pain, petechia,
ADULT/ADOLESCENT/ CHILD/INFANT 7 months & older, splenomegaly, skin rash, thrombocytopenia, transfusion
initially 5 micrograms/kg once daily; adjust dose based reaction, upper respiratory tract infection, urinary tract
on ANC and clinical response; mean dose is 1.2 infection, vomiting
micrograms/kg daily; Less Common: Anaphylaxis, capillary leak syndrome,
Severe chronic neutropenia, cyclic, by SC injection, cerebral hemorrhage, constipation, decreased bone
ADULT/ADOLESCENT/ CHILD/INFANT 7 months & older, mineral density, decreased hemoglobin, diarrhea,
initially 5 micrograms/kg once daily; adjust the dose ethema nodosum, exacerbation of psoriasis, facial
based on ANC and clinical response; mean dose is 2.1 edema, hematuria, hemoptysis, hepatomegaly,
micrograms/kg daily. hypersensitivity reaction, renal insufficiency,
Primary prophylaxis for children with high likelihood of hypersensitivity angiitis, injection site reaction,
febrile neutropenia (e.g., children receiving dose-intense hypotension, malaise, mouth pain, oropharyngeal pain,
chemotherapy for Ewing’s sarcoma/Primitive osteoporosis, peripheral edema, proteinuria, pulmonary
neuroectodermal tumors, rhabdomyosarcoma), 5-10 hemorrhage, pulmonary infiltrates, severe sickle cell
mcg/kg 48-72 hours after completion of chemotherapy. crisis, respiratory distress syndrome, splenic rupture,
Sweet’s syndrome, tachycardia, weakness, urticaria,
Dose Adjustment: wheezing
Renal Impairment:
If patient develops glomerulonephritis, consider dose Drug Interactions:
reduction or treatment interruption. Monitor closely with:
Increases risk of adverse or toxic effects of the following
Precautions: drugs:
Allergic reactions (serious allergic reactions, including Bleomycin (pulmonary toxicity), Cyclophosphamide
anaphylaxis may occur; may be managed

375
 ANTINEOPLASTIC AND IMMODULATING AGENTS

Avoid concomitant use with: alpha interferon therapy and in patients 18 years and
Increases risk of adverse or toxic effects of Topotecan older who have relapsed following alpha interferon
therapy; initial treatment of clinically aggressive follicular
Drugs that may potentiate the release of neutrophils‚ such non-Hodgkin lymphoma in patients 18 years and older;
as lithium‚ should be used with caution treatment of hairy cell leukemia in patients 18 years and
older; adjuvant to surgical treatment of malignant
DRUG-DIAGNOSTIC TEST INTERACTION. May interfere with bone melanoma in patients 18 years and older who are free of
imaging studies, increased hematopoietic activity of the bone disease but at high risk for systemic recurrence, within
marrow may appear as transient positive bone imaging changes.
56 days of surgery
Administration:
For IV administration, administer as a short infusion over Contraindications: Decompensated liver disease;
15–30 minutes for chemotherapy-induced neutropenia,
autoimmune hepatitis; combination therapy with
by continuous infusion for chemotherapy-induced
interferon alfa-2b and ribavirin in women who are
neutropenia, or as an infusion of no longer than 24 hours pregnant, in males with pregnant partners, in patients
for bone marrow transplantation. with hemoglobinopathies, or in creatinine clearance <50
mL/minute
For SC administration, administer into the outer upper
arm, abdomen (except within 2 inches of navel), front
Dose:
middle thigh, or the upper outer buttocks area. Rotate
Hairy cell leukemia, by IM or SC injection, ADULT, 2 million
the injection site. Do NOT inject into areas that are units/m2 3 times weekly for up to 6 months, may
tender, red, bruised, hardened, or scarred, or sites with continue treatment with sustained treatment response;
stretch marks. discontinue for disease progression or failure to respond
after 6 months.
L

Do NOT administer earlier than 24 hours after or in the Lymphoma, follicular, by SC injection, ADULT, 5 million units
24 hours prior to cytotoxic chemotherapy. 3 times weekly for up to 18 months.
Malignant melanoma, maintenance, by SC injection,
Should NOT be routinely used in the treatment of ADULT,10 million units/m2 3 times weekly for 48 weeks.
established neutropenic fever. AIDS-related Kaposi’s sarcoma, by IM or SC injection,
ADULT, 30 million units/m2 3 times weekly until disease
Vials may be diluted in D5W to >15 mcg/mL for infusion. DO progression or until maximal response has been
NOT dilute with saline at any time, because the product achieved after 16 weeks.
may precipitate. Chronic hepatitis B, by IM or SC injection, ADULT, 5 million
For 5-15 mcg/mL dilution: Add human albumin to a final units daily or 10 million units 3 times weekly for 16
concentration of 2 mg/mL to protect from adsorption to weeks; CHILD 1–17 years, 3 million units/m2 3 times
plastic materials weekly for 1 week, followed by 6 million units/m2 3 times
weekly (maximum, 10 million units per dose; total
Pregnancy Category: C duration of therapy, 16–24 weeks).
Chronic hepatitis C, by IM or SC injection, ADULT, 3 million
ATC Code: L03AA02 units 3 times weekly; in normalization of ALT at 16
weeks, continue treatment if tolerated for 18–24
months; consider discontinuation if normalization does
INTERFERONS not occur at 16 weeks; CHILD 1–17 years, with ribavirin,
3–5 million units/m2 3 times weekly for 48 weeks
regardless of HCV genotype (maximum, 3 million units
Rx INTERFERON ALFA-2b (HUMAN) per dose).

Inj.: 3 million IU and 5 million IU per mL vial + diluent (IM, Dose Adjustment:
SC) Renal Impairment:
In impaired renal function and CrCl ≥50 mL/minute, use
Binds to a cell wall receptor to initiate intracellular activity combination therapy with ribavirin (hepatitis C) with
resulting in induction of gene transcription, cellular caution.
growth inhibition, alteration of the state of cellular If a patient with lymphoma (follicular) develops a serum
differentiation, interference with oncogene expression, creatinine >2 mg/dL, permanently discontinue.
alteration of cell surface antigen expression, increase in
phagocytic activity of macrophages, and augmentation Hepatic Impairment:
of cytotoxicity of lymphocytes for target cells. If patient develops severe (grade 3) hepatic injury or hepatic
decompensation (Child-Pugh class B and C),
Indications: Treatment of AIDS-related Kaposi’s sarcoma in permanently discontinue.
18 years and older; treatment of chronic hepatitis B in If a patient with lymphoma (follicular) develops an AST >5
patients 1 year and older with compensated liver times ULN, permanently discontinue.
disease; treatment of chronic hepatitis C in patients 18 If ALT/AST increases to >5 to 10 times ULN during induction
years and older with compensated liver disease who and maintenance of malignant melanoma, temporarily
have a history of blood or blood-product exposure and/or withhold. Resume with a 50% dose reduction when
are hepatitis C virus (HCV) antibody-positive; treatment adverse reaction abates. If ALT/AST increases to >10
of chronic hepatitis C in patients 3 years and older with times ULN, permanently discontinue.
compensated liver disease previously untreated with

376
ANTINEOPLASTIC AND IMMODULATING AGENTS

Toxicity: May cause or aggravate fatal or life-threatening

Hematologic toxicity: autoimmune disorders, ischemic disorders, or
If ANC <500/mm3 or platelets <25,000/mm3, infectious disorders. Monitor closely with periodic
discontinue treatment. clinical and laboratory evaluations. Discontinue for
severe persistent or worsening symptoms. Some
Neuropsychiatric disorders during treatment: cases may resolve with discontinuation.
In clinical depression or other psychiatric problem, monitor
closely during and for 6 months after treatment. Autoimmune disease (e.g. thrombocytopenia, vasculitis,
In severe depression or other psychiatric disorder, Raynaud’s disease, rheumatoid arthritis, lupus
discontinue treatment. erythematosus, and rhabdomyolysis; worsening of
In persistent or worsening psychiatric symptoms, suicidal psoriasis and sarcoidosis have been reported)
ideation, or aggression towards others, discontinue Hypersensitivity (acute hypersensitivity reactionshave been
treatment and follow with appropriate psychiatric rarely reported; transient rashes have occurred in some
intervention. patients following injection but have not necessitated
treatment interruption)
In follicular lymphoma: Flu-like symptoms (fever and flu-like symptoms commonly
In neutrophils >1,000/mm3 to <1,500/mm3, reduce dose occur)
by 50%, may re-escalate to starting dose when Bone marrow suppression (potentially severe cytopenia,
neutrophils return to >1,500/mm3. aplastic anemia, or hemolytic anemia may occur;
In severe toxicity where neutrophils <1,000/mm3 or hemolytic anemia has been observed)
platelets <50,000/mm3, temporarily withhold treatment. Coagulation disorders (use with caution; monitor closely)
In AST >5 times ULN or serum creatinine >2 mg/dL, Hypertriglyceridemia.
permanently discontinue. Cardiovascular disease (e.g. hypotension, arrhythmia,

L
tachycardia, cardiomyopathy and/or MI;monitor
In hairy cell leukemia: baseline and periodic ECGs; supraventricular
In platelet count <50,000/mm3, administer by SC injection arrhythmias occur rarely and are associated with
ONLY. preexisting cardiac disease or prior therapy with
In severe toxicity, reduce dose by 50%; or temporarily cardiotoxic agents).
withhold and resume with 50% dose reduction. Cerebrovascular events (hemorrhagic and ischemic
Permanently discontinue if persistent or recurrent severe cerebrovascular events have been observed);
toxicity is noted. neuropsychiatric disorders (depression psychosis,
mania, suicidal ideation, suicide attempts, completed
Chronic hepatitis B: suicides, homicidal ideation may occur; if psychiatric
In WBC <1,500/mm3, granulocytes <750/mm3, or platelet symptoms persist or worsen, or suicidal or homicidal
count <50,000/mm3, other laboratory abnormality, or ideation or aggressive behavior towards others is
severe adverse reaction, reduce dose by 50%, may re- identified, discontinue treatment and follow the patient
escalate to starting dose upon resolution of hematologic closely; careful neuropsychiatric monitoring is
toxicity. Discontinue for persistent intolerance. recommended during and for 6 months after treatment
In WBC <1,000/mm3, granulocytes <500/mm3, or platelet in patients who develop psychiatric disorders).
count <25,000/mm3, permanently discontinue. Dental and periodontal disorders (dry mouth leading to
teeth and mucous membrane damage may occur;
Chronic hepatitis C: damage may occur in chronic therapy);
In severe toxicity, reduce dose by 50% or temporarily Ocular effects (e.g. decreased or loss of vision, macular
withhold until toxicity subsides. Permanently discontinue edema, retinal hemorrhages, cotton wool spots, optic
for persistent toxicities after dosage reduction. neuritis, papilledema, serious retinal detachment, and
retinal artery or vein thrombosis; monitor closely;
AIDS-related Kaposi sarcoma: perform a complete eye exam promptly if ocular
In severe toxicity, reduce dose by 50% or temporarily symptoms develop).
withhold, may resume at reduced dose with toxicity Diabetes (discontinue if diabetes cannot be effectively
resolution. Permanently discontinue for persistent or managed with medication; use with caution in patients
recurrent toxicities. with a history of diabetes mellitus, particularly if prone to
DKA).
Malignant melanoma: Hepatic effect (hepatotoxicity, some fatal, transient
In severe toxicity including neutrophils >250/mm3 to increase in ALT (≥2 times baseline), jaundice, hepatic
<500/mm3 or ALT/AST >5 to 10 times ULN, temporarily encephalopathy, or hepatic failure may occur; worsening
withhold and resume with a 50% dose reduction when and potentially fatal liver disease has been reported;
adverse reaction abates. patients with cirrhosis are at increased risk of hepatic
In neutrophils <250/mm3, ALT/AST >10 times ULN, or decompensation).
severe and persistent adverse reactions, permanently Pulmonary effects (dyspnea, pulmonary infiltrates,
discontinue. pulmonary hypertension, interstitial pneumonitis,
pneumonia, bronchiolitis obliterans, and sarcoidosis
Precautions: may be induced or aggravated by treatment, sometimes
WARNING: May cause or aggravate severe resulting in respiratory failure or fatality; monitor closely
neuropsychiatric adverse events. Monitor closely with and consider discontinuing treatment with evidence of
periodic clinical evaluations. Discontinue treatment impaired pulmonary function).
for severe persistent or worsening symptoms.

377
 ANTINEOPLASTIC AND IMMODULATING AGENTS

Thyroid disorders (hyperthyroidism or hypothyroidism may psychosis, pulmonary embolism, pulmonary fibrosis,
occur; discontinue interferon use in patients who pulmonary hypertension, pulmonary infiltrates,
develop thyroid abnormalities during treatment and in Raynaud's phenomenon, rectal hemorrhage, reduced
patients with thyroid disease who subsequently cannot ejection fraction, renal failure, renal insufficiency, pure
maintain normal ranges with thyroid medication). red cell aplasia, respiratory insufficiency, retinal cotton-
Elderly (higher doses may result in increased CNS toxicity, wool spot, retinal detachment (serous), retinal
e.g., obtundation, coma) thrombosis, retinal vein occlusion, rheumatoid arthritis,
Children (suicidal ideation or attempts may occur more rhabdomyolysis, sarcoidosis, seizure, sexual disorder,
frequently). skin photosensitivity, spondylitis, sepsis, Stevens-
Johnson syndrome, stomatitis, suicidal ideation,
Adverse Drug Reactions: syncope, systemic lupus erythematosus, thrombotic
Common: Abdominal pain, agitation, amenorrhea, alopecia, thrombocytopenic purpura, tachycardia, tendonitis,
amnesia, anemia, anorexia, anxiety, arthralgia, back thrombosis, tissue necrosis at injection site, toxic
pain, bronchitis, candidiasis, chest pain, chills, epidermal necrolysis, upper respiratory tract infection,
confusion, constipation, cough, depression, dermatitis, tremor, urinary incontinence, urticaria, uterine
diaphoresis, diarrhea, dizziness, drowsiness, dysgeusia, hemorrhage, vasculitis, Vogt-Koyanagi-Harada
dyspepsia, decreased libido, dyspnea, edema, epistaxis, syndrome, wheezing
fatigue, fever (children), gingivitis, headache, herpes Rare: Aplastic anemia
virus infection, hypertension, flu-like symptoms,
hypoesthesia, infection, injection site reaction, insomnia, Drug Interactions:
lack of concentration, irritability, loose stools, malaise, Monitor closely with:
leukopenia, myalgia, nasal congestion, nausea, Increases risk of adverse or toxic effects of the following
neutropenia, pain, paresthesia, pharyngitis, polyuria, drugs:
L

pruritus, purpura, right upper quadrant pain, rigors, Ribavirin (hemolytic anemia), Zidovudine
sinusitis, skeletal pain, skin rash, thrombocytopenia,
vertigo, weight loss, urinary tract infection, vomiting, Avoid concomitant use with:
weakness, xeroderma, xerostomia Increases risk of adverse or toxic effects of Interferon Alfa-
Less Common: Abnormal hepatic function tests, abscess, 2b:
aggressive behavior, alcohol intolerance, amyotrophy, Dipyrone (agranulocytosis; pancytopenia)
anaphylaxis, angina pectoris, angioedema, aphasia,
aphthous stomatitis, arteritis, arthritis, ascites, asthma, Increases risk of adverse or toxic effects of the following
ataxia, atrial fibrillation, auditory impairment, Bell’s drugs:
palsy, blurred vision, bradycardia, biliary colic, Aldesleukin (myocardial and renal toxicity), Clozapine
bronchoconstriction, bronchospasm, bronchiolitis (agranulocytosis), Telbivudine (peripheral neuropathy)
obliterans, cardiac arrhythmia, cardiac failure,
cardiomegaly, cardiomyopathy, carpal tunnel syndrome, Increases serum concentration of Tizanidine
cerebrovascular accident, colitis, coma, conjunctivitis,
coronary artery disease, cyanosis, cystitis, dehydration, Reduces therapeutic effect of BCG (Intravesical)
diabetes mellitus, dysphasia, dysuria, eczema,
epidermal cyst, erythema, erythema multiforme, Administration: For parenteral administration. Allow to
erythematous rash, esophagitis, exacerbation of reach room temperature prior to injection.
psoriasis, exacerbation of sarcoidosis, cellulitis,
extrapyramidal reaction, extrasystoles, flushing, For IM administration, administer dose in the evening to
folliculitis, fungal infection, gastritis, goiter, GI enhance tolerability. Rotate injection sites. Preferred
hemorrhage, granulocytopenia, hallucination, hearing sites for injection are anterior thigh, deltoid, and
loss, heart valve disease, hematuria, hemolytic anemia, superolateral buttock. In hairy cell leukemia treatment, if
hepatic encephalopathy, hemoptysis, hepatitis, platelets are <50,000/mm3, administer by SC injection
hepatotoxicity, hirsutism, hypercalcemia, hyperglycemia, ONLY.
hypersensitivity reaction (acute), hyperbilirubinemia, hot
flash, hypertriglyceridemia, hepatic failure, homicidal For SC administration, rotate injection site. Preferred
ideation, hyperthyroidism, hypochromic anemia, sites for injection are abdomen (except around the
hyporeflexia, hypotension, hypothermia, immune navel), anterior thigh, and outer upper arm. Administer
thrombocytopenia, hypoventilation, impotence, dose in the evening if possible to enhance tolerability.
interstitial pneumonitis, jaundice, leg cramps, Patient should be well hydrated.
leukorrhea, hypothyroidism, lichenoid dermatitis, lipoma,
lymphadenitis, lymphadenopathy, macular edema, NOTE: Associated with moderate emetic potential.
lymphocytosis, lymphocytopenia, optic neuritis, Antiemetics may be recommended to prevent nausea
maculopapular rash, mania, mastitis, menorrhagia, and vomiting.
migraine, mucositis, myocardial infarction, myositis,
nephrotic syndrome, nervousness, neuralgia, Consider premedication with acetaminophen prior to
neuropathy, nocturia, nystagmus, palpitations, administration to reduce the incidence of some adverse
pancreatitis, pelvic pain, pancytopenia, papilledema, reactions. Not all dosage forms and strengths are
paranoia, periarteritis nodosa, peripheral ischemia, appropriate for all indications.
peripheral neuropathy, photophobia, pituitary
insufficiency, pneumonia, pneumothorax, pleural
effusion, proteinuria, psoriasis, psychoneurosis,

378
ANTINEOPLASTIC AND IMMODULATING AGENTS

Due to differences in dosage, patients should not change 48 weeks, regardless of HCV
Co-infection
brands of interferons without the concurrence of their genotype (without other HCV
health care provider. with HIV
antiviral drugs)
NOTE: Discontinue in patients with HCV (genotype 1) after 12
Pregnancy Category: C; X (in combination with ribavirin) weeks if HCV RNA does not decrease by at least 2 log
(compared to pretreatment) or if detectable HCV RNA is
present at 24 weeks.
ATC Code: L03AB05
When used in combination with other antiviral drugs, refer to
individual agents for duration of therapy.

Chronic hepatitis C, by SC injection, ADOLESCENT and

Rx PEGINTERFERON ALFA-2a CHILD ≥5 years, with ribavirin, 180 micrograms/1.73 m2
x body surface area (BSA) once weekly (maximum dose,
Inj.: 135 micrograms/0.5 mL pre-filled syringe (SC) 180 micrograms);
Duration of therapy based on genotype:
An alpha interferon subtype, which binds to a cell wall Genotype Duration of therapy
receptor to initiate intracellular activity resulting in
induction of gene transcription, cellular growth inhibition, Genotypes 1, 4, 5, 6 48 weeks
alteration of the state of cellular differentiation, Genotype 2, 3 24 weeks
interference with oncogene expression, alteration of cell
NOTE: Children who reach their 18th birthday during treatment
surface antigen expression, increase in phagocytic should remain on the pediatric regimen until completion of
activity of macrophages, and augmentation of therapy.
cytotoxicity of lymphocytes for target cells.

L
Chronic hepatitis B, by SC injection, 180 micrograms once
Indications: Management of HBeAg positive and negative in weekly for 48 weeks.
adults, chronic hepatitis B virus (HBV) infection who have
compensated liver disease and evidence of viral Dose Adjustment:
replication and liver inflammation; Management of Renal Impairment:
chronic hepatitis C (CHC) with compensated liver disease For patients with CrCl <30 mL/minute, 135 micrograms
in adults; Treatment of pediatric patients ≥5 years with once weekly and monitor for toxicity.
CHC and compensated liver disease; management of For patients with end-stage renal disease (ESRD) requiring
chronic hepatitis C in compensated liver disease, in hemodialysis, 135 mcg once weekly and monitor for
patients with contraindications, or in significant toxicity. If severe adverse reactions or laboratory
intolerance to other HCV antiviral drugs abnormalities occur, reduce dose to 90 micrograms
once weekly until adverse reactions resolve. If
NOTE: NOT for the treatment of chronic HCV who previously intolerance persists after dose adjustment, discontinue.
failed therapy with an interferon alfa.
NOT for treatment of CHC who have had solid organ Hepatic Impairment:
transplantation. For HCV or HBV in adult patients with ALT progressively
rising above baseline, decrease dose to 135 micrograms
Contraindications: Autoimmune hepatitis; hepatic once weekly or temporarily discontinue. Monitor
decompensation in cirrhotic patients (Child-Pugh score transaminases more frequently. If ALT continues to rise
>6, class B and C) before treatment; hepatic despite dose reduction or ALT increase is accompanied
decompensation with Child-Pugh score ≥6 in cirrhotic by increased bilirubin or hepatic decompensation,
CHC coinfected with HIV before treatment; neonates and discontinue therapy immediately. Resume therapy after
infants (due to benzyl alcohol component); pregnancy; ALT flare subsides.
men whose female partners are pregnant For HCV in children with ALT ≥5 but <10 x ULN, decrease
interferon dose to 135 micrograms per 1.73 m2 x BSA
Dose: once weekly. Monitor weekly. Further modify dose if
Chronic hepatitis C, mono-infection or co-infection with HIV, needed until ALT stabilizes or decreases. For persistent
by SC injection, ADULT, as monotherapy or in ALT ≥10 x ULN, discontinue treatment.
combination with ribavirin, 180 micrograms once weekly
for 48 weeks; Toxicity:
Duration of combination therapy for mono-infection For HCV in adolescents and children ≥5 years with
based on genotype: moderate-to severe adverse reactions, initially decrease
Genotype Duration of therapy to 135 micrograms/1.73 m2 x BSA once weekly. Further
Genotypes Refer to the individual HCV reduce dose to 90 micrograms/1.73 m2 x BSA once
1, 2 antiviral agents weekly; or 45 micrograms/1.73 m2 x BSA once weekly if
24 weeks (peginterferon + reaction persists or recurs.
Genotype 3 ribavirin without other HCV
antiviral drugs) Based on hematologic parameters:
48 weeks (peginterferon + If ANC 750–999/mm3, week 1 to 2, 135 micrograms per
Genotype 4 ribavirin without other HCV 1.73 m2 x BSA once weekly; weeks 3 to 48, no
antiviral drugs) modification.
If ANC 500–749/mm3, week 1 to 2, delay or hold dose until
Genotypes
No dosing recommendations ANC >750/mm3 then resume dose with 135
5, 6
micrograms/1.73 m2 x BSA once weekly. Assess WBC

379
 ANTINEOPLASTIC AND IMMODULATING AGENTS

weekly for 3 weeks to verify ANC>750/mm3; weeks 3 to Growth impairment (height and weight may be decreased in
48, 135 micrograms per 1.73 m2 x BSA once weekly. pediatric use; closely monitor growth in children during
If ANC 250 to 499/mm , week 1 to 2, delay or hold dose
3 and after therapy until growth catch-up has occurred)
until ANC >750/mm3 then resume dose with 90 Thyroid disorders
micrograms/1.73 m2 x BSA once weekly; weeks 3 to 48, Gastrointestinal effects (e.g. GI hemorrhage, ulcerative and
delay or hold dose until ANC >750/mm3 then resume hemorrhagic/ischemic colitis; may be severe and/or life-
dose with 135 micrograms/1.73 m2 x BSA once weekly. threatening; Pancreatitis
If ANC <250/mm3 or in febrile neutropenia, discontinue Hepatic effects (monitor hepatic function closely during
treatment. use); Hepatitis B (transient and potentially severe
If platelet count <50,000/mm3, 90 micrograms/1.73 m2 x increases in serum ALT may occur during or after
BSA once weekly. treatment)
Renal impairment
For HCV / HBV in adults with moderate-to-severe adverse Ophthalmic effects (e.g. decreased or loss of vision and
reactions, decrease to 135 micrograms weekly for initial retinopathy, including macular edema, optic neuritis,
dose reduction. Further dose reductions to 90 papilledema, retinal hemorrhages, serous retinal
micrograms weekly may be necessary in some cases if detachment, cotton wool spots, and retinal artery or vein
reaction persists or recurs. thrombosis; prior to use, all patients should have a visual
exam)
Based on hematologic parameters:
If ANC <750/mm3, 135 micrograms once weekly. SKILLED TASKS. May impair ability to perform tasks, which
If ANC <500/mm3, suspend therapy until ANC require mental alertness, like driving or operating
>1,000/mm3, then restart at 90 micrograms once machinery.
weekly.
L

If platelet count <50,000/mm3, 90 micrograms once Adverse Drug Reactions:

weekly. Common: Abdominal pain, alopecia, anemia, anorexia,
If platelet count <25,000/mm3, discontinue therapy. anxiety, arthralgia, back pain, bacterial infection, blurred
vision, cough, depression, dermatitis, diaphoresis,
Precautions: dizziness, dyspnea, diarrhea, eczema, fatigue, growth
suppression (children), headache, hepatic
WARNING: Peginterferon alfa-2a may cause or
decompensation, hyperthyroidism, hypothyroidism,
aggravate fatal or life-threatening neuropsychiatric,
injection site reaction, fever, insomnia, irritability,
autoimmune, ischemic, and infectious disorders.
lymphocytopenia, lack of concentration, memory
Withdraw therapy in patients with persistently severe
impairment, mood changes, myalgia, nervousness,
or worsening signs or symptoms of these conditions.
neutropenia, nausea, pain, pruritus, rigors,
Use with caution in the elderly. Certain adverse effects thrombocytopenia, vomiting, weakness, weight loss,
(e.g., neuropsychiatric, cardiac, flu-like reactions) xeroderma, skin rash, xerostomia
may be more severe. Less Common: Aggressive behavior, anaphylaxis, angina
pectoris, angioedema, aplastic anemia, auditory
Autoimmune disease (e.g. thyroiditis, thrombotic impairment, autoimmune disorders, bipolar mood
thrombocytopenic purpura, idiopathic thrombocytopenic disorder, bronchiolitis obliterans, bronchoconstriction,
purpura, rheumatoid arthritis, interstitial nephritis, cerebral hemorrhage, chest pain, cholangitis, colitis,
systemic lupus erythematosus, myositis, hepatitis, and coma, corneal ulcer, cardiac arrhythmia, dehydration,
psoriasis) dyspepsia, diabetes mellitus, erythema multiforme
Hypersensitivity reactions major, endocarditis, dyspnea on exertion, exfoliative
Bone marrow suppression (e.g. severe cytopenias and dermatitis, GI hemorrhage, hallucination, hearing loss,
aplastic anemia) decreased hematocrit and hemoglobin, hepatic
Infectious disorders (interferon therapy is commonly insufficiency, exacerbation of hepatitis B, graft rejection
associated with flu-like symptoms, including fever) (hepatic, renal), hyperglycemia, hypersensitivity reaction,
Cardiovascular disease (hypertension, chest pain, MI, and hyperpigmentation, hypertension, hypoglycemia,
supraventricular arrhythmias) influenza, interstitial pneumonitis, liver steatosis,
Pulmonary effects (may cause or aggravate dyspnea, macular edema, mania, myocardial infarction, myositis,
pulmonary infiltrates, pneumonia, bronchiolitis optic neuritis, pancreatitis, papilledema, peptic ulcer,
obliterans, interstitial pneumonitis, pulmonary peripheral neuropathy, pneumonia, psychiatric
hypertension, and sarcoidosis, which may result in disturbance, psychosis, pulmonary embolism, pulmonary
potentially fatal respiratory failure) infiltrates, pure red cell aplasia, retinal thrombosis (in
CNS depression artery or vein), retinal cotton-wool spot, retinal
Ischemic disorders (reported in patients without risk factors detachment, retinal hemorrhage, retinopathy,
for stroke) rheumatoid arthritis, sarcoidosis, seizures, SJS,
Neuropsychiatric disorders (e.g. depression, suicidal substance overdose, SLE, supraventricular arrhythmia,
ideation, suicide attempt, homicidal ideation, drug thrombotic thrombocytopenic purpura, suicidal ideation,
overdose, and relapse of drug addiction) suicide, urticaria, vesiculobullous reaction, vision loss
Dermatologic effects (e.g. serious cutaneous reactions,
including vesiculobullous eruptions, SJS, and exfoliative Drug Interactions:
dermatitis) Monitor closely with:
Diabetes (may require adjustments in antidiabetic Increases risk of adverse or toxic effects of Ribavirin
medications) (hemolytic anemia), Zidovudine

380
ANTINEOPLASTIC AND IMMODULATING AGENTS

Avoid concomitant use with: Infection (various infections, including CMV, or reactivation
Increases risk of adverse or toxic effects of the following of infection may occur)
drugs: Infusion site reactions (e.g. pain, swelling, or redness)
Aldesleukin (myocardial and renal toxicity), Clozapine Malignancies (e.g. secondary malignancies, including
(agranulocytosis), Dipyrone (agranulocytosis; lymphoma and post-transplant lymphoproliferative
pancytopenia), Telbivudine (peripheral neuropathy) disease (PTLD))
Serum sickness (anaphylaxis may occur, some fatal;
Increases serum concentration of Tizanidine respiratory distress may indicate an anaphylactoid
reaction)
Reduces therapeutic effect of this drug: Renal failure
BCG (Intravesical)
Adverse Drug Reactions:
Administration: For SC administration, administer in the Common and Less Common: Arthralgia, abnormal
abdomen or thigh. Rotate injection site. Administer on involuntary movements, abnormal renal and/or liver
the same day and at approximately the same time each function tests, acute renal failure, chills, bradycardia,
week. burning sensation in the soles or palms, chest and/or
back pain, CHF, dizziness, dyspnea, edema, fever, GI
NOTE: Due to differences in dosage, do NOT change brands disturbances, headache, hepatosplenomegaly,
of interferons without the concurrence of healthcare hypertension, hypotension, iliac vein obstruction,infusion
provider. site reactions, laryngospasm, leukopenia, malaise,
lymphadenopathy, myalgia, myocarditis, night sweats,
Pregnancy Category: C; X (combined with ribavirin) pain, paresthesia, proteinuria, pruritus, rash, renal artery
or deep-vein thrombosis, rigidity, seizures, soreness of

L
ATC Code: L03AB11 the mouth or throat, stomatitis, TEN, tachycardia,
thrombocytopenia, tremor, urticaria, weakness, wound
dehiscence
Rare: Fulminant hemolysis
IMMUNOSUPPRESSANTS
Drug Interactions:
Monitor closely with:
SELECTIVE IMMUNOSUPPRESSANTS Increases risk of adverse or toxic effects of the following
devices:
ANTILYMPHOCYTE Intrauterine Contraceptive Devices (infection)
Rx IMMUNOGLOBULIN (ALG)
(EQUINE) Avoid concomitant use with:
Increases risk of adverse or toxic effects of the following
Inj.: 100 mg/5 mL vial (IV) drugs:
Vaccines, Live (infection)
Polyclonal antibodies which is active against all lymphocyte
subsets. It is produced by the purification of sera from Reduces therapeutic effect of the following drugs:
immunized animals. Vaccines, Live (diminished immune response)

Indications: Adjunct to existing immunosuppressant Administration: Dilute in an appropriate infusion solution

regimens to treat acute rejection episodes in organ or (i.e., sodium chloride 0.9% or glucose 5% plus sodium
tissue transplantation; prophylaxis in combination with chloride at either 0.225% or 0.45%). The final
several immunosuppressant agents; severe aplastic concentration should not exceed 4 mg/mL
anemia
Administer the appropriately diluted infusion over at
Dose: least 4 hours, via an inline filter (0.2–1 micrometer), into
Prophylaxis of renal graft rejection, by IV infusion, 15 mg/kg a vein with rapid blood flow to prevent thrombophlebitis.
daily for 14 days, then every other day for 14 days, to a
NOTE: Premedication with antihistamines and/or
total of 21 doses in 28 days; give first dose within 24
corticosteroids may prevent or reduce the intensity of
hours before or after the transplant.
adverse effects.
Treatment of renal graft rejection, by IV infusion, ADULT,
10–15 mg/kg daily for 14 days; may administer
A skin sensitivity test is recommended before the first
additional alternate-day therapy, up to a total of 21
infusion.
doses; CHILD, 5–25 mg/kg daily.
Aplastic anemia, by IV infusion, 10–20 mg/kg daily for 8–
Pregnancy Category: C
14 days; may administer additional alternate-day
therapy, up to a total of 21 doses. (May refer to your
ATC Code: L04AA03
institutional guideline.)

Precautions:
Hemodialysis (clotting of arteriovenous fistulas may occur);
Hematologic effect (e.g. leukopenia or thrombocytopenia;
fulminant hemolysis rarely reported).

381
 ANTINEOPLASTIC AND IMMODULATING AGENTS

ANTITHYMOCYTE Drug Interactions:

Rx IMMUNOGLOBULIN (ATG) Monitor closely with:
Enhances therapeutic effect of Antithymocyte
(RABBIT) Immunoglobulin:
Trastuzumab (neutropenic effect)
Inj: 25 mg/5 mL vial (IV)
Increases risk of adverse or toxic effects of Antithymocyte
Polyclonal antibody which appears to cause Immunoglobulin:
immunosuppression by acting on T-cell surface antigens Denosumab (serious infection)
and depleting CD4 lymphocytes.
Reduces diagnostic effect of Coccidioides immitis Skin Test
Indications: Management of acute rejection of renal
transplant; used in conjunction with concomitant Avoid concomitant use with:
immunosuppression; severe aplastic anemia Enhances therapeutic effect of Antithymocyte
Immunoglobulin:
Contraindications: Acute or chronic infection Roflumilast (immunosuppressive effect)
Dose: Enhances therapeutic effect of Tofacitinib
(immunosuppressive effect)
WARNING: Should only be used by physicians
experienced in immunosuppressive therapy for the
Increases risk of adverse or toxic effects of Antithymocyte
treatment of renal transplant patients. Medical
Immunoglobulin:
surveillance is required during infusion.
Pimecrolimus
L

Tacrolimus, Topical
Acute renal transplant rejection, by IV infusion, 1.5 mg/kg
daily for 7–14 days. Increases risk of adverse or toxic effects of the following
Aplastic anemia, 3.5 mg/kg/day for 5 days; may administer drugs:
additional therapy Leflunomide (hematologic toxicity, i.e., pancytopenia,
agranulocytosis, thrombocytopenia); Natalizumab
Double check with FDA if approved indication (concurrent infection); Vaccines, Live (infection)

Dose Adjustment: Reduces therapeutic effect of the following drugs:

Obesity: BCG, Intravesical; Vaccines (diminished immune
Use actual body weight (full weight) for calculation of weight- response)
based dosing (mg/kg) for hematopoietic stemcell
transplant conditioning regimens. Administration: Infuse the first dose over at least 6 hours
through a high-flow vein. Administer subsequent doses
Toxicity: over at least 4 hours through an in-line 0.22–micron
If WBC count is 2,000–3,000 cells/mm3 or platelet count is filter.
50,000–75,000 cells/mm3, reduce dose by 50%. NOTE: Premedication with acetaminophen, antihistamines,
If WBC count is <2,000 cells/mm3 or platelet count is
and/or corticosteroids may reduce infusion-related
<50,000 cells/mm3, consider discontinuing treatment.
reactions.
Precautions:
Anaphylaxis Pregnancy Category: C
Cytokine release syndrome [CRS] (ranging from a mild, self-
limiting “flu-like reaction” to severe, life-threatening ATC Code: L04AA04
reactions with symptoms of hypotension, acute
respiratory distress syndrome, pulmonary edema,
myocardial infarction, and tachycardia) Rx EVEROLIMUS
Infection; Malignancy (lymphoma, post-transplant
lymphoproliferative disease [PTLD] or other
malignancies) Oral: 250 micrograms and 500 micrograms tablet
Hematologic toxicity (reversible neutropenia and
thrombocytopenia) Macrolide immunosuppressant and a mechanistic target ofr
apamycin (mTOR) inhibitor which has antiproliferative
Adverse Drug Reactions: and antiangiogenic properties.
Common: Abdominal pain, chills, antirabbit antibody
development, diarrhea, fever, cytomegalovirus infection, Indications: Prophylaxis of organ rejection in liver
dizziness, dyspnea, gastritis, GI moniliasis, headache, transplantation; prophylaxis of organ rejection in renal
herpes simplex infection, hyperkalemia, hypertension, transplant patients at low to moderate immunologic risk
malaise, nausea, leukopenia, oral moniliasis, pain,
peripheral edema, sepsis, systemic infection, Contraindications: Hypersensitivity to everolimus
tachycardia, thrombocytopenia, UTI, weakness
Less Common: Anaphylaxis, cytokine release syndrome,
PTLD, neutropenia, serum sickness

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ANTINEOPLASTIC AND IMMODULATING AGENTS

Dose: Breast cancer, PNET, RCC, renal angiomyolipoma, 7.5 mg

Breast cancer, advanced, hormone receptor-positive, HER2- once daily; may further reduce to 5 mg once daily if not
negative, by mouth, in combination with exemestane, 10 tolerated.
mg once daily, continue until no longer clinically Liver or renal transplantation, reduce initial dose by ~33%;
beneficial or until unacceptable toxicity. individualize subsequent dosing based on therapeutic
Advanced pancreatic neuroendocrine tumors (PNET), renal drug monitoring; target trough concentration is 3–8
angiomyolipoma, or renal cell cancer (RCC), by mouth, nanograms/mL.
10 mg once daily, continue until no longer clinically SEGA, 75% of usual dose based on calculated BSA, rounded
beneficial or until unacceptable toxicity. to the nearest strength; target trough concentration is 5–
Liver transplantation, rejection prophylaxis, by mouth, in 15 nanograms/mL; may increase dose within the target
combination with reduced doses of tacrolimus and range to achieve higher concentrations as tolerated
corticosteroids, initially 1 mg twice daily beginning at
least 30 days post-transplant; adjust maintenance dose Moderate impairment (Child-Pugh class B):
if needed at a 4 to 5-day interval based on serum Breast cancer, PNET, RCC, renal angiomyolipoma, 5 mg
concentrations, tolerability, and response; goal serum once daily; may further reduce to 2.5 mg once daily if not
concentration is between 3 and 8 nanograms/mL; if tolerated.
trough is <3 nanograms/mL, double total daily dose; if Liver or renal transplantation, reduce initial dose by ~50%;
trough >8 nanograms/mL on 2 consecutive measures, individualize subsequent dosing based on therapeutic
decrease dose by 0.25 mg twice daily. drug monitoring; target trough concentration is 3–8
Renal transplantation, rejection prophylaxis, by mouth, in nanograms/mL.
combination with induction of basiliximab, and SEGA, 50% of usual dose based on calculated BSA, rounded
concurrently with corticosteroids and reduced doses of to the nearest strength; target trough concentration is 5–
cyclosporine, initially 0.75 mg twice daily; adjust 15 nanograms/mL; may increase dose within the target

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maintenance dose if needed at a 4 to 5-day interval range if tolerated.
based on serum concentrations, tolerability, and
response; goal serum concentration is between 3 and 8 Severe impairment (Child-Pugh class C):
nanograms/mL; if trough is <3 nanograms/mL, double Breast cancer, PNET, RCC, renal angiomyolipoma,
total daily dose; if trough >8 nanograms/mL on 2 maximum dose is 2.5 mg once daily.
consecutive measures, decrease dose by 0.25 mg twice Liver or renal transplantation, reduce initial dose by ~50%;
daily. individualize subsequent dosing based on therapeutic
Subependymal giant cell astrocytoma (SEGA), by mouth, drug monitoring; target trough concentration is 3–8
ADULT and CHILD ≥1 year, initially 4.5 mg/m2 once daily; nanograms/mL.
round to nearest tablet size; if trough <5 nanograms/mL,
increase dose by 2.5 mg daily; if trough >15 Precautions:
nanograms/mL, reduce dose by 2.5 mg daily; if dose WARNING: Should only be used by physicians
reduction necessary inpatients receiving the lowest experienced in immunosuppressive therapy and
strength available, administer every other day; management of transplant patients. Adequate
laboratory and supportive medical resources must be
Dose Adjustment: readily available.
Concomitant CYP3A4 Inducer or Inhibitor and/or P- NOT recommended for use in heart transplant; has
glycoprotein Inhibitor use: immunosuppressant properties which may result in
For patients receiving concomitant strong CYP3A4 and/or p- infection.
glycoprotein inducers (e.g., carbamazepine,
phenobarbital, phenytoin, rifabutin, rifampin, Use may result in the development of malignancy,
rifapentine), double everolimus dose using increments of including lymphoma and skin cancer.
≤5 mg with careful monitoring up to a maximum An increased risk of renal arterial and venous
dailydose of 20 mg. If inducer is discontinued, allow 3–5 thrombosis has been reported with use in renal
days prior to reducing the everolimus dose to transplantation, which may result in graft loss.
recommended starting dose.
For patients receiving concomitant moderate CYP3A4 Angioedema
and/or p-glycoprotein inhibitors (e.g., amprenavir, Edema (generalized edema, including peripheral edema
aprepitant, diltiazem, erythromycin, fluconazole, and lymphedema, and local fluid accumulation, e.g.,
fosamprenavir, verapamil), reduce everolimus dose to pericardial effusion, pleural effusion, or ascites)
2.5 mg once daily; increase from 2.5–5 mg once daily Bone marrow suppression; Malignancy
based on patient tolerance; further reductions may be Fertility effects (e.g. menstrual irregularities, secondary
necessary for adverse reactions; if dose reduction is amenorrhea, and increases in luteinizing hormone and
required for patients receiving the lowest available follicle-stimulating hormone in females may occur;
strength, consider alternate-day dosing. If inhibitor is azoospermia and oligospermia in males; may cause
discontinued, allow 2–3 days prior to reducing the infertility).
everolimus dose to recommended starting dose. Hepatic artery thrombosis; Hepatic impairment
Hereditary galactose intolerance (may result in diarrhea and
Renal transplantation: malabsorption);
Adjust dose based on everolimus serum concentrations. Metabolic effects (e.g. hyperglycemia, hyperlipidemia, and
hypertriglyceridemia; increased risk for new-onset
Hepatic Impairment: diabetes)
Mild impairment (Child-Pugh class A):

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 ANTINEOPLASTIC AND IMMODULATING AGENTS

Infections (sepsis, respiratory failure, hepatic failure, or impairment), pyuria, procedural pain, prolonged PTT,
fatality may occur; polyomavirus infection in transplant proteinuria, pulmonary edema, pulmonary embolism,
patients may be serious and/or fatal; reactivation of renal artery thrombosis, pruritus, pyelonephritis, renal
hepatitis B) failure, renal insufficiency, renal tubular necrosis,
Mucositis or stomatitis respiratory tract infection, rhinitis, rhinorrhea, scrotal
Nephrotoxicity (e.g. elevations in serum creatinine, renal edema, sepsis, sinus congestion, sinusitis, skin lesion,
failure, and proteinuria; an increased incidence of rash, spondylitis, stomatitis, streptococcal pharyngitis,
infection and dose interruptions have been reported in syncope, tachycardia, thrombocytopenia, tinea pedis,
patients with CrCl ≤60 mL/minute) tremor, thrombocythemia, upper respiratory tract
Pulmonary toxicity (e.g. noninfectious pneumonitis, infection, urethritis, urinary retention, urinary tract
interstitial lung disease (ILD), and/or noninfectious infection, urinary urgency, uterine hemorrhage, vaginal
fibrosis, some fatal) hemorrhage, venous thromboembolism, viral infection,
Wound healing complication (may delay wound healing and vomiting, weakness, weight loss, wheezing, wound
increase the occurrence of wound-related infection, xeroderma, xerostomia
complications) Less Common: Ageusia, arterial thrombosis, aspergillosis,
azoospermia, cardiac arrest, cholecystitis, cholelithiasis,
Adverse Drug Reactions: complex regional pain syndrome, contact dermatitis,
Common: Abdominal distention, abdominal pain, abnormal eczema, excoriation, gastritis, infertility (male), hemolytic
hepatic function tests, acidosis, acneiform eruption, uremic syndrome, hypersensitivity angiitis, pancreatitis,
acne vulgaris, agitation, alopecia, amenorrhea, anemia, nephrotoxicity, noninfectious pneumonitis, oligospermia,
angina pectoris, angioedema, anorexia, anxiety, pericardial effusion, pharyngitis, pityriasis rosea,
arthralgia, ascites, atelectasis, atrial fibrillation, back Pneumocystis jiroveci, polyoma pneumonia, HBV
pain, bacteremia, behavioral problems, BK virus reactivation, progressive multifocal
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infection, bladder spasm, blurred vision, bronchitis, leukoencephalopathy, respiratory distress, seizure,
candidiasis, cardiac failure, cataract, cellulitis, chest thrombosis of vascular graft (kidney), thrombotic
discomfort, chest pain, chills, conjunctivitis, thrombocytopenic purpura
constipation, cough, cushingoid appearance,
cyanocobalamin deficiency, cystitis, decreased appetite, Drug Interactions:
deep vein thrombosis, dehydration, depression, diabetes Monitor closely with:
mellitus (new onset), diaphoresis, diarrhea, dizziness, Enhances therapeutic effect of Everolimus:
drowsiness, dyspepsia, dysgeusia, dysphagia, Trastuzumab (neutropenic effect)
dysmenorrhea, dyspnea, dysuria, edema, eyelid edema,
epigastric distress, epistaxis, erectile dysfunction, Increases risk of adverse or toxic effects of Everolimus:
erythema, fatigue, fever, flatulence, fluid retention, Denosumab (serious infections)
folliculitis, gastroenteritis, GERD, gingival hyperplasia,
gout, hallucination, headache, hematemesis, hematuria, Increases risk of adverse or toxic effects of the following
herpes virus infection, hemiparesis, hemorrhage, drugs:
hemorrhoids, hepatitis (non-infectious), hepatitis C, ACE Inhibitors, e.g., Captopril, Enalapril (angioedema)
hirsutism, hydronephrosis, hypercalcemia,
hypercholesterolemia, hyperparathyroidism, Reduces diagnostic effect of Coccidioides immitis Skin Test
hyperglycemia, hyperkalemia, hypermenorrhea,
hypersensitivity, hypertension, hypertensive crisis, Reduces therapeutic effect of the following drugs:
hypertrichosis, hypertriglyceridemia, hyperuricemia, Antidiabetic Agents e.g. Gliclazide
hypocalcemia, hypoesthesia, hypoglycemia,
hypokalemia, hypomagnesemia, hyponatremia, Avoid concomitant use with:
hypophosphatemia, hypotension, incisional pain, Decreases serum concentration of Everolimus:
infection, influenza, irregular menses, insomnia, Dabrafenib, Efavirenz
interstitial nephritis, iron deficiency, intestinal
obstruction, jaw pain, joint swelling, lethargy, Enhances therapeutic effect of Everolimus:
leukocytosis, leukopenia, lower respiratory tract Roflumilast (immunosuppressive effect), Tofacitinib
infection, lymphadenopathy, limb pain, (immunosuppressive effect)
lymphocytopenia, lymphorrhea, malaise, menstrual
disease ,migraine, mucositis, muscle spasm, Increases risk of adverse or toxic effects of Everolimus:
musculoskeletal pain, myalgia, myasthenia, nail disease, Cyclosporine, Systemic (nephrotoxicity), Dipyrone
nasal congestion, nasopharyngitis, nausea, neoplasm, (agranulocytosis, pancytopenia); Pimecrolimus;
neuralgia, neutropenia, night sweats, onychomycosis, Tacrolimus (Topical)
oral candidiasis, onychoclasis, oral herpes, oral mucosa
ulcer, oropharyngeal pain, otitis media,osteomyelitis, Increases risk of adverse or toxic effects of the following
osteonecrosis, osteoporosis, ovarian cyst, palmar- drugs:
plantar erythrodysesthesia, pain, palpitations, Clozapine (agranulocytosis), Leflunomide (hematologic
pancytopenia, paresthesia, perinephric abscess, toxicity), Natalizumab, (concurrent infection), Vaccines
perinephric hematoma, peripheral edema, peritoneal (Live) (infection)
effusion, pharyngolaryngeal pain, peritonitis, pleural
effusion, pneumonia, pneumonitis, pollakiuria, polyuria,
postoperative wound complication (incisional hernia,
lymphocele, seroma, wound dehiscence, wound healing

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Increases serum concentration of Everolimus: Dose Adjustment:

Conivaptan, Cyclosporine (Systemic), Fusidic Acid Renal Impairment:
(Systemic), Idelalisib, Mifepristone, P-glycoprotein / In renal transplant patients with GFR <25 mL/minute per
ABCB1 Inhibitors 1.73 m2 outside the immediate post-transplant period,
>1 g twice daily.
Reduces therapeutic effect of the following drugs:
BCG (Intravesical), Vaccines Precautions:
WARNING: Should only be used by physicians
FOOD INTERACTION. Grapefruit Juice may increase the experienced in immunosuppressive therapy and
serum concentration of Everolimus. management of transplant patients. Adequate
laboratory and supportive medical resources must
Administration: May be taken with or without food. Take be readily available.
consistently with regard to food to reduce variability.
Swallow whole with a glass of water. Do NOT break, Do NOT use mycophenolate mofetil and
chew, or crush. Do NOT administer crushed or broken mycophenolic acid dosage forms interchangeably
tablets. Avoid contact with or exposure to crushed or due to differences in absorption.
broken tablets.
May lead to an increased susceptibility to
NOTE: Limit exposure to sunlight and ultraviolet light by bacterial, viral, fungal, and protozoal infections,
wearing protective clothing and using effective including opportunistic infections.
sunscreen to minimize the risk for skin cancer.
May lead to an increased risk of development of

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For breast cancer, pancreatic neuroendocrine tumors,
lymphoma and other malignancies, i.e., skin.
renal cell cancer, renal angiolipoma, or SEGA, administer
at the same time each day.
Associated with an increased risk of congenital
For liver transplantation, administer consistently ~12 malformations and first trimester pregnancy loss
hours apart, at the same time as tacrolimus. when used by pregnant women. Females of
reproductive potential must be counseled about
For renal transplantation, administer consistently ~12 pregnancy prevention and planning.
hours apart, at the same time as cyclosporine.
Gastrointestinal disorders (e.g. gastric or duodenal ulcers,
Pregnancy Category: C GI bleeding and/or perforation)
Hypoxanthine-guaninephosphoribosyl transferase
ATC Code: L04AA18 deficiency
Lymphoproliferative disorders; Neutropenia; Pure red cell
aplasia [PRCA]
Infections; New or reactivated viral infections (e.g.
Rx MYCOPHENOLATE MOFETIL polyomavirus associated nephropathy (PVAN), JC virus-
associated progressive multifocal leukoencephalopathy
Oral: 500 mg tablet (PML), cytomegalovirus (CMV) infections, and
reactivation of hepatitis B (HBV) or hepatitis C (HCV))
It provides a cytostatic effect on T and B lymphocytes. It Renal impairment (increased toxicity).
inhibits inosine monophosphate dehydrogenase Pregnancy (consider alternative agents for women planning
(IMPDH), which inhibits denovo guanosine nucleotide pregnancy; external ear abnormalities, cleft lip and
synthesis, thus limiting T and B lymphocyte proliferation. palate, anomalies of the distal limbs, heart, esophagus,
kidney, and nervous system have been reported;
Indication: Prophylaxis of organ rejection spontaneous abortions have been noted; discontinue at
least 6 weeks prior to trying to conceive).
Contraindication: Hypersensitivity to mycophelate mofetil Elderly (at an increased risk of certain infections, GI
hemorrhage, and pulmonary edema).
Dose:
NOTE: Identify dosing with caution due to possibility of Adverse Drug Reactions:
increased hepatic, renal, or cardiac dysfunction. Common: Abdominal pain, abscess, acidosis, acne,
agitation, albuminuria, increased, alkalosis, alopecia,
Renal transplant, by mouth, ADULT, CHILD, and INFANT ≥3 amblyopia, anemia, angina, anorexia, anxiety, apnea,
months or BSA >1.5 m2, 1 g twice daily; doses>2 g daily arrhythmia, arterial thrombosis, arthralgia, ascites,
are not recommended; 1 g twice daily. asthma, atelectasis, atrial fibrillation, atrial flutter, back
Cardiac transplant or hepatic transplant, by mouth, ADULT, pain, bradycardia, bronchitis, bruising, Candida
1.5 g twice daily. infection, cardiac arrest, cardiac failure, cataract,
cellulitis, chest pain, chills with fever, cholangitis,
cholestatic jaundice, CMV tissue invasive disease, CMV
viremia or syndrome, coagulation disorder, confusion,
conjunctivitis, constipation, cough, cyst, Cushing's
syndrome, dehydration, delirium, depression, diabetes

385
 ANTINEOPLASTIC AND IMMODULATING AGENTS

mellitus, diaphroresis, diarrhea, dizziness, dyspepsia, Avoid concomitant use with:

dysphagia, dyspnea, dysuria, ear disorder, edema, Decreases serum concentration of Mycophenolate:
emotional lability, enlarged abdomen, epistaxis, Bile Acid Sequestrants, e.g. Ursodeoxycholic Acid,
esophagitis, extrasystole, eye hemorrhage, facial edema, Cholestyramine Resin, Cyclosporine, Magnesium Salts,
fever, flatulence, gout, flu-like syndrome, fungal Rifamycin Derivatives, e.g., Rifampicin, Rifaximin,
dermatitis, gastritis, gum hyperplasia, gastroenteritis, GI Sevelamer
hemorrhage, GI moniliasis, hyper-hypophosphatemia,
increased gamma glutasyl transferase, gingivitis, Decreases serum concentration of the following drugs:
hallucinations, headache, hematuria, hemoptysis, Contraceptives, Estrogens and Progestins
hemorrhage, hernia, herpes simplex infection, herpes
zoster cutaneous disease, hiccup, hirsutism, Enhances therapeutic effect of Mycophenolate:
hydronephrosis, hypercalcemia, hypocalcemia, Roflumilast (immunosuppressive effect)
hypercholesterolemia, hyper/hypovolemia, ileus,
hyperglycemia, hyperkalemia, hyperlipemia, Enhances therapeutic effect of Tofacitinib
hypertension, hypertonia, hyperuricemia, (immunosuppressive effect)
hyperventilation, hypochloremia, hypoesthesia,
hypoglycemia, hypokalemia, hypomagnesemia, Increases risk of adverse or toxic effects of Mycophenolate:
hyponatremia, hypoproteinemia, hypotension, Pimecrolimus, Tacrolimus (Topical)
hypothyroidism, hypoxia, infection, impotence, infection,
insomnia, joint disorder, lacrimation disorder, leg Increases risk of adverse or toxic effects of the following
cramps, leukocytosis, leukopenia, liver damage, lung drugs:
disorder, malaise, melena, mouth ulceration, myalgia, Leflunomide (hematologic toxicity), Natalizumab
myasthenia, nausea, neck pain, neoplasm, nervousness, (concurrent infection), Live Vaccines (infection)
L

neuropathy, neutropenia, oral moniliasis, orthostatic

hypotension, osteoporosis, pain, pallor, palpitation, Increases serum concentration of Mycophenolate:
pancytopenia, parathyroid disorder, paresthesia, pelvic Probenecid
pain, pericardial effusion, peripheral edema, peripheral
vascular disorder, peritonitis, petechia, pharyngitis, Reduces absorption of Mycophenolate:
pleural effusion, pneumonia, pneumothorax, Antacids [except Sodium Bicarbonate]
polycythemia, prostatic disorder, prothrombin time
increased, pruritus, psychosis, pulmonary edema, Reduces therapeutic effect of the following drugs:
pulmonary hypertension, pyelonephritis, rash, renal BCG (Intravesical), Vaccines (immune response)
failure, respiratory acidosis, respiratory moniliasis,
respiratory tract infection, rhinitis, scrotal edema, Administration: To be taken on an empty stomach, 1 hour
seizure, sepsis, sinusitis, skin carcinoma, skin before or 2 hours after meals, to avoid variability in
hypertrophy, skin ulcer, somnolence, sputum increased, mycophenolate absorption.
stomach disorder, stomach ulcer, stomatitis,
supraventricular extrasystoles, supraventricular May be administered with food in stable renal transplant
tachycardia, tachycardia, thirst, syncope, thinking patients when necessary.
abnormal, thrombocytopenia, increased thromboplastin
time, thrombosis, tinnitus, tremor, urinary tract disorder, MISSED DOSE: Administer as soon as remembered. If it is
vasodilation, vasospasm, increased venous pressure, close to the next scheduled dose, skip the missed dose
ventricular extrasystole, ventricular tachycardia, vertigo, and resume at next regularly scheduled time. Do NOT
vesiculobullous rash, vision abnormal, voice alteration, double a dose to make up for a missed dose.
vomiting, weakness, weight gain/loss, xerostomia
Less Common: Atypical mycobacterial infection, BK virus- Females of reproductive potential should have a
associated nephropathy, bronchiectasis, colitis, GI negative pregnancy test with a sensitivity of ≥25 mIU/mL
perforation, infectious endocarditis, interstitial lung immediately before therapy and the test should be
disorder, intestinal villous atrophy, lymphoproliferative repeated 8–10 days later. Pregnancy tests should be
disease, lymphoma, malignancy, meningitis, progressive repeated during routine follow-up visits. They are also
multifocal leukoencephalopathy, pancreatitis, required to have contraceptive counseling and use
pulmonary fibrosis (fatal), pure red cell aplasia, acceptable birth control unless heterosexual intercourse
tuberculosis is completely avoided. Intrauterine device, tubal
sterilization, or vasectomy of the female patient's partner
Drug Interactions: are acceptable contraceptive methods that can be used
Monitor closely with: alone. Hormonal contraceptives require the use of an
Enhances therapeutic effect of Mycophenolate: additional barrier method because mycophenolate
Trastuzumab (neutropenic effect) affects the effectiveness of hormonal contraceptive
agents.
Increases risk of adverse or toxic effects of Mycophenolate:
Denosumab (serious infection) NOTE: Limit exposure to sunlight and ultraviolet light by
wearing protective clothing and using effective
Reduces diagnostic effect of Coccidioides immitis Skin Test sunscreen to minimize the risk for lymphoproliferative
disorders.

Pregnancy Category: D

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ANTINEOPLASTIC AND IMMODULATING AGENTS

ATC Code: Not available Antineoplastic and Immunomodulating Agents for other
information.

MYCOPHENOLIC ACID Pregnancy Category: D

Rx
(AS MYCOPHENOLATE SODIUM)
ATC Code: L04AA06
Oral: 360 mg tablet

Mycophenolic acid has a cytostatic effect on T and B Rx SIROLIMUS

lymphocytes. It inhibits inosine monophosphate
dehydrogenase (IMPDH), which inhibits de novo
guanosine nucleotide synthesis, thus limiting T and B Oral: 0.5 mg and 1 mg tablet
lymphocyte proliferation.
Inhibits the regulatory kinase, mTOR (mechanistic target of
Indication: Prophylaxis of organ rejection rapamycin). This inhibition suppresses cytokine
mediated T-cell proliferation and the proliferation of
Contraindication: Hypersensitivity to mycophenolic acid lymphangioleiomyomatosis cells, thus preventing acute
rejection of allografts and prolongs graft survival.
Dose:
Renal transplant, by mouth, ADULT, 720 mg twice daily Indications: Management of lymphangioleiomyomatosis;
(total daily dose, 1440 mg); CHILD ≥5 years, usual dose, prophylaxis of organ rejection in renal transplants
400 mg/m2 per dose twice daily (maximum dose, 720

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mg twice daily); Dose:
Low-to-moderate immunologic risk renal transplant, by
Dose Adjustment: mouth, ADULT and CHILD ≥13 years or<40 kg, in
Weight-based: combination with cyclosporine and corticosteroids,
For BSA >1.58 m2, 720 mg twice daily (maximum, 1,440 mg initially, 3 mg/m2 on day 1 as loading dose, followed by 1
daily). mg/m2 once daily as maintenance;
For BSA 1.19–1.58m2, 540 mg twice daily (maximum, ADULT and CHILD ≥13 years or ≥40 kg, 6 mg on day 1 as
1,080 mg daily). loading dose, followed by 2 mg once daily as
For BSA <1.19 m2, use is not recommended maintenance
[NOTE: May be withdrawn after 2–4 months, in conjunction with
Administration: To be taken on an empty stomach, 1 hour an increase in sirolimus dosage].
before or 2 hours after meals, to avoid variability in High immunologic risk renal transplant patients, by mouth,
mycophenolate absorption. ADULT, in combination with cyclosporine and
corticosteroids for the first year, 15 mg on day 1 as
May be administered with food in stable renal transplant loading dose, followed by 5 mg daily as maintenance;
patients when necessary. obtain trough concentration between days 5–7 and
adjust accordingly; continue concurrent cyclosporine +
MISSED DOSE: Administer as soon as remembered. If it is sirolimus + corticosteroid therapy for 1 year following
close to the next scheduled dose, skip the missed dose transplantation; further adjustment of the regimen must
and resume at next regularly scheduled time. Do NOT be based on clinical status [NOTE: Adjustment of
double a dose to make up for a missed dose. immunosuppressive therapy beyond 12 months should
be considered based on clinical judgment].
Females of reproductive potential should have a Lymphangioleiomyomatosis, by mouth, ADULT, initially 2 mg
negative pregnancy test with a sensitivity of ≥25 mIU/mL once daily; obtain trough concentration in 10–20 days
immediately before therapy and the test should be and adjust dose to maintain a target concentration of 5–
repeated 8–10 days later. Pregnancy tests should be 15 nanograms/mL.
repeated during routine follow-up visits. They are also
required to have contraceptive counseling and use Note: Maximum dose for all approved indications (Adults,
acceptable birth control unless heterosexual intercourse Geriatric, Adolescents) is 40 mg/day.
is completely avoided. Intrauterine device, tubal
sterilization, or vasectomy of the female patient's partner Dose Adjustment:
are acceptable contraceptive methods that can be used Hepatic Impairment:
alone. Hormonal contraceptives require the use of an For mild-to-moderate impairment (Child-Pugh classes A and
additional barrier method because mycophenolate B), reduce maintenance dose by ~33%.
affects the effectiveness of hormonal contraceptive For severe impairment (Child-Pugh class C), reduce
agents. maintenance dose by ~50%.

NOTE: Limit exposure to sunlight and ultraviolet light by Precautions:

wearing protective clothing and using effective WARNING: Should only be used by physicians
sunscreen to minimize the risk for lymphoproliferative experienced in immunosuppressive therapy and
disorders. management of transplant patients. Adequate
laboratory and supportive medical resources must be
See Mycophenolate Mofetil under Immunosuppressants – readily available.
Selective Immunosuppressants in Chapter 8:

387
 ANTINEOPLASTIC AND IMMODULATING AGENTS

segmental glomerulosclerosis, gingival hyperplasia,

Therapeutic drug monitoring is recommended,
headache, hemolytic-uremic syndrome, hepatic
however, variations in methods to determine
necrosis, herpes simplex infection, hepatotoxicity,
sirolimus whole blood concentrations, as well as
hyperglycemia, herpes zoster, hypercholesterolemia,
interlaboratory variations, may result in improper
incisional hernia, hypermenorrhea, hypersensitivity
dosage adjustments, which may lead to
angiitis, hypertension, hypertriglyceridemia,
subtherapeutic or toxic levels. Determine the assay
hypophosphatemia, hypervolemia, increased
method used to assure consistency, and be aware of
susceptibility to infection, hypokalemia, interstitial
alterations to assay method or reference range and
pulmonary disease (dose-related), joint disorders,
that values from different assays may not be
leukopenia, lymphedema, lymphocele, lympho
interchangeable.
proliferative disorder, pain, menstrual disease, myalgia,
May cause increased susceptibility to infection and the mycobacterium infection, nasopharyngitis, nausea,
development of lymphoma and other malignancies. nephrotic syndrome, neutropenia, osteonecrosis,
ovarian cyst, pancreatitis, pancytopenia, pericardial
NOT recommended for use in liver transplantation. effusion, pleural effusion, pneumonia due to
Associated with an increased risk of hepatic artery Pneumocystis jiroveci (P. carinii), peripheral edema,
thrombosis (HAT), graft failure, and increased pneumonia, progressive multifocal
mortality with evidence of infection. leukoencephalopathy, proteinuria, pseudomembranous
colitis, pulmonary alveolitis, pulmonary hemorrhage,
NOT recommended for use in lung transplantation. pulmonary embolism, pyelonephritis, renal disease,
Bronchial anastomotic dehiscence cases have been sepsis, skin carcinoma, reversible posterior
reported, mostly fatal. leukoencephalopathy syndrome, skin rash, stomatitis,
tachycardia, thrombocytopenia, thrombotic
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thrombocytopenic purpura, upper respiratory tract

Anaphylactic or hypersensitivity reactions (e.g. anaphylactic infection, tuberculosis, urinary tract infection, weight
or anaphylactoid reactions, angioedema, exfoliative loss, wound dehiscence, wound healing impairment
dermatitis, and hypersensitivity vasculitis); angioedema
Infections (opportunistic infections including activation of Drug Interactions:
latent viral infections, fatal infections, and sepsis may Monitor closely with:
occur; progressive multifocal leukoencephalopathy Enhances therapeutic effect of Sirolimus:
(PML), an opportunistic CNS infection caused by Trastuzumab (neutropenic effect)
reactivation of the JC virus, has been reported)
Interstitial lung disease (e.g. pneumonitis, bronchiolitis Increases risk of adverse or toxic effects of Sirolimus:
obliterans organizing pneumonia [BOOP], pulmonary Denosumab (serious infections)
fibrosis; may be fatal; may be associated with pulmonary
hypertension). Increases risk of adverse or toxic effects of ACE Inhibitors,
Hemolytic uremic syndrome (HUS); Thrombotic e.g., Captopril, Enalapril
thrombocytopenic purpura, or thrombotic
microangiopathy; Reduces diagnostic effect of Coccidioides immitis Skin Test
Hyperlipidemia
Lymphocele or fluid accumulation (e.g. peripheral edema, Reduces therapeutic effect of the following drugs:
lymphedema, ascites, and pleural and pericardial Antidiabetic Agents, Sipuleucel-T
effusions)
Malignancy (increased risk of other malignancies such as Avoid concomitant use with:
skin cancer) Decreases serum concentration of Sirolimus:
Proteinuria (may increase urinary protein excretion; new Dabrafenib, Efavirenz, Enzalutamide, Fosphenytoin,
onset nephrotic syndrome has been reported) Mitotane, Phenytoin, Rifampin
Renal effects (may increase serum creatinine and decrease
GFR; may delay recovery of renal function in patients Decreases serum concentration of Tacrolimus (Systemic)
with delayed allograft function)
Wound dehiscence or healing (may cause wound Enhances therapeutic effect of Sirolimus:
dehiscence and impaired healing) Roflumilast (immunosuppressive effect)
Children (safety and efficacy of de novo use of sirolimus
without cyclosporine have not been established; safety Enhances therapeutic effect of Tofacitinib
and efficacy have not been established in <13 years or (immunosuppressive effect)
in renal transplant patients <18 years).
Increases risk of adverse or toxic effects of Sirolimus:
Adverse Drug Reactions: Pimecrolimus, Tacrolimus
Common and Less Common: Abdominal pain, abnormal
hepatic function tests, acne vulgaris, amenorrhea, Increases risk of adverse or toxic effects of the following
anemia, anaphylactoid reaction, anaphylaxis, drugs:
angioedema, arthralgia, ascites, azoospermia, cardiac Clozapine (agranulocytosis), Cyclosporine (Systemic)
tamponade, chest pain, constipation, cytomegalovirus, (calcineurin inhibitor-induced hemolytic uremic
deep vein thrombosis, dehiscence (fascial), diabetes syndrome, thrombotic thrombocytopenic purpura, or
mellitus, diarrhea, dizziness, edema, epistaxis, Epstein- thrombotic microangiopathy), Dipyrone
Barr infection, exfoliative dermatitis, fluid retention, focal (agranulocytosis; pancytopenia), Leflunomide

388
ANTINEOPLASTIC AND IMMODULATING AGENTS

(hematologic toxicity such as pancytopenia, Precautions:

agranulocytosis, and/or thrombocytopenia),
WARNING: Should only be used by physicians
Natalizumab (concurrent infection), Tacrolimus
experienced in immunosuppressive therapy and
management of transplant patients. Adequate
Increases serum concentration of Sirolimus:
laboratory and supportive medical resources must
Boceprevir, Conivaptan, Crizotinib, Cyclosporine
be readily available.
(Systemic), Dasabuvir, Fluconazole, Fusidic Acid
(Systemic), Itraconazole, Ketoconazole (Systemic), Re-exposure to basiliximab with a subsequent
Macrolide Antibiotics [except Azithromycin, Fidaxomicin, course of therapy should only be done with
Spiramycin], Mifepristone, Ritonavir, Telaprevir; extreme caution.
Vaccines, Live (infection), Voriconazole

Reduces therapeutic effect of the following drugs: Anaphylactoid/hypersensitivity reactions

BCG (Intravesical), Vaccines (immune response) Diabetes (new-onset diabetes)
Human antimurine antibodies [HAMA] (lymphoproliferative
FOOD INTERACTION. Grapefruit Juice may decrease the clearance of disorders (may increase incidence)); opportunistic
Sirolimus. infections (may increase incidence))

Administration: Administer consistently with regards to Adverse Drug Reactions:

meals. Ingestion with high-fat meals decreases peak Common: Abdominal pain, abnormal heart sounds,
concentrations but increases AUC by 23–35%. abnormal vision, accidental trauma, acidosis, acne,
agitation, albuminuria, anemia, angina, anxiety,
Administer initial dose as soon as possible after arrhythmia (tachycardia), arthralgia, arthropathy, atrial

L
transplant. To be taken 4 hours after oral cyclosporine. fibrillation, back pain, bladder disorder, bronchitis,
bronchospasm, cataract, chest pain, conjunctivitis,
Do NOT crush, split, or chew the tablet. constipation, cough, cramps, cyst, cytomegalovirus
(CMV) infection, dehydration, depression, diabetes
NOTE: Limit exposure to sunlight and ultraviolet light by mellitus, diarrhea, fever, dizziness, dyspepsia, dyspnea,
wearing protective clothing and using effective dysuria, fluid overload, enlarged abdomen, esophagitis,
sunscreen to minimize the risk for malignancy. fatigue, flatulence, fracture, gastroenteritis, generalized
edema, genital edema (male), GI hemorrhage, gingival
Pregnancy Category: C hyperplasia, increased glucocorticoids, headache, heart
failure, hematoma, hematuria, hernia, herpes infection
ATC Code: L04AA10 (simplex and zoster), hypercholesterolemia, hyper-
/hypocalcemia, hyper-/hypokalemia, hyperglycemia,
insomnia, hyperlipemia, hypertension, hypertrichosis,
INTERLEUKIN INHIBITORS hyperuricemia, impotence, hypoesthesia, hypoglycemia,
hypomagnesemia, hyponatremia, leg pain, hypotension,
infection, upper respiratory infection, leukopenia,
Rx BASILIXIMAB moniliasis, malaise, melena, myalgia, nausea,
neuropathy, oliguria, pain, paresthesia, peripheral
edema, pharyngitis, pneumonia, polycythemia, pruritus,
Inj.: 20 mg vial (IV infusion)
pulmonary edema, purpura, rash, renal tubular necrosis,
rhinitis, rigors, sepsis, sinusitis, skin disorder, skin
Chimeric (murine/human) immunosuppressant monoclonal
ulceration, tremor, stomatitis, thrombocytopenia,
antibody, which blocks the alpha-chain of the interleukin-
thrombosis, ureteral disorder, urinary frequency, urinary
2 (IL-2) receptor complex. This receptor is expressed on
retention, urinary tract infection, viral infection, vomiting,
activated T-lymphocytes and is a critical pathway for
weakness, weight gain, wound complications
activating cell-mediated allograft rejection.
Less Common: Anaphylaxis, capillary leak syndrome,
cytokine release syndrome, diabetes (new onset),
Indication: Prophylaxis of acute organ rejection in renal
lymphoproliferative disease, hypersensitivity reaction
transplantation
Drug Interactions:
Dose:
Monitor closely with:
Acute renal transplant rejection prophylaxis, by IV infusion,
Enhances therapeutic effect of Basiliximab:
ADULT and CHILD≥35 kg, with cyclosporine and
Trastuzumab (neutropenic effect)
corticosteroids, 20 mg within 2 hours prior to transplant
surgery, followed by a second 20 mg dose 4 days after
Increases risk of adverse or toxic effects of
transplantation; withhold second dose if complications
Basiliximab:
occur;
Denosumab (serious infections)
CHILD<35 kg, with cyclosporine and corticosteroids, 10
mg within 2 hours prior to transplant surgery, followed by
Reduces diagnostic effect of Coccidioides immitis Skin Test
a second 10 mg dose 4 days after transplantation; the
second dose should be withheld if complications occur
Avoid concomitant use with:
(including severe hypersensitivity reactions or graft loss).
Enhances therapeutic effect of Basiliximab:
Roflumilast (immunosuppressive effect)

389
 ANTINEOPLASTIC AND IMMODULATING AGENTS

immunosuppressive agents, coal tar, or radiation

Enhances therapeutic effect of Tofacitinib therapy in patients with psoriasis; rheumatoid arthritis
(immunosuppressive effect) and psoriasis patients with primary or secondary
immunodeficiency excluding autoimmune disease,
Increases risk of adverse or toxic effects of Basiliximab: uncontrolled infection, or malignancy (excluding non-
Pimecrolimus, Tacrolimus (Topical), melanoma skin cancer)

Increases risk of adverse or toxic effects of the following Dose:

drugs: Psoriasis, by mouth, ADULT, initially 2.5 mg/kg daily, divided
Belimumab, Leflunomide (hematologic toxicity, such as twice daily; increase by 0.5 mg/kg daily if insufficient
pancytopenia, agranulocytosis, and/or response is seen after 4 weeks of treatment; additional
thrombocytopenia), Natalizumab (concurrent infection), dose increases may be made every 2 weeks if needed
Live Vaccines (infection) (maximum dose, 4 mg/kg daily) [NOTE: Discontinue if no
benefit is seen by 6 weeks of therapy at the maximum
Reduces therapeutic effect of the following drugs: dose. Once adequately controlled, decrease dose to the
BCG (Intravesical), Vaccines lowest effective dose; doses lower than 2.5 mg/kg daily
may be effective; treatment > 1 year is not
Administration: For IV administration only. Administer by IV recommended].
bolus infusion or IV infusion over 20–30 minutes. Rheumatoid arthritis, by mouth, ADULT, initially 2.5 mg/kg
daily, divided twice daily; may increase dose by 0.5–0.75
Administer only after assurance that patient will receive mg/kg daily if insufficient response is seen after 8 weeks
renal graft and immunosuppression. of treatment;additional dose increases may be made
again at 12 weeks (maximum dose, 4 mg/kg daily)
L

NOTE: Bolus dosing is associated with nausea, vomiting, [NOTE: Discontinue if no benefit is seen by 16 weeks of
and local pain at the injection site. therapy].
Solid organ transplant, newly transplanted patients, by
Pregnancy Category: B mouth, ADULT, administer initial dose 4–12 hours prior
to transplant or postoperatively,
ATC Code: L04AC02 Organ Dose Frequency
9 ± 3 mg/kg
Kidney
daily
CALCINEURIN INHIBITORS Liver
8 ± 4 mg/kg 2 divided
daily doses
7 ± 3 mg/kg
Heart
Rx CYCLOSPORINE (CICLOSPORIN) daily
Blood and marrow transplantation, by mouth, ADULT,
initially 12.5–15 mg/kg daily in 2 divided doses
Oral: 25 mg, 50 mg, and 100 mg capsule beginning 1 day prior to transplant, then ~12.5 mg/kg
100 mg/mL solution, 50 mL daily in 2 divided doses every 12 hours for at least 3–6
Opthalmic emulsion: 0.05%, 0.4 mL bottle months as maintenance; gradually decrease dose to
zero by 1 year following transplant. [NOTE: Patients who
Inhibits the production and release of interleukin II and develop GVHD after discontinuation of cyclosporine may
inhibits interleukin II-induced activation of resting T- be reinitiated on therapy with a loading dose of 10–12.5
lymphocytes. mg/kg followed by the previously established
maintenance dose. Patients with mild, chronic GVHD
Indications: Prophylaxis of organ rejection in kidney, liver, should be treated with lowest effective dose].
and heart transplants; prophylaxis of graft rejection Nephrotic syndrome, by mouth, ADULT, initially 3.5 mg/kg
following bone marrow transplantation; treatment of daily in 2 divided doses every 12 hours; titrate for
chronic organ rejection; treatment of severe, active induction of remission and renal function; individualize
rheumatoid arthritis (RA) not responsive to methotrexate maintenance dose based on proteinuria, serum
alone; treatment of severe, recalcitrant plaque psoriasis creatinine, and tolerability and maintained at lowest
in non-immunocompromised adults unresponsive to or effective dose (maximum dose: 5 mg/kg daily);
unable to tolerate other systemic therapy; induction and CHILD,initially 4.2 mg/kg daily in 2 divided doses every
maintenance of remission in steroid 12 hours; titrate for induction of remission and renal
dependent/resistant nephrotic syndrome due to function; individualize maintenance dose based on
glomerular disease (e.g. minimal change nephropathy, proteinuria, serum creatinine, and tolerability and
membranous glomerulonephritis, focal and segmental maintained at lowest effective dose (maximum dose: 6
glomerulosclerosis); maintenance of steroid induced mg/kg daily) [NOTE: Discontinue if no improvement is
remission in nephrotic syndrome allowing for steroid observed after 3 months.].
dose reduction or withdrawal; for the treatment of severe Severe aplastic anemia, non-HSCT eligible, by mouth,
aplastic anemia, in combination with Horse ATG; for ADULT and CHILD, 10 to 12 mg/kg per day for at least 4
steroid-refractory chronic immune thrombocytopenia to 6 months. Dosage adjustments may be required to
maintain trough blood levels of 200 to 400
Contraindications: Rheumatoid arthritis and psoriasis nanograms/mL. In responding children, cyclosporine is
patients with abnormal renal function, uncontrolled continued for a minimum of 12 months, followed by slow
hypertension, or malignancies; concomitant treatment tapering of the drug (0.25-0.5 mg/kg/month).
with PUVA or UVB therapy, methotrexate and other

390
ANTINEOPLASTIC AND IMMODULATING AGENTS

Dose Adjustment: Neurotoxicity (e.g. seizures and encephalopathy)

Renal Impairment: Thrombotic microangiopathy (syndromes of
Serum Dose microangiopathic hemolytic anemia and
Condition
Creatinine Levels Adjustment thrombocytopenia have occurred and may result in graft
Serum creatinine failure in transplant patients)
Severe
≥25% above
psoriasis Decrease dose Adverse Drug Reactions:
pretreatment
and by 25–50%; Common: Abdominal distress, diarrhea, dyspepsia, edema,
levels, consistent
abnormal discontinue if female genital tract disease, gingival hyperplasia,
for 2 weeks
renal not reversed headache, hirsutism, hypertension, hypertrichosis,
Serum creatinine
function after 2 dose increased susceptibility to infection, leg cramps, nausea,
≥50% above
during adjustments paresthesia, renal insufficiency, tremor, upper
pretreatment
treatment respiratory tract infection, urinary tract infection, viral
levels
Serum creatinine infection
Reduce dose; Less Common: Anaphylaxis, CNS toxicity, cholestasis,
≥30% above
Rheumatoid discontinue if exacerbation of psoriasis, fatigue, gout, hemolytic uremic
pretreatment
arthritis and not reversed syndrome, hepatitis, hyperbilirubinemia, hyperkalemia,
levels, consistent
abnormal within 30 days hypertrichosis, hypomagnesemia, impaired
for 2 weeks
renal consciousness, increased susceptibility to infection,
Reduce dose
function Serum creatinine hepatic insufficiency, jaundice, malignant lymphoma,
by 50%;
during ≥50% above migraine, myalgia, myopathy/rhabdomyolysis, myositis,
discontinue if
treatment pretreatment papilledema, progressive multifocal
not reversed
levels leukoencephalopathy, pseudotumor cerebri, pulmonary

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within 30 days
edema (noncardiogenic), renal disease (polyoma virus-
Nephrotic Initiate at 2.5
associated), reversible posterior leukoencephalopathy
syndrome mg/kg daily
syndrome, rhabdomyolysis, thrombotic microangiopathy
Serum creatinine
>30% above Drug Interactions:
Decrease dose
pretreatment Monitor closely with:
by 25–50%
levels, consistent Enhances absorption of Cyclosporine:
for 2 weeks Metoclopramide

Hepatic Impairment: Enhances therapeutic effect of Cyclosporine:

May require dose reduction. Undergoes extensive hepatic Cyclophosphamide (immunosuppressive effect),
metabolism. Trastuzumab (neutropenic effect)

Hypertension: Enhances therapeutic effect of the following drugs:

If sustained hypertension develops during therapy but there Neuromuscular-Blocking Agents e.g., Succinylcholine
is no history of hypertension, decrease dose by 25–50%
and discontinue if hypertension persists. Increase Increases risk of adverse or toxic effects of Cyclosporine:
frequency of blood pressure monitoring after each dose Aminoglycosides e.g., Streptomycin, Gentamicin
adjustment. (nephrotoxic effect), Amphotericin B (nephrotoxic effect),
Angiotensin II Receptor Blockers, e.g. Losartan,
Precautions: Candesartan (hyperkalemic effect), Denosumab (serious
infections); Melphalan (nephrotoxic effect); Sulfonamide
WARNING: Should only be used by physicians
Derivatives, e.g. Sulfamethoxazole (nephrotoxic effect)
experienced in immunosuppressive therapy and
management of transplant patients. Adequate
laboratory and supportive medical resources must Increases risk of adverse or toxic effects of the following
be readily available. drugs:
Imipinem (neurotoxic effect), Loop Diuretics, e.g.,
Some brands are not bioequivalent and cannot be Furosemide
used interchangeably. Minoxidil (severe hypertrichosis)

May cause hypertension. Reduces diagnostic effect of Coccidioides immitis Skin Test

Increased risk of lymphomas and other Reduces therapeutic effect of Glyburide

malignancies, some fatal, particularly skin
cancers. Avoid concomitant use with:
Decreases excretion of Cholic Acid
Renal impairment, including structural kidney
damage has occurred (dose-related). Decreases metabolism of Etoposide

Hyperkalemia; Hyperuricemia Decreases serum concentration of Cyclosporine:

Gingival hyperplasia; Rheumatoid arthritis Barbiturates, e.g., Phenobarbital, Bosentan,
Hepatotoxicity; Nephrotoxicity Carbamazepine, CYP3A4 Inducers, Dabrafenib,
Infections; Malignancy (e.g. skin cancer) Efavirenz, Enzalutamide, Fibric Acid Derivatives (e.g.,

391
 ANTINEOPLASTIC AND IMMODULATING AGENTS

Gemifibrozil), Fosphenytoin, Mitotane, Orlistat, TEST INTERACTION. Cross-reacts with radioimmunoassay

Phenytoin, Rifamycin Derivatives (e.g., Rifampicin), and fluorescence polarization immunoassay.
Somatostatin Analogs
Administration: Administer consistently with relation to time
Decreases serum concentration of Mycophenolate of day and meals.

Enhances therapeutic effect of Cyclosporine: For oral solutions, do NOT administer liquid from plastic
Echinacea, Roflumilast or styrofoam cup. May dilute with milk, chocolate milk, or
orange juice. Avoid changing diluents frequently.
Enhances therapeutic effect of Tofacitinib
(immunosuppressive effect) Mix thoroughly and drink at once. Use syringe provided
to measure dose. Mix in a glass container and rinse
Increases risk of adverse or toxic effects of Cyclosporine: container with more diluent to ensure total dose is taken.
Androgens, e.g. Testosterone (hepatotoxic effect) Do NOT rinse syringe before or after use to prevent dose
Eplerenone (hyperkalemic effect), Foscarnet variation.
(nephrotoxic effect), Methotrexate (nephrotoxicity),
NSAIDs (nephrotoxicity), Pimecrolimus, Potassium- NOTE: Limit exposure to sunlight and ultraviolet light by
Sparing Diuretics, e.g., Spironolactone wearing protective clothing and using effective
(hyperkalemic effect), Sirolimus (calcineurin inhibitor- sunscreen to minimize the risk for malignancy or skin
induced hemolytic uremic syndrome / thrombotic cancer.
thrombocytopenic purpura / thrombotic
microangiopathy), Tacrolimus (nephrotoxicity), Pregnancy Category: C
Temsirolimus (calcineurin inhibitor-induced hemolytic
L

uremic syndrome / thrombotic thrombocytopenic ATC Code: L04AD01

purpura / thrombotic microangiopathy)

Increases risk of adverse or toxic effects of the following

drugs: Rx TACROLIMUS
Caspofungin, Fibric Acid Derivatives, e.g., Gemfibrozil
(nephrotoxic effect), Leflunomide (hematologic toxicity Oral: 1 mg and 5 mg capsule
such as pancytopenia, agranulocytosis, and/or 1 mg and 5 mg slow-release capsules
thrombocytopenia), Methotrexate (nausea, vomiting,
oral ulcers, hepatotoxicity and/or nephrotoxicity), Suppresses cellular immunity, thus inhibiting T-lymphocyte
Natalizumab (concurrent infection), Tacrolimus activation, by binding to an intracellular protein, FKBP-12
(nephrotoxic effect), Vaccines, Live (infection) and complexes with calcineurin dependent proteins to
inhibit calcineurin phosphatase activity.
Increases serum concentration of Cyclosporine:
Amiodarone, Androgens e.g. Testosterone, Azole Indications: Prevention of organ rejection in heart, kidney,
Derivatives, Systemic, e.g., Ketoconazole, or liver transplant; treatment of refractory rejection in
Itraconazole [except Fluconazole] Non-dihydropyridine kidney or liver transplant; treatment of active rheumatoid
Calcium Channel Blockers (e.g., Verapamil, Diltiazem), arthritis in adult patients nonresponsive to DMARD
carvedilol, chloramphenicol, Crizotinib, CYP3A4 therapy or when DMARD therapy is inappropriate; for the
Inhibitors, Dasabuvir, Ezetimibe, Fusidic Acid (Systemic), prevention of GVHD in Allogeneic-HSCT, in combination
Methotrexate, Mifepristone, NSAIDs, Pravastatin, with MTX.
Protease Inhibitors (e.g. Lopinavir), Ritonavir, Simeprevir,
Tacrolimus, Telaprevir Dose:
Liver transplant, by mouth, ADULT, initially 0.1–0.15 mg/kg
Increases serum concentration of the following drugs: daily in 2 divided doses, given every 12 hours; titrate to
Afatinib, Aliskiren, Ambrisentan, Atorvastatin, target trough concentrations;
Boceprevir, Bosentan, Non-dihydropyridine Calcium CHILD, initially 0.15–0.20 mg/kg daily in 2 divided
Channel Blockers (e.g., Verapamil, Diltiazem), doses, given every 12 hours; titrate to target trough
Caspofungin, Colchicine (enhanced distribution), concentrations [NOTE: Initiate therapy in pediatric
Dabigatran Etexilate, Doxorubicin (Conventional), patients at the HIGH end of the recommended adult
Etoposide Phosphate, Everolimus, Fluvastatin, dosing ranges].
Lercanidipine, Methotrexate, Mitoxantrone, NSAIDs, Heart transplant, by mouth, ADULT, in combination with
Pazopanib, Pitavastatin, Pravastatin, Protease Inhibitors azathioprine or mycophenolate mofetil, initially 0.075
e.g. Lopinavir, Rosuvastatin, Silodosin, Simeprevir, mg/kg daily in 2 divided doses, given every 12 hours;
Simvastatin, Tacrolimus, Topotecan, Vincristine titrate to target trough concentrations.
(Liposomal) Kidney transplant, by mouth, ADULT, in combination with
azathioprine, initially 0.2 mg/kg daily; in combination
Reduces therapeutic effect of the following drugs: with mycophenolate mofetil, initially 0.1 mg/kg daily;
BCG, Intravesical, Vaccines (immune response) titrate to target trough concentrations; administer in 2
divided doses, given every 12 hours [NOTE: Administer
FOOD INTERACTION. Grapefruit Juice may increase the initial postoperative dose no sooner than 6 hours after
serum concentration of Cyclosporine by decreasing its liver or heart transplant and within 24 hours of kidney
metabolism.

392
ANTINEOPLASTIC AND IMMODULATING AGENTS

transplant or until renal function has recovered; titrate to cardiorespiratory arrest, cardiac failure, carpal tunnel
target trough concentrations.]. syndrome, cellulitis, cerebral infarction, cerebral
Rheumatoid arthritis, by mouth, ADULT, 3 mg once daily. ischemia, chest pain, chills, cholangitis, colitis,
Blood and marrow transplantation, by mouth, ADULT, 0.15 cholestatic jaundice, condyloma acuminatum,
mg/kg daily in 2 divided doses beginning 2 days prior to confusion, conjunctivitis, constipation, convulsions,
transplant, dose adjusted to maintain trough level cough, Cushing's syndrome, cystitis, cytomegalovirus
between 10-20 ng/mL, up to 3 months, thereafter, disease, decreased prothrombin time, dehydration, deep
adjust dose to keep trough level around 10 ng/ml. vein thrombophlebitis, deep vein thrombosis, delayed
gastric emptying, depression, dermal ulcer, dermatitis,
Dose Adjustment: dermatological reaction, diabetes mellitus (post-
Renal Impairment: transplant), diaphoresis, diarrhea, dizziness, drowsiness,
Use lowest recommended dose. Additional dose reductions duodenitis, dyspepsia, dysphagia, dyspnea, dysuria,
may be necessary. edema, emotional lability, emphysema, enlargement of
In patients who have undergone kidney transplant, and with abdomen, falling, Epstein-Barr virus infection,
postoperative oliguria, initiate therapy no sooner than 6 esophagitis, excessive crying, fever, exfoliative
hours and within 24 hours post-transplant, or until renal dermatitis, fatigue, flaccid paralysis, flatulence, flu-like
function displays evidence of recovery. symptoms, flushing, gastric ulcer, gastritis,
gastroenteritis, GERD, GI hemorrhage, GI perforation,
Hepatic Impairment: graft complications, hallucination, gout, headache,
Use lowest recommended dose. Additional dose reductions hematuria, hemolytic/hypochromic anemia,
may be necessary. hemorrhage, hemorrhagic stroke, hepatic injury, hearing
loss, hepatitis, hernia, herpes simplex infection,
Precautions: hirsutism, hiccups, hydronephrosis, hyper-/hypokalemia,

L
WARNING: Should be administered under the hypersensitivity reaction, hyperphosphatemia,
supervision of a physician experienced in hypercalcemia, hypoglycemia/ hyperglycemia,
immunosuppressive therapy and organ hypertension, hypertonia, hypertrophic cardiomyopathy,
transplantation in a facility appropriate for hypervolemia, hypocalcemia, hyponatremia, increased
monitoring and managing therapy. appetite, hypoesthesia, hypomagnesemia,
May contain lactose. NOT recommended for hypophosphatemia, hypotension, hypotrichosis,
patients who may be lactose intolerant. infection, leg cramps, insomnia, intestinal obstruction,
ischemic heart disease, jaundice, Kaposi’s sarcoma,
May be associated with the development of mood elevation, leukocytosis, leukopenia, localized
lymphoma and other malignancies. phlebitis, malignant neoplasm of bladder, malignant
Increased risk of infection, such as bacterial, viral, neoplasm of thyroid (papillary), mental status changes,
fungal, and protozoal infections, including muscle weakness of the extremities, myalgia,
opportunistic infections. myasthenia, MI, muscle spasm, myoclonus, nausea,
nervousness, neuropathy, neurotoxicity, nightmares,
Cardiovascular effects (e.g. myocardial hypertrophy, nocturia, neutropenia, oliguria, orthostatic hypotension,
prolongation of the QT/QTc and torsade de pointes); oral candidiasis, osteopenia, osteoporosis, otalgia, otitis
hypertension externa, otitis media, pancreatic disease (pseudocyst),
Diabetes mellitus, post-transplant (new-onset diabetes and pancreatitis, paresis, paresthesia, pericardial effusion,
insulin-dependent post-transplant diabetes mellitus may pancytopenia, peripheral edema, peripheral neuropathy,
occur); hyperkalemia (mild-to-severe); gastrointestinal peritonitis, pharyngitis, phlebitis, pleural effusion,
perforation peripheral vascular disease, pneumonia, pneumothorax,
Infections (may result in serious and fatal outcomes; latent polycythemia, polyoma virus infection, postoperative
viral infections may be activated); malignancy (e.g. pain, postoperative wound complication, proteinuria,
lymphoma, skin malignancies, post-transplant pruritus, skin rash, psychosis, pulmonary disease,
lymphoproliferative disorder; pure red cell aplasia / pulmonary edema, pulmonary infiltrates, rectal disease,
PRCA renal disease (BK nephropathy), renal function
Nephrotoxicity abnormality, renal tubular necrosis, respiratory
Neurotoxicity (including tremor, headache, coma, delirium, depression, respiratory failure, respiratory tract infection,
seizures, posterior reversible encephalopathy rhinitis, seizure, sepsis, tachycardia, serious infection,
syndrome). sinusitis, skin discoloration, skin neoplasm, skin
photosensitivity, stomach cramps, stomatitis, syncope,
Adverse Drug Reactions: thrombocytopenia, thrombosis, tinea versicolor, tinnitus,
Common: Abdominal pain, abnormal dreams, abnormal toxic nephrosis, tremor, urinary frequency, urinary
hepatic function tests, abnormality in thinking, abscess, incontinence, urinary retention, urinary tract infection,
acidosis, acne vulgaris, acute renal failure, agitation, urinary urgency, vasodilatation, ventricular premature
albuminuria, alkalosis, allergic rhinitis, alopecia, contractions, vaginitis, vertigo, visual disturbance, voice
amblyopia, amnesia, anasarca, anemia, angina pectoris, disorder, vomiting, weakness, weight changes, wound
anorexia, anuria, anxiety, aphasia, aphthous stomatitis, healing impairment, writing difficulty
arthralgia, arthropathy, ascites, asthma, ataxia, Less Common: Adult respiratory distress syndrome,
atelectasis, atrial fibrillation, atrial flutter, back pain, agranulocytosis, anaphylactoid reaction, basal cell
bacterial infection, bladder spasm, blood coagulation carcinoma, anaphylaxis, angioedema, biliary tract
disorder, blurred vision, bradycardia, brain disease, disease (stenosis), cerebrovascular accident, coma,
bronchitis, bruise, cardiac arrest, cardiac arrhythmia, deafness, delirium, disseminated intravascular

393
 ANTINEOPLASTIC AND IMMODULATING AGENTS

coagulation, dysarthria, blindness, graft versus host Spironolactone (hyperkalemic effect), Sirolimus,
disease, hemiparesis, hemolytic-uremic syndrome, Tacrolimus (Topical), Temsirolimus
hepatic cirrhosis, hepatic failure, hemorrhagic cystitis,
hepatic necrosis, hepatic veno-occlusive disease, Increases risk of adverse or toxic effects of the following
hepatosplenic T-cell lymphomas, hepatotoxicity, drugs:
hyperpigmentation, interstitial pulmonary disease, Clozapine (agranulocytosis), Cyclosporine, Systemic
leukemia, liver steatosis, lymphoproliferative disorder (nephrotoxic effect), Dipyrone (agranulocytosis;
(post-transplant or related to EBV), malignant lymphoma, pancytopenia), Leflunomide (hematologic toxicity such
malignant melanoma, multiorgan failure, as pancytopenia, agranulocytosis, and/or
leukoencephalopathy, mutism, prolonged partial thrombocytopenia), Natalizumab (concurrent infection),
thromboplastin time, osteomyelitis, optic atrophy, Sirolimus, Temsirolimus
photophobia, polyarthritis, progressive multifocal Vaccines, Live virus (infection)
leukoencephalopathy, prolonged QT interval, pulmonary
hypertension, pure red cell aplasia, quadriplegia, Increases serum concentration of Tacrolimus:
rhabdomyolysis, status epilepticus, septicemia, Antidepressants, Serotonin Reuptake Inhibitor /
reversible posterior leukoencephalopathy syndrome, Antagonist, Boceprevir, Chloramphenicol, Conivaptan,
squamous cell carcinoma, Stevens-Johnson syndrome, Crizotinib, Cyclosporine (Systemic), CYP3A4 Inhibitors,
SVT, supraventricular extrasystole, thrombocytopenic Dasabuvir, Fluconazole, Fusidic Acid, (Systemic),
purpura, thrombotic thrombocytopenic purpura, Grapefruit Juice, Itraconazole, Ketoconazole (Systemic),
torsades de pointes, toxic epidermal necrolysis, urticaria, Posaconazole, Protease Inhibitors, e.g., Lopinavir, Proton
venous thrombosis, ventricular fibrillation Pump Inhibitors, e.g., Omeprazole, Ritonavir,
Voriconazole
Drug Interactions:
L

Monitor closely with: Increases serum concentration of the following drugs:

Enhances therapeutic effect of Tacrolimus: Afatinib, Bosutinib, Colchicine (enhanced distribution),
Trastuzumab (neutropenic effect) Dabigatran Etexilate, Doxorubicin (Conventional),
Everolimus, Pazopanib, Silodosin, Topotecan, Vincristine
Enhances therapeutic effect of the following drugs: (Liposomal)
Moderate Risk QTc-Prolonging Agents, Indeterminate
Risk and Risk Modifying Reduces therapeutic effect of the following drugs:
BCG, Intravesical, Vaccines (immune response)
Increases risk of adverse or toxic effects of Tacrolimus:
Denosumab (serious infections), Levofloxacin, Systemic FOOD INTERACTION. Grapefruit juice may increase serum
(QTc-prolonging effect), NSAIDs (nephrotoxic effect) level and/or toxicity of tacrolimus.

Increases risk of adverse or toxic effects of the following Administration: May be administered with or without food. If
drugs: GI intolerance occurs and food becomes necessary,
Fenofibrate and its Derivatives (nephrotoxic effect) administer consistently with regard to timing and
composition of meals. Food decreases rate and extent of
Reduces diagnostic effect of Coccidioides immitis Skin Test absorption. High-fat meals have the most pronounced
effect.
Reduces therapeutic effect of Antidiabetic Agents
NOTE: If dosed once daily, administer in the morning. If twice
Avoid concomitant use with: daily, administer 12 hours apart. If the morning and
Decreases serum concentration of Tacrolimus: evening doses differ, administer the larger dose in the
Dabrafenib, Efavirenz, Enzalutamide, Mitotane, morning. If dosed 3 times daily, administer 8 hours apart.
Rifamycin Derivatives (e.g., Rifampicin), Sirolimus,
Temsirolimus For combination therapy with everolimus in liver
transplant, administer both doses at the same time.
Enhances absorption of Tacrolimus:
Ethyl Alcohol Immediate release and extended release capsules are
NOT interchangeable or substitutable. Serious adverse
Enhances therapeutic effect of Tacrolimus: events, including organ rejection, may occur.
Roflumilast (immunosuppressive effect)
Limit exposure to sunlight and ultraviolet light by wearing
Enhances therapeutic effect of the following drugs: protective clothing and using effective sunscreen to
Dronedarone (QTc-prolonging effect). Highest Risk QTc- minimize the risk for malignancy.
Prolonging Agents, (Indeterminate Risk and Risk
Modifying), Tofacitinib (immunosuppressive effect) Pregnancy Category: C

Increases risk of adverse or toxic effects of Tacrolimus: ATC Code: L04AD02

Cyclosporine, Systemic (nephrotoxic effect),
Eplerenone (hyperkalemic effect), Foscarnet
(nephrotoxic effect), Mifepristone (QTc-prolonging
effect), Pimecrolimus, Potassium-Sparing Diuretics, e.g.,

394
ANTINEOPLASTIC AND IMMODULATING AGENTS

OTHER IMMUNOSUPPRESSANTS Precautions:

WARNING: Should be prescribed by physicians
Rx AZATHIOPRINE familiar with the risks, including hematologic
toxicities and mutagenic potential. Adequate
Oral: 50 mg tablet laboratory and supportive medical resources must
be readily available.
An imidazolyl derivative of mercaptopurine, which
incorporates its metabolites into replicating DNA, Patients with thiopurine methyltransferase (TPMT)
stopping replication. It also blocks the pathway for purine activity are at risk for developing severe, life-
synthesis. threatening myelotoxicity. Conduct TPMT testing in
abnormally low CBC unresponsive to dose
Indications: Adjunctive therapy in prevention of rejection of reduction. Consider discontinuation in abnormal
kidney transplants; treatment of active rheumatoid blood counts unresponsive to dose reduction.
arthritis (RA); second line therapy for steroid-refractory
chronic idiopathic thrombocytopenic purpura (ITP). Increases risk of developing malignancy.
Lymphoma (post-transplant) and hepatosplenic T-
Contraindication: Pregnancy cell lymphoma (in inflammatory bowel disease)
have been reported.
Dose:
Renal transplantation, by mouth, ADULT, initially 3–5 mg/kg Gastrointestinal toxicity (e.g. severe nausea, vomiting,
daily, usually as a single daily dose, then 1–3 mg/kg daily diarrhea, rash, fever, malaise, myalgia, hypotension, and
as maintenance [NOTE: Treatment usually started the day of liver enzyme abnormalities)

L
transplant; has been initiated, rarely, 1–3 days prior to Hematologic toxicity (dose-related hematologic toxicities,
transplant]. i.e., leukopenia, thrombocytopenia, and anemias,
Rheumatoid arthritis, by mouth, ADULT, initially 1 mg/kg including macrocytic anemia or pancytopenia)
daily (50–100 mg) given once daily or divided twice daily Hepatotoxicity; Infections
for 6–8 weeks; may increase by 0.5 mg/kg every 4 Malignancy (HSTCL, a rare white blood cell cancer that is
weeks until response or up to 2.5 mg/kg daily; an usually fatal, may occur)
adequate trial should be a minimum of 12 weeks; reduce Elderly (increased toxicity)
dose by 0.5 mg/kg (~25 mg daily) every 4 weeks until
lowest effective dose is reached to determine Adverse Drug Reactions:
maintenance dose; may be discontinued abruptly but Common and Less Common: Abdominal pain, acute
monitor for delayed toxicities. myelocytic leukemia, alopecia, arthralgia, bone marrow
Steroid-refractory chronic idiopathic thrombocytopenic depression, anemia, diarrhea, fever, hemorrhage,
purpura, by mouth, the starting dosage is 1- hepatic veno-occlusive disease, hepatosplenic T-cell
3mg/kg/body weight/day and should be adjusted lymphomas, hepatotoxicity, hypersensitivity,
according to the clinical response and haematological hypotension, increased susceptibility to infection,
tolerance. The maintenance dosage required may range interstitial pneumonitis (reversible), JC virus infection,
from less than 1 mg/kg body weight/day to 3 leukopenia, macrocytic anemia, malaise, malignant
mg/kg/body weight/day depending on the clinical lymphoma, malignant neoplasm of skin, myalgia, nausea
condition being treated and the individual patient and vomiting, negative nitrogen balance, neoplasia,
response including haematological tolerance. pancreatitis, progressive multifocal
leukoencephalopathy, skin rash, steatorrhea, Sweet's
Dose Adjustment: syndrome (acute febrile neutrophilic dermatosis),
Geriatric: pancytopenia, thrombocytopenia
Start with lowest recommended adult dose. Adjust dose to
creatinine clearance. Drug Interactions:
Monitor closely with:
Renal Impairment: Decreases metabolism of Azathioprine:
For CrCl 10–50mL/minute and patients undergoing CRRT, 5-ASA Derivatives, e.g., Mesalazine, Sulfasalazine
administer 75% of normal dose.
For CrCl <10 mL/minute and patients undergoing Enhances therapeutic effect of Azathioprine:
hemodialysis, administer 50% of normal dose. ACE Inhibitors, e.g., Captopril, Enalapril
Oliguric patients, particularly those with tubular necrosis in (myelosuppressive effect), Sulfamethoxazole
the immediate post-transplant period may have delayed (myelosuppressive effect), Trastuzumab (neutropenic
clearance, administer lower doses. effect), Trimethoprim (myelosuppressive effect)

Increases risk of adverse or toxic effects of Azathioprine:

Denosumab (serious infections)

Increases risk of adverse or toxic effects of

Cyclophosphamide (hepatotoxic effect)

Reduces diagnostic effect of Coccidioides immitis Skin Test

395
 ANTINEOPLASTIC AND IMMODULATING AGENTS

Reduces therapeutic effect of Vitamin K Antagonists, e.g.,

Warfarin (anticoagulant effect)

Avoid concomitant use with:

Enhances immunosuppressive effect of Azathioprine:
Roflumilast

Enhances therapeutic effect of the following drugs:

Mercaptopurine (myelosuppressive effect)
Tofacitinib (immunosuppressive effect)

Increases risk of adverse or toxic effects of Azathioprine:

Pimecrolimus, Tacrolimus (Topical)

Increases risk of adverse or toxic effects of the following

drugs:
Leflunomide (hematologic toxicity such as pancytopenia,
agranulocytosis, and/or thrombocytopenia),
Natalizumab (concurrent infection), Live Vaccines
(infection)

Increases serum concentration of Azathioprine:

Allopurinol, Febuxostat, Ribavirin
L

Reduces therapeutic effect of the following drugs:

BCG (Intravesical), Vaccines (immune response)

Administration: Administering after meals or in divided

doses may decrease adverse GI events.
NOTE: When used concomitantly with allopurinol, reduce azathioprine
dose to one-third or one-fourth the usual dose. Patients with low
or absent TPMT activity may require further dose reductions or
discontinuation.

Limit exposure to sunlight and ultraviolet light by wearing

protective clothing and using effective sunscreen to minimize the
risk for malignancy.

Pregnancy Category: D

ATC Code: L04AX01

396
MUSCULO-SKELETAL SYSTEM

Neonates (regular use of high doses could impair platelet

MUSCULO-SKELETAL SYSTEM function and produce hypoprothrombinemia if neonatal
vitamin K stores are low; possible risk of Reye
syndrome).
Pregnancy (avoid analgesic doses, if possible, in the last few
ANTIINFLAMMATORY AND weeks).
ANTIRHEUMATIC PRODUCTS
Adverse Drug Reactions:
Common: Abdominal pain, asymptomatic blood loss, back
NON-SELECTIVE COX INHIBITORS pain, bleeding time increased, diarrhea, dyspepsia,
dyspnea, epistaxis, fatigue, GI irritation, headache,
malaise, melena, nausea, vomiting
Rx ASPIRIN Less Common: Anorexia, asthenia, confusion, dizziness,
fever, flushing, gastritis, hemorrhage rectum,
hemorrhoids, thirst, hypoglycemia (children),
Oral: 80 mg, 100 mg, 300 mg and 325 mg tablet
hypotension, myalgia, palpitations, syncope,
tachycardia, tinnitus, vertigo
An irreversible, cyclooxygenase (COX) inhibitor, which
Rare: Arrhythmia, convulsions, deafness, edema, GI ulcer
prevents platelet aggregation, and is useful in the long-
and perforation, intracranial hemorrhage,
term management of MI and the prevention of further
hypersensitivity reactions, including Stevens-Johnson
attacks.
syndrome; interstitial nephritis, iron-deficiency anemia,
myocarditis, paresthesia, renal insufficiency, seizures,
Indications: Pain and inflammation associated with
thrombocytopenia, toxic epidermal necrolysis
musculoskeletal and join disorders; juvenile rheumatoid
arthritis
Drug Interactions:

M
Monitor closely with:
Contraindications: Children and adolescents <16 years (risk
Enhances therapeutic effect of Aspirin:
of Reye syndrome); active peptic ulceration or bleeding
Valproic Acid (blood coagulation; platelet function)
GI ulcers; hemophilia and other bleeding disorders;
aspirin-sensitive asthma; thrombocytopenia; ulcerative
Enhances therapeutic effect of the following drugs:
colitis; lactating mothers; acute hemorrhagic stroke or
Oral Hypoglycemics, Phenytoin, Valproic Acid
intracerebral bleeding
Increases risk of adverse or toxic effects of Aspirin:
Dose:
Corticosteroids (GI bleeding and ulceration)
Pain and inflammation associated with musculoskeletal
and join disorders, by mouth, ADULT, initially 2.4–3.6 g
Increases risk of adverse or toxic effects of the following
daily in divided doses; usual maintenance dose, 3.6–5.4
drugs:
g daily.
Anticoagulant Therapy, e.g., Heparin, Warfarin
Juvenile rheumatoid arthritis, by mouth, CHILD, 80 to 100
(bleeding), Valproic Acid
mg/kg daily in 5 or 6 divided doses, up to 130 mg/kg
daily in acute exacerbations if necessary.
Avoid concomitant use with:
Increases excretion of Aspirin:
Dose Adjustment:
Antacids, e.g., Aluminum and Magnesium Hydroxide
Renal Impairment:
For mild-to-moderate renal impairment, dose adjustments
Increases risk of adverse or toxic effects of the following
are not necessary.
drugs:
For severe impairment, the drug is not recommended.
ACE Inhibitors, e.g., Enalapril (renal impairment when
aspirin is given in doses of >300 mg daily), NSAIDs, e.g.,
Hepatic Impairment:
Ibuprofen, Naproxen (gastric ulceration)
Avoid use in severe liver disease.
Reduces therapeutic effect of Aspirin:
Precautions:
NSAIDs, e.g., Ibuprofen, Naproxen (anti-platelet activity;
Increased risk of gastritis and GI bleeding;
cardioprotective effect)
Asthma;
Urticaria;
Reduces therapeutic effect of the following drugs:
Allergic disease;
ACE Inhibitors, e.g., Enalapril (hyponatremic and
Uncontrolled hypertension;
hypotensive effect), Diuretics, e.g., Spironolactone
Renal impairment (avoid use; due to sodium and water
(inhibition of renal prostaglandins)
retention – deterioration in renal function may increase
risk of GI bleeding);
Administration: Take tablets from packaging immediately
Hepatic impairment (avoid in severe impairment – there is
before use. Should be taken with food or immediately
increased risk of GI bleeding);
after meals.
G6PD-deficiency;
Dehydration;
Pregnancy Category: C; D in 3rd trimester
Gout;
Elderly;
ATC Code: Not Available

397
 MUSCULO-SKELETAL SYSTEM

Increased risk of serious GI adverse reactions,

Rx DICLOFENAC including bleeding, inflammation, ulceration, and
perforation of the stomach or intestines, which can
Oral: 25 mg and 50 mg tablet or capsule (as sodium or be fatal. May occur at any time during use and
potassium salt) without warning symptoms.
50 mg enteric-coated or MR tablet (as sodium salt) Do NOT interchange products. Different formulations
100 mg MR tablet or capsule (as sodium or of oral diclofenac are not bioequivalent, even if the
potassium salt) milligram strength is the same.
Inj.: 25 mg/mL (as sodium salt), 3 mL ampule (IM, IV)

A reversible cyclooxygenase­1 and 2 (COX­1 and -2) inhibitor Anaphylactoid reactions;

that acts by decreasing the formation of prostaglandin Skin reactions;
precursors. It exhibits antipyretic, analgesic, and anti- Asthma;
inflammatory properties. CNS effects e.g. drowsiness, dizziness, blurred vision, and
other neurologic effects;
Indications: Relief of signs and symptoms of rheumatoid Genitourinary effects e.g. cystitis, or hematuria;
arthritis and osteoarthritis; ankylosing spondylitis Hematologic effects e.g. anemia and prolonged bleeding
time;
Contraindications: Treatment of perioperative pain in the Dehydration;
setting of coronary artery bypass graft (CABG) surgery Hepatic effects;
[Inj.]: Moderate to severe renal impairment in the Renal effects;
perioperative period and who are at risk for volume Renal disease;
depletion Diabetes;
Elderly;
Dose: Lactation (breast-feeding is not recommended; use with
caution in breast­feeding women).
M

Rheumatoid arthritis, by mouth, ADULT, immediate-release

tablet, 150-200 mg daily in 3-4 divided doses;
delayed-release tablet, 150-200 mg daily in 3-4 divided SKILLED TASKS. May cause drowsiness or blurred vision.
doses; Avoid performing tasks, which require mental alertness,
extended-release tablet, 100 mg daily, may increase e.g., operating machinery or driving.
dose to 200 mg daily in 2 divided doses.
Osteoarthritis, by mouth, ADULT, immediate-release tablet, Adverse Drug Reactions:
150-200 mg daily in 3-4 divided doses; Common: Edema, MI, cerebrovascular accident,
delayed-release tablet, 150-200 mg daily in 2-4 divided hypertension, significant cardiovascular event,
doses; headache, dizziness, procedural pain, falling, pruritus,
extended-release tablet, 100 mg daily, may increase skin rash, exfoliative dermatitis, Stevens-Johnson
dose to 200 mg daily in 2 divided doses; syndrome, toxic epidermal necrolysis, constipation,
immediate-release capsule, 35 mg 3 times daily. abdominal pain or discomfort, fluid retention, diarrhea,
Ankylosing spondylitis, by mouth, ADULT, delayed-release dyspepsia, esophageal perforation, flatulence, UTI, GI or
tablet, 100-125 mg daily in 4-5 divided doses. duodenal ulcer, heartburn, intestinal perforation,
nausea, vomiting, bruise, anemia, hemorrhage,
Dose Adjustment: prolonged bleeding time, anaphylactoid reaction,
Geriatric: infusion site reaction, tinnitus, influenza, osteoarthritis,
Initiate therapy using the lowest recommended dose and arthralgia, back pain, limb pain, renal insufficiency, renal
frequency. function abnormality, wound healing impairment, GI
inflammation, upper respiratory tract infection,
Renal Impairment: nasopharyngitis, sinusitis, cough, bronchitis
In patients with advanced renal disease or significant renal Less Common: Abnormal dreams, agranulocytosis,
impairment, use is not recommended. alopecia, anaphylactoid reaction, anaphylaxis,
angioedema, anxiety, aplastic anemia, aseptic
Hepatic Impairment: meningitis, auditory impairment, azotemia, asthma,
May require dose adjustment. Drug undergoes extensive blurred vision, cardiac arrhythmia, cardiac failure,
hepatic metabolism. cerebrovascular accident, change in appetite, chest
In moderate to severe impairment, use of injectables is not pain, coma, confusion, colitis, congestive heart failure,
recommended (has not been studied). conjunctivitis, convulsions, cystitis, depression,
diaphoresis, diplopia, disorientation, drowsiness,
Precautions: dyspnea, dysuria, ecchymoses, eosinophilia, eructation,
erythema multiforme, esophageal ulcer, exfoliative
WARNING: May cause an increased risk of serious dermatitis, fever, esophagitis, fluid retention, fulminant
cardiovascular thrombotic events, MI, and stroke, hepatitis, gastritis, gastrointestinal hemorrhage,
which can be fatal. Risk may increase with duration glossitis, hallucination, hematemesis, hematuria,
of use. hearing loss, hemolytic anemia, hepatic failure, hepatic
necrosis, hepatotoxicity, peptic ulcer, hepatitis,
hypertension, hypotension, skin photosensitivity,
infection, insomnia, interstitial nephritis, intestinal
perforation, jaundice, sepsis, leukopenia,

398
MUSCULO-SKELETAL SYSTEM

lymphadenopathy, malaise, melena, memory Increases risk of adverse or toxic effects of Diclofenac:
impairment, meningitis, nervousness, oliguria, Dexketoprofen, Floctafenine, Ketorolac, Morniflumate,
palpitations, pancreatitis, pancytopenia, paresthesia, NSAIDs, Selective Serotonin Reuptake Inhibitors
pneumonia, polyuria, proteinuria, psychotic reaction, (antiplatelet effect), Sodium Phosphates (nephrotoxic
purpura, rectal hemorrhage, renal failure, renal papillary effect, specifically acute phosphate nephropathy),
necrosis, respiratory depression, seizure, stomatitis, Talniflumate
syncope, taste disorder, tachycardia, thrombocytopenia,
toxic epidermal necrolysis, tremor, urticaria, vasculitis, Increases risk of adverse or toxic effects of the following
vertigo, weakness, weight changes, xerostomia drugs:
Apixaban (bleeding), Corticosteroids Systemic
Drug Interactions: (nephrotoxicity; hypertension), COX-2 Inhibitors,
Monitor closely with: Cyclosporine Systemic (nephrotoxic effect), Herbs with
Decreases excretion of Aminoglycosides Anticoagulant / Antiplatelet Properties, Salicylates
[Choline Magnesium Trisalicylate] (bleeding),
Enhances therapeutic effect of the following drugs: Omacetaxine (bleeding-related events), Tenofovir
ACE Inhibitors (antihypertensive effect), Agents with (tenofovir-associated nephrotoxicity)
Antiplatelet Properties, Anticoagulants
Increases serum concentration of Diclofenac:
Increases risk of adverse or toxic effects of Diclofenac: Corticosteroids Systemic, Voriconazole
ACE Inhibitors (significantly decreased renal function),
Angiotensin II Receptor Blockers (significantly decreased Increases serum concentration of the following drugs:
glomerular filtration and renal function), (antiplatelet Corticosteroids Systemic, Lithium, Methotrexate,
effect), Dasatinib, Thrombolytic Agents (anticoagulant Pemetrexed, Tizanidine [if concomitant use cannot be
effect), Glucosamine Multivitamins / Fluoride with ADE, avoided, initiate tizanidine at 2 mg and increase in 2–4
Multivitamins / Minerals with ADEK, Folate, Iron, mg increments based on patient response]

M
Multivitamins / Minerals with AE, no Iron, Omega-3 Fatty
Acids, Pentoxifylline, Prostacyclin Analogues, Serotonin / Reduces absorption of Diclofenac:
Norepinephrine Reuptake Inhibitors, Tipranavir, Vitamin Bile Acid Sequestrants e.g. Cholestyramine
E, Antidepressants, Tricyclic or Tertiary Amine
(antiplatelet effect), Ibrutinib, Limaprost (antiplatelet Reduces therapeutic effect of the following drugs:
effect), Pentosan Polysulfate Sodium, Treprostinil Loop Diuretics (diuretic effect), Salicylates [Choline
(bleeding) Magnesium Trisalicylate] (cardioprotective effect),
Selective Serotonin Reuptake Inhibitors
Increases risk of adverse or toxic effects of the following
drugs: Administration: May be taken with food or milk to decrease
5-ASA Derivatives, Aliskiren, Tacrolimus Systemic GI distress.
(nephrotoxic effect), Bisphosphonate Derivatives (GI
ulceration; nephrotoxicity), Collagenase Systemic Do NOT crush modified-release tablets.
(injection site bruising and/or bleeding), Deferasirox (GI
ulceration, irritation, or bleeding), Deoxycholic Acid For IV route, administer as an IV bolus over 15 seconds.
(bleeding or bruising in the treatment area), Injection dosage form is not indicated for long-term use.
Desmopressin, Drospirenone (hyperkalemic effect),
Eplerenone, Potassium-sparing Diuretics (hyperkalemic NOTE: Some products may contain phenylalanine.
effect), Haloperidol (drowsiness; confusion),
Ibritumomab (impaired platelet function; increased risk Pregnancy Category: C; D (≥30 weeks gestation)
of bleeding), Obinutuzumab (serious bleeding-related
events), Porfimer, Verteporfin (photosensitizing effect), ATC Code: M01AB05
Quinolone Antibiotics e.g. Ciprofloxacin (neuroexcitatory
and/or seizure-potentiating effect), Salicylates
(bleeding), Tositumomab, Iodine I131 Tositumomab
OTC IBUPROFEN
Reduces therapeutic effect of the following drugs:
Aliskiren, Angiotensin II Receptor Blockers, Beta Blockers Oral: 200 mg and 400 mg tablet
[except Levobunolol, Metipranolol], Eplerenone, 100 mg/5 mL syrup/suspension, 60 mL
Hydralazine, Potassium-sparing Diuretics 200 mg/5 mL suspension, 60 mL
(antihypertensive effect), Prostaglandins Ophthalmic,
Thiazide Diuretics A propionic acid-derived, nonselective, nonsteroidal anti-
inflammatory medicine, which is useful for the
Avoid concomitant use with: management of pain due to inflammation.
Decreases serum concentration of Diclofenac:
Salicylates Indications: Acute pain and inflammation in rheumatic
diseases and other musculoskeletal disorders
Enhances therapeutic effect of the following drugs:
Dabigatran Etexilate, Rivaroxaban, Urokinase, Vitamin K Contraindications: Active or history of peptic ulceration
Antagonists (anticoagulant effect)

399
 MUSCULO-SKELETAL SYSTEM

Dose: Aspirin (antiplatelet activity; cardioprotective effect),

Inflammatory musculoskeletal disorders, by mouth, ADULT, Diuretics, e.g., Loop Diuretics, Thiazide Diuretics (diuretic
1.2–1.8 g daily in 3–4 divided doses, increased if effect)
necessary (maximum dose, 2.4 g daily; 3.2 g daily in
inflammatory disease); maintenance dose of 0.6–1.2 g Avoid concomitant use with:
daily may be sufficient. Enhances therapeutic effect of Vitamin K Antagonists, e.g.,
Warfarin (anticoagulant effect)
Dose Adjustment:
Renal and Hepatic Impairment: Increases risk of adverse or toxic effects of Ibuprofen:
Keep dose as low as possible. Alendronate (gastric ulceration), Drugs Affecting Clotting
Process, e.g., Ketorolac (bleeding, including GI bleeding),
Precautions: Vitamin K Antagonists, e.g., Warfarin (serious bleeding)
WARNING: Associated with an increased risk of
adverse cardiovascular thrombotic events, Increases risk of adverse or toxic effects of the following
including fatal MI and stroke. drugs:
May increase risk of GI irritation, inflammation, Drugs which are Renally Excreted, e.g., Calcineurin
ulceration, bleeding, and perforation. Inhibitors, Drugs which Increase Potassium
Concentration, e.g., Amiloride, Triamterene
(hyperkalemia)
Renal impairment;
Hepatic impairment; Reduces therapeutic effect of the following drugs:
Cardiac disease; Antihypertensives, e.g., Beta Blockers, ARBs
Coagulation defects; (hypotensive effect)
Allergic disorders.
Elderly; Administration: Should be taken with food.
Pregnancy (avoid use unless the potential benefit outweighs
M

risk; third trimester); Pregnancy Category: C, prior to 30 weeks gestation; D, ≥30

Lactation. weeks gestation
Adverse Drug Reactions: ATC Code: M01AE01
Common: Diarrhea, dizziness, dyspepsia, headache, GI
ulceration or bleeding, hemorrhage, hypertension,
nausea, raised liver enzymes, salt and fluid retention,
vomiting OTC NAPROXEN
Less Common: Bronchospasm, confusion, heart failure,
esophageal ulceration, hyperkalemia, rash, renal
Oral: 275 mg (as sodium salt) (250 mg base) and 550 mg
impairment
(as sodium salt) (500 mg base) tablet
Rare: Acute renal failure, aseptic meningitis, blood
dyscrasias, blurred vision, colitis, cystitis, fluid retention,
A naphthyl-propionic acid-derived, nonsteroidal anti-
hepatitis, stroke, anaphylactic and anaphylactoid
inflammatory medicine, that inhibits prostaglandin
reactions, interstitial nephritis, MI, nephrotic syndrome,
synthesis. It is pharmacologically related to ibuprofen but
photosensitivity reaction, Stevens-Johnson syndrome,
has a longer half-life.
tinnitus, toxic epidermal necrolysis, vertigo
Indications: Rheumatoid arthritis; osteoarthritis; ankylosing
Drug Interactions:
spondylitis; juvenile idiopathic arthritis; for the relief of
Monitor closely with:
signs and symptoms of tendonitis and bursitis; acute
Increases risk of adverse or toxic effects of Ibuprofen:
gout; management of pain due to inflammation (e.g.,
Angiotensin II Receptor Blockers (significantly decreased
period pain, migraine); management of primary
renal function), Corticosteroids Oral, e.g., Hydrocortisone
dysmenorrhea; inflammatory joint pain
(gastric ulceration), Digoxin (reduced renal function),
Other NSAIDs
Contraindications: Treatment of perioperative pain in the
setting of Coronary Artery Bypass Graft (CABG) surgery;
Increases risk of adverse or toxic effects of the following
active peptic ulcers; active GI inflammatory disease
drugs:
ACE Inhibitors (renal impairment; hyperkalemia),
Dose:
Atenolol, Ciprofloxacin, Levofloxacin (convulsions),
Acute gout, by mouth, ADULT, initially 750 mg, followed by
Digoxin (exacerbation of heart failure), Diuretics e.g.,
250 mg every 8 hours until the attack subsides.
Loop Diuretics, Thiazide Diuretics (nephrotoxicity)
Acute musculoskeletal disorders, by mouth, ADULT, initially
500 mg, then 250 mg 2-3 times daily.
Increases serum concentration of Digoxin
Ankylosing spondylitis, osteoarthritis, rheumatoid arthritis,
by mouth, ADULT, 500 mg to 1 g daily in 2 divided doses;
Reduces therapeutic effect of the following drugs:
may increase to 1.5 g daily of naproxen base if tolerating
ACE Inhibitors, Angiotensin II Receptor Blockers
well and clinically indicated (for a limited period, <6
(antihypertensive effect)
months).
Dysmenorrhea, by mouth, ADULT, initially 500 mg, followed
by 250 mg every 6-8 hours as required.

400
MUSCULO-SKELETAL SYSTEM

Inflammatory joint pain, by mouth, ADULT, 500 mg twice retention, gross bleeding or perforation; headache,
daily. heartburn, hemolysis, indigestion, lightheadedness,
Juvenile idiopathic arthritis, by mouth, CHILD >2 years, 10 nausea, palpitation, pruritus, pseudoporphyria, rash,
mg/kg daily in 2 divided doses (up to 15 mg/kg daily has skin eruption, stomatitis, tinnitus, ulcers, vertigo, visual
been tolerated). disturbance, vomiting
Pain (mild to moderate), acute tendonitis, bursitis, by Rare: Allergic pneumonitis, aplastic anemia, aseptic
mouth, ADULT, initially 500 mg, followed by 500 mg meningitis, cognitive dysfunction, erythema multiforme,
every 12 hours or 250 mg every 6-8 hours (maximum hemolytic anemia, hepatic impairment, non-peptic GI
daily dose; Day 1: 1.25 g naproxen base; subsequent ulceration, Stevens-Johnson syndrome, toxic epidermal
daily doses should not exceed 1 g naproxen base). necrolysis, ulcerative stomatitis, vasculitis

NOTE: For relief of acute pain, naproxen sodium may be Drug Interactions:
preferred due to more rapid absorption and onset. Monitor closely with:
Decreases excretion of Aminoglycosides
Dose Adjustment:
Renal Impairment: Increases risk of adverse or toxic effects of Naproxen:
In mild impairment, reduce dose due to nephrotoxicity. ACE Inhibitors (renal impairment), Angiotensin II
In moderate to severe impairment, avoid use. Receptor Blockers (decreased renal function),
Corticosteroids Oral (gastric ulceration), Other NSAIDs
Hepatic Impairment:
In severe impairment, avoid use due to hepatotoxicity. Increases risk of adverse or toxic effects of the following
drugs:
Precautions: ACE Inhibitors (hyperkalemia), Diuretics, e.g., Loop
WARNING: NSAIDs are associated with an increased Diuretics, Thiazide Diuretics (nephrotoxicity), Quinolone
risk of adverse cardiovascular thrombotic events, Antibiotics (neuroexcitatory and/or seizure-potentiating

M
including fatal MI and stroke. effect)
NSAIDs may increase risk of GI irritation,
inflammation, ulceration, bleeding, and Reduces therapeutic effect of the following drugs:
perforation. ACE Inhibitors, Angiotensin II Receptor Blockers
(antihypertensive effect), Diuretics, e.g., Loop Diuretics,
Thiazide Diuretics (renal function; diuretic effect)
Anaphylactoid reactions may occur (do not use in patients
who experience bronchospasm, asthma, rhinitis, or Avoid concomitant use with:
urticaria with aspirin or NSAID therapy); Enhances therapeutic effect of Vitamin K Antagonists, e.g.,
Cardiovascular events (use the lowest effective dose for the Warfarin
shortest duration of time, consistent with individual
patient goals); Increases risk of adverse or toxic effects of Naproxen:
CNS effects e.g. drowsiness, dizziness, blurred vision and Alendronate (gastric ulceration)
other neurologic effects;
In patients with history of GI diseases, or concurrent therapy Increases risk of adverse or toxic effects of the following
with aspirin, anticoagulants and/or corticosteroids, drugs:
smoking, use of alcohol, the elderly or debilitated Drugs affecting clotting process, e.g., Ketorolac
patients; (bleeding, including GI bleeding), Drugs which are renally
Hematologic effects e.g. prolonging bleeding time; excreted e.g., Calcineurin Inhibitors, Drugs which
Hyperkalemia (use of NSAID may increase the risk of increase Potassium Concentration, e.g., Amiloride,
hyperkalemia, particularly in the elderly, diabetics, or Triamterene (hyperkalemia), Vitamin K Antagonists e.g.,
renal disease); Warfarin (serious bleeding)
Skin reactions (discontinue use at first sign of skin rash or
hypersensitivity); Increases serum concentration of Digoxin
Aseptic meningitis;
Hepatic and renal impairment; Reduces therapeutic effect of the following drugs:
Hypertension; Antihypertensives, e.g., Beta Blockers, ARBs, Nitrates
Asthma (reduced antihypertensive effect)
Elderly;
Chronic use of NSAIDs in women of reproductive age may Administration: Administer with food, milk, or antacids to
be associated with infertility, which is reversible upon decrease GI adverse effects (drug may cause GI upset,
discontinuation; bleeding, ulceration, and perforation).
Breastfeeding.
Pregnancy Category: C
SKILLED TASKS. May impair ability to perform skilled tasks,
e.g., operating machinery or driving. ATC Code: M01AE02
Adverse Drug Reactions:
Common: Abdominal pain, bleeding time increased,
constipation, diaphoresis, diarrhea, dizziness,
drowsiness, dyspepsia, dyspnea, edema, flatulence, fluid

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 MUSCULO-SKELETAL SYSTEM

In patients with history of GI diseases (bleeding or ulcers),

Rx KETOPROFEN or concurrent therapy with aspirin, anticoagulants
and/or corticosteroids, smoking, use of alcohol, the
Oral: 100 mg tablet elderly or debilitated patients;
Inj.: 50 mg/mL, 2 mL ampule (IM) Hematologic effects (platelet adhesion and aggregation
may be decreased; thus prolonging bleeding time);
A reversible cyclooxygenase­1 and 2 (COX­1 and 2) inhibitor, Hyperkalemia;
which decreases formation of prostaglandin precursors. Ophthalmic events (blurred or diminished vision has been
It has antipyretic, analgesic, and anti-inflammatory reported);
properties. Skin reactions (may cause serious skin reactions;
discontinue use at first sign of skin rash or
Indications: Osteoarthritis; rheumatoid arthritis hypersensitivity);
Aseptic meningitis;
Contraindications: Perioperative pain in the setting of Hepatic and renal impairment;
coronary artery bypass graft (CABG) surgery Hypertension;
Asthma;
Dose: Surgical or dental procedures (withhold use for at least 4–6
Osteoarthritis or Rheumatoid Arthritis, by mouth, ADULT, 50 half-lives prior to surgical or dental procedures);
mg 4 times daily or 75 mg 3 times daily (maximum, 300 Elderly
mg daily). Pregnancy;
Chronic use of NSAIDs in women of reproductive age may
Dose Adjustment: be associated with infertility, which is reversible upon
Geriatric: discontinuation);
Initial dose should be decreased in patients >75 years. Use Breastfeeding (small amounts are excreted into breast
with caution when changing dosage. milk).
M

Renal Impairment: SKILLED TASKS. May impair ability to perform skilled tasks,
In patients with advanced renal disease, use is not e.g., operating machinery or driving.
recommended.
In patients with mild impairment, maximum dose is 150 mg Adverse Drug Reactions:
daily. Common: Peripheral edema, headache, depression,
In patients with severe impairment (GFR <25 mL/minute dizziness, dreams, insomnia, malaise, nervousness,
per 1.73 m2), maximum dose is 100 mg daily. somnolence, rash, dyspepsia, abdominal pain,
constipation, diarrhea, flatulence, nausea,
NOTE: Some products are contraindicated with severe gastrointestinal bleeding, peptic ulcer, anorexia,
impairment (refer to local product labeling). stomatitis, vomiting, urinary tract irritation, abnormal
liver function test, visual disturbances, tinnitus renal
Hepatic Impairment: dysfunction
In patients with hepatic impairment (serum albumin <3.5 Less Common: Agranulocytosis, allergic reaction, allergic
g/dL), maximum initial dose is 100 mg daily). rhinitis, alopecia, anaphylaxis, anemia, angioedema,
arrhythmia, aseptic meningitis, blurred vision, bone
NOTE: Some products are contraindicated with severe marrow suppression, bronchospasm, buccal necrosis,
impairment (refer to local product labeling). bullous rash, chills, cholestatic hepatitis, confusion, CHF,
conjunctivitis, cystitis, diabetes mellitus (aggravated),
Precautions: drowsiness, dysphoria, dyspnea, eczema, edema,
epistaxis, erythema multiforme, exfoliative dermatitis,
WARNING: May cause an increased risk of serious facial edema, fecal occult blood, fluid retention, gastritis,
cardiovascular thrombotic events, myocardial gastrointestinal perforation, GI ulceration, gynecomastia,
infarction (MI), and stroke, which can be fatal. hallucinations, hearing decreased, hematemesis,
hematuria, hemolytic anemia, hemoptysis, hepatic
Causes an increased risk of serious GI adverse dysfunction, hepatitis, hepatotoxicity (idiosyncratic).
reactions, including bleeding, ulceration, and Peripheral edema, headache, depression, dizziness,
perforation of the stomach or intestines, which can dreams, insomnia, malaise, nervousness, somnolence,
be fatal. These reactions can occur at any time rash, dyspepsia, abdominal pain, constipation, diarrhea,
during use and without warning symptoms. flatulence, nausea, GI bleeding, peptic ulcer, anorexia,
stomatitis, vomiting, urinary tract irritation, abnormal
liver function test, visual disturbances, tinnitus renal
Anaphylactoid reactions may occur (do not use in patients dysfunction, hot flashes, hypertension, hyponatremia,
who experience bronchospasm, asthma, rhinitis, or impotence, infection, interstitial nephritis, intestinal
urticaria with aspirin or NSAID therapy); ulceration, jaundice, laryngeal edema, leukopenia, libido
Cardiovascular events (use the lowest effective dose for the disturbance, melena, microvesicular steatosis, migraine,
shortest duration of time, consistent with individual myocardial infarction, nephrotic syndrome, onycholysis,
patient goals); palpitation, pancreatitis, peptic ulcer, peripheral
CNS effects (may cause drowsiness, dizziness, blurred neuropathy, peripheral vascular disease,
vision and other neurologic effects which may impair photosensitivity, polydipsia, polyuria, pruritus, purpura,
physical or mental ability); purpuric rash, renal failure, renal papillary necrosis,

402
MUSCULO-SKELETAL SYSTEM

retinal hemorrhage, septicemia, shock, Stevens-Johnson Selective Serotonin Reuptake Inhibitors (antiplatelet
syndrome, tachycardia, thrombocytopenia, toxic effect)
amblyopia, toxic epidermal necrolysis, tubulopathy,
ulcerative colitis, urticaria, vasodilation, xerostomia Enhances therapeutic effect of the following drugs:
Cyclosporine Systemic (nephrotoxic effect), Dabigatran
Drug Interactions: Etexilate, Rivaroxaban, Urokinase, Vitamin K Antagonists
Monitor closely with: e.g., Warfarin (anticoagulant effect)
Decreases excretion of the following drugs:
Aminoglycosides, Pralatrexate Increases risk of adverse or toxic effects of Ketoprofen:
Dexketoprofen, Diclofenac Systemic, loctafenine,
Enhances therapeutic effect of Ketoprofen: Ketorolac, Morniflumate, Sodium Phosphates
Tricyclic Antidepressants e.g., Antidepressants, Tertiary (nephrotoxic effect; acute phosphate nephropathy),
Amine, Dasatinib, Glucosamine, Iodine I131 Talniflumate, Tenofovir (Tenofovir-associated
Tositumomab, Multivitamins / Fluoride with ADE, nephrotoxicity)
Multivitamins / Minerals with ADEK, Folate, Iron,
Multivitamins / Minerals with AE, no Iron, Omega-3 Fatty Increases risk of adverse or toxic effects of the following
Acids, Other Agents with Antiplatelet Properties e.g., drugs:
Aspirin, Pentoxifylline, Prostacyclin Analogues, Serotonin Apixaban, Salicylates [except Choline Magnesium
/ Norepinephrine Reuptake Inhibitors e.g. Duloxetine, Trisalicylate] (bleeding), COX-2 Inhibitors e.g. Celecoxib,
Tipranavir, Vitamin E (anticoagulant effect) Omacetaxine (bleeding-related events),

Enhances therapeutic effect of the following drugs: Increases serum concentration of the following drugs:
Anticoagulants, Thrombolytic Agents (anticoagulant Dabigatran Etexilate, Lithium, Methotrexate,
effect) Pemetrexed, Tizanidine [if concomitant use cannot be
avoided, initiate Tizanidine at 2 mg and increase in 2–4

M
Increases risk of adverse or toxic effects of Ketoprofen: mg increments based on patient response]
ACE Inhibitors e.g. Enalapril (decreased renal function),
Angiotensin II Receptor Blockers e.g., Losartan Reduces absorption of Ketoprofen:
(significantly decreased glomerular filtration and renal Bile Acid Sequestrants e.g. Cholestryamine
function), Corticosteroids Systemic, Ibrutinib, Limaprost,
Nonsteroidal Anti-Inflammatory Agents, Pentosan Reduces therapeutic effect of the following drugs:
Polysulfate Sodium, Treprostinil (bleeding), Loop Diuretics (diuretic effect), Salicylates [except
Tositumomab (bleeding-related adverse events) Choline Magnesium Trisalicylate] (cardioprotective
effect), Selective Serotonin Reuptake Inhibitors e.g.,
Increases risk of adverse or toxic effects of the following Fluoxetine
drugs:
5-ASA Derivatives, Aliskiren, Tacrolimus, Systemic TEST INTERACTIONS: Interfere with tests used to detect
(nephrotoxic effect), Bisphosphonate Derivatives (GI albumin, bile salts, 17­ketosteroids or
ulceration; nephrotoxicity), Collagenase Systemic 17­hydroxycorticosteroids in urine and tests that rely
(injection site bruising and/or bleeding), Deferasirox (GI upon acid precipitation as an end-point or on color
ulceration, irritation, or bleeding), Deoxycholic Acid reactions for carbonyl groups.
(bleeding or bruising in the treatment area),
Desmopressin, Drospirenone (hyperkalemic effect), Administration: May be taken with food to reduce GI upset.
Eplerenone, Potassium-sparing Diuretics (hyperkalemic Administer with food or milk to minimize gastrointestinal
effect), Haloperidol (drowsiness; confusion), effects.
Ibritumomab (impaired platelet function; bleeding),
Obinutuzumab (serious bleeding-related events), Pregnancy Category: C
Porfimer, Verteporfin (photosensitizing effect),
Quinolone Antibiotics e.g. Levofloxacin (neuroexcitatory ATC Code: M01AE03
and/or seizure-potentiating effect), Salicylates
(bleeding),

Reduces therapeutic effect (antihypertensive effect) of the Rx MEFENAMIC ACID

following drugs:
ACE Inhibitors e.g. Enalapril, Aliskiren, Angiotensin II Oral: 250 mg and 500 mg tablet or capsule
Receptor Blockers, Beta Blockers [except Levobunolol,
Metipranolol], Hydralazine, Potassium-sparing Diuretics A fenamate-derived (anthranilic acid), nonsteroidal anti-
e.g. Eplerenone, Prostaglandins Ophthalmic, Thiazide inflammatory medicine, which possesses greater anti-
Diuretics e.g., Hydrochlorothiazide inflammatory and analgesic properties than ibuprofen or
aspirin.
Avoid concomitant use with:
Decreases serum concentration of Ketoprofen: Indications: Symptomatic relief of acute pain and
Salicylates inflammation; symptomatic relief of dysmenorrhea;
menorrhagia due to dysfunctional causes or the
Enhances therapeutic effect of Ketoprofen: presence of an IUD when organic pelvic pathology has
been excluded; premenstrual syndrome

403
 MUSCULO-SKELETAL SYSTEM

Contraindications: Patients with inflammatory bowel Less Common: Bronchospasm, confusion, esophageal
disease, GI ulcers and history of GI bleeding or ulceration, heart failure, hyperkalemia, rash, renal
perforation, related to NSAID therapy; active or history of impairment
recurrent peptic ulcer or hemorrhage; severe heart Rare: Similar to Ibuprofen; see under Ibuprofen
failure, hepatic failure, and renal failure; pain treatment
after coronary artery bypass surgery; during the last Drug Interactions:
trimester of pregnancy Monitor closely with:
Increases risk of adverse or toxic effects of Mefenamic Acid:
Dose: Angiotensin II Receptor Blockers e.g., Losartan
Dysmenorrhea, by mouth, ADULT, 500 mg 3 times daily, to (significant decrease in renal function), Corticosteroids
be administered on the onset of menstrual pain and Oral (gastric ulceration), Diuretics e.g., Loop Diuretics,
continue while symptoms persist according to the clinical Thiazide Diuretics (reduced renal function;
judgment of the physician. nephrotoxicity), Other NSAIDs
Menorrhagia, by mouth, ADULT, 500 mg 3 times daily,
starting with the onset of bleeding and associated Increases risk of adverse or toxic effects of the following
symptoms and continued according to the clinical drugs:
judgment of the physician. ACE Inhibitors e.g. Enalapril (renal impairment;
Premenstrual syndrome, by mouth, ADULT, 500 mg 3 times hyperkalemia)
daily, starting with the onset of symptoms and continued
until the anticipated cessation of symptoms according to Reduces therapeutic effect of the following drugs:
the judgment of the physician. ACE Inhibitors e.g. Enalapril, Angiotensin II Receptor
Blockers e.g., Losartan (antihypertensive effect),
Dose Adjustment: Diuretics e.g., Loop Diuretics, Thiazide Diuretics (diuretic
Renal and Hepatic Impairment: effect)
Use drug with caution for mild to moderate impairment.
M

Avoid concomitant use with:

Precautions: Enhances therapeutic effect of Vitamin K Antagonists, e.g.,
WARNING: NSAIDs are associated with an increased Warfarin (anticoagulant effect)
risk of adverse cardiovascular thrombotic events,
including fatal MI and stroke. Increases risk of adverse or toxic effects of Mefenamic Acid:
NSAIDs may increase risk of GI irritation, Alendronate (gastric ulceration)
inflammation, ulceration, bleeding, and
perforation. Increases risk of adverse or toxic effects of the following
drugs:
Drugs affecting clotting process e.g., Ketorolac
Undesirable effects may be minimized by using the lowest
(bleeding), Drugs which are renally excreted e.g.,
effective dose for the shortest duration necessary to
Calcineurin Inhibitors, Drugs which increase Potassium
control symptoms; Concentration e.g., Amiloride, Triamterene
Anemia, agranulocytosis, and Coombs’-positive (hemolytic (hyperkalemia), Vitamin K Antagonists e.g., Warfarin
anemia is seen with prolonged use; should not be given
(serious bleeding)
for longer than 7 days);
Use with caution among patients with history of GI diseases
Reduces therapeutic effect of the following drugs:
or bleeding;
Antihypertensives, e.g., Beta Blockers, ARBs, Nitrates
Hepatic and renal disease, hypoprothrombinemia, or
(reduced antihypertensive effect)
vitamin K deficiency;
Use with caution in patients with hypertension, CHF and Administration: Should be taken with food or immediately
cardiovascular disease; after meals.
May adversely affect BP control;
Anaphylactoid reactions may be seen; Pregnancy Category: C; D (prolonged use or near term)
Caution is required for patients suffering, or with a previous
history of, bronchial asthma (may precipitate ATC Code: M01AG01
bronchospasm);
Patient’s response to NSAIDs is variable, switch to another
preparation if the response is inadequate;
Monitor stool for blood and kidney function if NSAIDs are to
be used chronically (patients on prolonged therapy
should be kept under surveillance with particular
attention to liver dysfunction, rash, blood dyscrasias or
development of diarrhea);
Elderly;
Pregnancy (avoid during last trimester).

Adverse Drug Reactions:

Common: Diarrhea, dizziness, dyspepsia, GI ulceration or
bleeding, headache, hemorrhage, hypertension, nausea,
raised liver enzymes, salt and fluid retention, vomiting

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MUSCULO-SKELETAL SYSTEM

SELECTIVE COX 2 INHIBITOR Precautions:

WARNING: Associated with an increased risk of serious
(and potentially fatal) adverse cardiovascular events,
Rx CELECOXIB including MI, stroke, ischemic heart disease,
cerebrovascular disease, and congestive heart
Oral: 100 mg, 200 mg, and 400 mg capsule failure. This risk may increase with duration of use.
Patients with cardiovascular disease or risk factors
A diaryl-substituted, pyrazole-derived, selective COX-2 for cardiovascular disease may be at greater risk.
inhibitor, which is associated with less GI side effects NSAIDs cause an increased risk of serious GI adverse
and susceptibility to bruising and bleeding than events, including bleeding, ulceration, and
nonselective NSAIDs. perforation of the stomach or intestines, which can
be fatal. These events can occur at any time during
Indications: Relief of the signs and symptoms of their use and without warning symptoms.
osteoarthritis, ankylosing spondylitis, and rheumatoid Pre-existing renal impairment increases the risk of
arthritis; and short-term (≤7 days) management of NSAID-induced impairment.
moderate to severe acute injury (post-operative,
musculoskeletal or soft tissue), or following dental Hypertension, Congestive heart failure or cardiovascular
extraction disease;
GI diseases or bleeding (use with caution);
Contraindications: Active GI disease or bleeding; heart Vitamin K deficiency, or hypoprothrombinemia,
failure, angina, peripheral arterial disease or Anaphylactoid reactions;
cerebrovascular disease; perioperative setting of Asthma, especially with rhinitis or nasal polyps;
Coronary Artery Bypass Graft (CABG) surgery; third Persistent urinary symptoms, hematuria, or cystitis;
trimester of pregnancy; breastfeeding; severe liver Renal impairment;
impairment or active liver disease; severe renal

M
Elderly;
impairment; inflammatory bowel disease; known Pregnancy;
hyperkalemia Women (reconsider use if planning for pregnancy).
Dose: Adverse Drug Reactions:
NOTE: Risk of cardiovascular adverse events is dose- Common: Abdominal pain, back pain, cough, diarrhea,
related; do not use >200 mg daily long-term; use lowest dizziness, dyspepsia, fever, flatulence, headache,
effective dose for the shortest duration of time, insomnia, nasopharyngitis, nausea, peripheral edema,
consistent with patient treatment goals. pharyngitis, rash, rhinitis, sinusitis, upper respiratory
tract infection, vomiting
Acute dental pain, by mouth, ADULT, 400 mg, followed by Less Common: Alopecia, anemia, angina, anorexia, anxiety,
an additional 200 mg if needed on Day 1; maintenance arthrosis, bradycardia, bronchospasm, cellulitis, chest
dose, 200 mg twice daily, as needed, not to exceed 7 pain, constipation, cystitis, depression, dermatitis,
days. dryness of skin, dysphagia, dyspnea, facial edema,
Ankylosing spondylitis, by mouth, ADULT, up to 200 mg fatigue, gastroesophageal reflux, GI ulcer,
daily, in 1 or 2 divided doses twice daily. hypercholesterolemia, hypertension, hypokalemia, MI,
Osteoarthritis, by mouth, ADULT, 200 mg daily as a single migraine, myalgia, nervousness, pain palpitations,
dose or in 2 divided doses. paresthesia, photosensitivity, pruritus, sinus
Pain, acute (post-operative, musculoskeletal or soft tissue), tachycardia, somnolence, tinnitus, urinary frequency,
by mouth, ADULT, 400 mg as a single dose on the 1st urticaria, ventricular hypertrophy, vertigo, xerostomia
day, then 200 mg once or twice daily if needed Rare: Acute renal failure, agranulocytosis, anaphylactoid
(maximum, 7 days treatment). reactions, angioedema, aplastic anemia,
Rheumatoid arthritis, by mouth, ADULT, 100 mg twice daily; cerebrovascular accidents, CHF, cholelithiasis, colitis,
may be increased to 200 mg twice daily (short-term use DVT, erythema multiforme, esophageal perforation,
only). exfoliative dermatitis, gangrene, GI bleeding, hepatic
failure and necrosis, hepatitis, hypoglycemia,
Dose Adjustment: hyponatremia, intestinal obstruction and perforation,
Geriatric: intracranial hemorrhage, jaundice, leukopenia,
Initiate at the lowest recommended dose of the medicine in pancreatitis, pancytopenia, pulmonary embolism, renal
patients weighing <50 kg (AUC may be increased by papillary necrosis, sepsis, Stevens-Johnson syndrome,
50%). suicide, syncope, taste disturbance, thrombocytopenia,
thrombophlebitis, toxic epidermal necrolysis, vasculitis,
Hepatic Impairment: ventricular fibrillation
For mild-to-moderate hepatic impairment, dose reduction by
50% is warranted. Drug Interactions:
Monitor closely with:
Decreases excretion of the following drugs:
Aminoglycosides e.g. Streptomycin

405
 MUSCULO-SKELETAL SYSTEM

Enhances therapeutic effect of the following drugs: Contraindications: Hypersensitivity to atracurium besylate
Anticoagulants, Antidepressants, Benzodiazepines e.g. or any component of the formulation; known
Midazolam hypersensitivity to benzyl alcohol (multiple-dose vials)

Increases risk of adverse or toxic effects of Celecoxib: Dose:

Angiotensin II Receptor Blockers e.g. Losartan NOTE: Dose to effect. Doses will vary due to interpatient
(significant decrease in renal function) variability.

Increases risk of adverse or toxic effects of the following Adjunct to surgical anesthesia, by IV bolus, ADULT, 0.4–0.5
drugs: mg/kg, then 0.08–0.1 mg/kg after 20–45 minutes to
ACE Inhibitors e.g. Enalapril (significant decrease in renal maintain neuromuscular block; repeat dose at 15– to
function), Agents with Antiplatelet Properties e.g., 25–minute intervals as needed; CHILD >2 years and
NSAIDs, SSRIs (bleeding), Anticoagulants (serious ADOLESCENT, 0.4–0.5 mg/kg, then 0.08–0.1 mg/kg
bleeding), Haloperidol, Quinolone Antibiotics e.g. after 20–45 minutes; repeat dose at 15– to 25–minute
Levofloxacin (neuroexcitatory and/or seizure- intervals as needed; CHILD 1 month – 2 years, initially
potentiating effect) 0.3–0.4 mg/kg followed by maintenance doses as
needed;
Reduces therapeutic effect of the following drugs: If to be administered after succinylcholine for intubation
ACE Inhibitors e.g. Enalapril, Angiotensin II Receptor (balanced anesthesia), initiate at 0.3–0.4 mg/kg;
Blockers (antihypertensive effect), Diuretics e.g., Pretreatment or priming, administer 10% of intubating
Potassium-sparing Diuretics, Thiazide Diuretics, Beta dose given 2–4 minutes before the larger second dose.
Blockers (antihypertensive effect) [NOTE: Maintenance doses may be required with slightly
greater frequency in infants and children compared to
Avoid concomitant use with: adults. Initial dose may be reduced to 0.3–0.4 mg/kg in
Enhances therapeutic effect of Vitamin K Antagonists, e.g., patients with significant cardiovascular disease or
M

Warfarin (anticoagulant effect) history of elevated risk of histamine release. Priming may
be uncomfortable for the patient, may increase the risk
Increases risk of adverse or toxic effects of Celecoxib: of aspiration and difficulty swallowing. Intubating
Aspirin (increased rate of GI ulceration or other conditions after priming may not be as good as that seen
complications), Other NSAIDs with succinylcholine].
Maintenance infusion for continued surgical relaxation
Increases risk of adverse or toxic effects of Vitamin K during extended surgical procedures, by continuous IV
Antagonists, e.g., Warfarin (serious bleeding) infusion, ADULT and CHILD, at initial signs of recovery
from bolus dose, initiate at a rate of 9 to 10
Reduces therapeutic effect of the following drugs: micrograms/kg per minute (0.54–0.6 mg/kg per hour) ;
Loop Diuretics e.g. Furosemide (antagonism of block is usually maintained by a rate of 5–9
prostaglandin-mediated effect) micrograms/kg per minute (0.3–0.54 mg/kg per hour);
if under balanced anesthesia, administer 2–15
Administration: May be administered without regard to micrograms/kg per minute (0.12–0.9 mg/kg per hour).
meals.
Dose Adjustment:
Pregnancy Category: C; D in the 3rd trimester or near Obesity:
delivery. Morbidly-obese patients should be dosed using ideal body
weight or an adjusted body weight. Time to recovery of
ATC Code: M01AH01 twitch response may be prolonged.

Precautions:
Anaphylaxis;
MUSCLE RELAXANTS Bradycardia;
Cross-sensitivity;
Burn injury (resistance may occur if burns ≥20% of total
PERIPHERALLY-ACTING AGENTS body surface area).
Conditions which may antagonize neuromuscular blockade
(e.g., respiratory alkalosis, hypercalcemia,
Rx ATRACURIUM demyelinating lesions, peripheral neuropathies,
denervation, and muscle trauma may occur);
Inj.: 10 mg/mL (as besilate), 2.5 mL and 5 mL ampule (IV) Conditions which may potentiate neuromuscular blockade
(e.g., electrolyte abnormalities, neuromuscular diseases,
A non-depolarizing, neuromuscular-blocking agent that metabolic acidosis, metabolic alkalosis, respiratory
restricts neural transmission at the myoneural junction acidosis, Lambert-Eaton syndrome and myasthenia
by binding with cholinergic receptor sites. gravis may occur);
Elderly (use with caution; effects and duration are more
Indications: As an adjunct to general anesthesia; to variable; consider dose reduction);
facilitate endotracheal intubation; to provide skeletal Immobilized patients (resistance may occur);
muscle relaxation during surgery or mechanical Children.
ventilation

406
MUSCULO-SKELETAL SYSTEM

Some dosage forms may contain benzyl alcohol (amounts

≥99 mg/kg per day of benzyl alcohol have been Rx PANCURONIUM
associated with a potentially fatal toxicity called “gasping
syndrome” in neonates; see manufacturer’s labeling for Inj.: 2 mg/mL (as bromide), 2 mL ampule (IM, IV)
contents prior to administration in neonates).
Pregnancy (use with caution); A non-depolarizing, neuromuscular-blocking agent, that
Lactation (not known if excreted in breast milk). induces muscle relaxation by restricting neural
transmission at the myoneural junction after binding to
Adverse Drug Reactions: cholinergic receptor sites.
Common: Flushing
Less Common: Bronchial secretions, erythema, hives, Indications: Facilitation of endotracheal intubation and
itching, wheezing, allergic reaction, bradycardia, relaxation of skeletal muscles during surgery; facilitation
bronchospasm, dyspnea, hypotension, injection site of mechanical ventilation in ICU patients
reaction, seizure, acute quadriplegic myopathy
syndrome (prolonged use), laryngospasm, myositis Contraindication: Hypersensitivity to pancuronium,
ossificans (prolonged use), tachycardia, urticaria bromide, or any component of the formulation

Drug Interactions: Dose:

Monitor closely with: NOTE: Dose to effect. Doses will vary due to interpatient
Enhances therapeutic effect of Atracurium: variability.
Aminoglycosides e.g. Streptomyicn (respiratory
depressant effect), Calcium Channel Blockers e.g. Intubation, by IV injection, ADULT and CHILD, initially 0.06–
Amlodipine, Capreomycin (neuromuscular-blocking 0.1 mg/kg or 0.05 mg/kg after initial dose (maintenance
effect), Clindamycin Topical, Cyclosporine Systemic, dose, 0.01 mg/kg administered 60 to 100 minutes after
Inhalational Anesthetics, Lincosamide, Lithium, Loop initial dose, then 0.01 mg/kg every 25 – 60 minutes);

M
Diuretics, Magnesium Salts, Minocycline, Procainamide, Pretreatment or priming, 10% of intubating dose given
Quinidine, Spironolactone, Tetracycline Derivatives, 3–5 minutes before intubating dose.
Vancomycin ICU paralysis (e.g., facilitate mechanical ventilation) in
select adequately sedated patients, by IV bolus, ADULT
Increases risk of adverse or toxic effects of Atracurium: and CHILD, 0.06–0.1 mg/kg followed by either:
Ketorolac (apnea) By continuous infusion, 1–2 micrograms/kg per minute
(0.06–0.12 mg/kg per hour), or;
Increases risk of adverse or toxic effects of Cardiac By continuous infusion, 0.8–1.7 micrograms/kg per
Glycosides (arrhythmogenic effect) minute (0.048–0.102 mg/kg per hour); or
By intermittent bolus, 0.1–0.2 mg/kg every 1–3 hours.
Reduces therapeutic effect of Atracurium:
Acetylcholinesterase Inhibitors e.g., Neostigmine, Dose Adjustment:
Fosphenytoin-Phenytoin, Loop Diuretics Renal Impairment:
For patients with CrCl of 10–50 mL/minute or patients on
Avoid concomitant use with: CRRT, administer 50% of normal dose.
Enhances therapeutic effect of Atracurium: Avoid use in patients with CrCl <10 mL/minute, or patients
Colistimethate, Polymyxin B, Quinine on hemodialysis or peritoneal dialysis.

Increases risk of adverse or toxic effects of the following Hepatic Impairment:

drugs: Large doses may be required and problems may arise in
Corticosteroids, Systemic (increased muscle weakness; antagonism.
polyneuropathies; myopathies)
Obesity:
Administration: May be given undiluted as a bolus IV Use ideal body weight for obese patients.
injection or via continuous IV infusion.
Precautions:
Do NOT administer by IM as this may cause excessive
WARNING: Should be administered by adequately
tissue irritation.
trained individuals familiar with its use.
Use infusion solutions within 24 hours of preparation.
Cross-sensitivity (use extreme caution in patients with
Pregnancy Category: C previous anaphylactic reactions);
Burn injury (resistance may occur if burns ≥20% of total
ATC Code: M03AC04 body surface area);
Conditions which may antagonize neuromuscular blockade
(e.g., respiratory alkalosis, hypercalcemia,
demyelinating lesions, peripheral neuropathies,
denervation, and muscle trauma may occur);
Conditions which may potentiate neuromuscular blockade
(e.g., electrolyte abnormalities, neuromuscular diseases,
metabolic acidosis, metabolic alkalosis, respiratory

407
 MUSCULO-SKELETAL SYSTEM

acidosis, Lambert-Eaton syndrome and myasthenia ATC Code: M03AC01

gravis may occur).
Hepatic and renal impairment (use with caution);
Elderly;
Immobilized patients (resistance may occur). Rx ROCURONIUM
Some dosage forms may contain benzyl alcohol (amounts
≥99 mg/kg per day of benzyl alcohol have been Inj.: 10 mg/mL (as bromide), 5 mL ampule / vial (IV)
associated with a potentially fatal toxicity called “gasping
syndrome” in neonates; see manufacturer’s labeling for A non-depolarizing, neuromuscular-blocking agent with a
contents prior to administration in neonates); rapid to intermediate onset depending on the dose and
Pregnancy (may be used short-term in cesarean section; intermediate duration. It acts by competing for
reduced doses recommended in patients also receiving cholinergic receptors at the motor end-plate.
magnesium sulfate due to enhanced effects).
Indications: Adjunct to general anesthesia to facilitate both
Adverse Drug Reactions: rapid sequence and routine tracheal intubation; to
Common and Less Common: Elevated blood pressure and provide skeletal muscle relaxation during surgery or
cardiac output, tachycardia, edema, skin flushing, mechanical ventilation
circulatory collapse, rash, itching, erythema, burning Contraindication: Known hypersensitivity to rocuronium or
sensation along the vein, excessive salivation, profound other neuromuscular blocking agents
muscle weakness, wheezing, bronchospasm,
hypersensitivity reaction, acute quadriplegic myopathy Dose:
syndrome (prolonged use), anaphylactoid reactions, NOTE: Individualize doses and use a peripheral nerve
anaphylaxis, myositis ossificans (prolonged use) stimulator to monitor drug effect, need for additional
doses, adequacy of spontaneous recovery or
Drug Interactions: antagonism, and to decrease the complications of over
M

Monitor closely with: dosage if additional doses are administered.

Enhances therapeutic effect of Pancuronium:
Aminoglycosides (respiratory depressant effect), Tracheal intubation, by IV injection, ADULT, initially 0.6
Calcium Channel Blockers e.g., Amlodipine, Capreomycin mg/kg (expected to provide 31 (15–85) minutes of
(neuromuscular-blocking effect), Clindamycin (Topical), clinical relaxation under opioid, nitrous oxide, or oxygen
Cyclosporine (Systemic), Inhalational Anesthetics, anesthesia) [NOTE: Maximum blockade is achieved in
Lincosamide, Lithium, Loop Diuretics e.g., Furosemide, most patients in less than 3 minutes. Under halothane,
Magnesium Salts, Minocycline, Procainamide, Quinidine, isoflurane, and enflurane anesthesia, some extension of
Spironolactone, Tetracycline Derivatives, Vancomycin the period of clinical relaxation should be expected].
Rapid sequence intubation, by IV injection, ADULT, 0.6–1.2
Increases risk of adverse or toxic effects of Pancuronium: mg/kg (will provide excellent or good intubating
Ketorolac (apnea) conditions in most patients in less than 2 minutes).
Endotracheal intubation, mechanical ventilation in intensive
Increases risk of adverse or toxic effects of the following care, or muscle relaxant in general anesthesia, by IV
drugs: injection, ADULT, initially 600 micrograms/kg, may
Cardiac Glycosides e.g., Digoxin (arrhythmogenic effect) reduce to 75–100 micrograms/kg for prolonged
inhalational anesthesia; maintenance, 150
Reduces therapeutic effect of Pancuronium: micrograms/kg; ADULT ≥65 years, maintenance, 75–
Acetylcholinesterase Inhibitors e.g., Neostigmine, 100 micrograms/kg.
Fosphenytoin-Phenytoin, Loop Diuretics Rapid sequence intubation, by IV injection, ADULT, 1 mg/kg.
Avoid concomitant use with: Dose Adjustment:
Enhances therapeutic effect of Pancuronium: Geriatric:
Colistimethate, Polymyxin B, Quinine Use with caution. Patients ≥65 years exhibited a slightly
prolonged median clinical duration.
Increases risk of adverse or toxic effects of Pancuronium:
Theophylline Derivatives e.g., Aminophylline Renal Impairment and biliary tract disease:
Maintenance dose: 75–100 micrograms/kg per hour by
Increases risk of adverse or toxic effects of the following injection or 300–400 micrograms/kg per hour by
drugs: infusion.
Corticosteroids (Systemic) (increased muscle weakness;
polyneuropathies; myopathies) Hepatic Impairment:
Use with caution. Median clinical duration may be slightly
Reduces therapeutic effect of Pancuronium: prolonged.
Theophylline Derivatives e.g., Aminophylline Maintenance dose: 75–100 micrograms/kg per hour by
injection or 300–400 micrograms/kg per hour by
Administration: May be administered undiluted by rapid IV infusion.
injection.
Obesity:
Pregnancy Category: C Reduce dose based on the patient’s ideal body weight.

408
MUSCULO-SKELETAL SYSTEM

Patients with Prolonged Circulation Time: Antibiotics (prolongation of neuromuscular block)

Do not increase initial dosage to reduce onset time. When
feasible, allow more time for the drug to achieve onset of Increases risk of adverse or toxic effects of Rocuronium:
effect. Quinidine (recurrent paralysis)

Precautions: Reduces therapeutic effect of the following drugs:

WARNING: This drug should only be administered by Anticonvulsants, Calcium Chloride, Carbamazepine,
experienced clinicians or trained individuals Phenytoin [chronic administration], Potassium Chloride,
supervised by an experienced clinician familiar Protease Inhibitors e.g., Ritonavir
with the use, actions, characteristics, and
complications of neuromuscular blocking agents. Administration: For IV administration only.
Should not be administered unless facilities for
Inspect visually for particulate matter and clarity prior to
intubation, mechanical ventilation, oxygen therapy,
administration whenever solution and container permit.
and an antagonist are immediately available
Do NOT use solution if particulate matter is present.

Drugs or conditions causing potentiation of neuromuscular Pregnancy Category: C

block (administer rocuronium prior to potent inhalation
anesthesia to minimize potentiation); ATC Code: M03AC09
Anaphylaxis (may be life-threatening and fatal);
Cross-reactivity between neuromuscular blocking agents,
both depolarizing and nondepolarizing, has been
reported; SUXAMETHONIUM
Rx
Residual paralysis (extubate patient only after sufficient (SUCCINYLCHOLINE)
recovery from neuromuscular block);
Malignant hyperthermia (use with caution); Inj.: 20 mg/mL (as chloride), 10 mL vial (IV)

M
Prolonged circulation time;
QT interval prolongation; A short-acting muscle relaxant that acts like acetylcholine. It
Pulmonary vascular resistance (use with caution); produces depolarization of the motor end-plate at the
Extravasation (may be associated with signs and symptoms myoneural junction which causes sustained flaccid
of local irritation); skeletal muscle paralysis.
Cardiovascular disease;
Respiratory disease; Indications: To facilitate both rapid sequence and routine
Myasthenia gravis or myasthenic syndrome, e.g. Lambert- endotracheal intubation; to relax skeletal muscles during
Eaton; surgery
Biliary tract disease;
Neuromuscular disease; Contraindications: Personal or familial history of malignant
Previous poliomyelitis; hyperthermia; myopathies associated with elevated
Burn injury; serum creatine phosphokinase (CPK) values; acute
Severe electrolyte disturbances; phase of injury following major burns, multiple trauma,
Renal and hepatic impairment. extensive denervation of skeletal muscle, or upper motor
Elderly; neuron injury
Children;
Obesity; Dose:
Pregnancy (use with caution) NOTE: Dose to effect. Doses will vary due to interpatient
variability.
Initial dose of succinylcholine must be increased when
Adverse Drug Reactions: nondepolarizing agent pretreatment is used.
Common: Transient hypotension and hypertension,
anaphylaxis, residual paralysis, myopathy, increased Intubation, by IV injection, ADULT, 0.6 mg/kg (range, 0.3–
pulmonary vascular resistance; anaphylaxis (potentially 1.1 mg/kg); OLDER CHILD and ADOLESCENT, initially 1
fatal) mg/kg per dose (maintenance, 0.3–0.6 mg/kg every 5–
Less Common: Arrhythmia, abnormal electrocardiogram, 10 minutes as needed); YOUNGER CHILD, initially 2
tachycardia, nausea, vomiting, asthma, hiccup, rash, mg/kg per dose (maintenance, 0.3–0.6 mg/kg every 5–
injection site edema, pruritus 10 minutes as needed).
Rapid sequence intubation, by IV injection, ADULT, 1–1.5
Drug Interactions: mg/kg; OLDER CHILD and ADOLESCENT, initially 1
Enhances therapeutic effect of Rocuronium: mg/kg per dose (maintenance, 0.3–0.6 mg/kg every 5–
Antibiotics, Beta Blockers e.g., Propranolol, Calcium 10 minutes as needed); YOUNGER CHILD, initially 2
Channel Blockers e.g., Amlodipine, Corticosteroids, mg/kg per dose (maintenance, 0.3–0.6 mg/kg every 5–
Diuretics, Inhalation Anesthetics, Lithium (increased 10 minutes as needed).
duration), Local Anesthetics (increased duration), Muscle relaxant in general anesthesia, by IV injection,
Magnesium, Phenytoin [acute administration], ADULT, 0.3–1.1 mg/kg as single dose, supplementary
Procainamide (increased duration), Quinine doses of 50–100% the initial dose may be given at 5- to
10-minute intervals; CHILD 1-12 years, 1 mg/kg; CHILD
Increases risk of adverse or toxic effects of Rocuronium: <1 year, 2 mg/kg;

409
 MUSCULO-SKELETAL SYSTEM

for prolonged procedures, ADULT, 0.1 – 0.2% at 2.54 Analgesics Opioid (bradycardic effect), Cardiac
mg/minute, adjusted as necessary. Glycosides e.g., Digoxin (arrhythmogenic effect)

Dose Adjustment: Reduces therapeutic effect of Suxamethonium:

Obesity: Loop Diuretics e.g., Furosemide
Use ideal body weight for obese patients.
Avoid concomitant use with:
Precautions: Enhances therapeutic effect of Suxamethonium:
WARNING: Acute rhabdomyolysis with hyperkalemia, Colistimethate, Phenelzine (neuromuscular-blocking
ventricular arrhythmias and cardiac arrest have effect), Polymyxin B, Quinine
been reported (rarely) in children with undiagnosed
skeletal muscle myopathy. Prolonged resuscitation Increases risk of adverse or toxic effects of Suxamethonium:
may be required. Use in children should be Acetylcholinesterase Inhibitors e.g., Neostigmine
reserved for emergency intubation or where (prolonged neuromuscular blockade)
immediate airway control is necessary.
Increases serum concentration of Suxamethonium:
Patients with reduced plasma cholinesterase activity due to Acetylcholinesterase Inhibitors e.g., Neostigmine,
genetic abnormalities of plasma cholinesterase or when Cyclophosphamide, Echothiophate Iodide
associated with other conditions, e.g., pregnancy, severe
liver disease, renal disease (consider dose reduction); Administration: May be given by rapid IV injection without
Bradycardia; further dilution.
Intraocular pressure, IOP (use caution with narrow-angle
glaucoma or penetrating eye injuries); Pregnancy Category: C
Malignant hyperthermia (risk may be increased with
concomitant administration of volatile anesthetics); ATC Code: M03AB01
M

Vagal tone;
Burn injury;
Conditions which may antagonize neuromuscular blockade Rx VECURONIUM
(e.g., alkalosis, hypercalcemia, demyelinating lesions,
peripheral neuropathies, denervation, infection, muscle
trauma, and diabetes mellitus); Inj.: freeze-dried powder (as bromide), 4 mg/mL ampule +
Conditions which may potentiate neuromuscular blockade 1 mL solvent (IV)
(e.g., electrolyte abnormalities, severe hyponatremia,
severe hypocalcemia, severe hypokalemia, A non-depolarizing, neuromuscular-blocking agent that
hypermagnesemia, neuromuscular diseases, acidosis, prevents acetylcholine from binding to receptors on the
acute intermittent porphyria, Lambert-Eaton syndrome, motor end-plate thereby inhibiting depolarization. It has
myasthenia gravis, renal failure, and hepatic failure); a shorter duration of action than pancuronium.
Hyperkalemia;
Plasma pseudocholinesterase disorders; Indications: To facilitate endotracheal intubation; to relax
Elderly; skeletal muscles during surgery; to facilitate mechanical
Pregnancy (use with caution); ventilation in ICU patients
Lactation (use with caution).
Contraindication: Hypersensitivity to vecuronium or any
Adverse Drug Reactions: component of the formulation
Common and Less Common: Arrhythmias, bradycardia,
cardiac arrest, hypertension or hypotension, tachycardia, Dose:
rash, hyperkalemia, excessive salivation, jaw rigidity, NOTE: Dose to effect. Doses will vary due to interpatient
muscle fasciculation, postoperative muscle pain, variability.
rhabdomyolysis (with possible myoglobinuric acute renal
failure), increased intraocular pressure, acute renal Tracheal intubation, by IV injection, ADULT and CHILD,
failure (secondary to rhabdomyolysis), apnea, respiratory initially 0.08–0.1 mg/kg; pretreatment or priming, 10%
depression (prolonged), anaphylaxis, malignant of intubating dose given 3–5 minutes before intubating
hyperthermia, acute quadriplegic myopathy syndrome dose. [NOTE: If intubation is performed using
(prolonged use), myositis ossificans (prolonged use) succinylcholine, reduce initial vecuronium dose to 0.04–
0.06 mg/kg with inhalation anesthesia and 0.05–0.06
Drug Interactions: mg/kg with balanced anesthesia. Children 1­10 years
Monitor closely with: may require slightly higher initial doses and more
Enhances therapeutic effect of Suxamethonium: frequent supplementation].
Aminoglycosides (respiratory depressant effect), Maintenance for continued surgical relaxation (only after
Bambuterol, Capreomycin, Clindamycin Topical, return of neuromuscular function), by intermittent IV
Cyclosporine Systemic, Lincosamide, Lithium, Loop injection, ADULT, 0.01–0.015 mg/kg;
Diuretics, Magnesium Salts, Minocycline, Procainamide, by continuous IV infusion, ADULT, 0.8–1.2
Quinidine, Tetracycline Derivatives, Vancomycin micrograms/kg per minute (0.048–0.072 mg/kg per
hour).
Increases risk of adverse or toxic effects of the following [NOTE: Use lower end of the dosing range when
drugs: anesthesia is maintained with an inhaled anesthetic

410
MUSCULO-SKELETAL SYSTEM

agent, with the redosing interval guided by monitoring Some dosage forms may contain benzyl alcohol (see
with a peripheral nerve stimulator]. manufacturer’s labeling for contents prior to
ICU paralysis in selected adequately sedated patients, by IV administration in neonates);
administration, ADULT, initially 0.08–0.1 mg/kg by IV Elderly;
bolus, then by continuous IV infusion of 0.8–1.7 Immobilized patients (resistance may occur);
micrograms/kg per minute (0.048–0.102 mg/kg per Children;
hour) ; monitor depth of blockade every 1–2 hours Pregnancy;
initially until stable dose, then every 8–12 hours (usual Lactation.
maintenance infusion dose range, 0.8–1.2
micrograms/kg per minute (0.048–0.072 mg/kg per Adverse Drug Reactions:
hour); Less Common: Bradycardia, circulatory collapse, edema,
by intermittent IV bolus, 0.1–0.2 mg/kg per dose; may flushing; hypersensitivity reaction, itching, rash, acute
be repeated when neuromuscular function returns. quadriplegic myopathy syndrome (prolonged use),
[NOTE: Adjust rate of administration in increments of 0.3 myositis ossificans (prolonged use)
micrograms/kg per minute (or 0.018 mg/kg/hour) or by
50% reductions of previous dose according to peripheral Drug Interactions:
nerve stimulation response or desired clinical response. Monitor closely with:
Discontinue infusion if neuromuscular function does not Enhances therapeutic effect of Vecuronium:
return. When possible, minimize depth and duration of Aminoglycosides (respiratory depressant effect),
paralysis. It is recommended to stop the infusion daily for Calcium Channel Blockers, Capreomycin
some time until forced to restart based on patient (neuromuscular-blocking effect), Clindamycin (Topical),
condition to reduce post-paralytic complications]. Cyclosporine (Systemic), Dantrolene (neuromuscular-
blocking effect), Inhalational Anesthetics, Lincosamide,
Dose Adjustment: Lithium, Loop Diuretics, Magnesium Salts, Minocycline,
Geriatric: Piperacillin (neuromuscular-blocking effect),

M
Select doses with caution. Start at low end of dosage range Procainamide, Quinidine, Spironolactone, Tetracycline
and titrate slowly to evaluate response. Derivatives, Vancomycin

Pediatric: Increases risk of adverse or toxic effects of Vecuronium:

May require slightly higher initial doses and slightly more Ketorolac (apnea)
frequent supplementation
Increases risk of adverse or toxic effects of the following
Renal Impairment: drugs:
In patients who are anephric, clinical duration is prolonged. Cardiac Glycosides e.g., Digoxin (arrhythmogenic effect)

Hepatic Impairment: Reduces therapeutic effect of Vecuronium:

Dose reduction may be required. Acetylcholinesterase Inhibitors e.g., Neostigmine,
Fosphenytoin-Phenytoin, Loop Diuretics
Obesity:
For obese adult patients of ≥130% of IBW, use ideal body Avoid concomitant use with:
weight (IBW). Onset time may be slightly delayed using Enhances therapeutic effect of Vecuronium:
IBW. Colistimethate, Polymyxin B, Quinine

Precautions: Increases risk of adverse or toxic effects of the following

WARNING: Should be administered by adequately drugs:
trained individuals familiar with its actions, Corticosteroids (Systemic) (increased muscle weakness;
characteristics, and hazards polyneuropathies; myopathies)

Administration: Concentration of 1 mg/mL may be

Cross-sensitivity (use extreme caution in patients with administered by rapid IV injection.
previous anaphylactic reactions);
Prolonged paralysis; May be used for IV infusion in fluid-restricted patients.
Burn injury (resistance may occur if burns ≥20% of total
body surface area); Pregnancy Category: C
Conditions which may antagonize neuromuscular blockade
(e.g., respiratory alkalosis, hypercalcemia, ATC Code: M03AC03
demyelinating lesions, peripheral neuropathies,
denervation, and muscle trauma);
Conditions which may potentiate neuromuscular blockade
(e.g., electrolyte abnormalities, neuromuscular diseases,
metabolic acidosis, metabolic alkalosis, respiratory
acidosis, Lambert-Eaton syndrome and myasthenia
gravis);
Hepatic and renal impairment;
Respiratory disease;

411
 MUSCULO-SKELETAL SYSTEM

CENTRALLY ACTING AGENTS Administration: The lowest dose compatible with an optimal
response is recommended. If benefits are not evident
after a reasonable trial period, patients should be slowly
Rx BACLOFEN withdrawn from the drug.

Oral: 10 mg tablet Pregnancy Category: C

A GABA analog that acts as a muscle relaxant and anti- ATC Code: M03BX01
spastic by inhibiting both monosynaptic and polysynaptic
reflexes at the spinal level by hyperpolarizing afferent
terminals. Rx DIAZEPAM
Indication: For the alleviation of signs and symptoms of
spasticity resulting from multiple sclerosis Oral: 5 mg tablet
Inj.: 5 mg/mL, 2 mL ampule (IM, IV)
Dose:
NOTE: The determination of optimal dosage requires A benzodiazepine that binds to stereospecific
individual titration. Start therapy at a low dosage and benzodiazepine receptors on the postsynaptic GABA
increase gradually until optimum effect is achieved neuron which results to enhanced inhibitory effect of
(usually between 40-80 mg daily). GABA on neuronal excitability. This results to increased
neuronal membrane permeability to chloride ions.
Suggested dosage titration schedule:
5 mg 3 times a day for 3 days Indications: Skeletal muscle relaxant; preoperative or
10 mg 3 times a day for 3 days preprocedural sedation and amnesia
15 mg 3 times a day for 3 days
M

20 mg 3 times a day for 3 days Contraindications: Respiratory depression; marked

neuromuscular respiratory weakness, including unstable
Additional increases may be necessary. Maximum dose, 80 myasthenia gravis; acute pulmonary insufficiency; sleep
mg daily. apnea syndrome; phobic or obsessional states;
hyperkinesis; severe hepatic impairment
Dose Adjustment:
Renal Impairment: Dose:
Use with caution. Baclofen is primarily excreted unchanged NOTE: See Precautions prior to administration.
through the kidneys. Dose reduction may be necessary. Oral absorption is more reliable than IM.

Precautions: Muscle spasm, by IM or IV injection, ADULT, initially 5–10

WARNING: Slowly reduce dose when discontinued. mg, then 5–10 mg after 3–4 hours, if necessary [NOTE:
Hallucinations and seizures have occurred on Larger doses may be required if associated with tetanus].
abrupt withdrawal of baclofen. Muscle spasm associated with tetanus, by IM or IV injection,
CHILD ≥5 years, 5–10 mg per dose every 3 – 4 hours as
needed; CHILD <5 years and INFANT >30 days, 1–2 mg
Stroke;
per dose every 3–4 hours as needed.
Children;
Skeletal muscle relaxant (adjunct therapy), by mouth,
Pregnancy (use with caution);
ADULT, 2–10 mg 3–4 times daily; CHILD, 0.12–0.8
Lactation.
mg/kg per day in divided doses every 6–8 hours;
by IM or IV injection, CHILD, 0.04–0.3 mg/kg per dose
Adverse Drug Reactions:
every 2–4 hours to a maximum of 0.6 mg/kg within an
Common: Transient drowsiness, dizziness, weakness,
8–hour period if needed.
fatigue, confusion, headache, insomnia, hypotension,
nausea, constipation, urinary frequency, rash, pruritus,
Dose Adjustment:
ankle edema, excessive perspiration, weight gain, nasal
Geriatric:
congestion
Reduce dose.
Rare: Euphoria, excitement, depression, hallucinations,
paresthesia, muscle pain, tinnitus, slurred speech,
Renal Impairment:
coordination disorder, tremor, rigidity, dystonia, ataxia,
Reduce dose if used for prolonged periods.
blurred vision, nystagmus, strabismus, miosis, mydriasis,
diplopia, dysarthria, epileptic seizure, dyspnea,
Hepatic Impairment:
palpitation, chest pain, syncope, dry mouth, anorexia,
Reduce maintenance dose.
taste disorder, abdominal pain, vomiting, diarrhea,
positive test for occult blood in stool, enuresis, urinary
Precautions:
retention, dysuria, impotence, inability to ejaculate,
nocturia, hematuria WARNING: Overdose may produce coma and
respiratory depression.
Drug Interactions: No information found.
When given intravenously, agents for correcting
hypotension and facilities for supporting ventilation (e.g.,

412
MUSCULO-SKELETAL SYSTEM

AMBU bag, oxygen) in cases of respiratory depression

should be available. In such cases, the patient should be Rx EPERISONE HYDROCHLORIDE
referred to the nearest hospital immediately;
Hepatic impairment and renal impairment (avoid prolonged Oral: 50 mg tablet
use and abrupt withdrawal);
Respiratory disease; A centrally acting skeletal muscle relaxant used to improve
Muscle weakness may worsen; myotonic symptoms.
History of alcohol or drug abuse, marked personality
disorder (use only if the indication is clear, such as Indications: Used in the improvement of myotonic
seizure control) symptoms in cervical syndrome periarthritis of the
Porphyria; shoulder lumbago
Pregnancy (high doses during late pregnancy or labor may
cause neonatal hypothermia, hypotonia, and respiratory Contraindications: Children; pregnancy; kidney dysfunction;
depression) neonates
Breastfeeding (monitor infant for drowsiness).
Dose:
Adverse Drug Reactions: Muscle spasms, by mouth, ADULT, 50 mg every 8 hours.
Common: Coma or sensorial depression, hypotension,
respiratory depression Dose Adjustment:
Rare: Allergic reactions including anaphylaxis, jaundice, Geriatric:
transient elevated liver function tests Administer half the dose.

Drug Interactions: Precautions:

Monitor closely with: Hepatic Impairment;
Enhances therapeutic effect of Diazepam: Children (use is not recommended).

M
Amlodipine (hypotensive effect)
SKILLED TASKS. May impair ability to perform certain tasks,
Enhances therapeutic effect of the following drugs: e.g., operating machinery or driving.
CNS Depressants, e.g., Alcohol, Sedatives, Tranquilizers
(CNS depression; sedative effect), Enalapril, Adverse Drug Reactions:
Furosemide, Hydrochlorothiazide, Methyldopa, Nitrates, Common and Less Common: Weakness, dizziness,
e.g., Isosorbide Dinitrate (hypotensive effect), insomnia, drowsiness, numbness or trembling in the
extremities, hepatic and renal dysfunction,
Increases risk of adverse or toxic effects of Diazepam: hematological changes, skin rashes, itching, GI
Azole Derivatives, e.g., Fluconazole disturbances, urinary disorders
Rare: Shock
Increases risk of adverse or toxic effects of the following
drugs: Drug Interactions:
Chlorphenamine, Chlorpromazine (sedative effect), Avoid concomitant use with:
Seizure-inducing Drugs (lowers seizure threshold) Enhances therapeutic effect of Eperisone:
Tolperisone HCl
Reduces therapeutic effect of Diazepam:
Theophylline (sedative effects) Administration: Should be taken with food. Take after
meals.
Avoid concomitant use with:
Reduces therapeutic effect of Diazepam: Pregnancy Category: Varied classification, A / B / C
Rifampicin
ATC Code: M03BX09
Administration: For IV administration, give at a rate not
faster than 2 mg/minute.
DIRECTLY ACTING AGENTS
Avoid extravasation, intra-arterial and IM injection.

NOTE: Avoid dilution and infusion of injection, as diazepam Rx DANTROLENE

has a low solubility and adsorbs to PVC-giving sets.

Pregnancy Category: D Oral: 25 mg and 50 mg capsule (as sodium salt)

Inj.: 20 mg (as sodium salt) with 3 g mannitol/vial (for
ATC Code: Not Available reconstitution with 60 mL sterile water for injection)
(IV)

A skeletal muscle relaxant that acts directly on skeletal

muscles by interfering with release of calcium ions from
the sarcoplasmic reticulum. This prevents or reduces the
increase in myoplasmic calcium ion concentration.

413
 MUSCULO-SKELETAL SYSTEM

Indications: Treatment of spasticity associated with upper Hepatic disease (use oral therapy with caution)
motor neuron disorders (e.g., spinal cord injury, stroke, Pregnancy (closely monitor mother and newborn);
cerebral palsy, or multiple sclerosis) Lactation (low amounts are excreted into breast milk; use
with caution).
NOTE: Dantrolene prophylaxis is not recommended for most
MH-susceptible patients, provided non-triggering SKILLED TASKS. May impair ability to perform certain tasks,
anesthetics are used and an adequate supply of e.g., operating machinery or driving.
dantrolene is available.
Adverse Drug Reactions:
Contraindications: Active liver disease; should not be used Common: Tachycardia, drowsiness, dizziness, headache,
when spasticity is used to maintain posture/balance myasthenia, dysphagia, nausea, vomiting, cardiac
during locomotion or to obtain or maintain increased failure, phlebitis, variable blood pressure, chills, choking
function sensation, confusion, depression, insomnia, malaise,
nervousness, seizure, speech disturbance, diaphoresis,
Dose: eczematous rash, fatigue, hair disease (abnormal
NOTE: Individualize dose and titrate to maximum effect. Use growth), pruritus, urticaria, abdominal cramps, anorexia,
the lowest dose compatible with optimal response. Some constipation, diarrhea, dysgeusia, gastric irritation,
patients may not respond until a higher daily dosage is gastrointestinal hemorrhage, sialorrhea, crystalluria,
achieved. Each dose level should be maintained for 7 difficulty in micturition, erectile dysfunction, hematuria,
days to determine patient response. If no further benefit nocturia, urinary incontinence, urinary retention, urinary
observed with the higher dose level, then decrease frequency, anemia, aplastic anemia, leukopenia,
dosage to previous dose level. thrombocytopenia, lymphocytic lymphoma, local tissue
necrosis, back pain, myalgia, diplopia, epiphora, visual
Spasticity, by mouth, ADULT, initially 25 mg once daily for 7 disturbance, pleural effusion (with pericarditis),
days; increase to 25 mg 3 times daily for 7 days, increase respiratory depression, Acneiform eruption, Flushing,
M

to 50 mg 3 times daily for 7 days, and then increase to atrioventricular block, voice disorder, feeling abnormal,
100 mg 3 times daily; some patients may require 100 erythema, injection site reaction, hepatitis, limb pain,
mg 4 times daily (maximum dose, 400 mg daily); CHILD, blurred vision, dyspnea
initially 0.5 mg/kg per dose once daily for 7 days; Less Common: Fever, hepatic disease, Hepatotoxicity
increase to 0.5 mg/kg per dose 3 times daily for 7 days, Decrease in forced vital capacity, dyspnea, respiratory
increase to 1 mg/kg per dose 3 times daily for 7 days, muscle failure
and then increase to 2 mg/kg per dose 3 times daily; Rare: Pulmonary edema
some patients may require 2 mg/kg per dose 4 times
daily (maximum dose, 400 mg daily). Drug Interactions:
Monitor closely with:
Precautions: Enhances CNS depressant effect of Dantrolene:
WARNING: Potential for hepatotoxicity. Do NOT use in Doxylamine, Dronabinol, Hydroxyzine, Magnesium
conditions other than those recommended. Sulfate, Minocycline, Nabilone, Other CNS Depressants
Prescribe the lowest possible effective dose for the [except Nasal Levocabastine]
individual patient. If no observable benefit is
derived from dantrolene after a total of 45 days, Enhances therapeutic effect of the following drugs:
discontinue therapy. Alcohol, Mirtazapine (CNS depressant effect),
Metyrosine, Pramipexole, Ropinrole, Rotigotine (sedative
Use dantrolene only in conjunction with
effect), Vecuronium (neuromuscular-blocking effect)
appropriate monitoring of hepatic function,
including frequent determination of AST or ALT.
Increases risk of adverse or toxic effects of Dantrolene:
Greater risk of hepatic injury in women, patients Dexketoprofen, Lacidipine
>35 years, and patients taking other
medication(s). Increases risk of adverse or toxic effects of the following
drugs:
CNS effects (lightheadedness, dizziness, somnolence, and Rufinamide (sleepiness; dizziness), SSRI (psychomotor
vertigo may occur and may persist for 48 hours post- impairment)
dose);
Muscle weakness (e.g., loss of grip strength, weakness in Avoid concomitant use with:
the legs, dyspnea, respiratory muscle weakness, Decreases serum concentration of Dantrolene:
dysphagia, and decreased inspiratory capacity has Dabrafenib, Mitotane
occurred with IV dantrolene; monitor patients for the
adequacy of ventilation and for difficulty swallowing or Enhances therapeutic effect of Dantrolene:
choking); Droperidol, Perampanel, Sodium Oxybate (CNS
Dysphagia (use caution at meal time on day of depressant effect), Methotrimeprazine (potentiates CNS
administration); depressant effect) [if concomitant use cannot be
Photosensitivity (oral therapy may cause photosensitivity; avoided, reduce dantrolene dose by 50%], Tapentadol [if
discontinue if skin erythema occurs) concomitant use cannot be avoided, start tapentadol at
Cardiovascular and respiratory disease (use oral therapy 1/3 to ½ of the normal dose]
with caution).
Hepatotoxicity; Enhances therapeutic effect of the following drugs:

414
MUSCULO-SKELETAL SYSTEM

Azelastine (Nasal), Buprenorphine [if concomitant use Chronic gout, by mouth, ADULT, initially 100 mg once daily,
cannot be avoided, initiate buprenorphine patches at 5 increase at weekly intervals in increments of 100
micrograms/hour], Hydrocodone [if concomitant use mg/day as needed to achieve desired serum uric acid
cannot be avoided, start with a 20–30% lower level; usual dosage range, 200 to 300 mg daily in mild
hydrocodone dose], Orphenadrine, Paraldehyde, gout; 400–600 mg daily in moderate to severe
Suvorexant, Thalidomide, Zolpidem CNS depressant tophaceous gout (maximum daily dose, 800 mg).
effect), Management of hyperuricemia associated with
chemotherapy and/or radiation therapy, by mouth,
Increases risk of adverse or toxic effects of the following ADULT, 600–800 mg daily in divided doses; CHILD 6–10
drugs: years, 300 mg daily; CHILD <6 years, 150 mg daily.
Calcium Channel Blockers, Non-Dihydropyridine e.g. Recurrent calcium oxalate stones, by mouth, ADULT, 200–
(hyperkalemic and negative inotropic effects) 300 mg daily in single or divided doses; may adjust dose
as needed to control hyperuricosuria.
Administration: For IV preparation, reconstitute with 60 mL
sterile water for injection. Dose Adjustment:
Renal Impairment:
Therapeutic or emergency dose can be administered Lower doses are required in renal impairment due to
with rapid continuous IV push. Follow-up doses should be potential for accumulation of allopurinol and
administered over at least 1 minute (Ryanodex) or 1 hour metabolites.
(Dantrium, Revonto). For patients with CrCl 10–20 mL/minute, administer 200
mg daily.
EXTRAVASATION MANAGEMENT: Ensure proper needle or For patients with CrCl 3–10 mL/minute, administer ≤100
catheter placement prior to and during infusion to avoid mg daily.
extravasation. If extravasation occurs, stop infusion For patients with CrCl <3 mL/minute, administer ≤100
immediately and disconnect (leave cannula or needle in mg/dose at extended intervals.

M
place), then gently aspirate extravasated solution (do When used in the management of hyperuricemia associated
NOT flush the line). Remove needle or cannula and with chemotherapy, administer 50% of the dose.
elevate extremity. When used for gout, initiate therapy at 50–100 mg daily,
and gradually increase to a maintenance dose to achieve
Pregnancy Category: C a serum uric acid level of ≤6 mg/dL. Closely monitor
serum uric acid levels and for hypersensitivity.
ATC Code: M03CA01 In patients with stage 4 CKD or worse, initiate therapy at 50
mg daily, increasing the dose every 2–5 weeks to
achieve desired uric acid levels of ≤6 mg/dL. Doses
>300 mg daily are permitted so long as they are
ANTIGOUT PREPARATIONS accompanied by appropriate patient education and
monitoring for toxicity. Some patients may require
therapy targeted at a serum uric acid level <5 mg/dL to
Rx ALLOPURINOL control symptoms.
In patients undergoing hemodialysis, initiate therapy at 100
mg alternate days given post-dialysis, increase
Oral: 100 mg and 300 mg tablet cautiously to 300 mg based on response. If dialysis is
daily, an additional 50% of the dose may be required
A xanthine oxidase inhibitor that prevents the conversion of post-dialysis.
hypoxanthine to xanthine and eventually to uric acid. It
acts on purine catabolism, reducing the production of Precautions:
uric acid without disrupting the biosynthesis of vital Allergic reaction (discontinue at first sign of rash);
purines. Bone marrow suppression (use with caution);
Hepatotoxicity (ruse with caution in patients with preexisting
Indications: For chronic gout; management of recurrent hepatic impairment);
calcium oxalate calculi (with uric acid excretion >800 mg Renal impairment (use with caution; adjust doses as
daily in men and >750 mg daily in women); management recommended);
of primary or secondary gout (acute attack, tophi, joint Full effect on serum uric acid levels in chronic gout may take
destruction, uric acid lithiasis, and/or nephropathy); several weeks to become evident; gradual titration is
management of hyperuricemia associated with cancer recommended.
treatment for leukemia, lymphoma, or solid tumor Elderly (adjust dose based on renal function);
malignancies Lactation (use with caution).
Contraindication: Severe hypersensitivity reaction to Adverse Drug Reactions:
allopurinol or any component of the formulation Common: Skin rash, gout (acute), diarrhea, nausea.
Less Common: Abdominal pain, ageusia, agranulocytosis,
Dose: alopecia, angioedema, aplastic anemia, arthralgia,
NOTE: Oral doses >300 mg should be given in divided bronchospasm, cataract, cholestatic jaundice,
doses. drowsiness, dysgeusia, dyspepsia, ecchymoses,
eczematoid dermatitis, eosinophilia, epistaxis,
exfoliative dermatitis, fever, gastritis, gynecomastia,

415
 MUSCULO-SKELETAL SYSTEM

headache, hepatic necrosis, hepatitis, hepatomegaly,

hepatotoxicity (idiosyncratic), hypersensitivity reaction, Rx COLCHICINE
hyperbilirubinemia, leukocytosis, leukopenia, lichen
planus, macular retinitis, myopathy, necrotizing angiitis, Oral: 500 micrograms tablet
nephritis, neuritis, neuropathy, onycholysis, pancreatitis,
paresthesia, pruritus, purpura, renal failure, skin Colchicine disrupts cytoskeletal functions by inhibiting β-
granuloma (annulare), Stevens-Johnson syndrome, tubulin polymerization. It also prevents the activation,
thrombocytopenia, toxic epidermal necrolysis, toxic degranulation, and migration of neutrophils associated
pustuloderma, uremia, vasculitis, vesicobullous with mediating some gout symptoms.
dermatitis, vomiting
Indications: Management of acute gout; treatment of
Drug Interactions: familial Mediterranean fever in adults and children 4
Monitor closely with: years and older; prophylaxis and treatment of acute gout
Increases risk of adverse or toxic effects of Allopurinol: flares
Thiazide Diuretics e.g. Hydrochlorothiazie (allergic or
hypersensitivity reactions) Contraindications: Concomitant use of a P-glycoprotein (P-
gp) or strong CYP3A4 inhibitor in presence of renal or
Increases risk of adverse or toxic effects of the following hepatic impairment
drugs:
Amoxicillin, Ampicillin (allergic or hypersensitivity Dose:
reactions), Bendamustine (severe skin reactions), Familial Mediterranean fever, by mouth, ADULT, 1.2–2.4 mg
Cyclophosphamide (bone marrow suppression), Loop daily in 1–2 divided doses, increase or decrease dose in
Diuretics 0.3 mg daily increments based on efficacy or adverse
effects; CHILD >10 years and ADOLESCENT, initially 1.5
Avoid concomitant use with: mg daily in 1–2 divided doses; CHILD 5–10 years,
M

Enhances therapeutic effect of Vitamin K Antagonists, e.g., initially 1 mg daily in 1–2 divided doses; CHILD <5 years,
Warfarin (anticoagulant effect) initially 0.5 mg once daily.

Increases risk of adverse or toxic effects of Allopurinol: NOTE: Titrate dosage in increments of 0.25 mg (maximum
ACE Inhibitors (allergic or hypersensitivity reactions) daily dose, 2 mg).

Increases risk of adverse or toxic effects of Pegloticase Gout, flare treatment, by mouth, ADULT, initially 1 mg at first
(blunts increases in serum urate) sign of flare, followed by 0.5 mg every 2 to 6 hours
(maximum cumulative dose, 2.5 mg in the first 24 hours
Increases serum concentration of the following drugs: and 6 mg over 4 days); following acute treatment course,
Azathioprine [active metabolite/s, specifically wait 3 days before administering additional colchicine.
mercaptopurine] [if concomitant use cannot be avoided, Gout, prophylaxis, by mouth, ADULT, 0.5 mg once weekly or
reduce azathioprine dose 1/3 to ¼ of usual dose], up to 0.5 mg 2–3 times daily.
Didanosine, Mercaptopurine [active thioguanine
nucleotides] [if concomitant use cannot be avoided, Dose Adjustment:
reduce mercaptopurine dose to 1/3 to ¼ of usual dose] Geriatric:
Use with caution. Reduce prophylactic daily dose by 50% in
Reduces absorption of Allopurinol: individuals >70 years.
Antacids [except Sodium Bicarbonate]
Renal Impairment:
Reduces therapeutic effect of Tegafur Dose adjustment may be required. Consult product labeling.

Administration: Administer after meals with plenty of fluid. Familial Mediterranean fever:
In patients with CrCl of 30–80 mL/minute, monitor closely
Administer fluids to yield neutral or slightly alkaline urine for adverse effects. Dose reduction may be necessary.
and an output of ~2 L in adults. In patients with CrCl <30 mL/minute, initiate therapy at 0.3
mg daily. Use caution if dose is titrated. Monitor for
Pregnancy Category: C adverse effects.
In patients undergoing dialysis, administer 0.3 mg as a
ATC Code: M04AA01 single dose. Use caution if dose is titrated. Dosing can be
increased with close monitoring. Monitor for adverse
effects. Colchicine is not removed by dialysis.

Gout prophylaxis:
In patients with CrCl of 30–80 mL/minute, dose adjustment
is not required. Monitor closely for adverse effects.
In patients with CrCl <30 mL/minute, initiate therapy at 0.3
mg daily. Use caution if dose is titrated. Monitor for
adverse effects.
In patients undergoing dialysis, administer 0.3 mg twice
weekly. Monitor closely for adverse effects.

416
MUSCULO-SKELETAL SYSTEM

Gout flare treatment: oligospermia, pancytopenia, peripheral neuritis, purpura,

In patients with CrCl of 30–80 mL/minute, dose adjustment rhabdomyolysis, thrombocytopenia, toxic neuromuscular
is not required. Monitor closely for adverse effects. disease
In patients with CrCl <30 mL/minute, consider dosage
reduction. Do not repeat treatment more frequently than Drug Interactions:
every 14 days. Monitor closely with:
In patients undergoing dialysis, administer 0.6 mg as a Increases risk of adverse or toxic effects of Colchicine:
single dose. Do not repeat treatment more frequently Fibric Acid Derivatives e.g. Clofibrate (myopathy),
than every 14 days. Colchicine is not removed by dialysis. Diltiazem (myopathic effect; rhabdomyolysis)
In patients undergoing hemodialysis, avoid chronic use.
Reduces therapeutic effect of Choline C11
Hepatic Impairment:
Dose adjustment may be required. Consult product labeling. Avoid concomitant use with:
Decreases serum concentration of Cyanocobalamin
Familial Mediterranean fever:
In mild to moderate impairment, use with caution. Monitor Increases risk of adverse or toxic effects of Colchicine:
closely for adverse effects. HMG-CoA Reductase Inhibitors e.g., Simvastatin
In severe impairment, consider dose adjustment. (myopathic effect; rhabdomyolysis)

Gout prophylaxis: Increases serum concentration of Colchicine:

In mild to moderate impairment, monitor closely for adverse Conivaptan, Fosamprenavir, Fusidic Acid Systemic,
effects. Grapefruit Juice, HMG-CoA Reductase Inhibitors e.g.,
In severe impairment, consider dose adjustment. Simvastatin, Idelalisib, Mifepristone, P-glycoprotein /
ABCB1 Inhibitors (increases distribution into certain
Gout flare treatment: tissues, e.g., brain), Stiripentol, Telaprevir, Tipranavir

M
In mild to moderate impairment, monitor closely for adverse
effects. TEST INTERACTION. May cause false-positive results in
In severe impairment, do not repeat treatment course more urine tests for erythrocytes or hemoglobin.
frequently than every 14 days.
Administration: Administer with water and maintain
Precautions: adequate fluid intake. May be administered without
WARNING: Hazardous agent. Use appropriate regard to meals.
precautions for handling and disposal.
May be taken without regard to meals. May need to
supplement with vitamin B12. Avoid grapefruit juice.
Blood dyscrasias (e.g., myelosuppression and aplastic
anemia). Pregnancy Category: C
Gastrointestinal symptoms (dose reduction is
recommended in patients who develop gastrointestinal ATC Code: M04AC01
symptoms);
Neuromuscular toxicity (patients with renal dysfunction and
elderly patients are at increased risk);
Renal and hepatic impairment (clearance is decreased; DRUGS FOR TREATMENT OF
monitor closely for adverse effects or toxicity; fatal BONE DISEASE
toxicity has been reported);
Colchicine is not an analgesic and should not be used to
treat pain from other causes;
Accidental and intentional fatal overdoses have been
Rx ALENDRONATE
reported. Dosage associated with fatal toxicity is
variable. Oral: 10 mg and 70 mg tablet (as sodium salt)
Elderly (consider dose adjustment; more toxic in older
adults, particularly in the presence of renal, A bisphosphonate, which inhibits bone resorption via
gastrointestinal, or cardiac disease); actions on osteoclasts or on osteoclast precursors. The
Pregnancy; use of this drug can indirectly increase bone mineral
Lactation (excreted in breast milk). density.

Adverse Drug Reactions: Indications: Treatment and prevention of osteoporosis in

Common: GI disease, diarrhea, vomiting, nausea, fatigue, postmenopausal females and males; treatment of
headache, gout, abdominal cramps, abdominal pain, Paget’s disease of the bone in patients who are
pharyngolaryngeal pain symptomatic, at risk for future complications, or with
Less Common: Alopecia, aplastic anemia, skin rash, alkaline phosphatase ≥2 times the upper limit of normal;
azoospermia, bone marrow, dermatitis, depression, treatment of glucocorticoid-induced osteoporosis in
granulocytopenia, hepatotoxicity, disseminated IV males and females with low bone mineral density who
coagulation, hypersensitivity reaction, lactose are receiving a daily dosage ≥7.5 mg of prednisone (or
intolerance, leukopenia, maculopapular rash, myalgia, equivalent)
myasthenia, myopathy, myotonia, neuropathy,

417
 MUSCULO-SKELETAL SYSTEM

Contraindications: Hypocalcemia; abnormalities of the dysphagia, gastric ulcer, melena, musculoskeletal pain,
esophagus (e.g., stricture, achalasia) which delay muscle cramps, esophageal ulcer / stricture / erosions
esophageal emptying; inability to stand or sit upright for Less Common: Alopecia, anastomotic ulcer, angioedema,
at least 30 minutes atrial fibrillation, dizziness, duodenal ulcer, dysgeusia,
episcleritis, erythema, erosive esophagitis, esophageal
Dose: perforation, esophageal spasm, esophageal ulcer,
NOTE: Consider discontinuing after 3–5 years of use in esophagitis, exacerbation of asthma, femur fracture,
patients at low-risk for fracture. Patients should receive fever, flu-like symptoms, hypocalcemia (symptomatic),
supplemental calcium and vitamin D if dietary intake is hypersensitivity reaction, joint swelling,
inadequate. lymphocytopenia, malaise, malignant neoplasm of
esophagus, myalgia or arthralgia (occasionally severe),
Osteoporosis, prophylaxis, by mouth, ADULT oropharyngeal ulcer; ostealgia, osteonecrosis (jaw),
(postmenopausal female), 5 mg once daily or 35 mg peripheral edema, pruritus, skin rash, Stevens-Johnson
once weekly. syndrome, toxic epidermal necrolysis, urticaria, vertigo,
Osteoporosis, treatment, by mouth, ADULT weakness
(postmenopausal female), 10 mg once daily or 70 mg Rare: Scleritis, skin photosensitivity, uveitis
once weekly; ADULT (male), 10 mg once daily or 70 mg
once weekly. Drug Interactions:
Paget’s disease of the bone, by mouth, ADULT, 40 mg once Monitor closely with:
daily for 6 months. Increases risk of adverse or toxic effects of Alendronate:
Corticosteroid-induced osteoporosis, by mouth, ADULT, 5 Aminoglycosides e.g. Streptomycin (hypocalcemic
mg daily; ADULT (postmenopausal female not receiving effect), Aspirin (upper GI adverse events), NSAIDs (GI
estrogen) 10 mg daily. ulceration; nephrotoxicity), Systemic Angiogenesis
Inhibitors (osteonecrosis of the jaw)
RE-TREATMENT: Following a 6-month post-treatment
M

evaluation period, treatment with alendronate may be Increases risk of adverse or toxic effects of Deferasirox (GI
considered in patients who have relapsed based on ulceration, irritation, or bleeding)
increases in serum alkaline phosphatase, which should
be measured periodically. Re-treatment may also be Reduces therapeutic effect of Alendronate:
considered in those who failed to normalize their serum Proton Pump Inhibitors
alkaline phosphatase.
Avoid concomitant use with:
Dose Adjustment: Decreases serum concentration of Alendronate [if
Renal Impairment: concomitant use cannot be avoided, separate
In patients with CrCl<35 mL/minute, use is not administration times by at least 30 minutes]:
recommended. Antacids [except Magaldrate, Sodium Bicarbonate],
Calcium Salts, Iron Salts [except Ferric Carboxymaltose,
Precautions: Ferric Gluconate, Ferric Pyrophosphate Citrate,
Bone fractures (atypical femur fractures have been Ferumoxytol, Iron Dextran Complex, Iron Sucrose],
reported, including subtrochanteric femur and Magnesium Salts, Multivitamins / Minerals with ADEK,
diaphyseal femur; may cause prodromal pain weeks or Folate, Iron, Multivitamins / Minerals with AE, no Iron
months before the fracture occurs); bone, joint, or
muscle pain (symptoms usually resolve upon Reduces therapeutic effect of the following drugs:
discontinuation); Parathyroid Hormone (interferes with normalization of
Osteonecrosis of the jaw; blood calcium concentrations)
Gastrointestinal mucosa irritation;
Hypocalcemia (has been reported; correct hypocalcemia TEST INTERACTIONS. May interfere with diagnostic imaging
prior to therapy initiation; ensure adequate calcium and agents such as technetium-99m-diphosphonate in bone
vitamin D intake); scans
Renal impairment;
Elderly (advise patient to report any lower extremity, jaw, or Administration: Must be taken with plain water first thing in
muscle pain that cannot be explained or lasts longer the morning and ≥30 minutes before the first food,
than 2 weeks); beverage, or other medication(s) of the day. All food and
Pregnancy (discontinue use in women of reproductive beverages interfere with absorption. Co-administration
potential as early as possible prior to a planned with dairy products may decrease alendronate
pregnancy; use in premenopausal women should be absorption. Food and beverages (especially orange juice,
reserved for rapid bone loss; monitor exposed infants for coffee, and mineral water) may reduce the absorption of
hypocalcemia after birth); alendronate as much as 60%. Do NOT take with mineral
Lactation (not known if excreted into breast milk). water or with other beverages. Instruct patients to stay
upright and not to lie down for at least 30 minutes and
Adverse Drug Reactions: until after first food of the day to reduce esophageal
Common: Headache, hypocalcemia, hypophosphatemia, irritation.
abdominal pain, acid regurgitation, dyspepsia, nausea,
flatulence, diarrhea, gastroesophageal reflux disease, Swallow tablet whole. Do NOT chow or suck.
constipation, abdominal distension, gastritis, vomiting,

418
MUSCULO-SKELETAL SYSTEM

MISSED DOSE (once weekly): If a once-weekly dose is Elderly (advise patient to report any lower extremity, jaw, or
missed, it should be given the next morning after muscle pain that cannot be explained or lasts longer
remembered. May then return to the original once- than 2 weeks; if on concomitant diuretic therapy, closely
weekly schedule (original scheduled day of the week). Do monitor serum electrolytes).
NOT give 2 doses on the same day. Pregnancy (not known if it crosses the placenta; fetal
exposure is expected; most sources recommend
Pregnancy Category: C discontinuation in women of reproductive potential as
early as possible prior to a planned pregnancy; use in
ATC Code: M05BA04 premenopausal women should be reserved for rapid
bone loss; monitor exposed infants for hypocalcemia
after birth);
ALENDRONATE + Lactation (not known if excreted into breast milk).
Rx
CHOLECALCIFEROL (VIT D3)
Adverse Drug Reactions:
Common: Headache, hypocalcemia, abdominal pain,
Oral: 70 mg (as sodium) + 5,600 IU tablet
hypophosphatemia, acid regurgitation, nausea,
dyspepsia, flatulence, diarrhea, constipation, GERD,
Alendronate is a bisphosphonate, which inhibits bone
esophageal ulcer, abdominal distension, gastritis,
resorption via actions on osteoclasts or on osteoclast
vomiting, dysphagia, gastric ulcer, melena,
precursors.
musculoskeletal pain, muscle cramps
Cholecalciferol is a fat-soluble vitamin D, which helps
Less Common: Alopecia, angioedema, anastomotic ulcer,
increase GI absorption of calcium and its assimilation
atrial fibrillation, dizziness, duodenal ulcer, dysgeusia,
into bones.
episcleritis, erosive esophagitis, erythema, esophageal
perforation, esophageal spasm, esophageal ulcer,
Indications: Treatment of osteoporosis in postmenopausal
esophagitis, joint swelling, exacerbation of asthma,
females; to increase bone mass in males with

M
femur fracture, flu-like symptoms, hypocalcemia
osteoporosis
(symptomatic), hypersensitivity reaction,
lymphocytopenia, malaise, malignant neoplasm of
Contraindications: Hypocalcemia; abnormalities of the
esophagus, oropharyngeal ulcer, myalgia or arthralgia
esophagus (e.g., stricture or achalasia) which delay
(occasionally severe), ostealgia, osteonecrosis (jaw),
esophageal emptying; inability to stand or sit upright for
peripheral edema, pruritus, skin rash, Stevens-Johnson
at least 30 minutes
syndrome, toxic epidermal necrolysis, urticaria, vertigo,
fever, weakness
Dose:
Rare: Scleritis, skin photosensitivity, uveitis
NOTE: Consider discontinuing after 3–5 years of use in
patients at low-risk for fracture. Patients should receive
Drug Interactions:
supplemental calcium and vitamin D if dietary intake is
Monitor closely with:
inadequate.
Increases risk of adverse or toxic effects of Alendronate:
Aminoglycosides (hypocalcemic effect), Aspirin (upper GI
Osteoporosis, by mouth, ADULT, 1 tablet (alendronate 70
adverse events), NSAIDs (GI ulceration; nephrotoxicity),
mg/cholecalciferol 5,600 units) once weekly.
Systemic Angiogenesis Inhibitors (osteonecrosis of the
jaw)
Dose Adjustment:
Renal Impairment:
Increases risk of adverse or toxic effects of Cholecalciferol:
In patients with CrCl<35 mL/minute, use is not
Danazol (hypercalcemic effect)
recommended.
Increases risk of adverse or toxic effects of the following
Precautions:
drugs:
Bone fractures;
Cardiac Glycosides e.g. Digoxin (arrhythmogenic effect),
Bone, joint, or muscle pain (symptoms usually resolve upon
Deferasirox (GI ulceration, irritation, or bleeding)
discontinuation);
Osteonecrosis of the jaw;
Reduces therapeutic effect of Alendronate:
Gastrointestinal mucosa irritation (use with caution);
Proton Pump Inhibitors
Gastrointestinal malabsorption syndrome (increased doses
of vitamin D supplementation may be required; monitor
Avoid concomitant use with:
25-hydroxy vitamin D levels).
Increases risk of adverse or toxic effects of Cholecalciferol:
Hypercalcemia (may exacerbate hypercalcemia and/or
Multivitamins / Fluoride with ADE, Other Vitamin D
hypercalciuria; monitor serum and urine calcium levels);
Analogs
Hypocalcemia or vitamin D deficiency (has been reported;
correct hypocalcemia and/or vitamin D deficiency prior
Reduces therapeutic effect of Parathyroid Hormone
to therapy initiation; ensure adequate calcium and
(interferes with normalization of blood calcium
vitamin D intake).
concentrations)
Renal impairment (use with caution);
Hepatic impairment (cholecalciferol may not be adequately
TEST INTERACTIONS. May interfere with diagnostic imaging
absorbed in patients who have malabsorption due to
agents such as technetium-99m-diphosphonate in bone
inadequate bile production);
scans.

419
 MUSCULO-SKELETAL SYSTEM

Administration: Must be taken with plain water first thing in Dose:

the morning and ≥30 minutes before the first food, Prevention of postmenopausal osteoporosis, by mouth,
beverage, or other medication(s) of the day. All food and ADULT, 300 micrograms once a day, continuous or in
beverages interfere with absorption. Co-administration cyclical regimens (e.g. 25 days on therapy then 5 days
with dairy products may decrease alendronate off); adjust dose based on bone mineral density and
absorption. Food and beverages (especially orange juice, clinical response; lowest effective dose should be used
coffee, and mineral water) may reduce the absorption of
alendronate as much as 60%. Do NOT take with mineral Administration: To reduce the risk of endometrial cancer,
water or with other beverages. Instruct patients to stay consider adding progestin in the therapy when
upright and not to lie down for at least 30 minutes and prescribing estrogen for a postmenopausal woman with
until after first food of the day to reduce esophageal a uterus. A woman without a uterus does not need
irritation. progestin, however, hysterectomized women with a
history of endometriosis may need a progestin. Use
Swallow tablet whole. Do NOT chow or suck. estrogen-alone, or in combination with a progestin with
the lowest effective dose and for the shortest duration
Ensure adequate calcium and vitamin D intake. If dietary possible. This drug may be taken without regard to
intake is inadequate, dietary supplementation is meals.
recommended.
Calcium: 1,000 mg daily (men: 50 to 70 years) or 1,200 See Conjugated Estrogen under Sex Hormones and
mg/day (women ≥51 years and men ≥71 years) Modulators of the Genital System – Estrogens in Chapter
Vitamin D: 800 to 1,000 int. units daily (men and women 5: Genito Urinary System and Sex Hormones for other
≥50 years); Recommended Dietary Allowance (RDA): information.
600 int. units daily (men and women ≤70 years) or 800
int. units daily (men and women ≥71 years) Pregnancy Category: X
M

MISSED DOSE (once weekly): If a once-weekly dose is ATC Code: G03CA57

missed, it should be given the next morning after
remembered; may then return to the original once-
weekly schedule (original scheduled day of the week). Do
NOT give 2 doses on the same day. OTHER DRUGS FOR DISORDERS OF
THE MUSCULO-SKELETAL SYSTEM
Pregnancy Category: C

ATC Code: M05BB03 DISEASE MODIFYING ANTIRHEUMATIC

DRUGS (DMARDS)

Rx CONJUGATED ESTROGEN Rx AZATHIOPRINE

Oral: 625 micrograms and 1.25 mg tablet Oral: 50 mg tablet

Estrogen products mimic endogenous estrogens in the body An imidazolyl derivative of mercaptopurine. This purine
that are responsible for the development and metabolite is incorporated into replicating DNA and halts
maintenance of the female reproductive system and replication by blocking purine synthesis. The
secondary sexual characteristics. Estrogens modulate 6­thioguanine nucleotide metabolites appear to mediate
the pituitary secretion of luteinizing hormone and follicle- most of azathioprine’s immunosuppressive and toxic
stimulating hormone through a negative feedback effects.
system thereby reducing elevated levels of these
hormones responsible for symptoms experienced by Indication: Management of active rheumatoid arthritis
postmenopausal women.
Contraindications: Pregnancy; patients with rheumatoid
Indication: Prevention of progression of osteoporosis arthritis and a history of treatment with alkylating agents
associated with estrogen deficiency in postmenopausal (e.g., cyclophosphamide, chlorambucil, melphalan) may
women have a prohibitive risk of malignancy with azathioprine
treatment
Contraindications: Angioedema or anaphylactic reaction to
estrogen or any component of the formulation; Dose:
undiagnosed abnormal genital bleeding; DVT or PE Rheumatoid arthritis, by mouth, ADULT and CHILD, initially
(current or history of); active or history of arterial 1 mg/kg daily (50-100 mg) given once daily or divided
thromboembolic disease (e.g., stroke, MI); breast cancer twice daily for 6-8 weeks; may increase by 0.5 mg/kg
(known, suspected or history of); estrogen-dependent every 4 weeks until response or up to 2.5 mg/kg daily;
tumor (known or suspected); hepatic impairment or an adequate trial should be a minimum of 12 weeks;
disease; known protein C, protein S, antithrombin maintenance dose, reduce dose by 0.5 mg/kg (~25 mg
deficiency or other known thrombophilic disorders; daily) every 4 weeks until lowest effective dose is
pregnancy reached; may be discontinued abruptly (monitor for
delayed toxicities).

420
MUSCULO-SKELETAL SYSTEM

Dose Adjustment: Adverse Drug Reactions:

Geriatric: Common: Malaise, nausea, vomiting, diarrhea, leukopenia,
Start with lowest recommended adult doses. Adjust dose to neoplasia, thrombocytopenia, hepatotoxicity, increased
creatinine clearance. susceptibility to infection, myalgia, fever
Less Common: Abdominal pain, acute myelocytic leukemia,
Renal Impairment: alopecia, anemia, arthralgia, bone marrow depression
For patients with CrCl 10-50 mL/minute, administer 75% of (dose-related), hemorrhage, hepatic veno-occlusive
normal dose. disease, hepatosplenic T-cell lymphomas (HSTCL),
For patients with CrCl <10 mL/minute, administer 50% of hepatotoxicity (idiosyncratic), hypersensitivity,
normal dose. hypotension, interstitial pneumonitis (reversible), JC
For patients receiving hemodialysis, administer 50% of virus infection, macrocytic anemia, malignant
normal dose and supplement with 0.25 mg/kg. lymphoma, malignant neoplasm of skin, negative
Oliguric patients, particularly those with tubular necrosis in nitrogen balance, pancreatitis, pancytopenia,
the immediate post­transplant period (cadaveric progressive multifocal leukoencephalopathy (potentially
transplant) may have delayed clearance and typically fatal), skin rash, steatorrhea, Sweet's syndrome (acute
receive lower doses. febrile neutrophilic dermatosis), post-transplant
lymphoma
Hepatic Impairment:
Reduce dose. Drug Interactions:
Monitor closely with:
Precautions: Enhances therapeutic effect of Azathioprine:
WARNING: Hazardous agent; use appropriate ACE Inhibitors, Trimethoprim (myelosuppressive effect),
precautions for handling and disposal. Trastuzumab (neutropenic effect), (myelosuppressive
effect)

M
WARNING: Chronic use for immunosuppression Enhances therapeutic effect of Sipuleucel-T
increases risk of malignancy, including
posttransplant lymphoma and hepato-splenic T- Increases risk of adverse or toxic effects of Azathioprine:
cell lymphoma in patients with inflammatory bowel ACE Inhibitors, Co-trimoxazole (hematologic
disease. abnormalities), Denosumab (serious infections)

Gastrointestinal toxicity (e.g. severe nausea, vomiting, Increases risk of adverse or toxic effects of
diarrhea, rash, fever, malaise, myalgia, hypotension, and Cyclophosphamide (hepatotoxic effect)
liver enzyme abnormalities generally reversible upon
discontinuation). Reduces diagnostic effect of Coccidioides immitis Skin Test
Hematologic toxicity (dose-related; leukopenia,
thrombocytopenia, and anemias may occur; may be Reduces therapeutic effect of Vitamin K Antagonists, e.g.,
severe and/or delayed; patients with intermediate Warfarin (anticoagulant effect)
thiopurine methyltransferase (TPMT) activity may be at
increased risk for hematologic toxicity at conventional Avoid concomitant use with:
azathioprine doses; patients with low or absent TPMT Decreases serum concentration of Azathioprine:
activity are at risk for severe, life-threatening Ribavirin
myelotoxicity; myelosuppression may be more severe
with renal transplants undergoing rejection; may require Enhances therapeutic effect of Azathioprine:
treatment interruption or dose reduction). Roflumilast (immunosuppressive effect)
Hepatotoxicity (transaminase, bilirubin, and alkaline
phosphatase elevations may occur; usually occurs within Enhances therapeutic effect of the following drugs:
6 months of transplant and is normally reversible with Mercaptopurine (myelosuppressive effect), Tofacitinib
discontinuation; rarely, hepatic sinusoidal obstruction (immunosuppressive effect)
syndrome [SOS], formerly called veno-occlusive disease
[VOD] has been reported; discontinue if hepatic SOS is Increases risk of adverse or toxic effects of Azathioprine:
suspected). Pimecrolimus
Infections (chronic immunosuppression increases the risk
of serious, sometimes fatal, infections; progressive Increases risk of adverse or toxic effects of the following
multifocal leukoencephalopathy [PML] caused by drugs:
reactivation of the JC virus, has been reported). Leflunomide (hematologic toxicity, such as
Hepatic and renal impairment (dosage reductions may be pancytopenia, agranulocytosis, and/or
necessary); thrombocytopenia), Natalizumab (concurrent infection),
TPMT deficiency (increased sensitivity to myelosuppressive Tacrolimus Topical, Vaccines (Live)
effects; consider TPMT testing in patients with
abnormally low CBC unresponsive to dose reduction); Increases serum concentration of Azathioprine:
Elderly; Allopurinol [if concomitant use cannot be avoided,
Lactation (breast­feeding is not recommended by the reduce azathioprine dose to 1/3 to ¼ of usual dose],
manufacturer due to potential for serious adverse Febuxostat
reactions in the nursing infant).

421
 MUSCULO-SKELETAL SYSTEM

Reduces therapeutic effect of Azathioprine: Neuromuscular effects e.g. myopathy, neuromyopathy, and
Ribavirin progressive weakness;
Ophthalmic effects e.g. loss of visual acuity, macular
Reduces therapeutic effect of the following drugs: pigmentary changes, and loss of foveal reflex;
BCG, Vaccines, Inactivated [complete all age-appropriate G6PD deficiency;
vaccinations at least 2 weeks prior to starting Hepatic impairment;
azathioprine; if vaccinated during azathioprine therapy, Porphyria and psoriasis;
revaccinate at least 3 months after discontinuation], Pediatric (use caution due to increased sensitivity to
Vaccines, Live [avoid azathioprine doses greater than 3 aminoquinolones).
mg/kg daily] Pregnancy (may decrease the incidence of cardiac
malformations associated with neonatal lupus);
Administration: Administer tablets after meals or in divided Lactation (excreted into breast milk).
doses to decrease adverse GI events.
SKILLED TASKS. May impair ability to perform skilled tasks,
Protect from light and moisture and store between 15– such as operating machinery or driving.
25°C.
Adverse Drug Reactions:
Pregnancy Category: D Common: Ataxia, dizziness, emotional disturbance,
headache, irritability, lassitude, nerve deafness,
ATC Code: Not available nervousness, nightmares, psychosis, seizure, suicidal
tendencies, vertigo, alopecia, bleaching of hair, bullous
rash, dyschromia, exacerbation of psoriasis, pruritus,
urticaria, exacerbation of porphyria, weight loss,
Rx HYDROXYCHLOROQUINE anorexia, diarrhea, nausea, stomach cramps, vomiting,
agranulocytosis, anemia, aplastic anemia, hemolysis,
M

Oral: 200 mg tablet (as sulfate) leukopenia, thrombocytopenia, hepatic insufficiency,

angioedema, myopathy, accommodation disturbance,
NOTE: Hydroxychloroquine sulfate 200 mg is equivalent to corneal changes, decreased visual acuity, epithelial
155 mg hydroxychloroquine base and 250 mg keratopathy, macular degeneration, macular edema,
chloroquine phosphate. maculopathy, nystagmus, optic disk disorder
(pallor/atrophy), retinal pigment changes, retinal
Indications: Management of systemic lupus erythematosus vascular disease, retinitis pigmentosa, retinopathy,
(SLE) and rheumatoid arthritis (RA) scotoma, vision color changes, visual field defect,
tinnitus, bronchospasm, respiratory failure (myopathy-
Contraindications: Pre-existing maculopathy of the eye; related)
retinal or visual field changes attributable to Less Common: Hypoglycemia (potentially fatal),
4­aminoquinolines; long-term use in children keratopathy
Rare: Cardiomyopathy
Dose:
Rheumatoid arthritis, by mouth, ADULT, initially 400 to 600 Drug Interactions:
mg daily taken with food or milk; increase dose gradually Avoid concomitant use with:
until optimum response level is reached; usually after 4– Increases risk of adverse or toxic effects of the following
12 weeks dose should be reduced by ½ to a drugs:
maintenance dose of 200 to 400 mg daily in 1–2 divided Artemether, Dapsone (hemolytic reactions),
doses (maximum daily dose, 6.5 mg/kg or 400 mg, Lumefantrine, Mefloquine (convulsions; QTc-
whichever is lower); CHILD, up to 6.5 mg/kg daily or 400 prolongation) [if concomitant use cannot be avoided,
mg, whichever is lower. delay administration of mefloquine until at least 12
Lupus erythematosus, by mouth, ADULT, 400 mg 1–2 times hours after the last dose of hydrochloroquine]
daily for several weeks to months depending on
response; 200–400 mg daily in 1 to 2 divided doses for Administration: Administer with food or milk.
prolonged maintenance therapy (maximum daily dose,
6.5 mg/kg or 400 mg, whichever is lower). Pregnancy Category: Not classified

Dose Adjustment: ATC Code: Not available

Renal and Hepatic Impairment:
Dose adjustment may be necessary.

Precautions:
WARNING: Should be prescribed only by physicians
familiar with its use. May cause dizziness and
blurred vision.

Cardiovascular effects e.g. rare cardiomyopathy in long term

use; hematologic effect e.g. agranulocytosis, aplastic
anemia, and thrombocytopenia;

422
MUSCULO-SKELETAL SYSTEM

NOTE: Optimal intrathecal chemotherapy dosing should be

Rx METHOTREXATE based on age rather than on body surface area (BSA) as
CSF volume correlates with age and not to BSA.
Oral: 2.5 mg tablet (as base or sodium salt)
Inj.: 5 mg/mL (as sodium salt), 3 mL vial (IM, IV) Doses ≥250 mg/m2 (≥12 g/m2 in children) are
25 mg/mL (as base), 2 mL ampule / vial (IM, IV, associated with moderate emetic potential. Antiemetics
intrathecal) may be given to prevent nausea and vomiting.
25 mg/mL (as sodium salt, preservative-free), 2 mL
ampule / vial (IM, IV, intrathecal) Doses >500 mg/m2 require leucovorin calcium rescue.
100 mg/mL (as base), 10 mL vial Doses between 100–500 mg/m2 may require leucovorin
100 mg/mL (as sodium salt, preservative-free), 10 calcium rescue.
mL vial (IM, IV, intrathecal)
See Methotrexate under Antineoplastic Agents –
A folate antimetabolite that inhibits DNA synthesis and Antimetabolites in Chapter 8: Antineoplastic and
repair, and cellular replication. Methotrexate irreversibly Immunomodulating Agents for other information.
binds to and inhibits dihydrofolate reductase thereby
preventing the formation of reduced folates and Pregnancy Category: X
thymidylate synthetase. The use of this drug results to
the inhibition of purine and thymidylic acid synthesis. ATC Code: Not available

Indications: Severe, active rheumatoid arthritis (RA); active

polyarticular-course juvenile idiopathic arthritis (pJIA)

Contraindications: Breast­feeding; pregnancy; alcoholism;

alcoholic liver disease or other chronic liver disease;

M
immunodeficiency syndrome; preexisting blood
dyscrasias

Dose:
RA, by mouth, ADULT, initially 7.5 mg once weekly or 2.5 mg
every 12 hours for 3 doses per week; adjust dose
gradually to optimal response;
alternatively, 10-15 mg once weekly, increased by 5 mg
every 2-4 weeks (maximum dose, 20-30 mg once
weekly);
by intramuscular injection, 7.5 mg once weekly; adjust
dose gradually to optimal response;
by mouth, ADULT >60 years, initially 5-7.5 mg per week,
not to exceed 20 mg per week.
pJIA, by mouth or IM injection, CHILD, initially 10 mg/m2
once weekly, adjust gradually to optimum response;
doses up to 20-30 mg/m2 once weekly have been used.

NOTE: Doses above 20 mg (20 mg/m2 in children) once

weekly are associated with an increased incidence of
toxicity.
Doses between 100–500 mg/m2 may require leucovorin
calcium rescue. Doses >500 mg/m2 require leucovorin
calcium rescue.

Administration:
For oral administration, administer without regard to
food. This is the preferred route for low doses.

For IV administration, administer as slow IV push at a

rate of 10 mg/minute, as bolus injection, or as 24-hour
continuous infusion. The route and rate of administration
depends on indication and/or protocol.

For intrathecal administration, do NOT prepare during

the preparation of any other agents. After preparation,
store in an isolated location or container clearly marked
with a label "intrathecal" use only. Administer only with
other medications intended for administration into the
central nervous system.

423
 NERVOUS SYSTEM

NERVOUS SYSTEM Note: Minimum Alveolar Concentration (MAC) decreases

with increasing age. Adjust dose accordingly.
Precautions:
Patient with or at risk of raise intracranial pressure; Patients
at risk of QT prolongation; Neuromuscular diseases e.g.
ANESTHETICS Duchenne muscular dystrophy; Chronic renal or hepatic
impairment.
Children (safety has not been investigated in non- intubated
ANESTHETICS, GENERAL patients < 2 years)
Pregnancy and lactation.
HALOGENATED HYDROCARBONS
SKILLED TASKS. May impair ability to perform tasks, which
require mental alertness, like driving or operating
Rx DESFLURANE machinery.

Inhalation: 240 mL bottle Adverse Drug Reactions:

Common: Decreased oxygen saturation, bradycardia,
Desflurane is a highly fluorinated, volatile methyl ethyl hypertension (including malignant hypertension), nodal
esther used for maintenance of general anesthesia. It arrhythmia, shivering, tachycardia, headache, nausea,
enhances inhibitory postsynaptic activity and inhibits vomiting, sialorrhea, laryngospasm, conjunctivitis,
excitatory synaptic activity, resulting in reversible loss of cough, breath-holding, apnea, increased bronchial
consciousness and of pain sensations, suppression of secretions, pharyngitis.
voluntary motor activity, reduction of autonomic reflexes, Less Common: Abdominal pain, acute pancreatitis,
and sedation of respiratory and the cardiovascular agitation, asthma, atrial fibrillation, bigeminy, blood
system. coagulation disorder, bronchospasm, cardiac
arrhythmia, cholestasis, dizziness, dyspnea, erythema,
Indications: Induction and maintenance of anesthesia. hemoptysis, hemorrhage, hepatic failure, hepatic
necrosis, fever, hepatitis (including cytolytic hepatitis),
N

Contraindications: Known or suspected genetic hepatotoxicity, hyperkalemia, hypokalemia, hypokinesia

susceptibility to malignant hyperthermia; induction of (ventricular), hypoxia, hypotension, shock, ischemic
anesthesia in pediatric patients; history of moderate-to- heart disease, leukocytosis, malaise, malignant
severe hepatic impairment following anesthesia with hyperthermia, metabolic acidosis, myalgia, pruritus,
halogenated agents and not otherwise explained; history respiratory distress, respiratory failure, rhabdomyolysis,
of hepatitis or in whom hepatic dysfunction, jaundice, scleral icterus, seizure, myocardial infarction, torsade de
unexplained fever, leukocytosis, or eosinophilia has pointes, urticaria, vasodilatation, ventricular dysfunction,
occurred due to a halogenated inhalational anesthetic. weakness.

Dose: Drug Interactions:

Anesthesia, induction, by inhalation, ADULT, initially 3%; Avoid concomitant use with:
increase by 0.5–1% increments every 2–3 breaths; end Enhances therapeutic effect of the following drugs:
tidal concentrations 4–11% v/v [NOTE: Inspired Blood pressure-lowering agents; Hypotension-
concentrations >12% have been safely administered associated agents (hypotensive effect); Dopamine;
during induction and may require a reduction of nitrous Epinephrine (nasal; oral inhalation and systemic);
oxide or air]. Norepinephrine (arrhythmogenic effect); Metyrosine;
Anesthesia, maintenance, by inhalation, ADULT, 2.5 to 8.5% Ropinirole, Rotigotine, Pramipexole (sedative effect);
v/v with or without concomitant nitrous oxide; CHILD, Neuromuscular-blocking Agents, Nondepolarizing, e.g.,
5.2–10% with or without nitrous oxide. Atracurium (neuromuscular-blocking effect)
NOTE: Not indicated as induction agent or for maintenance QTc-prolonging Agents (QTc-prolonging effect)
of anesthesia in non-intubated children <6 years.
Increases risk of adverse or toxic effects of Desflurane:
Dosing based on patient’s age and Minimum Alveolar Ephedrine nasal and systemic (arrhythmogenic effect);
Concentration (MAC): Methylphenidate (hypertensive effect); Other CNS
MAC with 100% MAC with 60% Depressants; Rufinamide (sleepiness and dizziness)
Age
Oxygen N2O/ 40% O2
Increases risk of adverse or toxic effects of the following
9 months 10% 7.5%
drugs:
3 years 8.9% 6.4% Amifostine (hypotensive effect); Fenoterol, Formoterol,
25 years 7.3% 4% Isoproterenol, Metaraminol (arrhythmogenic effect);
45 years 6% 2.8% SSRIs (psychomotor impairment)
70 years 5.2% 1.7%
Administration: Inhalation via desflurane-specific calibrated
Dose Adjustment: heated vaporizer
Geriatric: Geriatric dose requires approximately 70% the
adult dose in 100 % oxygen and 40% the adult dose of NOTE: Monitor BP, heart rate and rhythm, temperature,
nitrous oxide oxygen saturation, end-tidal CO2 and end-tidal
desflurane concentration prior to and throughout

424
NERVOUS SYSTEM

procedure. Monitor signs and symptoms of airway Ephedrine nasal and systemic (arrhythmogenic effect);
narrowing for pediatric patients. Methylphenidate (hypertensive effect); Succinylcholine
Assess for malignant hyperthermia, hypercapnia, muscle (malignant hyperthermia)
rigidity, tachycardia, cyanosis, arrhythmias, hypotension
or hypertension. Increases risk of adverse or toxic effects of the following
drugs:
Pregnancy Category: B Fenoterol, Formoterol, Isoproterenol, Metaraminol
(arrhythmogenic effect); Other CNS depressants
ATC Code: N01AB07
Prolongs recovery from anesthesia:
Ketamine
Rx HALOTHANE Administration: Inhalation via halothane-specific calibrated
vaporizer
Inhalation: 250 mL bottle
NOTE: Monitor pulse and BP.
Halothane is a non-flammable, halogenated, hydrocarbon
inhalational anesthetic. It provides relatively rapid Pregnancy Category: C
induction with little or no excitement, though analgesia
may not be adequate. ATC Code: N01AB01

Indication: Induction and maintenance of general

anesthesia.
Rx ISOFLURANE
Contraindications: Known or suspected susceptibility to
malignant hyperthermia; raised cerebrospinal fluid Inhalation: 100 mL and 250 mL bottle
pressure; history of unexplained jaundice or acute
hepatic damage from previous exposure to halothane; Isoflurane is a highly halogenated methyl ester that

N
outpatient dental surgery in children <18 years; produces profound respiratory depression. Inhaled
obstetrical anesthesia except when uterine relaxation is anesthetics alter activity of neuronal ion channels,
required. particularly the fast-synaptic neurotransmitter receptors.
They can also depress myocardial contractility, decrease
Dose: blood pressure and sympathetic nervous activity.
Anesthesia, induction, by inhalation, ADULT, 0.5% v/v in
oxygen or mixture of nitrous oxide and oxygen, increase Indication: Induction and maintenance of general
gradually according to response to a concentration of 2– anesthesia.
4% v/v, CHILD, 1.5–2% v/v.
Anesthesia, maintenance, by inhalation, ADULT, 0.5 to 2% Contraindications: Known or suspected genetic
v/v depending on the flow rate used, CHILD, 0.5–1.5% susceptibility to malignant hyperthermia; history of
v/v. hepatitis following halogenated inhalational anesthetic;
history of liver dysfunction, jaundice or unexplained
Precautions: fever, leucocytosis, or eosinophilia following halogenated
Pheochromocytoma; myasthenia gravis; renal failure; pre- anesthetic administration.
existing hepatic disease.
Children. Dose:
Pregnancy and lactation. Anesthesia, induction, by inhalation, ADULT, 1.5–3% with
oxygen or oxygen-nitrous oxide mixture.
Adverse Drug Reactions: Anesthesia, induction, by inhalation, ADULT, 0.5% v/v with
Rare: Post-operative nausea, vomiting, shivering, oxygen or oxygen and nitrous oxide mixture, increased to
respiratory depression, respiratory arrest, hypotension, 1.5–3% v/v with oxygen or oxygen-nitrous oxide mixture.
skeletal muscle relaxation, hepatic necrosis, Anesthesia, maintenance, by inhalation, ADULT, 1 to 2.5%
hyperpyrexia, bradycardia, cardiac arrest, hypotension. v/v with concomitant oxygen and nitrous oxide mixture,
Potentially fatal: Hepatotoxicity, malignant hyperthermia, then 1.5–3.5% v/v with oxygen alone.
cardiac arrhythmias. Anesthesia, maintenance during caesarian section, ADULT
women, 0.5–0.75% v/v with oxygen and nitrous oxide
Drug Interactions: mixture.
Avoid concomitant use with:
Enhances therapeutic effect of the following drugs: Precautions:
Dopamine, Epinephrine (nasal, oral inhalation and Increased intracranial pressure; Coronary artery disease;
systemic), Norepinephrine (arrhythmogenic effect); Patients at risk of QT prolongation and
Hypotensive Agents, e.g., Hexamethonium Bromide, bronchoconstriction; Hypotension; Hypovolemia;
Trimetaphan Camsilate; Neuromuscular-blocking Neuromuscular disease, e.g., Duchenne muscular
Agents; Nondepolarizing (neuromuscular-blocking dystrophy; myasthenia gravis; mitochondrial disorders;
effect) Addison’s disease; Myxedema; Hepatic impairment:
Carboxyhemoglobinemia (do not allow CO2 absorbents in
Increases risk of adverse or toxic effects of Halothane: anesthetic apparatus to dry out when delivering

425
 NERVOUS SYSTEM

isoflurane to minimize the risk of developing hepatic impairment associated with halogenated
carboxyhemoglobinaemia); Hemodynamically anesthetics.
compromised and debilitated patients.
Children (use with caution in <3 years); Pregnancy and Dose:
lactation. Anesthesia, induction and maintenance, by inhalation,
ADULT, 0.5–3% v/v with or without the concomitant use
Drug Interactions: of nitrous oxide; amnesia and loss of awareness occurs
Avoid concomitant use with: at 0.6%.
Enhances therapeutic effect of the following drugs:
Blood pressure-lowering agents, (hypotensive effect); Patient Age and Minimum Alveolar Concentration
Dopamine; Epinephrine nasal; oral inhalation and (MAC)
systemic, Norepinehrine (arrhythmogenic effect); MAC with
Metyrosine; Pramipexole (sedative effect); MAC with 100% 65%
Neuromuscular-blocking Agents; Nondepolarizing Age
Oxygen N2O/
(neuromuscular-blocking effect); QTc-prolonging Agents 35% O2
(QTc-prolonging effect); Ropinirole; Rotigotine (sedative 0–1 month
effect) old full-
3.3% -
term
Increases risk of adverse or toxic effects of Isoflurane: neonates
Bambuterol; Ephedrine, Nasal and Systemic 1 to <6
(arrhythmogenic effect); Methylphenidate (hypertensive 3% -
months
effect); Rufinamide (sleepiness and dizziness)
6 months to
2.8% 2%
<1 year
Increases risk of adverse or toxic effects of the following
drugs: 1 to <3
2.8% 2%
Fenoterol; Formoterol; Isoproterenol; Metaraminol years
(arrhythmogenic effect); Other CNS depressants; SSRIs 3–12 years 2.5% -
(psychomotor impairment) 25 years 2.6% 1.4%
N

40 years 2.1% 1.1%

Administration: Administer via isoflurane-specific calibrated 60 years 1.7% 0.9%
vaporizer or vaporizer with calculated flow required.
80 years 1.4% 0.7%
Use an ultra-short-acting barbiturate to avoid coughing,
breath-holding, or laryngospasm during induction. Dose Adjustment:
Renal and Hepatic Impairment:
NOTE: Select premedication based on the need of the Use with caution in severe impairment. Safety has not been
individual patient, considering that secretions are weakly established.
stimulated by isoflurane, and the heart rate tends to be
increased. The use of anticholinergic drugs is a matter of Precautions:
choice. Increased intracranial pressure; Neuromuscular disease
e.g. Duchenne muscular dystrophy; mitochondrial
Pregnancy Category: C disorder; Hypovolemia; Hypotension; Hemodynamically
compromised patients; Patients at risk of QT
ATC Code: N01AB06 prolongation; Hepatic and renal impairment
Children; Pregnancy and lactation

Adverse Drug Reactions:

Rx SEVOFLURANE Common: Hypotension, tachycardia, bradycardia,
hypertension, agitation, drowsiness, shivering, dizziness,
Inhalation: 250 mL bottle headache, hypothermia, myoclonus, delirium
(emergence), sialorrhea, cough, airway obstruction,
Sevoflurane is a fluorinated isopropyl esther. It may act by laryngospasm, breath-holding, apnea, fever
interfering with the release and re- uptake of Less Common: Acidosis, albuminuria, amblyopia,
neurotransmitters at post- synaptic terminals and/or anaphylactoid reaction, anaphylaxis, atrial arrhythmia,
alter ionic conduction following receptor activation. It bigeminy, bronchospasm, atrial fibrillation, cardiac
also activates GABA receptors that produces general arrhythmia, chest discomfort, complete AV block,
anesthetic effect, a decrease in myocardial contractility confusion, conjunctivitis, crying, dysgeusia, ST-segment
and mean arterial pressure and increases respiratory depression on ECG, dyspnea, extrasystoles
rate. (supraventricular), facial edema, glycosuria,
hemorrhage, hepatic failure, hepatic insufficiency,
Indication: Induction and maintenance of general hepatic necrosis, hepatitis, hepatotoxicity (idiosyncratic),
anesthesia. hiccups, hypertonia, hyperbilirubinemia, hyperglycemia,
hypoxia, hypersensitivity reaction, hyperkalemia
Contraindications: Known or suspected susceptibility to (pediatric; postoperative), hyperventilation,
malignant hyperthermia; history of moderate to severe hypophosphatemia, hypoventilation, insomnia,
jaundice, leukocytosis (transient), malignant

426
NERVOUS SYSTEM

hyperthermia, myoglobinuria, nervousness, oliguria, Dose:

pain, pharyngitis, pruritus, second degree Anesthesia, induction, by IV injection or continuous IV
atrioventricular block, skin rash, stridor, syncope, infusion, ADULT, 100–150 mg of a 2.5 or 5% solution
thrombocytopenia, tooth enamel damage (fluorosis), injected over 10–15 seconds, repeat every 30–60
urinary retention, urticaria, ventricular premature seconds according to response or as a continuous
contractions, weakness, wheezing, xerostomia infusion of a 0.2 or 0.4% solution (maximum, 500 mg;
Rare: Seizure maximum dose in pregnancy, 250 mg); CHILD, 2–7
mg/kg over 10–15 seconds, repeat after 1 minute if
Drug Interactions: needed.
Avoid concomitant use with:
Enhances therapeutic effect of the following drugs: Dose Adjustment:
Blood pressure-lowering agents and Hypotensive agents Geriatric:
(hypotensive effect); Use with caution. Dose reduction or small doses are
Dopamine; Epinephrine nasal, oral inhalation and advisable.
systemic; Norepinephrine (arrhythmogenic effect);
Metyrosine, Pramipexole, Ropinirole, Rotigotine Renal Impairment:
(sedative effect); Neuromuscular-blocking Agents; Use with caution as hypnotic effect may be prolonged or
Nondepolarizing (neuromuscular-blocking effect); QTc- potentiated. If CrCl<10 mL/minute, administer at 75% of
prolonging Agents (QTc-prolonging effect) normal dose.

Increases risk of adverse or toxic effects of Sevoflurane: Hepatic Impairment:

Bambuterol; Epinephrine nasal, oral inhalation and Use with caution. Reduce doses.
systemic (arrhythmogenic effect); Methylphenidate
(hypertensive effect); Rufinamide (sleepiness and Precautions:
dizziness) Severe CV, respiratory, renal, hepatic, or endocrine disease;
Hypotension; Shock; Hypovolemia; Conditions in which
Increases risk of adverse or toxic effects of the following hypnotic effects may be potentiated; History of severe
drugs: asthma; Severe cardiac disease; Severe anemia;

N
Fenoterol; Formoterol; Isoproterenol; Metaraminol Hyperkalemia; Toxemia Myasthenia gravis; Myxedema;
(arrhythmogenic effect); Other CNS depressants; SSRIs Muscular dystrophies; Adrenocortical insufficiency;
(psychomotor impairment) Increased intracranial pressure
Elderly; Pregnant
Administration: Administer via sevoflurane-specific Lactation (excreted in breastmilk; monitor infant for
calibrated vaporizers. Use with caution in low-flow or possible adverse effects).
closed-circuit systems since sevoflurane is unstable and
may liberate potentially toxic breakdown products. Adverse Drug Reactions: Coughing, hiccupping, sneezing,
muscle twitching, laryngospasm, bronchospasm. tissue
Pregnancy Category: B necrosis (IV-related). severe arterial spasm with burning
pain (intra-arterial), blanching of forearm and hands and
ATC Code: N01AB08 gangrene of digits (intra-arterial), respiratory depression,
arrhythmias, circulatory failure, anaphylactoid reactions,
myocardial depression, arrhythmias, delirium, headache,
BARBITURATES, PLAIN amnesia, seizures, rash, abdominal pain, rectal irritation,
diarrhea, cramping, apnea, hiccups, sneezing, coughing,
thrombophlebitis, pain at injection site, salivation,
Rx THIOPENTAL SODIUM shivering.

Drug Interactions:
Inj.: 500 mg vial (IV)
Monitor closely with:
1 g vial + 50 mL diluent (IV)
Enhances therapeutic effect of Thiopental:
Brimonidine (Topical); Doxylamine; Dronabinol;
Thiopental is an ultrashort-acting thiobarbiturate with
Hydroxyzine; Magnesium sulphate; Minocycline;
anesthetic activity that binds to the chloride site of the
Nabilone
GABAA/chloride receptor complex resulting in inhibitory
actions of GABAA in the brain. This leads to synaptic
Enhances therapeutic effect of the following drugs:
inhibition, decreased neuronal excitability, glutamate
Diazoxide; Hypotensive agents (hypotensive effect); Ethyl
response and induction of anesthesia but not analgesia.
alcohol; Meperidine (CNS depressant effect);
Pramipexole, Ropinirole, Rotigotine (sedative effect)
Indication: Induction of anesthesia.
Enhances absorption of Theophylline Derivatives [except
Contraindications: Variegate or acute intermittent
Dyphylline]
porphyria; absence of suitable veins for IV
administration; status asthmaticus; dyspnea or
Increases metabolism of Thiopental:
respiratory obstruction; severe cardiovascular disease or
Pyridoxine
hypotension; Addison’s disease; hepatic dysfunction;
myxedema.
Increases metabolism of the following drugs:

427
 NERVOUS SYSTEM

Paracetamol; Calcium Channel Blockers; Propacetamol; NOTE: IV infusion of concentrated solutions (e.g., 5%) may
Rifamycin Derivatives cause thrombophlebitis. Repeated doses may result in
prolonged drug effect because of accumulation.
Increases risk of adverse or toxic effects of Thiopental:
Antipsychotic Agents; Phenothiazines; CNS Depressants Pregnancy Category: C
[except Levocabastine]; Ketamine; Primidone;
Rufinamide (sleepiness and dizziness) ATC Code: N01AF03

Increases risk of adverse or toxic effects of the following

drugs: OTHER GENERAL ANESTHETICS
Paracetamol, Proparacetamol (liver damage); SSRIs
(psychomotor impairment); Thiazide diuretics
(orthostatic hypotension)
Rx KETAMINE

Reduces therapeutic effect of Thiopental: Inj.: 50 mg/mL (as hydrochloride), 10 mL vial (IM, IV)
Aminophylline
Ketamine is a cyclohexane derivative that binds to the
Reduces therapeutic effect of the following drugs: NMDA receptor and blocks glutamate. At low doses, it
Paracetamol; Propacetamol produces analgesia and modulate central sensitization,
hyperalgesia, and opioid tolerance. It also reduces
Avoid concomitant use with: polysynaptic spinal reflexes and produces a cataleptic-
Decreases metabolism of Thiopental: like state in which the patient is dissociated from the
Chloramphenicol surrounding environment.

Decreases serum concentration of Thiopental: Indications: Induction and maintenance of anesthesia;

Mefloquine endotracheal intubation; sedation or analgesia of
critically-ill patients.
Decreases serum concentration of the following drugs:
N

Doxycycline; Lamotrigine; Ulipristal Contraindications: Conditions in which an increase in blood

pressure or intraocular pressure; infants <3 months of
Enhances therapeutic effect of Thiopental: age; known or suspected schizophrenia.
Droperidol (CNS depressant effect); Droperidol,
Sulfisoxazole Dose:
Anesthesia, induction, by IM injection, ADULT, 6.5–13
Enhances therapeutic effect of the following drugs: mg/kg, ADOLESCENT <16 years, CHILD and INFANT ≥3
Buprenorphine [initiate buprenorphine patches at 5 months, 5–10 mg/kg;
micrograms/hour when used concomitantly], by IV infusion, ADULT, 1–4.5 mg/kg, ADOLESCENT <16
Hydrocodone [consider starting with a 20–30% lower years, CHILD, and INFANT ≥3 months, 1–3 mg/kg.
hydrocodone dose when used concomitantly]; Anesthesia, maintenance, by IM injection, ADULT,
Mirtazapine, Orphenadrine, Paraldehydye, Suvorexant, supplemental doses of ½ to full induction dose or by
Thalidomide, Zolpidem (CNS depressant effect) continuous infusion of 0.1 to 0.5 mg/minute;
ADOLESCENTS ≥16 years, supplemental doses of ½ to
Increases metabolism of the following drugs: full induction dose as needed.
Cyclosporine (Systemic); Tricyclic Antidepressants e.g Endotracheal intubation, by IV infusion, ADOLESCENT,
Amytriptyline; Vitamin K Antagonists, e.g., Warfarin CHILD, and INFANT, 1–2 mg/kg as part of rapid
sequence sedation.
Increases risk of adverse or toxic effects of the following Sedation or analgesia, critically-ill patients, by IV infusion,
drugs: ADOLESCENT, CHILD, and INFANT ≥5 months, initially
Azelastine (Nasal) (CNS depressant effect); 0.5–2 mg/kg, then by continuous IV infusion at a rate of
Somatostatin Acetate (barbiturate effects, including 5–20 micrograms/kg per minute; start at lower dose and
sedative effects) titrate to effect.

Reduces therapeutic effect of Thiopental: Dose Adjustment:

Mefloquine Geriatric:
Avoid in older adults with risk factors for coronary artery
Reduces therapeutic effect of the following drugs: disease.
Estrogen and Progestin contraceptives (contraceptive Renal Impairmet:
failure) Reduce dose for moderate impairment. Do not use in severe
impairment.
Administration: Administer by IV infusion. Avoid intra-arterial
administration.

Avoid extravasation.

The patient must always lie supine as even a small

overdose can cause hypotension.

428
NERVOUS SYSTEM

Precautions: Increases serum concentration of Ketamine:

WARNING: Should only be used by experienced Diazepam
personnel who are not actively engaged in the
procedure or surgery. If used in a non-intubated Reduces therapeutic effect of Ketamine:
and/or nonmechanically ventilated patient, Thiopental (antagonistic effect)
qualified personnel and appropriate equipment for
rapid institution of respiratory and/or Administration:
cardiovascular support must be immediately For deep IM administration, inject into large muscle
available. mass.

Chronic alcoholic or acutely alcohol-intoxicated patients; For IV administration, administer bolus or induction
Cardiac decompensation; Pre-anesthesia elevated CSF doses over 1 minute or at a rate of 0.5 mg/kg per minute.
pressure; Globe injuries; Increased intraocular pressure, A more rapid administration may result in respiratory
e.g., glaucoma; Neurotic traits or psychiatric illness, e.g., depression and enhanced pressor response. May
schizophrenia, acute psychosis. Acute intermittent administer over 2–3 minutes. May be administered as a
porphyria; Seizures; Hyperthyroidism; Pulmonary or continuous IV infusion.
upper respiratory infection; Intracranial mass lesions;
Head injury or hydrocephalus; Hypovolemia; NOTE: May administer atropine, scopolamine, or another
Dehydration; Cardiac disease, especially coronary artery drying agent prior to induction and at appropriate
disease, e.g., CHF, MI, myocardial ischemia. intervals to decrease hypersalivation. Titrate dose for
Pregnancy and lactation. desired effect

Adverse Drug Reactions: Pregnancy Category: B

Common: Confusion, delirium, dreamlike state, excitement,
hallucinations, irrational behavior, vivid imagery, ATC Code: N01AX03
hypertonia (tonic-clonic; high-dose), sedation,
hypertension or hypotension, bradycardia, cardiac
arrhythmia, increased cerebrospinal fluid pressure,
NITROUS OXIDE

N
increased pulse, drug dependence, psychotomimetic Rx
phenomena (euphoria, dysphasia, psychomotor
retardation, vivid dreams, nightmares, impaired Inhalation: Anesthetic gas
attention, memory and judgment, illusions,
hallucinations, altered body image, blunted affect), CNS Nitrous Oxide is an odorless gas that serves as an
depression, erythema (transient), morbilliform rash anesthetic and analgesic. At high concentrations, it
(transient), rash at injection site, central diabetes causes a narcotic effect and may replace oxygen,
insipidus, anorexia, nausea, sialorrhea, bladder causing asphyxiation.
dysfunction (reduced capacity), cystitis (including cystitis
noninfective, cystitis interstitial, cystitis ulcerative, Indications: Surgical sedation and anesthesia; dental
cystitis erosive, cystitis hemorrhagic), vomiting, dysuria, sedation and anesthesia.
hematuria, urinary frequency, urinary incontinence,
urinary urgency, anaphylaxis, pain at injection site, Contraindications: Patients with demonstrable collections
laryngospasm, diplopia, increased intraocular pressure, of air in the pleural, pericardial, or peritoneal space;
nystagmus, hydronephrosis, airway obstruction, apnea, intestinal obstruction; occlusion of the middle ear;
respiratory depression, syncope, delirium, dizziness, arterial air embolism; decompression sickness; chronic
blurred vision, altered hearing. obstructive airway disease; emphysema; recent
pneumoencephalography
Drug Interactions:
Avoid concomitant use with: Dose:
Enhances sedative effect of the following drugs: Dental sedation and analgesia, by inhalation, ADULT, 25–
Metyrosine; Pramipexole; Ropinirole; Rotigotine 50% nitrous oxide with oxygen.
Surgical sedation and analgesia, by inhalation, ADULT, 25–
Increases risk of adverse or toxic effects of Ketamine: 50% nitrous oxide with oxygen;
Diazepam; Other CNS depressants Rufinamide General anesthesia, by inhalation, ADULT, 40–70% via
(sleepiness and dizziness); Theophylline, Thiopental mask or endotracheal tube.
(seizures, by reducing the seizure threshold)
NOTE: Minimal alveolar concentration (MAC), which can be
Increases risk of adverse or toxic effects of the following considered the ED50 of inhalational anesthetics, is 105%;
drugs: delivery in a hyperbaric chamber is necessary to use as
Atracurium, Tubocurarine (respiratory depression with a complete anesthetic. When administered at 70%, MAC
apnea); CNS Depressants, e.g., Phenothiazine, Sedating of other anesthetics is reduced by half.
H1 Blockers, Skeletal Muscle Relaxants (CNS depression;
respiratory depression); Dextromethorphan; Dose Adjustment:
Halogenated Anesthetics (bradycardia; hypotension; Renal and Hepatic Impairment:
decreased cardiac output) No information found
Memantine; SSRIs (psychomotor impairment); Thyroid
Hormones (hypertension)

429
 NERVOUS SYSTEM

Precautions:
Addictive (may be associated with abuse and/or addiction); ICU sedation in intubated mechanically-ventilated patients,
Body space volume expansion; Bone marrow by IV infusion, ADULT, initially 5 micrograms/kg per
suppression (prolonged use may produce bone marrow minute or 0.3 mg/kg per hour; increase by 5–10
suppression; increased risk in vitamin B12 deficiency and micrograms/kg per minute or 0.3–0.6 mg/kg per hour
other nutritional deficiencies); Neurologic effects every 5–10 minutes until desired sedation level is
(increased risk in vitamin B12 deficiency and other achieved; usual maintenance dose is 5–50
nutritional deficiencies); micrograms/kg per minute or 0.3–3 mg/kg per hour;
Vitreoretinal surgery (may increase intraocular pressure reduce dose after adequate sedation is established and
resulting in retinal artery occlusion, ischemia, or optic adjust to response [NOTE: Daily interruption with re-
nerve damage and vision loss). titration or a light target level of sedation is
recommended to minimize prolonged sedative effects].
Adverse Drug Reactions: Nausea, vomiting, neurologic Induction of general anesthesia, by IV push, ADULT <55
effects (prolonged use) years (healthy adults with ASA-PS 1 or 2), 2–2.5 mg/kg
Rare: Hypotension, CNS stimulation, confusion, dizziness, (about 40 mg every 10 seconds until onset of induction),
headache, nausea, vomiting, apnea ADULT (debilitated patients with ASA-PS 3 or 4), use 80%
of healthy adult dose, reduce dose after adequate
Drug Interactions: sedation is established and adjust to response [NOTE:
Avoid concomitant use with: Daily interruption with re-titration or a light target level of
Enhances sedative effect of the following drugs: sedation is recommended to minimize prolonged
Pramipexole; Ropinirole; Rotigotine sedative effects];
CHILD 3–16 years (healthy children with ASA-PS 1 or 2),
Increases risk of adverse or toxic effects of Ketamine: 2.5–3.5 mg/kg over 20–30 seconds; use a lower dose
CNS depressants; Rufinamide (sleepiness and dizziness) for children ASA-PS 3 or 4.
Maintenance of general anesthesia, by IV infusion, ADULT
Increases risk of adverse or toxic effects of SSRIs <55 years (healthy adults with ASA-PS 1 or 2), initially
(psychomotor impairment) 100–200 micrograms/kg per minute or 6–12 mg/kg per
hour for 10–15 minutes; usual maintenance infusion
N

Administration: For the maintenance of anesthesia, always rate is 50 to 100 micrograms/kg per minute or 3–6
mix nitrous oxide with at least 30% oxygen using a mg/kg per hour to optimize recovery time;
compressed-gas anesthetic machine. by IV infusion, ADULT >60 years (debilitated with ASA-PS
3 or 4), 50–100 micrograms/kg per minute or 3–6
Administer oxygen briefly during emergence from mg/kg per hour;
prolonged anesthesia with nitrous oxide to prevent by IV push, ADULT (debilitated patients with ASA-PS 3 or
diffusion hypoxia. 4), 1–1.5 mg/kg (about 20 mg every 10 seconds until
onset of induction);
Pregnancy Category: C CHILD 2 months to 16 years (healthy children with ASA-
PS 1 or 2), 125–300 micrograms/kg per minute or 7.5–
ATC Code: N01AX13 18 mg/kg per hour; after 30 minutes, if clinical signs of
light anesthesia are absent, decrease infusion rate;
by IV intermittent bolus, CHILD ≤5 years, 25–50 mg
increments as needed [NOTE: May require larger
Rx PROPOFOL
infusion rates].
Monitored anesthesia care sedation, by slow IV push and
Inj.: 10 mg/mL, 20 mL ampule (IV) slow IV infusion, ADULT <55 years (healthy adults with
10 mg/mL, 50 mL pre-filled syringe (IV) ASA-PS 1 or 2), 100–150 micrograms/kg per minute or
10 mg/mL, 20 mL and 50 mL vial (IV) 6–9 mg/kg per hour for 3–5 minutes; alternatively, by
slow IV injection, 0.5 mg/kg over 3–5 minutes followed
Propofol facilitates inhibitory neurotransmission mediated by IV infusion of 25–75 micrograms/kg per minute or
by GABA and is associated with minimal respiratory 1.5–4.5 mg/kg per hour;
depression and a short half-life with a duration of action by IV infusion, ADULT >60 years (debilitated with ASA-PS
of 2–10 minutes. It may also reduce glutamatergic 3 or 4), use 80% of healthy adult dose;
activity through NMDA receptor blockade. by intravenous bolus, ADULT (debilitated or ASA-PS 3 or
4), use 80% of healthy adult dose;
Indications: Induction and maintenance of general ADULT <55 years (healthy adults with ASA-PS 1 or 2),
anesthesia; monitored anesthesia care sedation, ICU incremental bolus doses of 10 or 20 mg;
sedation in intubated mechanically-ventilated patients. ADULT (debilitated or ASA-PS 3 or 4), use 80% of healthy
adult dose.
Contraindications: Hypersensitivity to eggs, egg products,
soybeans, or soy products; hypersensitivity to lipid Dose Adjustment:
emulsions; children ≤18 years of age receiving intensive Geriatric, Debilitated Patients, ASA-PS 3 or 4:
care; where general anesthesia or sedation is Use a lower induction dose, a slower maintenance rate of
contraindicated; pregnancy; lactation. administration, and avoid rapidly delivered boluses to
reduce the incidence of unwanted cardiorespiratory
Dose: depressive events.
NOTE: Individualize dose, and titrate to response.

430
NERVOUS SYSTEM

Pediatric: Increases risk of adverse or toxic effects of Propofol:

Consult local regulations and individual institutional policies Alfentanil (opisthotonos, which is the severe
and procedures. Individualize doses based on total body hyperextension and spasticity resulting in arching or
weight and titrate to the desired clinical effect. Wait at bridging position, and/or tonic clonic seizures); CNS
least 3–5 minutes between dose adjustments to depressants; Rifampin (hypotensive effect); Rufinamide
clinically assess drug effects. Use smaller doses when (sleepiness and dizziness)
used with opioids.
Increases risk of adverse or toxic effects of SSRIs
Alcohol Use: (psychomotor impairment)
For general anesthesia, increase dose with chronic
alcoholism and decrease dose with acutely intoxicated Increases serum concentration of the Ropivacaine
(alcoholic) patients.
Administration: Administer by IV push or by continuous IV
Precautions: infusion. Shake well before use. Do not use if there is
evidence of excessive creaming or aggregation, if large
WARNING: Should only be used by experienced droplets are visible, or if there are other forms of phase
personnel who are not actively engaged in the separation indicating that the stability of the product has
procedure or surgery. If used in a non-intubated been compromised. Slight creaming, which should
and/or nonmechanically ventilated patient, disappear after shaking, may be visible upon prolonged
qualified personnel and appropriate equipment for standing.
rapid institution of respiratory and/or
cardiovascular support must be immediately Avoid rapid bolus injection and large bolus doses in high
available. risk patients. Emulsion formulation of propofol 2%
should ONLY be used in children >3 years.
Hypovolemia; Epilepsy; Lipid disorders; Increased
intracranial pressure. Strict aseptic technique must be maintained in handling.
Elderly; Children. Do NOT use if contamination is suspected. Tubing and
any unused portions of propofol vials should be

N
STORAGE AND STABILITY. Store between 4-25°C. Do NOT freeze. discarded after 12 hours.

Adverse Drug Reactions: Do NOT administer through the same IV catheter with
Common: Hypotension, hypertension, bradycardia, cardiac blood or plasma. Do NOT use filter <5 micron for
arrhythmia, low cardiac output, tachycardia, involuntary administration.
body movements, skin rash, pruritus,
hypertriglyceridemia, respiratory acidosis (during Use larger veins of forearm or antecubital fossa to
weaning), pain at injection site (includes stinging), apnea reduce pain associated with injection. One mL of
Less Common: Agitation, amblyopia, anaphylaxis, lidocaine 1% solution may be used prior to
anaphylactoid reaction, anticholinergic syndrome, administration or may be added to propofol immediately
asystole, atrial arrhythmia, atrial premature contractions, prior to administration in a quantity not to exceed 20 mg
bigeminy, chills, cloudy urine, cough, decreased lung lidocaine per 200 mg propofol to reduce pain associated
function, delirium, dizziness, drowsiness, fever, flushing, with injection.
hair discoloration (green), hemorrhage, hypertonia,
hypomagnesemia, hypoxia, infusion-related reaction Avoid abrupt discontinuation prior to weaning or daily
(propofol-related infusion syndrome), infusion site wake up assessments as this can result in rapid
reaction (including pain, swelling, blisters and/or tissue awakening, anxiety, agitation, and resistance to
necrosis), laryngospasm, leukocytosis, limb pain, loss of mechanical ventilation. Wean the infusion rate so the
consciousness (postoperative; with or without increased patient awakens slowly. Discontinue opioids and
muscle tone), myalgia, nail discoloration (green paralytic agents prior to weaning. Long-term infusions
nailbeds), nausea, pancreatitis, paresthesia, phlebitis, can result in some tolerance. Taper propofol infusions to
pulmonary edema, rhabdomyolysis, sialorrhea, syncope, prevent withdrawal.
thrombosis, urine discoloration (green), ventricular
premature contractions, visual disturbance, wheezing NOTE: Pain management requires specific use of analgesic
Rare: Myoclonus (including seizure and opisthotonos) agents, at effective dosages as propofol lacks analgesic
properties. Titrate propofol separately from the analgesic
Drug Interactions: agent.
Avoid concomitant use with:
Enhances therapeutic effect of Propofol: Pregnancy Category: B
Valproate
ATC Code: N01AX10
Enhances therapeutic effect of the following drugs:
Blood Pressure-lowering Agents (antihypertensive
effect); CNS Depressants (sedative, anesthetic, and
cardiorespiratory effects); Hypotension-associated
Agents (hypotensive effect); Pramipexole, Ropinirole,
Rotigotine (sedative effect); QTc-prolonging Agents (QTc-
prolonging effect)

431
 NERVOUS SYSTEM

ANESTHETICS, LOCAL Adverse Drug Reactions:

Rare: Hypotension, chills, dizziness, drowsiness, loss of
ESTERS OF AMINOBENZOID ACID consciousness, nervousness, seizure, urticaria, nausea,
vomiting, methemoglobinemia, anaphylaxis,
hypersensitivity reaction, tremor, blurred vision, miosis,
Rx TETRACAINE tinnitus

Drug Interactions:
Inj.: 20 mg sterile powder (as hydrochloride), ampule Monitor closely with:
(spinal) Reduces diagnostic effect of Technetium Tc 99m
Tilmanocept
Tetracaine prevents the generation and transmission of
impulse along nerve fibers and at nerve endings; Avoid concomitant use with:
depolarization and ion-exchange are inhibited. In Enhances therapeutic effect of the following drugs:
general, loss of pain occurs before loss of sensory, Neuromuscular-blocking agents e.g., Succinylcholine
autonomic and motor functions. (neuromuscular-blocking effect)
Indication: Spinal anesthesia Increases risk of adverse or toxic effects of Tetracaine:
Hyaluronidase
Contraindications: Low plasma cholinesterase
concentrations; complete heart block; bronchoscopy or Increases risk of adverse or toxic effects of the following
cystoscopy. drugs:
Bupivacaine (Liposomal) [administer at least 20 minutes
Dose: or more apart]
NOTE: Dose varies with the anesthetic procedure, the
degree of anesthesia required, and the individual patient Increases serum concentration of Tetracaine:
response. Anticholinesterases
N

Anesthesia extending up to costal margin, by subarachnoid Reduces therapeutic effect of Tetracaine:

injection, ADULT, 15 mg; doses up to 20 mg may be given Aminosalicylic acid, Sulfonamide (antagonistic effect)
but are reserved for exceptional cases.
Low spinal anesthesia, saddle block, by subarachnoid Administration: Administer by subarachnoid injection for
injection, ADULT and CHILD, 2–5 mg. spinal anesthesia.
Perineal anesthesia, by subarachnoid injection, ADULT and
CHILD, 5 mg. Before injection, withdraw syringe plunger to make sure
Perineal and lower extremities, by subarachnoid injection, injection is not into a vein or an artery.
ADULT and CHILD, 10 mg.
Spinal anesthesia, by subarachnoid injection, CHILD >15 For spinal anesthesia for adults, dilute to a 1% solution
kg, 0.2–0.3 mg/kg; CHILD 5–15 kg, 0.3–0.4 mg/kg; with an equal volume of CSF immediately prior to
NEONATE <5 kg (PCA <60 weeks), 0.4–1 mg/kg administration; or 5 mg of powder dissolved in 1 mL of
(maximum dose should not exceed usual procedure- CSF and administer slowly at a rate of 1 mL over 5
specific adult doses as noted above). seconds.
Dose Adjustment: For low spinal (saddle block) anesthesia in vaginal
Elderly, Acutely ill Patients, Debilitated Patients, Obstetric delivery, administer 2–5 mg as a hyperbaric solution.
Patients, and Patients with Increased Intra-abdominal
Pressure: Pregnancy Category: C
Use with caution. Dose reduction may be required.
ATC Code: N01BA03
Precautions:
WARNING: Should be used by dental practitioners
and/or clinicians well-trained in the diagnosis and AMIDES
management of emergencies that may arise from
the use of these agents. Resuscitative equipment,
oxygen, and other resuscitative drugs should be Rx BUPIVACAINE
available for immediate use.
Inj.: 0.5% (as hydrochloride), 5 mL, 10 mL, and 20 mL vial
Shock (This should be treated before the administration of 0.5% (as hydrochloride), 5 mL, 10 mL, 20 mL, and 50
anaesthetic); Cardiovascular disease; Cerebrospinal mL ampule /vial (local infiltration)
diseases; Hypovolemic shock or altered coagulation 0.5% (as hydrochloride), 4 mL ampule (spinal) with
status; Epilepsy; Impaired cardiac conduction or 8% dextrose
respiratory function; Hepatic impairment; Myasthenia 0.5% (as hydrochloride) (isobaric), 5 mL ampule
gravis; Decreased plasma esterase levels; (spinal)
Hyperthyroidism.
Pregnancy. Bupivacaine blocks the generation and the conduction of
nerve impulses, by binding to the intracellular portion of

432
NERVOUS SYSTEM

sodium channels and blocks sodium influx into nerve Precautions:

cells. This leads to lose of sensation for pain,
temperature, touch and proprioception, and eventually WARNING: Should be administered by clinicians well-
skeletal muscle tone. trained in the diagnosis and management of
emergencies that may arise from the use of these
Indications: Infiltration of local anesthesia, caudal block agents. Resuscitative equipment, oxygen, and
(preservative-free), epidural block (preservative-free), other resuscitative drugs should be available for
peripheral nerve block, sympathetic nerve block, immediate use.
retrobulbar anesthesia, spinal anesthesia.
The 0.75% concentration is NOT for use as
Contraindications: Obstetrical paracervical block obstetrical anesthesia. Its use Cardiac arrest with
anesthesia; use as IV regional anesthesia (Bier block). difficult resuscitation or death has been reported
with its use for epidural anesthesia in obstetrical
Dose: patients. Cardiac arrest has occurred after
NOTE: Dose varies with anesthetic procedure, area to be convulsions resulting from systemic toxicity,
anesthetized, vascularity of tissues, number of neuronal presumably following unintentional IV injection.
segments to be blocked, depth of anesthesia, degree of Reserve use of 0.75% concentration for surgical
muscle relaxation required, duration of anesthesia procedures where a high degree of muscle
desired, individual tolerance, and the physical condition relaxation and prolonged effect are necessary.
of the patient.
Cardiac arrest and death have occurred with IV
Administer the smallest dose and concentration required regional anesthesia administration (Bier block).
to produce the desired result.

Local anesthesia local infiltration, by SC or IM injection, Delay in proper management of dose-related

ADULT, 0.25% up to a maximum of 175 mg; perform toxicity, underventilation from any cause and/or
aspiration prior to each injection, however, absence of altered sensitivity may lead to the development of
blood in the syringe does not guarantee that IV injection acidosis, cardiac arrest, and possibly death.

N
has been avoided.
Caudal block, by injection into the caudal end of the spinal Cardiovascular effects; Cardiovascular disease;
canal, ADULT, 15–30 mL of 0.25% or 0.5%. Cross-sensitivity (cross-sensitivity with amide type local
Epidural block other than caudal block, by epidural anesthetics have been reported);
injection, ADULT, 10–20 mL of 0.25% or 0.5% in 3–5 mL Chondrolysis (primarily of the shoulder joint, has occurred
increments, allowing sufficient time to detect toxic following continuous intra-articular infusion; destruction
manifestations of inadvertent IV or intrathecal of articular cartilage has occurred when infused directly
administration; or 10–20 mL of 0.5% solution, up to 1%; into the shoulder);
Non-obstetric surgery, by epidural injection, ADULT, 10–20 Seizures (convulsions due to systemic toxicity leading to
mL of 0.75% solution up to 1.5% as a single dose. cardiac arrest have been reported);
Surgical procedures requiring a high degree of muscle Respiratory arrest (have been associated with rare
relaxation and prolonged effects only, except obstetrical occurrences of sudden respiratory arrest, especially
cases, by epidural injection, ADULT, 10–20 mL of 0.75%. when administered near the head or neck);
Peripheral nerve block, by injection onto or near the nerve, Hepatic impairment; Renal impairment (substantially
ADULT, 5 mL of 0.25% or 0.5% (maximum total daily excreted by the kidney; increased risk of toxic reactions);
dose, 400 mg). Sulfite allergy (may contain sodium metabisulfite; use with
Sympathetic nerve block, by injection onto or near the caution);
nerve, ADULT, 20–50 mL of 0.25%. Elderly (patients >65 years may be at an increased risk for
Retrobulbar anesthesia, by injection into retrobulbar space, developing hypotension while undergoing anesthesia
ADULT, 2–4 mL of 0.75%. with bupivacaine);
Spinal anesthesia, by intrathecal injection, ADULT, Children (insufficient data available on the use in patients
preservative-free solution of 0.75% in 8.25% dextrose; <12 years; use with caution);
for lower extremity and perineal procedures, 1 mL; Pregnancy (no adequate and well-controlled studies);
for lower abdominal procedures, 1.6 mL; Lactation (excreted in breastmilk).
for normal vaginal delivery, 0.8 mL, higher doses may be
required in some patients; Adverse Drug Reactions:
for Caesarean delivery, 1-–1.4 mL. Common: Anxiety, anaphylactoid reaction, apnea,
angioedema, blurred vision, bradycardia, cardiac arrest,
Dose Adjustment: chills, chondrolysis, CNS excitation and/or depression,
Geriatric, Acutely ill Patients, and Debilitated Patients: constriction of pupils, decreased cardiac output,
Use with caution. Dose reduction may be required. depression of myocardium, dizziness, drowsiness
merging into unconsciousness, heart block, hypotension,
Hepatic Impairment and/or Cardiac Disease: hypoventilation, miosis, nausea, palpitations, pruritus,
Reduce doses. respiratory arrest, restlessness, tinnitus, tremors,
urticaria, ventricular arrhythmia, vomiting, weakness.
Less Common: Backache, convulsions, cranial nerve palsy,
fecal incontinence, headache, loss of anal sphincter
control, loss of perineal sensation, paralysis of lower

433
 NERVOUS SYSTEM

extremities, meningismus, paresthesia, persistent Duration of anesthetic effect may be prolonged by the addition of
anesthesia, seizure, septic meningitis, sexual disorder epinephrine.
(loss of function), slowing of labor, urinary incontinence,
urinary retention. Pregnancy Category: C
Rare: Erythema, angioneurotic edema, tachycardia,
sneezing, syncope, excessive sweating, elevated ATC Code: N01BB01
temperature, anaphylactoid-like symptoms.

NOTE: Incidence of adverse reactions is difficult to define.

Most effects are dose-related and are often due to
Rx LIDOCAINE
accelerated absorption from the injection site,
unintentional IV injection, or slow metabolic degradation. Inj.: 1% (as hydrochloride), 20 mL ampule
The development of any CNS symptoms may be an early 2% (as hydrochloride), 2 mL, 5 mL, 20 mL, and 50 mL
indication of more significant toxicity (seizure). ampule/vial (IM/IV)
2% (20 mg/mL) (as hydrochloride), 5 mL and 50 mL
Drug Interactions: vial (epidural, local infiltration)
Monitor closely with: 2% (as hydrochloride), 1.8 mL carpule (with
Enhances therapeutic effect of Bupivacaine: epinephrine) (local infiltration)
Lidocaine, Mexiletine (additive systemic effect) Topical: 10% spray (as hydrochloride), 50 mL

Increases risk of adverse or toxic effects of Antiarrhythmics A moderately long-acting, local anesthetic, which blocks
(myocardial depression) initiation and transmission of nerve impulses at the site
of application by stabilizing neuronal membrane and
Reduces diagnostic effect of Technetium Tc 99m inhibition of Na ion movements.
Tilmanocept
Indication:
Avoid concomitant use with: [Injection]: Surface anesthesia of mucous membranes;
Enhances therapeutic effect of Neuromuscular-blocking infiltration anesthesia; peripheral and sympathetic nerve
N

Agents (neuromuscular-blocking effect) block.

[Topical]: Local anesthetic for oral mucous membrane.
Increases risk of adverse or toxic effects of Bupivacaine:
Hyaluronidase Contraindications: Adjacent skin infection or inflamed skin
to the proposed site of injection; concomitant therapy
Increases risk of adverse or toxic effects of the following with anticoagulants or an abnormal bleeding tendency;
drugs: severe anemia or heart disease; spinal or epidural
Blood pressure-lowering agents; Hypotensive agents anesthesia in dehydrated or hypovolemic patients.
(hypotension); Bupivacaine, Liposomal [administer at
least 20 minutes or more apart]; Ergot Alkaloids, Dose:
Vasopressor drugs (severe, persistent hypertension or NOTE: Dose varies with anesthetic procedure, area to be
cerebrovascular accidents) anesthetized, vascularity of tissues, number of neuronal
segments to be blocked, depth of anesthesia, degree of
Administration: Do NOT use solutions containing muscle relaxation required, duration of anesthesia
preservatives for epidural or caudal blocks. Avoid rapid desired, individual tolerance, and the physical condition
injection of large volume. Use fractional (incremental) of the patient.
doses when feasible.
Administer the smallest dose and concentration required
Use an infusion pump to slowly administer local to produce the desired result.
anesthetics to or around surgical wound sites and/or Local or percutaneous infiltration and peripheral nerve
near peripheral nerves for postoperative analgesia. block, by SC or ID injection, ADULT, 5–300 mg.
Cutaneous infiltration, by SC injection, ADULT, maximum of
Avoid IV injections. Perform aspiration prior to 4.5 mg/kg per dose, not to exceed 300 mg; do not repeat
administration. Re-position the needle until no return of within 2 hours, ADOLESCENT and CHILD, use solutions
blood can be elicited by aspiration. However, absence of <2% for larger volumes (maximum dose, 5 mg/kg per
blood in the syringe does NOT guarantee that IV injection dose, not to exceed 300 mg/dose); do not repeat within
has been avoided. Intravenous regional anesthesia (Bier 2 hours.
block) is not recommended; Intraosseous line or infusion pain, local injectable
anesthesia, by intraosseous injection, ADULT, initially 40
Mixing or the prior or intercurrent use with other local mg of 2% preservative-free solution over 1–2 minutes;
anesthetic is not recommended due to insufficient data usual dose range is 20–50 mg/dose (maximum dose,
on the clinical use of such mixtures. 20–50 mg/dose); ADOLESCENT, CHILD, and INFANT,
initially 0.5 mg/kg of 1% or 2% preservative-free solution
NOTE: A test dose is recommended prior to epidural over 1–2 minutes; usual dose range is 20–50 mg/dose
administration (prior to initial dose) and all reinforcing (maximum dose, 20–50 mg/dose).
doses with continuous catheter technique. [NOTE: After administration of initial dose, allow
lidocaine to dwell for up to 1 minute then follow with NS
flush, immediately follow with a second lower (50% dose

434
NERVOUS SYSTEM

reduction) lidocaine dose over 30–60 seconds has occurred following continuous intra-articular
(maximum repeat dose, 20 mg/dose); if discomfort infusion; destruction of articular cartilage has occurred
reoccurs, may repeat doses at a maximum frequency of when infused directly into the shoulder); Seizures
every 45 minutes during intraosseous access, not (convulsions due to systemic toxicity leading to cardiac
exceeding 3 mg/kg in 24 hours. arrest have been reported). Sulfite allergy (may contain
Each intraosseous access device has as specific sodium metabisulfite; use with caution).
minimum weight and age in addition to specific Solutions containing epinephrine should be used with
instruction for insertion and validation. Consult product caution for ring block of digits or appendages to prevent
specific information for more detail]. risk of ischemic necrosis. Increased risk of arrhythmias
Peripheral nerve block, CHILD, 505 micrograms/kg. has been reported.
(maximum safe doses of lidocaine for ADULT and CHILD Elderly (increased sensitivity); Children <6 months (more
are: 4 mg/kg for the 1% lidocaine). sensitive to toxic effects). Pregnancy (avoid large doses
Topical anesthesia, by topical administration, ADULT, apply during third trimester to diminish risk of neonatal
to affected area ≤4 times daily as needed, respiratory depression, hypotonia and bradycardia after
paracervical block); Lactation
Maximum Dose
Usual Procedure Procedures [Topical]:
Route Application to broken or inflamed skin may lead to
Dose <1 >5
minute minutes increased systemic absorption. Do not leave on large
body areas for >2 hours.
20–60
Nasal 600 mg 500 mg Pregnancy (amount absorbed varies by dose administered,
mg
duration of exposure, and site of application; cumulative
20– exposure from all routes of administration should be
Oropharyngeal 500 mg 600 mg
200 mg considered).
Respiratory 50–
400 mg 600 mg
tract 400 mg Adverse Drug Reactions:
Trachea [Injection]:
50– Common: Blurred vision, chest pain, confusion,
Larynx 200 mg 400 mg

N
200 mg disturbances in vision, dizziness, drowsiness, dyspnea,
Bronchi
flushing, headache, lightheadedness, nausea,
Topical anesthesia, by topical administration, ADOLESCENT paresthesia, tinnitus, tremors
and CHILD ≥2 years, Less Common: Arrhythmias, bradycardia, cardiac arrest,
coma, heart block, hypotension, muscle twitching,
recurrence of SVT, respiratory depression, restlessness,
Route Maximum Dose
seizures
Laryngotracheal 3 mg/kg Rare: Bronchospasm, convulsions, hypersensitivity
Nasal reactions, paraplegia, unconsciousness.
4–5 mg/kg
Oropharyngeal
[Topical]:
NOTE: Dose varies with age and weight. Common: Blanching or redness of the skin (temporary)
Rare: Anaphylactic reactions
Dose Adjustment: Application site reactions: Abnormal sensation, altered
Geriatric, Pediatric, Acutely ill, and Debilitated Patients: temperature sensation, burning sensation, edema,
Administer reduced doses commensurate with their age erythema, itching, pallor or blanching (application time
and physical status. >2 hours), rash, redness, sore throat, hoarseness, loss
of voice
Renal Impairment: Systemic reactions: Angioedema, bronchospasm,
Reduce dose during prolonged infusion (>24 hours) or bradycardia, hypotension, CNS excitation and/or
repeated IV doses. depression, confusion, dizziness, double or blurred
vision, drowsiness, nervousness, euphoria, respiratory
Hepatic Impairment: depression, shock, tinnitus, tremors, twitching,
In severe disease, lower doses may be needed. unconsciousness, vomiting
Consider administering ½ of its dose during prolonged NOTE: Systemic reactions are unlikely due to small dose
infusion (>24 hours) or repeated IV doses. absorbed but may occur with repeated doses or
application to large surface areas
Precautions:
[Injection]: Drug Interactions:
Severe bradycardia, heart block or impaired cardiac Monitor closely with:
conduction (local anesthetics enhance conduction Increases risk of adverse or toxic effects of Lidocaine due to
defects); Severe shock; Respiratory impairment; Renal increased serum concentration:
and hepatic impairment; Epilepsy; Porphyria; Beta Blockers e.g., Propranolol
Neuromuscular diseases, e.g., myasthenia gravis
(increases sensitivity to local anesthetics; may increase Avoid concomitant use with:
muscle weakness and depress respiration with central Increases risk of adverse or toxic effects of the following
neural blockade); Neurological disease (may worsen drugs:
condition). Chondrolysis (primarily of the shoulder joint,

435
 NERVOUS SYSTEM

Bupivacaine [never use in combination]; Drugs that

depresses cardiac contractility and conduction (heart Rx ROPIVACAINE
failure; significant bradyarrhythmia)
Inj.: 10 mg/mL (as hydrochloride), 10 mL ampule (IV)

Reduces therapeutic effect of Lidocaine: Ropivacaine is a local anesthetic of the amide type with
Diuretics, e.g., Furosemide, Hydrochlorothiazide analgesic activity. It binds to voltage-gated sodium ion
channels in the neuronal membrane resulting in a
Reduces therapeutic effect of the following drugs: stabilization of the membrane and inhibition of
Antiarrhythmics, e.g., Amiodarone, Sotalol, Disopyramide depolarization. This blocks nerve impulse generation and
(antagonistic effect) propagation, resulting in a reversible loss of sensation.

Administration: Indications: Surgical anesthesia, labor pain management,

For parenteral administration, use an infusion pump to postoperative pain management.
slowly administer lidocaine to or around surgical wound
sites and/or near nerves for pre- or postoperative Contraindications: IV regional anesthesia (Bier block),
regional anesthesia. obstetric paracervical block anesthesia.

Do NOT use solutions containing preservatives for Dose:

epidural or spinal anesthesia. NOTE: Dose varies with anesthetic procedure, area to be
anesthetized, vascularity of tissues, number of neuronal
Avoid IV injections. Perform aspiration prior to segments to be blocked, depth of anesthesia, degree of
administration. muscle relaxation required, duration of anesthesia
desired, individual tolerance, and the physical condition
Visually inspect for particulate matter and discoloration of the patient.
prior to administration whenever the solution and
container permit. Solutions that are discolored and/or Administer the smallest dose and concentration required
contain particulate matter should NOT be used. Unused to produce the desired result.
N

portion should be discarded.

Caudal block, central nerve blocks or anesthesia, by
For intradermal injection, use only on intact skin and on injection into the caudal end of the spinal canal, CHILD
skin locations where an adequate seal can be and INFANT, 0.5–1 mL/kg of a 0.2% (2 mg/mL) solution
maintained. Do NOT use on body orifices, mucous (maximum volume, 25 mL).
membranes, around the eyes, or on areas with a Epidural block, central nerve blocks or anesthesia, by
compromised skin barrier. epidural injection, ADOLESCENT, CHILD, and INFANT, 0.7
mL/kg of a 0.2% (2 mg/mL) solution; for infants requiring
For topical administration, apply a moderately thick layer repeat injections, a decreased dose may be necessary to
to affected area (~1/8 inch thick), and allow time for prevent drug accumulation; if at least 45 minutes since
numbness to develop, approximately 20–60 minutes. initial dose, reduce dose to 1/3 of the initial; if at least
Reapply if needed. It is unnecessary to dry the site prior 90 minutes since initial dose, reduce dose to half of the
to application. initial; if additional doses are necessary, reduce doses to
half of the previous dose.
Do NOT use in large quantities, particularly over raw Epidural, continuous infusion for central nerve blocks or
surfaces or blistered areas. Avoid contact with eyes, in anesthesia, by epidural injection, INFANT <3 months,
case of accidental contact with eyes, rinse immediately 0.5–1 mL/kg of a 0.2% (2 mg/mL) solution as a bolus
with copious amounts of eyewash and seek treatment by injection; a more dilute solution (e.g., 0.1% or 1 mg/mL)
an eye care specialist. may be required to ensure adequate volume and
minimize toxicity; follow with continuous epidural
Keep out of reach of children. If swallowed, get medical infusion of 0.2% (2 mg/mL) solution at 0.2 mg/kg per
help or contact a Poison Control Center right away. hour; ADOLESCENT, CHILD, and INFANT ≥3 months, 0.5–
1 mL/kg of a 0.2% (2 mg/mL) solution as a bolus
NOTE: When used in mouth or throat, topical anesthesia
injection, administered over 3–5 minutes, followed by
may impair swallowing and increase risk of aspiration.
continuous epidural infusion at 0.4 mg/kg per hour.
Avoid food for ≥60 minutes following oral or throat
Field block, surgical anesthesia, by injection onto or near
application, especially in children. Numbness may
the nerve, ADULT, 1–40 mL of a 0.5% solution.
increase the danger of tongue or buccal biting trauma.
Infiltration or minor nerve block, postoperative pain
Avoid ingesting food or chewing gum while mouth or
management, by injection onto or near the nerve, ADULT,
throat is anesthetized. Excessive doses or frequent
1–100 mL of a 0.2% solution; or 1–40 mL of a 0.5%
application may result in high plasma levels and serious
solution.
adverse effects. Strictly adhere to dosing instructions.
Labor pain management, lumbar epidural, by epidural
Use measuring devices to measure the correct volume,
injection, ADULT, initially 10–20 mL of a 0.2% solution;
if applicable, to ensure accuracy of dose.
the continuous infusion dose is 6–14 mL/hour of a 0.2%
solution with incremental injections of 10–15 mL/hour
Pregnancy Category: B
of a 0.2% solution.
ATC Code: N01BB02

436
NERVOUS SYSTEM

Lumbar epidural block, cesarean section, by epidural other resuscitative drugs should be available for
injection, ADULT, 20–30 mL dose of a 0.5% solution; or immediate use.
15–20 mL dose of a 0.75% solution.
Lumbar epidural block, surgical anesthesia, by epidural
injection, ADULT, 15–30 mL of a 0.5% solution; 15–25 CNS toxicity (restlessness, anxiety, tinnitus, dizziness,
mL of a 0.75% solution; or 15 to 20 mL of a 1% solution. blurred vision, tremors, depression, or drowsiness may
Lumbar or thoracic epidural, postoperative pain be early warning signs of CNS toxicity); Seizures
management, by epidural injection, ADULT, the (convulsions due to systemic toxicity leading to cardiac
continuous infusion dose is 6–14 mL/hour of a 0.2% arrest have been reported); Neurological and psychiatric
solution. disorders (may be at greater risk for toxicity).
Major nerve block, surgical anesthesia, by injection onto or Chondrolysis (primarily of the shoulder joint, has
near the nerve, ADULT, 35–50 mL of a 0.5% solution; or occurred following continuous intra-articular infusion;
10–40 mL of a 0.75% solution destruction of articular cartilage has occurred when
Peripheral nerve block, postoperative pain management, by infused directly into the shoulder); Respiratory arrest
injection onto or near the nerve, ADULT, the continuous (have been associated with rare occurrences of sudden
infusion dose is 5–10 mL/hour of a 0.2% solution. respiratory arrest). Cardiovascular disease (may be at
Peripheral nerve blocks or local anesthesia, single injection, greater risk for toxicity); Porphyria; Hepatic impairment
by injection onto or near the nerve, ADOLESCENT, CHILD, (undergoes hepatic metabolism; at an increased risk for
and INFANT ≥6 months, extrapolate dosing based on developing toxic drug levels); Renal impairment (renally
adult experience (maximum dose, 3 mg/kg per dose excreted; may be at greater risk for toxicity); Acutely ill
based on lean body mass); for infants <6 months, reduce and debilitated patients (may be at greater risk for
dose by 30%; volume of dose (mL/kg) and concentration toxicity).
of solution are site-specific based on anatomy and Elderly (may be at greater risk for toxicity; cardiovascular
variable among patients and procedure, using a 0.2%- adverse events may be age-related; more common in
0.5% (2-5 mg/mL) solution, patients >61 years of age); Children (use extra
precaution to ensure accuracy and minimize potential
Site Dose toxicity).
Head and neck blocks 0.05 mL/kg

N
Maxillary nerve 0.15 mL/kg Adverse Drug Reactions:
Brachial plexus 0.2–0.3 mL/kg Common and Less Common: Bradycardia, chest pain,
Digital nerve 0.05 mL/kg hypertension, hypotension (dose-related; age-related),
Transversus abdominis plane 0.2–0.5 mL/kg tachycardia, anxiety, dizziness, headache, hypoesthesia,
Ilioinguinal nerve 0.075 mL/kg paresthesia, rigors, chills, shivering, pruritus,
Rectus sheath 0.1–0.2 mL/kg hypokalemia, nausea, oral paresthesia, vomiting,
oliguria, urinary retention, urinary tract infection, anemia,
Femoral nerve 0.2–0.4 mL/kg
back pain, dyspnea, fever.
Sciatic nerve 0.2–0.3 mL/kg Rare: Angioedema, apnea (associated with epidural block in
head/neck region), bronchospasm, cardiac insufficiency,
Peripheral nerve blocks or local anesthesia, continuous chondrolysis (continuous intra-articular administration),
peripheral nerve block infusion, by injection onto or near circulatory shock, dyskinesia, hypersensitivity reaction,
the nerve, ADOLESCENT, CHILD, and INFANT ≥6 months, seizure, hallucination, hyperthermia, laryngeal edema,
administer a bolus dose dependent on the nerve myocardial infarction, skin rash, syncope, tinnitus,
catheter location using a 0.2% (2 mg/mL) solution; usual urticaria, ventricular arrhythmia.
dose range is 0.5–1.32 mg/kg; higher bolus dose may
be required; for continuous peripheral nerve block Drug Interactions:
infusion, 0.2–0.25 mg/kg per hour of a 0.2% (2 mg/mL) Monitor closely with:
solution. Reduces diagnostic effect of Technetium Tc 99m
Spinal anesthesia, by intrathecal injection, ADOLESCENT Tilmanocept
≤17 years, CHILD, and INFANT, 0.5 mg/kg of
preservative-free 0.5% (5 mg/mL) isobaric solution via Avoid concomitant use with:
the LP site at L 3–5 (maximum dose, 20 mg/dose). Enhances therapeutic effect of the following drugs:
Thoracic epidural block, surgical anesthesia, by epidural Blood Pressure-lowering Agents (antihypertensive
injection, ADULT, 5–15 mL dose of a 0.5% or 0.75% effect); Hypotension-associated Agents (hypotensive
solution. effect); Neuromuscular-blocking Agents e.g.,
Succinylcholine
Dose Adjustment:
Geriatric: Increases risk of adverse or toxic effects of Ropivacaine:
Use with caution. Initial dose reductions may be necessary. Hyaluronidase

Precautions: Increases risk of adverse or toxic effects of Bupivacaine

WARNING: Should be administered by clinicians well- (Liposomal)
trained in the diagnosis and management of
emergencies that may arise from the use of these Administration: Administered by local infiltration, epidural
agents. Resuscitative equipment, oxygen, and block and epidural infusion, or intermittent bolus.

437
 NERVOUS SYSTEM

Do NOT administer large volume of anesthetic rapidly,

including emergency situations where rapid Life-threatening respiratory depression. Serious,
administration is necessary. life-threatening, or fatal respiratory depression
may occur. Monitor closely for respiratory
Use an infusion pump to slowly administer local depression, especially during initiation or dose
anesthetics to or around surgical wound sites and/or escalation. Carbon dioxide retention from opioid-
near peripheral nerves for postoperative analgesia. induced respiratory depression can exacerbate
the sedating effects of opioids.
Avoid IV injections. Perform aspiration prior to
administration. Re-position the needle until no return of
blood can be elicited by aspiration. However, absence of Neonatal opioid withdrawal syndrome.
blood in the syringe does NOT guarantee that IV injection Prolonged use during pregnancy can result in
has been avoided. IV regional anesthesia (Bier block) is neonatal opioid withdrawal syndrome, which
not recommended. may be life-threatening if not recognized and
treated. If opioid use is required for a prolonged
NOTE: A test dose of short-acting local anesthetic containing period in a pregnant woman, advise the patient
epinephrine (e.g., 3–5 mL) is recommended prior of the risk of neonatal opioid withdrawal
administration. Incremental ropivacaine dosing is syndrome and ensure that appropriate
recommended. treatment will be available.

Pregnancy Category: B Risks from concomitant use with

benzodiazepines or other CNS depressants.
ATC Code: N01BB09 Concomitant use with benzodiazepines or other
CNS depressants, including alcohol, may result
in profound sedation, respiratory depression,
coma, and death. Reserve concomitant
ANALGESICS prescribing with benzodiazepines or other CNS
depressants in patients for whom alternative
N

treatment options are inadequate.

OPIOIDS
Accidental ingestion. Accidental ingestion of
NATURAL OPIUM ALKALOIDS even 1 dose, especially by children, can result in
a fatal overdose.
General Information
Safety and handling. Accidental dermal
Natural opium alkaloids are opioid analgesics extracted exposure should be treated by the removal of
from Papaver somniferum. It belongs to a class of any contaminated clothing and rinsing the
medicines used to provide relief from moderate-to- affected area with water.
severe acute or chronic pain.

Mode of Action: Pre-synaptically, opioids block calcium CNS depression or coma (may cause CNS depression;
channels on nociceptive afferent nerves to inhibit increased susceptibility to intracranial effects of CO2
release of neurotransmitters such as substance P and retention);
glutamate, which contribute to nociception. Post- Delirium tremens; Head trauma and increased intracranial
synaptically, opioids open potassium channels which pressure (exaggerated elevation of ICP may occur);
hyperpolarize cell membranes, increasing the required Seizure disorders (may cause or exacerbate seizures);
action potential to generate nociceptive transmission. Constipation (may cause or aggravate constipation; chronic
use may result in obstructive bowel disease; may also be
Precautions: problematic in patients with unstable angina and/or
post-myocardial infarction);
Abdominal conditions (may obscure diagnosis or clinical
WARNING: Addiction, abuse, and misuse. Exposes
course of patients with acute abdominal conditions; may
patients and other users to the risks of opioid
worsen GI ileus due to reduced GI motility);
addiction, abuse, and misuse, which can lead to
Biliary tract impairment (may cause constriction of
overdose and death. Assess each patient's risk
sphincter of Oddi diminishing biliary and pancreatic
prior to prescribing. Monitor all patients regularly
secretions);
for development of these behaviors or
conditions. Risk of opioid abuse is increased in Inflammatory bowel disorders;
Pancreatitis;
patients with a history or family history of alcohol
Hepatic and renal impairment;
or drug abuse or mental illness.
Hypotension with or without hypovolemia (may cause
severe hypotension, including orthostatic hypotension
and syncope);
Cardiac arrhythmias;
Severe bronchial asthma;
Sleep-disordered breathing;

438
NERVOUS SYSTEM

Phenanthrene hypersensitivity (cross-sensitivity may occur); Increases risk of adverse or toxic effects of the following
Sulfite allergy (may contain sulfites); drugs:
Obesity; Anticholinergic Agents (constipation and urinary
Thyroid dysfunction; retention); Antipsychotic Agents; Phenothiazines
Adrenocortical insufficiency (long-term opioid use may (hypotensive effect); Desmopressin; Diuretics;
cause secondary hypogonadism, which may lead to Ramosetron (constipating effect); SSRIs (serotonin
sexual dysfunction, infertility, mood disorders, and syndrome; psychomotor impairment)
osteoporosis);
Prostatic hyperplasia or urinary stricture; Reduces therapeutic effect of the following drugs:
Mental health conditions, e.g., depression, anxiety Pegvisomant
disorders, post-traumatic stress disorder (increased risk
for opioid use disorder and overdose); Psychosis; Acute Avoid concomitant use with:
alcoholism; History of substance abuse; Decreases serum concentration of Opioids:
Cachectic or debilitated patients (greater potential for Clopidogrel
critical respiratory depression, even at therapeutic
dosages); Enhances therapeutic effect of Opioids:
Opioid depended patient; Anesthetics; Antipsychotics; Anxiolytics; Hypnotics;
Elderly (may be more sensitive to adverse effects, including Tricyclic antidepressants (depressant effects);
life-threatening respiratory depression; may be Droperidol
particularly susceptible to the CNS depressant and
constipating effects; increased potential for risks and Enhances therapeutic effect of the following drugs:
overdose); Hydrocodone [consider starting at a 20–30% lower
Children (increased sensitivity to respiratory depression; hydrocodone dose when used concomitantly];
infants <3 months are more susceptible to respiratory Orphenadrine, Paraldehyde, Perampanel, Tapentadol
depression and/or apnea); [start tapentadol at one-third to one-half of the normal
Pregnancy (prolonged use can result in neonatal opioid dose when used concomitantly], Thalidomide, Zolpidem
withdrawal syndrome, which may be life-threatening if (CNS depressant effect)
not recognized and treated; has been shown to have

N
embryolethal and fetotoxic effects in animal studies; Increases risk of adverse or toxic effects of Opioids:
adverse events have been observed in some animal MAO Inhibitors e.g. Selegeline
reproduction studies; crosses the placenta; use if
parenteral morphine during labor have the potential to Increases risk of adverse or toxic effects of Azelastine
interfere with a newborn's natural reflex to nurse within (Nasal) (CNS depressant effect)
the first few hours after birth);
Lactation (excreted in breastmilk; maternal use can Reduces therapeutic effect of the following drugs:
potentially lead to serious adverse events, including Clopidogrel (antiplatelet effect); Mixed Agonist /
death, in nursing infants; monitor nursing infant for Antagonist Opioids; Naltrexone
apnea and sedation).
FOOD INTERACTONS. Alcoholic beverages or ethanol-
SKILLED TASKS. May impair ability to perform tasks, which containing products may result in a rapid release of the
require mental alertness, like driving or operating entire dose.
machinery.
Administration: Inspect parenteral drug products visually for
Drug Interactions: particulate matter before opening the ampule. Inspect
Monitor closely with: after removing contents from the ampule for color. Do
Decreases metabolism of Opioids: NOT use if the solution contains a precipitate, which does
Somatostatin Analogs e.g. Octreotide not disappear upon shaking.

Enhances therapeutic effect of Opioids: Patients taking opioids chronically may become tolerant
Amphetamines (analgesic effect); Brimonidine, Topical; and require doses higher than the usual dosage range to
Cannabis; Doxylamine, Dronabinol; Magnesium sulfate; maintain the desired effect. Tolerance can be managed
Minocycline; Nabilone; Tetrahydrocannabinol (CNS by appropriate dose titration. There is no optimal or
depressant effect); maximal dose for opioids in chronic pain. The
Domperidone appropriate dose is one that relieves pain throughout its
dosing interval without causing unmanageable side
Enhances therapeutic effect of the following drugs: effects. Consider total daily dose, potency, prior opioid
Ethyl alcohol; Mirtazapine (CNS depressant effect); use, degree of opioid experience and tolerance,
Pramipexole, Ropinirole, Rotigotine (sedative effect); conversion from previous opioid (including formulation),
SSRIs (serotonergic effect) patient’s general condition, concurrent medications, and
type and severity of pain during prescribing.
Increases excretion of Opioids:
Ammonium Chloride Initiate therapy at the lowest effective dosage using
immediate-release opioids. Tailor opioid-containing
Increases risk of adverse or toxic effects of Opioids: analgesic regimen to each patient's needs based on the
CNS Depressants; Rufinamide (sleepiness and type of pain being treated, route of administration,
dizziness); Succinylcholine (bradycardic effect)

439
 NERVOUS SYSTEM

degree of tolerance for opioids, age, weight, and medical suspension, initially 15–60 mg every 4 hours as needed,
condition. Titrate doses to pain relief or prevention. titrate as needed to pain relief or prevention (maximum
total daily dose, 360 mg); patients with prior opioid
Opioid tolerance is defined as patients already taking at exposure may require higher initial doses; for moderate
least 60 mg oral morphine daily, 25 micrograms pain, initiate dose at 30–60 mg; CHILD <12 years, 0.5–
transdermal fentanyl per hour, 30 mg oral oxycodone 1 mg/kg every 4–6 hours daily (maximum 240 mg daily).
daily, 8 mg oral hydromorphone daily, 25 mg oral
oxymorphone daily, or an equivalent dose of another Dose Adjustment:
opioid for at least 1 week. Geriatric:
Use with caution. Consider initiation at the low end of the
Abrupt discontinuation following prolonged use may lead dosing range. Reduced initial dosages may be necessary.
to withdrawal symptoms. Gradually titrate dose
downward when discontinuing. Do NOT discontinue Renal Impairment:
abruptly. For GFR >50 mL/minute, dose adjustment is not necessary.
For GFR 10–50 mL/minute and in patients receiving
NOTE: Opioids should not be used as first-line therapy for continuous renal replacement therapy (CRRT),
chronic pain management (pain >3 months or beyond administer 75% of dose.
time of normal tissue healing) due to limited short-term For GFR <10 mL/minute, administer 50% of dose.
benefits, undetermined long-term benefits, and
association with serious risks. Hepatic Impairment:
Lower initial doses or longer dosing intervals followed by
Opioids decrease bowel motility. Consider preventative careful titration are recommended.
measures (e.g., stool softener, increased fiber) to reduce
the potential for constipation. Precautions:

Concurrent use of mixed agonist / antagonist (e.g., WARNING: Risk of medication errors. Ensure
pentazocine, nalbuphine, butorphanol) or partial agonist accuracy when prescribing, dispensing, and
(e.g. buprenorphine) analgesics may precipitate administering codeine suspension. Dosing
errors due to confusion between mg and mL
N

withdrawal symptoms and/or reduced analgesic efficacy

in patients following prolonged therapy with mu opioid and can result in accidental overdose and
agonists. death.

Ultra-rapid metabolism and other risk factors

for life-threatening respiratory depression in
Rx CODEINE children. Life-threatening respiratory
depression and death have occurred in
children, mostly following tonsillectomy and/or
Oral: 30 mg MR capsule (as phosphate) adenoidectomy. Many of the children had
10 mg/5 mL suspension, 60 mL evidence of being ultra-rapid metabolizers of
codeine due to a CYP-450 2D6 polymorphism.
Codeine alters the perception of and response to pain by
binding to opiate receptors in the CNS, blocking the Interactions with drugs affecting CYP-450
ascending pain pathways. It also helps suppress cough isoenzymes. The use of CYP-450 3A4
by direct action in the medulla. inducers, 3A4 inhibitors, or 2D6 inhibitors with
codeine requires careful consideration of the
Indication: Relief of mild to moderately severe pain when effects on the parent drug, codeine, and the
use of an opioid analgesic is appropriate. active metabolite morphine.
Contraindications: Children <12 years; postoperative
management in children <18 years who have undergone CYP2D6 ultra-rapid metabolizers (may have extensive
tonsillectomy and/or adenoidectomy; significant conversion to morphine and thus increased opioid-
respiratory depression; acute or severe bronchial mediated effects).
asthma in an unmonitored setting or in the absence of
resuscitative equipment; known or suspected GI Adverse Drug Reactions:
obstruction, including paralytic ileus; acute ulcerative Common: Physical dependence, tolerance, opioid-induced
colitis; acute alcoholism; head injury; raised intracranial hyperalgesia, increased biliary tract pressures and/or
pressure; concurrent use with MAOIs or use of MAOIs spasm, opioid-induced constipation, nausea, vomiting,
within the last 14 days; children <1 year. respiratory depression (dose-related), drowsiness (dose-
related), delirium, bradycardia, cardiac arrest, circulatory
Dose: depression, flushing, hypertension, hypotension,
Relief of mild to moderately severe pain, by mouth, ADULT palpitations, shock, syncope, tachycardia, abnormal
(opioid-naive patients), dreams, agitation, anxiety, apprehension, ataxia, chills,
MR capsule, initially 50 mg every 12 hours; titrate at depression, disorientation, dizziness, dysphoria,
intervals of ≥48 hours until adequate analgesia has been euphoria, fatigue, hallucination, headache, increased
achieved (maximum daily dose, 600 mg), patients intracranial pressure, insomnia, nervousness,
requiring higher doses should be switched to an opioid paresthesia, sedation, shakiness, taste disorder, vertigo,
approved for use in severe pain; diaphoresis, pruritus, skin rash, urticaria, abdominal

440
NERVOUS SYSTEM

cramps, abdominal pain, anorexia, diarrhea, NOTE: Some contraindications are product specific. See
pancreatitis, xerostomia, urinary hesitancy, urinary detailed product prescribing information.
retention, hypersensitivity reaction, laryngospasm,
muscle rigidity, tremor, weakness, blurred vision, Dose:
diplopia, miosis, nystagmus, visual disturbance, NOTE: Tailor dosing based on patient's needs, type of pain
bronchospasm, dyspnea, respiratory arrest being treated, route of administration, degree of
tolerance for opioids, age, weight, and medical condition.
Administration: The optimal analgesic dose varies widely among
For oral suspensions, shake well before use. Administer patients. Titrate doses to pain relief/prevention.
with an accurate measuring device, such as a calibrated
oral syringe or a measuring cup. Do NOT use a household Acute pain, moderate to severe, by mouth, ADULT (opioid
teaspoon or tablespoon to measure dose. naïve), as immediate-release tablet or capsule, initially
15–30 mg every 4 hours as needed; patients with prior
For MR tablets, swallow whole. Do NOT chew, dissolve, opioid exposure may require higher initial doses; CHILD
or crush. All strengths may be halved, except the 50 mg >6 months and <50 kg, as immediate-release tablet or
tablets. Half tablets should also be swallowed intact. capsule, 0.15–0.3 mg/kg every 3–4 hours as needed; if
pain is severe, an initial dose of 0.3 mg/kg may be
Pregnancy Category: C administered;
by IM or SC injection, ADULT (opioid naïve), initially 5–10
See General Information on Natural Opium Alkaloids under mg every 4 hours as needed; usual range, 5–15 mg
Analgesics – Opioids in Chapter 10: Nervous System for every 4 hours as needed; patients with prior opioid
other information. exposure may require higher initial doses; CHILD >6
months and <50 kg, 0.1–0.2 mg/kg;
ATC Code: Not available by IV injection, ADULT (opioid naïve), initially 2.5–5 mg
every 3–4 hours; patients with prior opioid exposure may
require higher initial doses.
[NOTE: Administer 2–3 mg every 5 minutes until pain
Rx MORPHINE relief or if associated sedation, oxygen saturation <95%,

N
or serious adverse event occurs, may be appropriate in
Oral: 10 mg, 20 mg, and 30 mg tablet / capsule (as sulfate) treating acute moderate-to-severe pain in immediate
10 mg, 30 mg, and 60 mg MR tablet (as sulfate) postoperative period or the emergency department;
Inj.: 10 mg/mL (as sulfate), 1 mL ampule (IM, IV, SC) maximum cumulative dose prompting reevaluation of
16 mg/mL (as sulfate), 1 mL ampule (IM, IV, SC) continued morphine use and/or dose should be included
as part of any medication order intended for short-term
Morpine is a mu receptor agonist in the CNS and PNS. It use.]; CHILD >6 months and <50 kg, 0.05–0.3 mg/kg
binds to opioid receptors in the CNS, causing inhibition every 3–4 hours as needed, not to exceed 10 mg per
of ascending pain pathways, altering the perception of dose;
and response to pain, as well as producing generalized by continuous IV or SC infusion, ADULT, 0.8–10
CNS depression. mg/hour; usual range is up to 80 mg/hour; may
administer a loading dose prior to initiating the infusion;
Indication: ADULT (critically ill patients), usual range Is 2–30
[Oral]: Relief of moderate to severe acute and chronic pain mg/hour; ADULT (patient-controlled analgesia), usual
for which use of an opioid analgesic is appropriate; concentration is 1 mg/mL; usual demand dose is 1 mg,
management of pain severe enough to require daily, ranging from 0.5–2.5 mg; lockout interval is 5–10
around-the-clock, long-term opioid treatment and for minutes; CHILD >6 months and <50 kg, initially 10–30
which alternative treatment options are inadequate. micrograms/kg per hour, titrate as needed to control
[Injection]: Relief of severe pain, such as MI and severe pain; CHILD >6 months and <50 kg (patient-controlled
injuries; relief of dyspnea of acute left ventricular failure analgesia; opioid-naive), consider using lower end of
and pulmonary edema; preanesthetic medication; dosing range; usual concentration is 1 mg/mL; usual
management of pain for extended periods without demand dose is 0.02 mg/kg per dose ranging from
attendant loss of motor, sensory, or sympathetic 0.01–0.03 mg/kg per dose; lockout interval is 8–10
function. minutes; usual basal rate is 0–0.03 mg/kg per hour.
Chronic pain, by mouth, ADULT (opioid-tolerant), as MR
Contraindications: tablet, 90–120 mg once daily at the same time each day;
[Oral]: GI obstruction and hypercarbia. ADULT (opioid naïve), initially 30 mg once daily; adjust in
[Injection]: Severe respiratory depression; acute or severe increments ≤30 mg daily every 3–4 days (maximum
asthma (in an unmonitored setting or without dose, 1,600 mg daily).
resuscitative equipment); known or suspected paralytic
ileus; presence of infection at infusion site; concomitant Dose Adjustment:
anticoagulant therapy; uncontrolled bleeding diathesis; Geriatric and Debilitated Patients:
heart failure due to chronic lung disease; cardiac Use with caution. May require reduced doses.
arrhythmias; increased intracranial pressure; head
injuries; brain tumors; acute alcoholism; deliriums Renal Impairment:
tremens; seizure disorders; use during labor when a For CrCl 10–50 mL/minute and patients on CRRT,
premature birth is anticipated. administer 75% of normal dose.

441
 NERVOUS SYSTEM

For CrCl <10 mL/minute and patients on peritoneal dialysis, urticaria, intracranial pressure increased, laryngospasm,
administer 50% of normal dose. menstrual irregularities, miosis, myoclonus, nystagmus,
paradoxical CNS stimulation, respiratory arrest, sepsis,
Hepatic Impairment: thermal dysregulation, toxic psychoses, urinary tract
Substantial extrahepatic metabolism may occur. spasm.
In cirrhosis, increases in half-life and AUC may require dose
adjustment. Administration:
For oral administration, swallow MR tablets whole. Do
Precautions: NOT crush, chew, or dissolve to prevent the rapid release
of a potentially fatal dose of morphine. Take consistently
WARNING: Risk of overdose. NOT recommended for
with regards to meals.
single-dose IV, IM, or SC administration because of
the very large amount of morphine in the ampule
Administration with food may increase bioavailability.
and the associated risk of overdosage.
Morphine may cause GI upset. Take with food if GI upset
Naloxone injection and resuscitative equipment occurs.
should be immediately available for use in case of
life-threatening or intolerable side effects and Avoid alcohol. Do NOT administer with alcoholic
whenever therapy is being initiated, the reservoir is beverages or ethanol-containing prescription or
being refilled, or any manipulation of the reservoir nonprescription products.
system is taking place.
Establish a patient's morphine requirement using
Each ampule contains a large amount of a potent immediate-release tablets or capsules. Conversion to
narcotic which has been associated with abuse and MR tablets may be considered when chronic, continuous
dependence among healthcare providers. Due to treatment is required. Reserve the use of higher doses in
the limited indications for this product, the risk of opioid-tolerant patients only. Reserve use of MR tablets
overdosage and the risk of its diversion and abuse, in patients for whom alternative treatment options are
it is recommended that special measures be taken ineffective, not tolerated, or would be otherwise
to control this product within the hospital or clinic, inadequate to provide sufficient management of pain.
N

including wastage and access.

When administering by IV push, dilute with sterile water
Adverse Drug Reactions: or NS to a concentration of 1 mg/mL in adults or 0.1–1
Common: Circulatory depression, flushing, shock, mg/mL in children. Administer slowly over 4–5 minutes.
bradycardia, hypotension, atrial fibrillation, chest pain,
edema, hypertension, palpitation, syncope, tachycardia, Repeated SC administration causes local tissue
vasodilation, dysphonia, physical and psychological irritation, pain, and induration.
dependence, sedation, drowsiness, dizziness, confusion,
amnesia, fever, agitation, anxiety, apathy, apprehension, The use of IM injections is no longer recommended for
ataxia, chills, coma, delirium, depression, dream repeated administration due to painful administration,
abnormalities, euphoria, false sense of well-being, variable absorption, and lag time to peak effect.
hallucination, hypoesthesia, insomnia, lethargy, malaise,
nervousness, restlessness, seizure, slurred speech, Do NOT use unless the solution is colorless or pale
somnolence, vertigo, pruritus (dose related), dry skin, yellow.
rash, urticaria, antidiuretic hormone release,
hypogonadism, gynecomastia, hypokalemia, Protect from light.
hyponatremia, decreased libido, constipation, nausea,
vomiting, abdominal distension, abdominal pain, NOTE: Conversion from parenteral to MR tablet. Substantial
anorexia, biliary colic, diarrhea, dyspepsia, dysphagia, interpatient variability exists in relative potency.
flatulence, gastroenteritis, GERD, GI irritation, paralytic Therefore, it is safer to underestimate a patient's daily
ileus, rectal disorder, taste perversion, weight loss, oral morphine requirement and provide breakthrough
xerostomia, bladder spasm, dysuria, abnormal pain relief with immediate-release morphine. Consider
ejaculation, impotence, decreased urination, the parenteral to oral morphine ratio.
leukopenia, thrombocytopenia, pain at injection site,
decreased bone mineral density, weakness, arthralgia, Parenteral to oral morphine ratio. Between 2–6 mg of
back pain, bone pain, foot drop, gait abnormalities, oral morphine may be required for analgesia equivalent
paresthesia, rigors, skeletal muscle rigidity, amblyopia, to 1 mg of parenteral morphine. An oral dose 3 times the
conjunctivitis, tremor, eye pain, vision problems or daily parenteral dose may be sufficient in chronic pain
disturbance, decreased oxygen saturation, oliguria, settings.
asthma, atelectasis, dyspnea, hiccups, pulmonary
edema (noncardiogenic), hypoxia, hypercapnia, Pregnancy Category: C
respiratory depression, rhinitis, flulike syndrome,
diaphoresis, infection, thirst, histamine release, voice See General Information on Natural Opium Alkaloids
alteration, withdrawal syndrome. under Analgesics – Opioids in Chapter 10: Nervous
Less Common: Amenorrhea, anaphylaxis, apnea, biliary System for other information.
tract spasm, bronchospasm, blurred vision, cardiac
arrest, decreased cough reflex, dehydration, intestinal ATC Code: N02AA01
obstruction, diplopia, disorientation, hemorrhagic

442
NERVOUS SYSTEM

Hepatic Impairment:
Rx OXYCODONE Initiate at doses 33–50% of usual initial dose have been
recommended. If reduced dose is less than smallest
Oral: 10 mg, 20 mg, 40 mg, and 80 mg (as hydrochloride) available dosage form, consider alternative analgesic.
tablet/prolonged-release or controlled release tablet
5 mg capsule Precautions:
Inj.: 10 mg/mL, 1 mL and 2 mL ampule (IV infusion)
WARNING: Cytochrome P450 3A4 Interaction. The
concomitant use of oxycodone with all CYP-450 3A4
Oxycodone binds to opiate receptors in the CNS, causing
inhibitors may result in an increase in oxycodone
inhibition of ascending pain pathways, altering the
plasma concentrations, which could increase or
perception of and response to pain and produces
prolong adverse drug effects and may cause
generalized CNS depression.
potentially fatal respiratory depression.
Discontinuation of a concomitantly used CYP3A4
Indication: Persistent moderate-to-severe acute and chronic
inducer may result in an increase in oxycodone
pain.
plasma concentration.
Contraindications: Significant respiratory depression;
hypercarbia; acute or severe bronchial asthma in an Adverse Drug Reactions:
unmonitored setting or in the absence of resuscitative Common: Physical dependence, tolerance, opioid-induced
equipment; known or suspected GI obstruction, including hyperalgesia, hypogonadism, opioid-induced
paralytic ileus; suspected surgical abdomen; any disease constipation, increased biliary tract pressures and/or
or condition that affects bowel transit; mild, intermittent, spasm, respiratory depression (dose-related), delirium,
or short duration pain that can be managed with other hypogonadism, urinary retention, edema, itching,
pain medications; acute pain (controlled release); sweating, injection site reaction, allergic reaction,
chronic obstructive airway; status asthmaticus; cor nausea, vomiting, drowsiness (dose-related), edema,
pulmonale; acute alcoholism; delirium tremens; flushing, hypertension, children and adolescents may
convulsive disorders; severe CNS depression; increased experience the following: tachycardia, headache, fatigue,
cerebrospinal or intracranial pressure; head injury; MAO lethargy, pain, decreased oxygen saturation,

N
inhibitors (concomitant use within 14 days of each hypochloremia, hyponatremia, weight loss, GERD, febrile
other); pregnancy; use during labor and delivery; neutropenia, limb pain and seroma. Orthostatic
breastfeeding. hypotension, drowsiness, dizziness, abnormal dreams,
abnormality in thinking, anxiety, confusion, drug
Dose: withdrawal, dysphoria, euphoria, chills, insomnia,
Persistent moderate-to-severe acute and chronic pain, by irritability, nervousness, twitching, withdrawal syndrome,
mouth, ADULT, as immediate release form, initially 5–15 migraine, depression, hypoesthesia, agitation,
mg every 4–6 hours as needed with an average dosing paresthesia pruritus, diaphoresis, excoriation,
range of 5–10 mg per dose; for severe chronic pain, hyperhidrosis, skin rash, hyperglycemia, xerostomia,
administer on a regularly scheduled basis, every 4–6 diarrhea, anorexia, dyspepsia, abdominal pain, gastritis,
hours, at the lowest dose that will achieve adequate hiccups, upper abdominal pain, nausea, vomiting,
analgesia; dysuria, urinary retention, constipation, weakness,
ADULT (opioid naïve), as controlled release form, initially arthralgia, back pain, musculoskeletal pain, myalgia,
5–10 mg every 12 hours (maximum, 400 mg daily); tremor, blurred vision, cough, dyspnea, oropharyngeal
by IV injection, ADULT, 1–10 mg over 1–2 minutes, may pain, fever, cardiac failure, vasodilatation, neuralgia,
repeat nor more often than every 4 hours; personality disorder, thrombophlebitis, skin
by IV infusion, ADULT, initially 2 mg per hour, increase as photosensitivity, gout, gingivitis, glossitis, urinary tract
needed. infection, anemia, leukopenia, hypersensitivity, infection,
Patient-controlled analgesia (PCA), by IV infusion, ADULT, hemorrhage, arthritis, laryngospasm, neck pain,
0.03 mg/kg, administer with a minimum lock-out time of pathological fracture, bronchitis, ostealgia, sepsis,
5 minutes. epistaxis, respiratory depression, pharyngitis, pulmonary
disease, rhinitis, sinusitis, accidental injury.
NOTE: Oxycodone ER capsules are not bioequivalent to ER Less Common: Abnormal gait, abnormal stools, aggressive
tablets. Doses of ER capsules is expressed as oxycodone behavior, amenorrhea, amnesia, anaphylactoid reaction,
base. Doses of ER tablets is expressed as oxycodone anaphylaxis, chest pain, choking sensation; gag reflex
hydrochloride. and dysphagia (controlled release tablets), cholestasis,
cough, dehydration, dental caries, depersonalization,
Dose Adjustment: diverticulitis (exacerbation), drug abuse, disturbed sleep,
Geriatric: drug dependence, dysgeusia, emotional lability,
Initiate therapy at low end of dosing range and use caution. exfoliative dermatitis, flatulence, eructation,
hallucination, hematuria, histamine release,
Renal Impairment: hyperkinesia, hypertonia, hypogonadism, increased
For CrCl <60 mL/minute, initiate at the low end of the appetite, hyperalgesia, hyponatremia, hypotonia,
dosing range and adjust dose as clinically indicated. impotence, rase, increased heart rate, increased
Doses 33–50% of usual initial dose have been intracranial pressure, increased thirst, intestinal
recommended. obstruction, lymphadenopathy, memory impairment,
mood changes, malaise, neonatal withdrawal, night
sweats, palpitations, pharyngeal edema, polyuria,

443
 NERVOUS SYSTEM

restlessness, seizure, SIADH, speech disturbance, Surgery adjunct to regional anesthesia, by slow IV infusion,
stomatitis, stupor, suicidal ideation, suicidal tendencies, ADULT, 50–100 micrograms over 1–2 minutes.
syncope, tinnitus, urticaria, vasodilatation, vertigo, visual Surgery adjunct to anesthesia, by IV infusion, ADOLESCENT
disturbance, voice disorder, xeroderma. and CHILD ≥2 years; 2–3 micrograms/kg per dose every
1–2 hours as needed.
Administration: For oral administration, may be taken with Surgery, postoperative recovery, by slow IV infusion, ADULT,
or without food. Administering with food may delay its 50–100 micrograms every 1–2 hours as needed.
onset.
Dose Adjustment:
Swallow tablet whole. Do NOT moisten, dissolve, cut, Geriatric patients are twice as sensitive as younger patients
crush, break, or chew. Administer controlled release to the effects of fentanyl. Determine dose based on age,
tablets one at a time and each followed with water weight, physical status, underlying disease states, other
immediately after placing in the mouth. drugs used, type of anesthesia used, and the surgical
procedure to be performed.
NOTE: Reserve use of 80 mg tablets for opioid-tolerant
patients only. Precautions:

Pregnancy Category: B WARNING: Cytochrome P450 3A4 Interaction. Use

with strong or moderate CYP3A4 inhibitors may
See General Information on Natural Opium Alkaloids result in increased effects and potentially fatal
under Analgesics – Opioids in Chapter 10: Nervous respiratory depression. Discontinuation of a
System for other information. concomitant CYP3A4 inducer may result in
increased fentanyl concentrations. Monitor
ATC Code: N02AA05 patients receiving any CYP 3A4 inhibitor or
inducer.

PHENYLPIPERIDINE Life-threatening respiratory depression. Serious,

life-threatening, or fatal respiratory depression
N

may occur. Monitor closely for respiratory

Rx FENTANYL depression, especially during initiation or dose
escalation. Carbon dioxide retention from opioid-
Inj.: 50 micrograms/mL (as citrate), 2 mL and 10 mL induced respiratory depression can exacerbate
ampule (IV) the sedating effects of opioids.

NOTE: The 50 mcg/mL, 10 mL prep is restricted to Abuse, misuse, and diversion. Users are exposed
pain management of terminal cancer patients. to the risks of addiction, abuse, and misuse,
potentially leading to overdose and death. Assess
80- 100 times more potent than morphine and has high each patient’s risk prior to prescribing. Monitor all
lipid solubility and quickly crosses the blood-brain patients for development of these behaviors or
barrier, producing a rapid but short-onset of analgesia. It conditions. Risk for opioid abuse is increased in
increases pain threshold, alters pain reception and patients with a personal or family history of
inhibits ascending pain pathways by binding to substance abuse, including drug or alcohol abuse
stereospecific receptors w/in the CNS. or addiction, or mental illness.

Indication: Adjunct to general or regional anesthesia.

See General Information on Natural Opium Alkaloids
Contraindications: Septicemia; severe hemorrhage or under Analgesics – Opioids in Chapter 10: Nervous
shock; local infection at proposed injection site; System for other precautions.
disturbances in blood morphology and/or anticoagulant
SKILLED TASKS. May impair a bility to perform tasks, which
therapy.
require mental alertness, like driving or operating
machinery.
Dose:
Surgery, premedication, by slow IV infusion, ADULT, 50–100
Adverse Drug Reactions:
micrograms 30–60 minutes prior to surgery; or 25–50
Common: Bradycardia, chest wall rigidity (high dose),
micrograms given shortly before induction.
edema, cardiac arrhythmia, cardiorespiratory arrest,
Surgery adjunct to general anesthesia, by slow IV infusion,
chest pain, deep vein thrombosis, flushing, hypertension,
ADULT,
hypotension, orthostatic hypotension, palpitations,
low dose, 1–2 micrograms/kg depending on indication;
peripheral edema, sinus tachycardia, syncope,
moderate dose with a sedative / hypnotic, 25–50
tachycardia, vasodilatation, CNS depression, confusion,
micrograms every 15–30 minutes (0.5–2
dizziness, drowsiness, fatigue, headache, sedation,
micrograms/kg per hour), discontinue infusion 30–60
abnormal dreams, abnormal gait, abnormality in
minutes prior to the end of surgery to allow adequate
thinking, agitation, altered sense of smell, amnesia,
ventilation upon emergence from anesthesia;
anxiety, ataxia, chills, depression, disorientation,
Surgery adjunct to general anesthesia, by IV bolus, ADULT,
dysphoria, euphoria, hallucination, hypoesthesia,
high dose, 4–20 micrograms/kg, then 2–10
insomnia, irritability, lack of concentration, lethargy,
micrograms/kg per hour.

444
NERVOUS SYSTEM

malaise, mental status changes, migraine, nervousness, Succinylcholine (bradycardic effect)

neuropathy, paresthesia, restlessness, rigors, paranoia,
speech disturbance, stupor, vertigo, withdrawal Reduces diagnostic effect of Ioflupane I123
syndrome, diaphoresis, alopecia, cellulitis, decubitus
ulcer, hyperhidrosis, night sweats, erythema, pallor, Increases risk of adverse or toxic effects of the following
papule, pruritus, skin rash, dehydration, hot flash, drugs:
hypercalcemia, hyperglycemia, hypocalcemia, Anticholinergic Agents e.g., Atropine (constipation and
hypokalemia, hypoalbuminemia, hypomagnesemia, urinary retention); Antipsychotic Agents (neuroleptic
hyponatremia, weight loss, constipation, nausea, malignant syndrome); Desmopressin; Diuretics,
vomiting, xerostomia, abdominal distention, abdominal Metoclopramide (symptoms consistent with serotonin
pain, anorexia, biliary tract spasm, decreased appetite, syndrome; neuroleptic malignant syndrome);
diarrhea, dysgeusia, dyspepsia, flatulence, gastritis, Ramosetron (constipating effect)
gastroenteritis, GERD, GI hemorrhage, hematemesis,
hiccups, intestinal obstruction, rectal pain, dysuria, Avoid concomitant use with:
erectile dysfunction, mastalgia, UTI, urinary Enhances therapeutic effect of Fentanyl:
incontinence, urinary retention, vaginitis, vaginal Droperidol
hemorrhage, anemia, lymphadenopathy, bruise,
leukopenia, neutropenia, thrombocytopenia, ascites, Enhances therapeutic effect of the following drugs:
jaundice, hypersensitivity reaction, application site Eluxadoline (constipating effect); Hydrocodone [consider
erythema, application site pain or irritation, muscle starting at a 20–30% lower hydrocodone dose when
rigidity, weakness, arthralgia, back pain, limb pain, used concomitantly], Methotrimeprazine, Orphenadrine,
myalgia, tremor, miosis, blepharoptosis, blurred vision, Paraldehyde, Perampanel, Suvorexant, Tapentadol [start
diplopia, dry eye syndrome, strabismus, swelling of eye, tapentadol at one-third to one-half of the normal dose
renal failure, dyspnea, respiratory depression, apnea, when used concomitantly], Thalidomide, Zolpidem (CNS
asthma, asthma, atelectasis, bronchitis, cough, dyspnea depressant effect)
(exertional), epistaxis, hemoptysis, flu-like symptoms,
hypoventilation, laryngitis, hypoxia, nasopharyngitis, Increases risk of adverse or toxic effects of the following
pharyngolaryngeal pain, pharyngitis, pneumonia, rhinitis, drugs:

N
sinusitis, upper respiratory tract infection, wheezing, Nasal (CNS depressant effect); Dapoxetine; MAO
fever. Inhibitors (serotonergic effect; serotonin syndrome);
Less Common: Amblyopia, anaphylaxis, angina pectoris, Serotonin Modulators [except Tedizolid] (serotonin
anorgasmia, aphasia, bladder pain, bronchospasm, CNS syndrome)
stimulation, cold and clammy skin, decreased libido,
delirium, depersonalization, dizziness (paradoxical), drug Increases serum concentration of Fentanyl:
dependence (physical and psychological; with prolonged Conivaptan; Crizotinib; Dasabuvir; Fusidic Acid,
use), dysesthesia, emotional lability, eructation, Systemic; Mifepristone [do NOT administer within 2
esophageal stenosis, exfoliative dermatitis, falling, fecal weeks of each other]; Ritonavir
impaction, flank pain, genitourinary tract spasm,
hematuria, hostility, hypertonia, hypogonadism, Reduces therapeutic effect of Fentanyl:
hypotonia, increased bronchial secretions, Mixed Agonist / Antagonist Opioids (analgesic effect);
laryngospasm, joint swelling, nocturia, oliguria, Naltrexone
pancytopenia, pleural effusion, polyuria, myasthenia,
pustules, seizure, stertorous breathing, urticaria, vertigo, Reduces therapeutic effect of the following drugs:
voice disorder. Clopidogrel (antiplatelet effect)
Mixed Agonist / Antagonist Opioids e.g.
Drug Interactions: Naltrexone
Monitor closely with:
Enhances therapeutic effect of Fentanyl: FOOD INTERACTONS. Fentanyl concentrations may be
Amphetamines (analgesic effect); Brimonidine (Topical); increased by grapefruit juice. Avoid concurrent intake of
Doxylamine; Dronabinol, Hydroxyzine; Magnesium large quantities (>1 quart daily) of grapefruit juice.
sulfate; Minocycline, Nabilone (CNS depressant effect)
Administration: Administer by slow IV infusion over 3–5
Enhances therapeutic effect of the following drugs: minutes.
Beta- blockers e.g. Propranolol; Non- dihydropyridine
Calcium channel blockers e.g. Verapamil; (bradycardic Rapid IV infusion may result in skeletal muscular and
effect; antihypertensive effect); Ethyl alcohol (CNS chest wall rigidity, impaired ventilation, or respiratory
depressant effect); Pramipexole, Ropinirole, Rotigotine distress or arrest. Nondepolarizing skeletal muscle
(sedative effect) relaxant may be required.

Increases excretion of Fentanyl: Prolonged use may cause tolerance, psychological and
Ammonium Chloride physical dependence.

Increases risk of adverse or toxic effects of Fentanyl: Tailor each opioid-containing analgesic regimen based
Antipsychotic Agents, Phenothiazines (hypotensive on patient's needs, type of pain being treated, route of
effect); CNS Depressants; Rufinamide (sleepiness and administration, degree of tolerance for opioids, age,
dizziness); weight, and medical condition. The optimal analgesic

445
 NERVOUS SYSTEM

dose varies widely among patients. Titrate doses to pain NOTE: NOT recommended for use in children as an
relief or prevention. analgesic. NOT recommended for the management of
chronic pain.
Concurrent use of mixed agonist / antagonist analgesics
or partial agonist analgesics may precipitate withdrawal Dose Adjustment:
symptoms and/or reduced analgesic efficacy in patients Geriatric:
following prolonged therapy with mu opioid agonists. Avoid use. If used for acute pain, limit to 1–2 doses.

Abrupt discontinuation following prolonged use may lead Renal Impairment:

to withdrawal symptoms. Gradually taper dose to avoid Avoid use.
this risk.
Hepatic Impairment:
Pregnancy Category: C Use with caution in severe impairment. Consider lower initial
dose when initiating therapy. An increased opioid effect
ATC Code: N02AB03 may be seen in patients with cirrhosis.
Sickle-cell Disease:
Use with caution and decrease initial dose. NOT
recommended for use in this population and should only
Rx PETHIDINE (MEPERIDINE) be used if vaso-occlusive crisis occurs and only if it is the
only effective opioid for the patient.
Inj.: 50 mg/mL (as hydrochloride), 2 mL ampule (IM, IV,
SC) Precautions:
WARNING: Abuse, misuse, and diversion. Users are
Meperidine binds to the opioid receptors in the CNS, exposed to the risks of addiction, abuse, and
causing inhibition of ascending pain pathways, altering misuse, potentially leading to overdose and death.
the perception of and response to pain and producing Monitor all patients for development of these
generalized CNS depression. behaviors or conditions. Risk for opioid abuse is
increased in patients with a personal or family
N

Indications: Management of moderate-to-severe pain; history of substance abuse, including drug or

adjunct to anesthesia and preoperative sedation. alcohol abuse or addiction, or mental illness.
Contraindications: Use with or within 14 days of MAO
inhibitors; severe respiratory insufficiency. Hypovolemia (Use with caution); Cardiovascular disease;
Supraventricular tachycardia; Pre-existing respiratory
Dose: compromise, e.g., hypercapnia, hypoxia; COPD or other
Pain, analgesic, by IM or SC injection, ADULT, 50–150 mg obstructive airway disease. Adrenal insufficiency; Thyroid
every 3–4 hours as needed; CHILD, 1.1–1.8 mg/kg per dysfunction; History of drug abuse or acute alcoholism;
dose every 3–4 hours as needed (maximum, 50–150 Morbidly obese; Sickle-cell disease; Biliary tract disorder;
mg/dose). Hepatic or renal impairment (Avoid use); Prostatic
Pain, preoperative, by IM or SC injection, ADULT, 25-100 mg hyperplasia. CNS depression (Avoid use); Coma (Avoid
given 1 hour before surgery; use); Head injury (Use with extreme caution); Intracranial
by IM injection, CHILD, 1–2 mg/kg given 1 hour before lesions; Elevated intracranial pressure; Toxic psychoses;
surgery. Elderly and debilitated patients;
Pain, postoperative, by IM or SC injection, ADULT, 25–100 Pregnancy (avoid prolonged use or high doses at term);
mg every 2–3 hours if necessary; Lactation
by IM injection, CHILD, 0.5–2 mg/kg every 2–3 hours if
SKILLED TASKS. May impair ability to perform tasks, which
necessary.
require mental alertness, like driving or operating
Pain, moderate to severe acute pain, by IM or SC injection,
machinery.
ADULT, 25–100 mg; CHILD 2 months to 12 years, 0.5–2
mg/kg; CHILD 12–18 years, 20–100 mg, repeat dose
Adverse Drug Reactions:
every 4–6 hours if needed;
Common: Bradycardia, cardiac arrest, circulatory
by slow IV injection, ADULT, 25–50 mg, repeat after 4
depression, flushing, hypotension, palpitations, syncope,
hours; ADOLESCENT 12–18 years, 25–50 mg every 4–6
tachycardia, agitation, confusion, shock, delirium,
hours if needed CHILD ≥12 years and NEONATE, 0.5–1
disorientation, dizziness, drug dependence (physical),
mg/kg every 10–12 hours, if needed in those up to 2
hallucination, headache, habituation, increased
months and every 4–6 hours if needed in older children;
intracranial pressure, seizure, involuntary muscle
by IV injection, CHILD ≥1 month, 1 mg/kg as loading dose
movements (muscle twitching, myoclonus), mood
followed by 100–400 micrograms/kg per hour by
changes (euphoria, dysphoria), sedation, serotonin
continuous IV infusion adjusted according to response.
syndrome, skin rash, diaphoresis, pruritus, urticaria,
Pain, obstetrical analgesia, by IM or SC injection, ADULT,
biliary colic, constipation, nausea, spasm of sphincter of
50–100 mg when pain or contraction becomes regular,
Oddi, vomiting, xerostomia, urinary retention,
may repeat every 1–3 hours if needed (maximum, 400
anaphylaxis, histamine release, injection site reaction
mg in 24 hours).
(pain, wheal, flare), hypersensitivity reaction, tremor,
weakness, visual disturbance, respiratory arrest,
respiratory depression, dyspnea.

446
NERVOUS SYSTEM

Less Common: Hypogonadism Mixed Agonist / Antagonist Opioids (analgesic effect);

Naltrexone
Drug Interactions:
Monitor closely with: Reduces therapeutic effect of Clopidogrel (antiplatelet
Enhances therapeutic effect of Pethidine: effect)
Amphetamines (analgesic effect); Barbiturates e.g.
Phenobarbital, Brimonidine (Topical); Administration: May be administered by IM, SC, or IV
Tetrahydrocannabinol, Doxylamine; Dronabinol, injection. IV push should be administered slowly using a
Magnesium sulfate; Minocycline, Nabilone (CNS diluted solution. 10 mg/mL has been recommended.
depressant effect)
Abrupt discontinuation following prolonged use may also
Enhances therapeutic effect of the following drugs: lead to withdrawal symptoms.
Antiemetics 5HT3 Antagonists e.g., Ondansetron
(serotonin syndrome); Ethyl alcohol (CNS depressant NOTE: IM administration is preferred when repeated doses
effect); Pramipexole, Ropinirole (sedative effect) are required.

Increases excretion of Pethidine: Pregnancy Category: C

Ammonium Chloride; Barbiturates e.g. Phenobarbital
ATC Code: N02AB02
Increases risk of adverse or toxic effects of Pethidine:
Anticholinergic Agents e.g., Atropine (constipation and
urinary retention); Antipsychotic Agents, Phenothiazines MORPHINAN DERIVATIVES
(hypotensive effect); CNS Depressants; Rufinamide
(sleepiness and dizziness); Succinylcholine (bradycardic
effect) Rx BUTORPHANOL

Increases risk of adverse or toxic effects of the following Inj.: 2 mg/mL (as tartrate), 1 mL and 2 mL ampule/vial
drugs: (IM, IV)

N
Antipsychotic Agents (neuroleptic malignant syndrome);
Desmopressin; Diuretics; Metoclopramide (serotonin Butorphanol causes inhibition of the ascending pain
syndrome; neuroleptic malignant syndrome); pathways, altering the perception of and response to
Ramosetron (constipating effect) pain, producing analgesia, respiratory depression, and
sedation similar to opioids.
Avoid concomitant use with:
Decreases serum concentration of Pethidine: Indication: Management of pain when the use of an opioid
Protease Inhibitors e.g. Lopinavir analgesic is appropriate.
Enhances therapeutic effect of Pethidine: Contraindication: Hypersensitivity to butorphanol or any
Droperidol, Hydroxyzine Methotrimeprazine (CNS component of the formulation.
depressant effect) [reduce codeine dose by 50% with
concomitant use] (CNS depressant effect) Dose:
Pain, by IM injection, ADULT, initially 2 mg, may repeat every
Enhances therapeutic effect of the following drugs: 3–4 hours as needed; usual range, 1–4 mg every 3–4
Hydrocodone (CNS depressant effect) [consider starting hours as needed;
at a 20–30% lower hydrocodone dose when used by IV injection, ADULT, initially 1 mg, may repeat every 3–
concomitantly], Paraldehyde, Sodium oxybate, 4 hours as needed; usual range, 0.5–2 mg every 3–4
Suvorexant, Tapentadol [start tapentadol at one-third to hours as needed.
one-half of the normal dose when used concomitantly], Preoperative medication, by IM injection, ADULT, 2 mg 60–
Thalidomide, Zolpidem (CNS depressant effect) 90 minutes before surgery.
Supplement to balanced anesthesia, by IV injection, ADULT,
Increases risk of adverse or toxic effects of Pethidine: 2 mg shortly before induction and/or an incremental
MAO Inhibitors (serotonin syndrome); dose of 0.5–1 mg (up to 0.06 mg/kg), depending on
Protease Inhibitors e.g. Lopinavir previously administered sedative, analgesic, and
hypnotic medications.
Increases risk of adverse or toxic effects of the following Pain during labor, by IM or IV injection, ADULT (female with
drugs: fetus >37 weeks gestation and no signs of fetal distress),
Azelastine(Nasal) (CNS depressant effect); Dapoxetine; 1–2 mg, may repeat in 4 hours during early labor.
Serotonin Modulators [Except Tedizolid] (serotonin
syndrome) Dose Adjustment:
Geriatric and Renal and Hepatic Impairment:
Increases serum concentration of toxic metabolites of Initiate at ½ of the recommended dose, repeat doses must
Pethidine: be based on initial response rather than fixed intervals,
Protease Inhibitors e.g. Lopinavir but should generally be 6 hours apart.
Reduces therapeutic effect of Pethidine: Precautions:

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 NERVOUS SYSTEM

CNS Depressants [except Levocabastine];

WARNING: Abuse, misuse, and diversion. Users are Rufinamide (sleepiness and dizziness); Succinylcholine
exposed to the risks of addiction, abuse, and (bradycardic effect)
misuse, potentially leading to overdose and death.
Monitor all patients for development of these Increases risk of adverse or toxic effects of the following
behaviors or conditions. Risk for opioid abuse is drugs:
increased in patients with a personal or family Desmopressin; Diuretics; Ramosetron (constipating
history of substance abuse, including drug or effect); SSRIs (serotonin syndrome; psychomotor
alcohol abuse or addiction, or mental illness. impairment)

Head injury (Use with extreme caution); Increased Avoid concomitant use with:
intracranial pressure; CNS depression; Acute MI; Enhances therapeutic effect of Butorphanol:
Ventricular dysfunction; Coronary insufficiency; Droperidol
Hypercapnia or hypoxia; COPD; Adrenal insufficiency;
Biliary tract dysfunction; Prostatic hyperplasia; Thyroid Enhances therapeutic effect of the following drugs:
dysfunction; Renal and hepatic impairment. Obese Buprenorphine, Orphenadrine, Paraldehyde,
patients; Patients at risk for drug abuse. Thalidomide, Zolpidem (CNS depressant effect)
Elderly (may be more sensitive to adverse effects).
Pregnancy (may cause neonatal withdrawal syndrome may Increases risk of adverse or toxic effects of Nasal Azelastine
occur in the newborn with prolonged use during (CNS depressant effect)
pregnancy);
Lactation. Reduces therapeutic effect of Butorphanol:
Naltrexone; Other Opioid Analgesics [except
SKILLED TASKS. May impair ability to perform tasks, which Buprenorphine, Butorphanol, Nalbuphine, Pentazocine]
require mental alertness, like driving or operating
machinery. Administration: Administer by IM or IV injection.

Adverse Drug Reactions: Abrupt discontinuation following prolonged use may also
N

Common: Palpitations, vasodilatation, drowsiness, lead to withdrawal symptoms.

dizziness, anxiety, burning sensation, confusion,
euphoria, floating feeling, headache, lethargy, Pregnancy Category: C
nervousness, paresthesia, cold and clammy skin,
diaphoresis, pruritus, nausea, vomiting, anorexia, ATC Code: N02AF01
constipation, unpleasant taste, stomach pain,
xerostomia, tremor, weakness, blurred vision, otalgia,
tinnitus, bronchitis, cough, dyspnea, nasal discomfort,
pharyngitis, rhinitis, epistaxis, sinus congestion, Rx NALBUPHINE
sinusitis, upper respiratory tract infection.
Less Common: Abnormal dreams, agitation, apnea, chest Inj.: 10 mg/mL (as hydrochloride), 1 mL ampule (IM, IV,
pain, convulsions, delusions, depression, drug SC)
dependence, dysphoria, hallucination, edema, hostility,
hypertension, hypogonadism, hypotension, respiratory Nalbuphine is a synthetic morphine opioid agonist-
depression, seizure, shallow respiration, speech antagonist analgesic and a phenanthrene derivative that
disturbance, skin rash, syncope, tachycardia, urination is a potent analgesic essentially equivalent to morphine
disorder, urticaria, vertigo, withdrawal syndrome. on a milligram basis and may produce the same degree
of respiratory depression.
Drug Interactions:
Monitor closely with: Indications: Management of pain severe enough to require
Enhances therapeutic effect of the following drugs: an opioid analgesic; supplement to balanced anesthesia;
Ethyl alcohol, Mirtazapine (CNS depressant effect); preoperative and postoperative analgesia; obstetrical
Pramipexole, Ropinirole, Rotigotine (sedative effect); analgesia during labor and delivery.
SSRIs (serotonergic effect)
Contraindications: Significant respiratory depression; acute
Enhances therapeutic effect of Butorphanol: or severe bronchial asthma in an unmonitored setting or
Amphetamines (analgesic effect); Brimonidine (Topical); in the absence of resuscitative equipment; known or
Doxylamine; Dronabinol; Hydroxyzine; Magnesium suspected GI obstruction, including paralytic ileus.
sulfate; Minocycline, Nabilone; Tetrahydrocannabinol
(CNS depressant effect) Dose:
NOTE: Individualize doses based on severity of pain, patient
Increases excretion of Butorphanol: response, prior analgesic treatment experience, and risk
Ammonium Chloride factors for addiction, abuse, and misuse.

Increases risk of adverse or toxic effects of Butorphanol: Moderate to severe pain, by IM or SC injection, or by IV
Anticholinergic Agents e.g., Atropine (constipation and infusion, ADULT, 10 mg every 3-6 hours as needed based
urinary retention); Antipsychotic Agents, Phenothiazines on a 70 kg patient; may titrate dose to appropriate effect
(hypotensive effect);

448
NERVOUS SYSTEM

(maximum single dose in nonopioid-tolerant patients, 20 Adverse Drug Reactions:

mg; maximum daily dose, 160 mg). Common: Sedation, sweaty or clammy, nausea, vomiting,
dizziness or vertigo, dry mouth, headache.
Dose Adjustment: Less Common: Nervousness, restlessness, crying,
Geriatric: depression, euphoria, floating, hostility, unusual dreams,
Initiate therapy with reduced doses and use with caution. confusion, faintness, dysphoria, feeling of heaviness,
hallucinations, numbness, tingling, unreality,
Renal and Hepatic Impairment: bradycardia, tachycardia, hypotension, hypertension,
Reduce dose. cramps, dyspepsia, bitter taste, depression, dyspnea,
asthma, itching, burning, urticaria, speech difficulty,
Precautions: urinary urgency, blurred vision, flushing and warmth,
anaphylactic or anaphylactoid and other serious
WARNING: Life-threatening respiratory depression.
hypersensitivity reactions.
Serious, life-threatening, or fatal respiratory
depression may occur, particularly when used
Drug Interactions:
concomitantly with other opioids or CNS
Monitor closely with:
depressants. Monitor for respiratory depression, Enhances therapeutic effect of Butorphanol:
especially during initiation of nalbuphine or Amphetamines (analgesic effect)
following a dose increase.

Risks from concomitant use with benzodiazepines Enhances therapeutic effect of the following drugs:
or other CNS depressants. May result in profound Pramipexole, Ropinirole, Rotigotine (sedative effect);
sedation, respiratory depression, coma, and Selective Modulators (serotonergic effect)
death. Reserve concomitant prescribing of
nalbuphine and benzodiazepines or other CNS Reduces therapeutic effect of the following drugs:
depressants for use in patients for whom Buprenorphine; Prokinetics
alternative treatment options are inadequate.
Limit doses and durations to the minimum Increases risk of adverse or toxic effects of the following
required. Follow patients for signs and symptoms drugs:

N
of respiratory depression and sedation. Buprenorphine (opioid withdrawal); Desmopressin;
Diuretics; Ramosetron (constipating effect); Selective
Modulators (serotonin syndrome); SSRIs (psychomotor
Should be administered by personnel trained in
impairment)
the use of IV anesthetics and the management of
the respiratory effects of potent opioids.
Increases risk of adverse or toxic effects of Butorphanol:
Resuscitative and intubation equipment and
Anticholinergic Agents (constipation and urinary
oxygen should be readily available.
retention); CNS Depressants; Rufinamide (sleepiness
and dizziness); Succinylcholine (bradycardic effect)
Abuse, misuse, and diversion. Users are exposed
to the risks of addiction, abuse, and misuse, Avoid concomitant use with:
potentially leading to overdose and death. Monitor Reduces therapeutic effect of Butorphanol:
all patients for development of these behaviors or Nalmefene; Naltrexone; Other Opioid Analgesics [except
conditions. Risk for opioid abuse is increased in Buprenorphine, Butorphanol, Nalbuphine, Pentazocine]
patients with a personal or family history of
substance abuse, including drug or alcohol abuse Administration: For IM or SC injection, administer undiluted.
or addiction, or mental illness.
For IV infusion, administer undiluted over at least 2–3
Chronic pulmonary disease (monitor for decreased minutes. Larger induction doses should be administered
respiratory drive including apnea); Adrenal insufficiency over 10–15 minutes.
(monitor for nausea, vomiting, anorexia, fatigue,
weakness, dizziness, and low blood pressure); Head Inspect visually for particulate matter and discoloration
injury and increased intracranial pressure (may obscure prior to administration whenever solution and container
the clinical course of patients with head injuries); Renal permit.
or hepatic impairment; Biliary tract surgery (may cause
spasm of the sphincter of Oddi); Myocardial infarction; NOTE: When discontinuing therapy, decrease dose by 25–
Cardiovascular effects (monitor for bradycardia); 50% every 2–4 days. Monitor carefully for signs or
Cachectic or debilitated patients (life-threatening symptoms of withdrawal. If patient displays withdrawal
depression is more likely to occur); symptoms, increase dose to previous level and then
Elderly (life-threatening depression is more likely to occur); reduce dose more slowly by increasing interval between
Children (safety and effectiveness in patients <18 years dose reductions, decreasing amount of daily dose
have not been established); Pregnancy (severe fetal reduction, or both.
bradycardia has been reported when used during labor;
sinusoidal fetal heart rate pattern associated with the Pregnancy Category: B
use of nalbuphine has been reported); Lactation
(monitor nursing infants for excess sedation and ATC Code: N02AF02
respiratory depression).

449
 NERVOUS SYSTEM

OTHER OPIOIDS Renal Impairment:

Immediate Modified
CrCl Parenteral
release release
Rx TRAMADOL
≥30
Reduce dose
mL/min
Oral: 50 mg capsule (as hydrochloride) 50–100 50–100 mg
100 mg, 150 mg, and 200 mg MR tablet (as 10–30 mg every every 12
hydrochloride) mL/min 12 hours Do not hours
50 mg dispersible tablet (as hydrochloride) (maximum, administer
Inj.: 50 mg/mL (as hydrochloride), 1 mL and 2 mL ampule <10 200 mg Not
(IM, IV, SC) mL/min daily) recommended

Tramadol is a centrally-acting, synthetic opioid analgesic. It Hepatic Impairment:

alters perception and response to pain by binding to mu-
Modified
opiate receptors in the CNS. Severity Immediate release
release
Mild-to-
Indications: Relief of moderate to moderately-severe pain; Reduce dose
moderate
around-the-clock management of moderate to
moderately-severe pain; management of postoperative Do not
Severe
pain. administer
50 mg every 12
Cirrhosis
Contraindications: Acute intoxication with alcohol, hours
hypnotics, centrally-acting analgesics, opioids, or
psychotropic drugs; severe or acute bronchial asthma; Precautions:
hypercapnia; significant respiratory depression in the WARNING: Neonatal opioid withdrawal syndrome.
absence of appropriately monitored setting and/or Prolonged use during pregnancy can result in
resuscitative equipment; uncontrolled seizures; use neonatal opioid withdrawal syndrome, which may
within 14 days of a MAO inhibitor e.g. Selegeline; use for
N

be life-threatening if not recognized and treated. If

narcotic withdrawal treatment. opioid use is required for a prolonged period in a
pregnant woman, advise the patient of the risk of
Dose: neonatal opioid withdrawal syndrome and ensure
Moderate-to-severe pain, by mouth, ADULT, ADOLESCENT, that appropriate treatment will be available.
and CHILD >12 years,
as capsule, 50–100 mg every 4 hours as needed Emotional disturbance or depression; History of epilepsy or
(maximum, 400 mg daily); risk of seizure; Head injury; Increased intracranial
as MR tablet, initially 50–100 mg once or twice daily pressure; Renal and hepatic impairment.
(maximum daily dose, 400 mg); Elderly (may be more sensitive to adverse effects);
as dispersible tablet, 50–100 mg every 4–6 hours Children (opioid withdrawal syndrome in neonates, may be
(maximum, 400 mg daily); life-threatening).
by IV or IM injection, ADULT, ADOLESCENT, and CHILD Pregnancy (may cause neonatal withdrawal syndrome with
>12 years, 50–100 mg every 4–6 hours (maximum 600 prolonged use during pregnancy);
mg daily). Lactation.
Postoperative pain, by IV injection, ADULT, initially 100 mg
as a single dose, followed by 50 mg every 10–20 SKILLED TASKS. May impair ability to perform tasks, which
minutes for the first hour (maximum cumulative initial require mental alertness, like driving or operating
dose, 250 mg/hour, including the first dose); administer machinery.
subsequent doses at 50–100 mg every 4–6 hours
(maximum cumulative dose, 600 mg daily). Adverse Drug Reactions:
Common: Flushing, orthostatic hypotension, chest pain,
Dose Adjustment: hypertension, peripheral edema, vasodilation, dizziness,
Geriatric: headache, drowsiness, CNS stimulation, insomnia,
Use with caution. Initiate at the low end of the dosing range. agitation, anxiety, apathy, chills, confusion,
When administering immediate release formulations, do depersonalization, depression, euphoria, hypertonia,
not exceed 300 mg daily. hypoesthesia, ataxia, lethargy, malaise, nervousness,
Avoid use of MR tablets in elderly patients >75 years. If pain, paresthesia, restlessness, rigors, sleep disorder,
used, increase dosing interval and use with great withdrawal syndrome, fatigue, vertigo, pruritus,
caution. diaphoresis, dermatitis, skin rash, hot flash,
hyperglycemia, constipation, nausea, vomiting, weight
loss, xerostomia, dyspepsia, diarrhea, anorexia,
abdominal pain, decreased appetite, flatulence, sore
throat, menopausal symptoms, pelvic pain, prostatic
disease, urine abnormality, urinary tract infection,
urinary frequency, urinary retention, weakness,
arthralgia, back pain, myalgia, neck pain, tremor, blurred
vision, miosis, visual disturbance, cough, dyspnea,

450
NERVOUS SYSTEM

nasopharyngitis, bronchitis, pharyngitis, respiratory Enhances therapeutic effect of Tramadol:

congestion, rhinitis, rhinorrhea, sinusitis, sneezing, Droperidol, Sodium oxybate (CNS depressant effect)
upper respiratory tract infection, accidental injury, fever,
flu-like syndrome. Enhances therapeutic effect of the following drugs:
Less Common: Abnormal dreams, abnormal gait, amnesia, Carbamazepine, Hydrocodone [start with a 20–30%
anaphylactoid reaction, anaphylaxis, anemia, lower hydrocodone dose when using together with any
angioedema, appendicitis, bradycardia, bronchospasm, other CNS depressant]; Orphenadrine; Paraldehyde,
cataract, cellulitis, cholecystitis, cholelithiasis, cold and Suvorexant; Tapentadol [start tapentadol at one-third to
clammy skin, convulsions, deafness, cognitive one-half of normal dose if used concomitantly];
dysfunction, delirium, disorientation, diverticulitis, Thalidomide; Zolpidem (CNS depressant effect); MAO
dysgeusia, dysphagia, dysuria, ECG abnormality, edema, Inhibitors (neuroexcitatory and/or seizure-potentiating
decreased libido, fecal impaction, gout, GI hemorrhage, effect; serotonergic effect); SSRIs [except Tedizolid]
gastroenteritis, hematuria, hepatic failure, hallucination, (serotonergic effect); Tricyclic Antidepressants
hepatitis, hypersensitivity, hypersensitivity reaction, (serotonergic effect; seizure)
hypotension, hypoglycemia, irritability, ischemic heart
disease, joint stiffness, lack of concentration, menstrual Increases risk of adverse or toxic effects of Tramadol:
disease, migraine, movement disorder, muscle cramps, SSRIs (neuroexcitatory and/or seizure-potentiating
muscle spasm, muscle twitching, mydriasis, myocardial effect; serotonin syndrome); Tricyclic Antidepressants
infarction, night sweats, palpitations, pancreatitis, (neuroexcitatory and/or seizure-potentiating effect)
peripheral edema, otitis, peripheral ischemia,
pneumonia, proteinuria, pulmonary embolism, sedation, Increases risk of adverse or toxic effects of the following
pulmonary edema, seizure, serotonin syndrome, drugs:
shivering, skin vesicle, speech disturbance, Stevens- Dapoxetine; MAO Inhibitors (serotonin syndrome;
Johnson syndrome, stomatitis, suicidal tendencies, seizures); Mixed Agonist / Antagonist Opioids (analgesic
tachycardia, thrombocytopenia, syncope, tinnitus, toxic effect); Selective Modulators [except Tedizolid]
epidermal necrolysis, urticaria. (serotonin syndrome)

Drug Interactions: Reduces therapeutic effect of Tramadol:

N
Monitor closely with: Naltrexone
Increases excretion of Tramadol:
Ammonium Chloride Reduces therapeutic effect of Carbamazepine

Enhances therapeutic effect of Tramadol: TEST INTERACTION. May produce a false-positive result in
Amphetamines (analgesic effect); Brimonidine (Topical); the urine detection of phencyclidine.
Doxylamine; Dronabinol; Hydroxyzine; Magnesium
sulfate; Minocycline; Nabilone Administration:
For oral administration, swallow whole. Do not crush,
Enhances therapeutic effect of the following drugs: chew, or split. May be taken without regard to meals but
Antipsychotic Agents, Phenothiazines (hypotensive administer consistently either with or without meals.
effect); Ethyl alcohol (CNS depressant effect);
Pramipexole, Ropinirole, Rotigotine (sedative effect); Parenteral administration may be administered by IM or
Vitamin K Antagonists, e.g., Warfarin (anticoagulant IV injection. For IV administration, inject slowly over 2–3
effect) minutes or further dilute in LR or D5W and administer as
an infusion.
Increases risk of adverse or toxic effects of Tramadol:
Anticholinergic Agents (constipation and urinary Pregnancy Category: C
retention); CNS Depressants; Rufinamide (sleepiness
and dizziness); Succinylcholine (bradycardic effect) ATC Code: N02AX02

Increases risk of adverse or toxic effects of the following

drugs:
Antipsychotic Agents (neuroleptic malignant syndrome;
serotonin syndrome); Desmopressin; Diuretics;
Metoclopramide (serotonin syndrome; neuroleptic
malignant syndrome); Ramosetron (constipating effect)

Reduces therapeutic effect of Tramadol:

Antiemetics (5HT3 Antagonists)

Reduces therapeutic effect of Buprenorphine

Avoid concomitant use with:

Decreases serum concentration of Tramadol:
Carbamazepine; Dabrafenib; Mitotane

451
 NERVOUS SYSTEM

OTHER ANALGESICS AND ANTIPYRETICS

OTC IBUPROFEN
NON-OPIOID ANALGESICS
Oral: 200 mg and 400 mg tablet
100 mg/5 mL syrup / suspension, 60 mL
Rx DICLOFENAC 200 mg/5 mL suspension, 60 mL

Inhibits synthesis of prostaglandins in body tissuesby

Oral: 25 mg and 50 mg (as sodium or potassium salt) inhibiting cyclooxygenase-1 and 2 resulting prevention of
tablet/capsule inflammation useful for pain management. It has anti-
50 mg (as sodium salt) enteric coated tablet or MR inflammatory, analgesic and antipyretic properties.
tablet
100 mg (as sodium or potassium salt) MR Indications: Acute pain and inflammation in rheumatic
tablet/capsule diseases and other musculoskeletal disorders; mild-to-
Inj.: 25 mg/mL (as sodium salt), 3 mL ampule (IM, IV) moderate pain, including dysmenorrhea and headache;
pain in children; acute migraine attack.
A reversible cyclooxygenase1 and 2 (COX1 and 2) enzyme
inhibitor resulting in decreased formation of Contraindications: Active or history of peptic ulceration.
prostaglandin precursors. It exhibits antipyretic,
analgesic, and anti-inflammatory properties. Dose:
Mild-to-moderate pain, pyrexia and inflammatory
Indication: Management of mild to moderate acute pain and musculoskeletal disorders, by mouth, ADULT, 1.2–1.8 g
moderate to severe acute pain. daily in 3–4 divided doses, increased if necessary to
maximum 2.4 g daily (3.2 g daily in inflammatory
Contraindications: Patients who have experienced asthma, disease); maintenance dose of 0.6–1.2 g daily may be
urticaria, or other allergic-type reactions after taking sufficient.
aspirin or other NSAIDs; treatment of perioperative pain Pain, by mouth, CHILD, 20–40 mg/kg daily in divided doses
in the setting of coronary artery bypass graft (CABG) (maximum, 1.2 g daily); CHILD 8–12 years, 200 mg 3–4
N

surgery; moderate to severe renal impairment in the times daily; CHILD 3–7 years, 100 mg 3–4 times daily;
perioperative period and who are at risk for volume CHILD 1–2 years, 50 mg 3–4 times daily. [NOTE: NOT
depletion. recommended for children <7 kg].

Dose: Dose Adjustment:

Analgesia, by IV injection, ADULT, 37.5 mg every 6 hours as Renal and Hepatic Impairment:
needed (maximum daily dose, 150 mg). Keep dose as low as possible.
Dose Adjustment: Precautions:
Geriatric:
Initiate therapy using the lowest recommended dose and WARNING: Cardiovascular risks. NSAIDs are
frequency. associated with an increased risk of adverse
cardiovascular thrombotic events, including fatal
Renal Impairment: MI and stroke.
In patients with advanced renal disease or significant renal
impairment, use is not recommended. Gastrointestinal events. NSAIDs may increase risk
of GI irritation, inflammation, ulceration, bleeding,
Hepatic Impairment: and perforation.
May require dose adjustment. Drug undergoes extensive
hepatic metabolism. Renal impairment (monitor renal function;); Hepatic
In moderate to severe impairment, use of injectables is not impairment (increased risk of GI bleeding and can cause
recommended (has not been studied). fluid retention; avoid use in severe liver disease); Allergic
disorders; Cardiac disease; Coagulation defects.
Administration: Administer as an IV bolus over 15 seconds. Elderly; Pregnancy (avoid use unless the potential benefit
outweighs risk; third trimester); Lactation (amount is too
NOT indicated for long-term use. small to be harmful; short courses safe in usual doses).

NOTE: Some products may contain phenylalanine. Adverse Drug Reactions:

Common: Diarrhea, dizziness, dyspepsia, headache, GI
See Diclofenac under Antiinflammatory and ulceration or bleeding, hypertension, nausea,
Antirheumatic Products – Non-selective COX hemorrhage, raised liver enzymes, salt and fluid
Inhibitors in Chapter 9: Musculo-Skeletal System for retention, vomiting.
other information. Less Common: Bronchospasm, esophageal ulceration,
heart failure, hyperkalemia, rash, confusion, renal
Pregnancy Category: C; D (≥30 weeks’ gestation) impairment.
Rare: Acute renal failure, aseptic meningitis, blood
ATC Code: Not Available dyscrasias, blurred vision, colitis, cystitis, fluid retention,
anaphylactic and anaphylactoid reactions, hepatitis,

452
NERVOUS SYSTEM

interstitial nephritis, MI, nephrotic syndrome,

photosensitivity reaction, Stevens-Johnson syndrome, Indications: Management of painful conditions, including
stroke, tinnitus, toxic epidermal necrolysis, vertigo. rheumatoid arthritis, osteoarthritis, ankylosing
spondylitis, acute gout, and inflammation or pain
Drug Interactions: following surgery.
Monitor closely with:
Increases risk of adverse or toxic effects of Ibuprofen: Contraindications: Perioperative pain in coronary artery
ACE Inhibitors (renal impairment and hyperkalemia); bypass graft (CABG) surgery; active peptic ulcer or
Angiotensin II Receptor Blockers (significant decrease in cerebrovascular bleeding; history of NSAID-induced GI
renal function) bleeding or perforation; concomitant use with high-dose
methotrexate (≥15 mg/week) or ciprofloxacin; severe
Increases risk of adverse or toxic effects of the following edema; severe hepatic or renal impairment; use in third
drugs: trimester of pregnancy; use in children.
Atenolol; Ciprofloxacin; Levofloxacin (convulsions);
Digoxin (exacerbation of heart failure; reduced renal Dose:
function); Diuretics, e.g., Loop Diuretics, Thiazide NOTE: Use the lowest effective dose for the shortest
Diuretics (reduced renal function; nephrotoxicity); Oral duration of time, consistent with individual patient goals,
Corticosteroids, e.g., Hydrocortisone (gastric ulceration); to reduce risk adverse events.
Other NSAIDs
Avoid long-term administration. Transition to oral therapy
Reduces therapeutic effect of the following drugs: to oral therapy after initial improvement.
ACE Inhibitors, Angiotensin II Receptor Blockers
(antihypertensive effect); Aspirin (antiplatelet activity; Pain, by IM injection, ADULT, 50–100 mg daily in 1 or 2
cardioprotective effect); Diuretics (diuretic effect) divided doses; may administer up to 100 mg twice daily
for severe pain (maximum, 200 mg in 24 hours for up to
Avoid concomitant use with: 3 days).
Enhances therapeutic effect of Vitamin K Antagonists, e.g.,
Warfarin (anticoagulant effect) Dose Adjustment:

N
Geriatric:
Increases risk of adverse or toxic effects of Ibuprofen: Start at lower end of dosing range. Use with caution.
Alendronate (gastric ulceration); Drugs Affecting Clotting
Process, e.g., Ketorolac (bleeding; GI bleeding); Drugs Renal and Hepatic Impairment:
that increase Potassium Concentration, e.g., Amiloride, Use with caution in mild-to-moderate impairment. Use is
Triamterene (hyperkalemia) contraindicated in severe impairment.

Increases risk of adverse or toxic effects of the following Precautions:

drugs: WARNING: Cardiovascular risks. NSAIDs are
Antihypertensives, e.g., Beta Blockers, ARBs, Nitrates associated with an increased risk of adverse
(increased BP); Drugs that are renally excreted, e.g., cardiovascular thrombotic events, including fatal
Calcineurin Inhibitors; Vitamin K Antagonists, e.g., MI and stroke. Use is contraindicated for the
Warfarin (serious bleeding) treatment of perioperative pain in CABG surgery.
Gastrointestinal events. NSAIDs may increase risk
Reduces therapeutic effect of the following drugs: of GI irritation, inflammation, ulceration, bleeding,
Antihypertensives, e.g., Beta Blockers, ARBs, Nitrates and perforation.
(antihypertensive effect)
History of GI disease, e.g. bleeding or ulcer;
Administration: Should be taken with food.
Hypertension;
Renal or hepatic impairment;
Pregnancy Category: C, prior to 30 weeks gestation;
Elderly (at greater risk of serious GI events, hyperkalemia,
D, ≥30 weeks gestation
and renal toxicity);
Pregnancy (crosses the placenta; cardiovascular anomalies
ATC Code: Not available
and cleft palate following use in the first trimester;
myocardial degenerative changes, prenatal constriction
of the ductus arteriosus, fetal tricuspid regurgitation,
Rx KETOPROFEN failure of the ductus arteriosus to close postnatally
following use in the third trimester);
Lactation (excreted in breastmilk).
Oral: 100 mg tablet
Inj.: 50 mg/mL, 2 mL ampule (IM) SKILLED TASKS. May impair ability to perform tasks, which
require mental alertness, like driving or operating
Reversibly inhibits COX-1 and COX-2 resulting in decreased machinery.
formation of prostaglandin precursors and induces a
decrease of prostaglandin synthesis in CNS and PNS. It Adverse Drug Reactions:
also inhibits lipoxygenase, resulting in a decreased Common: Peripheral edema, headache, depression,
leukotriene production and decreased dizziness, abnormal dreams, insomnia, malaise,
polymorphonuclear neutrophil activation. nervousness, somnolence, rash, dyspepsia, abdominal

453
 NERVOUS SYSTEM

pain, constipation, diarrhea, flatulence, nausea, GI effect); Deferasirox (GI ulceration or irritation; GI
hemorrhage, peptic ulcer, anorexia, stomatitis, vomiting, bleeding)
urinary tract irritation, abnormal hepatic function tests,
visual disturbance, tinnitus, renal insufficiency. Increases risk of adverse or toxic effects of the following
Less Common: Agranulocytosis, allergic reaction, allergic drugs:
rhinitis, alopecia, anaphylaxis, anemia, angioedema, Deoxycholic Acid (bleeding or bruising in the treatment
arrhythmia, aseptic meningitis, blurred vision, bone area); Desmopressin;
marrow suppression, bronchospasm, buccal necrosis, Drospirenone; Eplerenone, Potassium- sparing diuretics
bullous rash, chills, cholestatic hepatitis, confusion, CHF, (hyperkalemic effect); Haloperidol (drowsiness and
conjunctivitis, diabetes mellitus (aggravated), cystitis, confusion); Ibrutinib; Iodine I131 Tositumomab, (bleeding-
drowsiness, dysphoria, dyspnea, eczema, edema, related adverse events); Obinutuzumab (serious
epistaxis, erythema multiforme, exfoliative dermatitis, bleeding-related events); Porfimer, Verteporfin
facial edema, fecal occult blood, fluid retention, gastritis, (photosensitizing effect); Quinolone Antibiotics
GI perforation, GI ulceration, gynecomastia, decreased (neuroexcitatory and/or seizure-potentiating effect);
hearing, hallucinations, hematemesis, hemolytic Tacrolimus, Systemic (nephrotoxic effect)
anemia, hematuria, hemoptysis, hepatic dysfunction,
hepatitis, hepatotoxicity (idiosyncratic), hot flashes, Reduces therapeutic effect of the following drugs:
hypertension, hyponatremia, impotence, intestinal ACE Inhibitors; Aliskiren; Angiotensin II Receptor
ulceration, interstitial nephritis, infection, leukopenia, Blockers; Eplerenone, Hydralazine, Potassium- sparing
laryngeal edema, libido disturbance, jaundice, diuretics; Thiazide Diuretics (antihypertensive effect);
microvesicular steatosis, melena, migraine, MI, Prostaglandins, Ophthalmic.
nephrotic syndrome, onycholysis, palpitation,
pancreatitis, peptic ulcer, peripheral neuropathy, Agents with Antiplatelet Properties may enhance the
peripheral vascular disease, photosensitivity, polydipsia, effect of Urokinase.
polyuria, pruritus, purpura, purpuric rash, renal failure,
renal papillary necrosis, retinal hemorrhage, septicemia, Risk X: Avoid combination
shock, Stevens-Johnson syndrome, tachycardia,
thrombocytopenia, toxic amblyopia, toxic epidermal NSAID (Nonselective) may enhance the anticoagulant
N

necrolysis, ulcerative colitis, tubulopathy, urticaria, effect of Vitamin K Antagonists.

vasodilation, xerostomia.
Risk D: Consider therapy modification
Drug Interactions:
Monitor closely with: Avoid concomitant use with:
Decreases bioavailability of Ketoprofen: Decreases absorption of Ketoprofen:
Aminoglycosides (in premature infants) Bile Acid Sequestrants

Enhances therapeutic effect of Ketoprofen: Enhances therapeutic effect of Ketoprofen:

Antidepressants; Tricyclic and Tertiary Amine; SSRIs (antiplatelet effect)
Glucosamine; Multivitamins / Fluoride with ADE,
Multivitamins / Minerals with ADEK, Folate, Iron, Enhances therapeutic effect of the following drugs:
Multivitamins / Minerals with AE, No iron, Omega 3 fatty Dabigatran Etexilate, Rivaroxaban, Urokinase, Vitamin K
acids, Pentoxiflylline, Prostacyclin analogues, Serotonin antagonists e.g., Warfarin (anticoagulant effect)
/ Norepinephrine Re- Uptake Inhibitors, Tipranavir,
Vitamin E (antiplatelet effect); Pentosan Polysulfate
Sodium (bleeding) Increases risk of adverse or toxic effects of Ketoprofen:
Dexketoprofen; Diclofenac, Systemic; Ketorolac, Nasal and
Systemic; Sodium Phosphates (nephrotoxic effect,
Enhances therapeutic effect of the following drugs:
specifically, acute phosphate nephropathy)
Agents with Antiplatelet Properties, e.g., P2Y12
Inhibitors, NSAIDs, SSRIs (antiplatelet effect);
Anticoagulants, Thrombolytic agents (anticoagulant Increases risk of adverse or toxic effects of the following
effect); Prostaglandins, Ophthalmic, Vitamin K drugs:
antagonists (anticoagulant effect [consider therapy Apixaban (bleeding); COX2 Inhibitor; Cyclosporine,
modifications]) Systemic (nephrotoxic effect); Herbs with Anticoagulant
or Antiplatelet Properties, e.g., Alfalfa, Anise, Bilberry
(bleeding); Omacetaxine (bleeding-related events);
Increases risk of adverse or toxic effects of Ketoprofen:
Salicylates [except Choline Magnesium Trisalicylate]
Angiotensin II Receptor Blockers (significant decrease in
renal function); Corticosteroids, Systemic; Other NSAIDS (bleeding); Tenofovir

Increases risk of adverse or toxic effects of the following Increases serum concentration of Ketoprofen:
drugs: Cyclosporine, Systemic
5-ASA Derivatives (nephrotoxic effect); ACE Inhibitors
(decrease in renal function); Aliskiren (nephrotoxic Increases serum concentration of the following drugs:
effect;); Bisphosphonate Derivatives (GI ulceration; Cyclosporine, Systemic; Dabigatran Etexilate; Lithium;
nephrotoxicity); Collagenase, Systemic (injection site Methotrexate; Pemetrexed [avoid NSAIDs for 2–5 days
bruising and/or bleeding); Dasatinib (anticoagulant prior to, and 2 days after pemetrexed]

454
NERVOUS SYSTEM

Reduces therapeutic effect of the following drugs: by IV injection, ADULT <65 years, 30 mg single dose;
Loop Diuretics (diuretic effect); Salicylates [except ADULT ≥65 years, renally impaired and/or <50 kg (110
Choline Magnesium Trisalicylate] (cardioprotective lbs), 15 mg single dose.
effect); SSRIs Multiple-dose treatment, by IM or IV injection, ADULT <65
years, 30 mg every 6 hours (maximum daily dose, 120
TEST INTERACTION. May interfere with urine tests that rely mg); ADULT ≥65 years, renally impaired and/or <50 kg
on acid precipitation as an endpoint or on color reactions (110 lbs), 15 mg every 6 hours (maximum daily dose, 60
for carbonyl groups, including detection of albumin, bile mg).
salts, 17ketosteroids or 17hydroxycorticosteroids in
urine. NOTE: For breakthrough pain, do not increase dose or
frequency. Consider supplementing regimen with low
Administration: To be administered by deep IM injection into doses of opioids “prn” unless otherwise contraindicated.
the gluteal muscle every 4 hours.
Dose Adjustment:
Pregnancy Category: C Geriatric:
For IM injection, initially 10 mg single dose, then administer
ATC Code: Not available the lowest effective dose every 4–6 hours as needed
(maximum total daily dose, 60 mg for not more than 5
days).
For IV bolus, 15 mg single dose over a minimum of 15
Rx KETOROLAC seconds, or 15 mg every 6 hours (maximum total daily
dose, 60 mg for not more than 5 days).
Inj.: 30 mg/mL (as tromethamol), 1 mL ampule (IM, IV)
Renal Impairment:
Reversibly and non-selectively inhibits COX-1 and COX-2 In moderately elevated serum creatinine, reduce daily dose
enzymes, resulting in decreased formation of by half, not to exceed 60 mg daily.
prostaglandin precursors. It exhibits minimal anti- In advanced renal impairment, use is contraindicated.
inflammatory effect at its analgesic dose.

N
Hepatic Impairment:
Indication: Short-term (≤5 days) management of moderately In mild-to-moderate impairment, use with caution as it may
severe acute pain requiring analgesia at the opioid level, cause elevation of liver enzymes. Discontinue if clinical
usually in a postoperative setting. signs and symptoms of liver disease develop.
In severe impairment or active hepatic disease, use is
Contraindications: Active or history of peptic ulcer disease; contraindicated.
recent or history of GI bleeding or perforation; advanced
renal impairment; patients at risk for renal failure due to Precautions:
volume depletion; use in labor and delivery; use in WARNING: Ketorolac is indicated for the short-term
nursing mothers; use as prophylactic analgesic before (up to 5 days) management of moderately severe
any major surgery; intra-operative use when hemostasis acute pain that requires analgesia at the opioid
is critical; suspected or confirmed cerebrovascular level. It is NOT indicated for minor or chronic
bleeding, hemorrhagic diathesis, incomplete painful conditions. It is a potent NSAID analgesic,
hemostasis, and those at high risk of bleeding; and its administration carries many risks. NSAID-
concomitant use with aspirin, NSAIDs, or probenecid; related adverse events can be serious, especially
neuraxial administration. when used inappropriately. Increasing dose
beyond what is recommended will not provide
Dose: better efficacy but will result in an increased risk
Short-term management of moderate-to-severe acute pain, of serious adverse events.
by IM injection, ADULT ≥50 kg, initially 10 to 30 mg as a
single dose, then every 4–6 hours as needed (maximum Gastrointestinal Effects. Can cause peptic ulcers,
total daily dose, 90 mg for up to 2 days); utilize lowest GI bleeding and/or perforation. It is
effective dose; contraindicated in active peptic ulcer disease,
ADULT <50 kg, initially 10 mg as a single dose, then the recent GI bleeding or perforation, and in a history
lowest effective dose every 4–6 hours as needed of peptic ulcer disease or GI bleeding.
(maximum total daily dose, 60 mg for not more than 5
days); Risk of Bleeding. Inhibits platelet function. May
by IV bolus, ADULT ≥50 kg, 30 mg single dose over a cause increased risk of bleeding.
minimum of 15 seconds; or 30 mg every 6 hours
(maximum total daily dose, 120 mg for not more than 5 Hypersensitivity. Hypersensitivity reactions,
days); ADULT <50 kg or ≥65 years, 15 mg as a single ranging from bronchospasm to anaphylactic
dose over a minimum of 15 seconds; or 15 mg every 6 shock, have occurred. Contraindicated in patients
hours (maximum total daily dose, 60 mg for not more with previously demonstrated hypersensitivity to
than 5 days). ketorolac or allergic manifestations to aspirin or
Single-dose treatment, by IM injection, ADULT <65 years, 60 other NSAIDs.
mg single dose; ADULT ≥65 years, renally impaired
and/or <50 kg (110 lbs), 30 mg single dose;

455
 NERVOUS SYSTEM

and/or azotemia, nephritis, hyponatremia,

Intrathecal or Epidural Administration. NOT for hyperkalemia, hemolytic uremic syndrome.
intrathecal or epidural administration due to its Rare: Postoperative wound hemorrhage.
alcohol content.
Drug Interactions:
Concomitant Use with NSAIDs. Has cumulative Monitor closely with:
risks of inducing serious NSAID-related adverse Decreases excretion of the following drugs:
events. Aminoglycosides [in premature infants]
Pralatrexate
Special populations. Adjust doses for patients ≥65
years, patients <50 kg (110 lbs), and patients with Enhances therapeutic effect of Ketorolac:
moderately elevated serum creatinine. Total dose Dasatinib, Glucosamine, Limaprost, Multivitamins /
should NOT exceed 60 mg daily. Minerals with ADEK, Folate, Iron, Multivitamins /
Minerals with AE, no Iron, Omega- 3 fatty acids,
Labor, Delivery, and Nursing. Has prostaglandin Prostacyclin analogues, SNRIs, SSRIs, Tricyclic anti-
synthesis inhibitory effect. May adversely affect depressants, Tertiary amine, Vitamin E, Systemic
fetal circulation and inhibit uterine musculature or (anticoagulant effect)
contraction, increasing the risk of uterine
hemorrhage. Use in nursing mothers has potential Enhances therapeutic effect of the following drugs:
adverse effects of prostaglandin-inhibiting drugs Prostaglandins, Ophthalmic; Thrombolytic agents;
on neonates. Urokinase; Vitamin K antagonists e.g., Warfarin
(anticoagulant effect)
History of hypertension and/or heart failure;
Predisposition to reduced blood volume and/or renal blood Increases risk of adverse or toxic effects of Ketorolac:
flow; ACE Inhibitors (significant decrease in renal function);
Mild renal or hepatic impairment; Agents with Antiplatelet Properties, e.g., P2Y12
Patient weighing <50 kg; Inhibitors, NSAIDs, SSRIs (antiplatelet effect);
Elderly (more susceptible to hyperkalemia and GI Angiotensin II Receptor Blockers (significant decrease in
N

complications, e.g., GI ulcerations, bleeding, and renal function); Corticosteroids, Systemic; Diclofenac,
perforation); Systemic; Ethyl alcohol, Flunarizine (GI bleeding); Loop
Children (safety and efficacy in patients <16 years have not Diuretics, Thiazide diuretics, Thiazide- like diuretics
been established); (nephrotoxic effect); Pentosan Polysulfate Sodium
Pregnancy (no adequate and well-controlled studies of its (bleeding); Sodium Phosphates (nephrotoxic effect,
use in pregnant women); specifically, acute phosphate nephropathy)
Lactation (may have possible adverse effects of
prostaglandin-inhibiting drugs on neonates). Increases risk of adverse or toxic effects of the following
drugs:
SKILLED TASKS. May impair ability to perform tasks, which 5-Aminosalicylic Acid Derivatives; Aliskiren; Cyclosporine,
require mental alertness, like driving or operating Systemic; Tacrolimus, Systemic; Tenofovir (nephrotoxic
machinery. effect); Aminolevulinic Acid, Systemic and Topical;
Porfimer; Verteporfin (photosensitizing effect);
Adverse Drug Reactions: Angiotensin II Receptor Blockers (decrease glomerular
Common: Edema, hypertension, pruritus, rash, nausea, filtration and renal function); Apixaban; Dabigatran;
dyspepsia, GI fullness, diarrhea, GI pain, constipation, Bisphosphonate Derivatives (GI ulceration;
vomiting, stomatitis, purpura, flatulence, headache, nephrotoxicity); Deferasirox (GI ulceration, irritation, or
drowsiness, dizziness, sweating, injection site pain. bleeding); Deoxycholic Acid (bleeding or bruising in the
Less Common: Weight gain, infections, asthenia, fever, treatment area); Desmopressin; Drospirenone,
palpitation, pallor, syncope, urticaria, gastritis, rectal Eplerenone, Potassium- sparing diuretics (hyperkalemic
bleeding, eructation, anorexia, increased appetite, effect); Haloperidol (drowsiness and confusion);
epistaxis, anemia, tremors, eosinophilia, abnormal Iodine I131; Neuromuscular-blocking Agents,
dreams, hallucinations, euphoria, extrapyramidal Nondepolarizing (apnea); Quinolones (neuroexcitatory
symptoms, vertigo, paresthesia, insomnia, nervousness, and/or seizure-potentiating effect)
excessive thirst, depression, dry mouth, abnormal
thinking, inability to concentrate, hyperkinesis, stupor,
dyspnea, pulmonary edema, rhinitis, abnormal taste, Reduces absorption of Ketorolac:
cough, abnormal vision, blurred vision, tinnitus, hearing Bile Acid Sequestrants; Cholestyramine
loss, hematuria, proteinuria, oliguria, urinary retention,
polyuria, increased urinary frequency, hypersensitivity Reduces therapeutic effect of the following drugs:
reactions, myalgia, hypotension, flushing, Stevens- ACE Inhibitors; Aliskiren; Angiotensin II Receptor
Johnson syndrome, Lyell’s syndrome, exfoliative Blockers; Beta- blockers; Eplerenone, Potassium-
dermatitis, maculo-papular rash, urticaria, peptic sparing diuretics (antihypertensive effect); Loop
ulceration, GI hemorrhage, GI perforation, acute Diuretics (diuretic effect); Prostaglandins, Ophthalmic;
pancreatitis, melena, thrombocytopenia, liver failure, SSRIs; Thiazide Diuretics; Thiazide-like Diuretics
hepatitis, cholestatic jaundice, psychosis, leukopenia,
convulsions, aseptic meningitis, asthma, bronchospasm, Avoid concomitant use with:
acute renal failure, flank pain with or without hematuria Decreases serum concentration of Ketorolac:

456
NERVOUS SYSTEM

Salicylates e.g. Aspirin Rx (Inj.) PARACETAMOL

OTC (Oral; Rectal) (ACETAMINOPHEN)
Enhances therapeutic effect of the following drugs:
Anticoagulants (anticoagulant effect)
Oral: 300 mg and 500 mg tablet
100 mg/mL drops (alcohol-free), 15 mL
Increases risk of adverse or toxic effects of Ketorolac:
120 mg/5 mL (125 mg/5 mL) syrup / suspension
Dexketoprofen; Ketorolac, Nasal; Phenylbutazone
(alcohol-free), 30 mL, 60 mL, and 120 mL
250 mg/5 mL syrup / suspension (alcohol-free), 30
Increases risk of adverse or toxic effects of the following
mL, 60 mL, and 120 mL
drugs:
Rectal: 125 mg and 250 mg suppository
Aspirin (bleeding); Pentoxifylline (bleeding); NSAIDs; COX-
Inj.: 150 mg/mL solution for injection, 2 mL ampule (IM,
2 Selective; Salicylates (bleeding)
IV)
10 mg/mL solution for infusion, 50 mL and 100 mL
Increases serum concentration of Ketorolac:
vial (IV)
Probenecid
Inhibits COX-1 and COX-2 and has no significant anti-
Reduces therapeutic effect of the following drugs:
inflammatory activity and is particularly useful for
Aspirin, Salicylates (cardioprotective effect)
treating mild-to-moderate pain, for reducing fever, and in
patients where salicylates and other NSAIDs are
Administration: May be used as a single or multiple dose on
contraindicated.
a regular or “prn” schedule.
Indications: Management of mild- moderate pain, fever.
For IV bolus, administer over a minimum of 15 seconds.
Contraindications: Severe hepatic impairment or severe
For IM injection, administer slowly and deeply into the
active liver disease.
muscle.
Dose:
Inspect visually for particulate matter and discoloration
Mild-to-moderate pain, pyrexia, by mouth, ADULT, 0.5–1 g

N
prior to administration.
every 4–6 hours (maximum, 4 g daily); CHILD 6–12
years, 250–500 mg; CHILD 1–5 years, 120–250 mg;
Peel back needle wrapping and expose needle hub.
CHILD 3 months to 1 year, 60–125 mg or 10–15 mg/kg
Avoid touching the hub. Aseptically remove rubber
per dose; may repeat doses in children every 4–6 hours
protective cap from the syringe. Attach needle to syringe
if necessary (maximum, 4 doses in 24 hours);
hub with a twist, keeping needle sheath intact. Remove
by rectum, ADULT, ADOLESCENT, and CHILD ≥12 years,
needle sheath and inject medication. Do NOT recap
650 mg every 4–6 hours (maximum daily dose, 3,900
needles, purposely bend, or break by hand to prevent
mg); CHILD >6 up to 12 years, 325 mg every 4–6 hours
needle-stick injuries. Dispose of used syringe in
(maximum daily dose, 1,625 mg); CHILD >3 to 6 years,
accordance with applicable medical waste regulations
120 mg every 4–6 hours (maximum daily dose, 600 mg);
and guidelines.
CHILD and INFANT 12–36 months, 80 mg every 4–6
NOTE: The analgesic effect begins in approximately 30 hours (maximum daily dose, 400 mg); INFANT 6–11
minutes with maximum effect in 1–2 hours after months, 80 mg every 6 hours (maximum daily dose, 320
injection. Duration of analgesic effect is usually 4–6 mg daily);
hours. by IV injection, ADULT ≥50 kg, 650 mg every 4 hours or
1,000 mg every 6 hours (maximum single dose, 1,000
Do NOT mix in a small volume with morphine sulfate, mg per dose; maximum daily dose, 4 g daily); ADULT <50
meperidine hydrochloride, promethazine hydrochloride, kg, 15 mg/kg every 6 hours or 12.5 mg/kg every 4 hours
or hydroxyzine hydrochloride. This will result in (maximum single dose, 15 mg/kg per dose or 750
precipitation of ketorolac from solution. mg/dose; maximum daily dose, 75 mg/kg or 3.75 g);
CHILD 2–12 years, 15 mg/kg every 6 hours or 12.5
Correct hypovolemia prior to administration. Switch mg/kg every 4 hours (maximum single dose, 15 mg/kg
patients to alternative analgesics as soon as possible. per dose or 750 mg; maximum daily dose, 75 mg/kg or
Do NOT administer for more than 5 days. 3.75 g).
Post-immunization pyrexia, by mouth, INFANT 2–3 months,
Pregnancy Category: C; D in 3rd trimester 10–15 mg/kg per dose followed by a second dose, if
necessary, 4–6 hours later [NOTE: Warn parents to seek
ATC Code: Not available medical advice if pyrexia persists after the second dose].
Treatment of acute migraine attack, by mouth, ADULT, 0.5–
1 g at first sign of attack, repeated every 4 to 6 hours if
necessary, (maximum, 4 g daily); CHILD 6–12 years,
250–500 mg at the first sign of attack, repeated every
4–6 hours if necessary (maximum, 4 doses in 24 hours).
Pain or fever, by mouth, pediatric dosing:

457
 NERVOUS SYSTEM

Weight Weight Dosage [Inj.]

Age Common: Hypertension, hypotension, peripheral edema,
(kg) (lbs) (mg)
2.7–5.3 6–11 0–3 months 40 tachycardia, headache, insomnia, agitation, anxiety,
4–11 fatigue, trismus, pruritus, skin rash, hypervolemia,
5.4–8.1 12–17 80 hypoalbuminemia, hypokalemia, hypophosphatemia,
months
nausea, vomiting, hypomagnesemia, constipation,
8.2–10.8 16–23 1–2 years 120
abdominal pain, diarrhea, oliguria, anemia, infusion site
10.9– reaction, limb pain, muscle spasm, periorbital edema,
24–35 2–3 years 160
16.3 atelectasis, abnormal breath sounds, dyspnea, hypoxia,
16.4– pleural effusion, pulmonary edema, stridor, wheezing,
36–47 4–5 years 240
21.7 fever
21.8– Less Common: Anaphylaxis, hepatic injury (dose-related),
48–59 6–8 years 320
27.2 hypersensitivity reaction, severe dermatological reaction
27.3– (acute generalized exanthematous pustulosis, Stevens-
60–71 9–10 years 400
32.6 Johnson syndrome, toxic epidermal necrolysis)
32.7–
72–95 11 years 480
43.2 Drug Interactions:
Monitor closely with:
NOTE: Infants <3 months should not be given paracetamol Enhances therapeutic effect of Vitamin K Antagonists, e.g.,
unless advised by a doctor. A dose of 10 mg/kg (5 mg/kg Warfarin (anticoagulant effect)
if jaundiced) is suitable.
Increases metabolism of Paracetamol:
Dose Adjustment: Barbiturates e.g. Phenobarbital; Carbamazepine
Renal Impairment:
Longer dosing intervals and reduce total doses. Avoid Increases risk of adverse or toxic effects of Paracetamol:
prolonged or repeated use. Barbiturates; Carbamazepine; Ethyl alcohol (liver
damage); Isoniazid
Hepatic Impairment:
N

Use with caution and avoid prolonged or repeated use in any Increases risk of adverse or toxic effects of the following
type of liver disease. Contraindicated in severe active drugs:
liver disease Dapsone, Topical; Fosphenytoin-Phenytoin; Imatinib;
Sorafenib (hepatotoxic effect); Nitric Oxide, Prilocaine,
Precautions: Sodium nitrite (significant methemoglobinemia)
WARNING: Massive overdose may cause hepatic
necrosis and, less frequently, renal damage. Less Reduces therapeutic effect of Paracetamol:
overdoses can frequently cause reversible Barbiturates, Carbamazepine
jaundice.
Has been associated with cases of acute liver Avoid concomitant use with:
failure, at times resulting in liver transplant and Decreases absorption of Paracetamol:
death. Most are associated with the doses that Cholestyramine Resin [administer 1 hour apart to
exceed the maximum daily limits, and often minimize this effect]
involve more than 1 paracetamol-containing
product. Increases risk of adverse or toxic effects of Dasatinib
(hepatotoxic effect)
Sodium restriction (soluble paracetamol products may
contain large amounts of sodium); Increases serum concentration of Paracetamol:
Phenylketonuria (soluble products of paracetamol may Dasatinib; Probenecid (increases the potential for
contain aspartame); formation of the toxic NAPQI metabolite); Sorafenib
Alcohol dependence; overdosage;
G6PD deficiency; TEST INTERACTION. May cause false-positive urinary 5-
Hepatic impairment and renal impairment; (dose-related hydroxyindoleacetic acid.
toxicity;
Avoid large doses, e.g., >4 g daily); Administration:
Pregnancy (not known to be harmful); For oral administration, may be taken with or without
Lactation (small amount is present in milk; short courses food. Taking with food may decrease GI upset. When
are safe in usual dosage; monitor infant). administering suspensions, shake well before use.

Adverse Drug Reactions: For rectal administration, remove the wrapper and insert
[Oral, Rectal] the suppository well up into the rectum.
Common and Less Common: Skin rash, nephrotoxicity
(chronic overdose), anemia, hyperuricemia, leukopenia, For IV administration, administer by IV infusion only.
neutropenia, renal disease, pancytopenia Administer undiluted over 15 minutes. Use within 6
Rare: Hypersensitivity reaction hours of opening vial or transferring to another container.

For doses <1,000 mg (<50 kg), withdraw the appropriate

dose from the vial and place in a separate empty, sterile

458
NERVOUS SYSTEM

container prior to administration. Small volume pediatric Precautions:

doses (up to 600 mg [60 mL]) may be placed in a syringe
WARNING: Neurologic. Must be used with caution in
and infused over 15 minutes via syringe pump.
patients with mixed seizures, including absences,
which can be exacerbated by carbamazepine. In
For 1,000 mg doses (≥50 kg), insert a vented IV set
case of exacerbation, the drug must be
through vial stopper.
discontinued.
Pregnancy Category: C
Hematologic effects (Obtain pretreatment complete blood
ATC Code: N02BE01 counts with platelet counts at baseline and periodically
thereafter; discontinue if there is significant bone
marrow depression); Dermatologic effects (discontinue if
DRUGS FOR NEUROPATHIC PAIN signs and symptoms of severe skin reaction appear);
psychosis (may activate latent psychosis); Hepatic
effects (evaluate baseline and periodic hepatic function
Rx CARBAMAZEPINE particularly in those with a history of liver disease; may
cause or aggravate liver disease; withdraw immediately
in case of aggravated liver dysfunction or active liver
Oral: 200 mg tablet
disease); Breakthrough bleeding (may be seen in women
200 mg and 400 mg MR tablet
taking oral contraceptives); may affect reliability of oral
100 mg/5 mL syrup, 120 mL
contraceptives, women of childbearing age must be
advised to use alternative forms of birth control.
Carbamazepine is an anti-seizure drug also used for
Elderly (increased risk for adverse effects, including liver
neuropathic pain. It limits the firing of action
dysfunction, and confusion and agitation); Pregnancy
potentials evoked by a sustained depolarization in
(increased risk for developmental disorders has been
cortical neurons by slowing the rate of recovery of
reported; rare reports of developmental disorders,
voltage-activated Na+ channels from inactivation.
including spina bifida, has been reported; can aggravate
folic acid deficiency so supplementation is
Indication: Idiopathic trigeminal neuralgia and painful

N
recommended before and during pregnancy; administer
diabetic neuropathy.
Vitamin K1 to the mother during the last weeks of
pregnancy and to the newborn to prevent bleeding
Contraindications: Atrioventricular block; bone marrow
disorders in the offspring); lactation (excreted in
depression; acute intermittent porphyria; combination
breastmilk; monitor infants closely for adverse
with MAO Inhibitors e.g. Selegeline
reactions).
Dose: SKILLED TASKS. May impair ability to perform tasks, which
NOTE: MR tablets are designed to be taken twice daily due require mental alertness, like driving or operating
to the controlled release of the active substance. machinery.
Idiopathic trigeminal neuralgia, by mouth, ADULT, initially
Adverse Drug Reactions:
100 mg 2 times daily, slowly raise the dosage until
Common: Ataxia, dizziness, drowsiness, fatigue, headache
freedom from pain is achieved (normally at 200 mg 3–4
diplopia, blurred vision, allergic reactions, urticaria (may
times daily), then gradually reduce dose to the lowest
be severe), leucopenia, thrombocytopenia, eosinophilia,
possible maintenance level; usual maintenance dose is
elevated gamma-GT (usually not clinically relevant),
400–800 mg daily in divided doses (maximum, 1.2 g
elevated alkaline phosphatase, nausea, vomiting, mouth
daily).
dryness, edema, increase in weight, hyponatremia,
Painful diabetic neuropathy, by mouth, ADULT, initially 100
reduced plasma osmolality.
mg 1–2 times a day, gradually increase depending on
Less Common: Abnormal involuntary movements,
response; average dose is 200 mg 2–4 times daily.
exfoliative dermatitis, erythroderma, diarrhea,
constipation.
Dose Adjustment:
Rare: Orofacial dyskinesia, oculomotor disorders, slurred
Geriatric: speech, peripheral neuritis, paresthesia, muscle
Select doses with caution. Generally, lower doses are
weakness, hallucinations, depression, restlessness,
started.
agitation, confusion, loss of appetite, lupus-
erythematosus like syndrome, pruritus, Stevens-Johnson
Renal Impairment: syndrome, acne, purpura, leukocytosis,
Use with caution. In moderate to severe impairment, reduce
lymphadenopathy, folic acid deficiency, hypertension or
doses.
hypotension, delayed multiorgan hypersensitivity,
disturbance in cardiac conduction, agranulocytosis,
Hepatic Impairment: aplastic anemia, pure red cell aplasia, megaloblastic
Drug is primarily metabolized in the liver. Use with caution
anemia, pancreatitis, anaphylactic reactions,
in advanced liver disease as metabolism is impaired.
arrhythmias, renal or urinary dysfunction.

NOTE: Particularly at the start of treatment, or if the initial

dose is too high, or in the elderly, certain adverse

459
 NERVOUS SYSTEM

reactions (e.g., CNS and GI symptoms, allergy) commonly In CrCl ≥60 mL/minute, administer 300–1,200 mg 3 times
occur. daily.
In CrCl >30 to 59 mL/minute, administer 200–700 mg
Drug Interactions: twice daily.
Monitor closely with: In CrCl >15 to 29 mL/minute, administer 200–700 mg once
Decreases bioavailability of Paracetamol daily.
In CrCl 15 mL/minute, administer 100–300 mg once daily.
Increases risk of adverse or toxic effects of the following In CrCl <15 mL/minute, reduce daily dose in proportion to
drugs: creatinine clearance based on dose for CrCl 15
Diuretics, e.g., Hydrochlorothiazide, Furosemide mL/minute (e.g., reduce dose by one-half [range: 50–
(symptomatic hyponatremia) 150 mg daily] for CrCl 7.5 mL/minute).
Isoniazid (isoniazid-induced hepatotoxicity) In ESRD requiring hemodialysis, adjust dose based on CrCl
Neuroleptics, e.g., Haloperidol (neurological adverse plus a single supplemental dose of 125–350 mg after
reactions) each 4 hours of hemodialysis.

Avoid concomitant use with: Precautions:

Decreases serum concentration of Oral Contraceptives Mixed seizures including absences; Acute pancreatitis
(discontinue if acute pancreatitis develops); Renal
Incompatible with the following products: impairment; Hemodialysis; Not recommended for
MAO Inhibitors e.g. Phenelzine patients who need to sleep during daytime and remain
awake at night.
Reduces therapeutic effect of Oral Contraceptives Elderly; Children; Pregnancy (crosses the placenta; adverse
events have been observed in animal reproduction
Administration: May be taken during, after, or between studies); Lactation (use only if the benefits to the mother
meals. For the syrup formulation, shake well before use. outweigh the potential risk to the infant).
Administer tablets with little liquid. Swallow MR tablets
unchewed with a little liquid. SKILLED TASKS. May impair ability to perform tasks, which
require mental alertness, like driving or operating
N

Pregnancy Category: D machinery.

ATC Code: N03AF01 Adverse Drug Reactions:

Common: Peripheral edema, dizziness, drowsiness,
vasodilatation, ataxia, fatigue, hostility, tremor,
emotional lability, hyperkinesia, abnormality in thinking,
Rx GABAPENTIN headache, abnormal gait, depression, amnesia,
nervousness, hyperesthesia, lethargy, pain, twitching,
Oral: 100 mg and 300 mg capsule vertigo, pruritus, weight gain, skin rash, hyperglycemia,
diarrhea, nausea and vomiting, xerostomia, constipation,
Gabapentin selectively binds to α2δ subunits of voltage- abdominal pain, dyspepsia, dry throat, dental disease,
sensitive calcium channels, causing closure of N and P/Q flatulence, increased appetite, urinary tract infection,
presynaptic calcium channels that diminishes excessive impotence, decreased white blood cell count,
neuronal activity and neurotransmitter release. leukopenia, infection, weakness, back pain, dysarthria,
myalgia, bone fracture, limb pain, viral infection,
Indication: Management of postherpetic neuralgia (PHN) in nystagmus, diplopia, blurred vision, conjunctivitis,
adults; neuropathic pain. nasopharyngitis, rhinitis, otitis media, bronchitis,
pharyngitis, respiratory tract infection, cough, fever.
Contraindication: Hypersensitivity to gabapentin or any Less Common: Acute renal failure, altered serum glucose,
component of the formulation. anemia, angina pectoris, angioedema, aphasia,
aspiration pneumonia, blindness, blood coagulation
Dose: disorder, bradycardia, brain disease, breast hypertrophy,
Postherpetic neuralgia, by mouth, ADULT, Day 1: 300 mg; bronchospasm, cardiac arrhythmia (various),
Day 2: 300 mg twice daily; Day 3: 300 mg 3 times daily; cerebrovascular accident, cardiac failure, colitis,
titrate dose as needed for pain relief, usually ranging confusion, Cushingoid appearance, CNS neoplasm,
from 1,800–3,600 mg daily in divided doses. DRESS syndrome, drug abuse, dyspnea, erythema
Neuropathic pain, by mouth, ADULT, initially, 300 mg on the multiforme, drug dependence, facial paralysis, fecal
1st day, 300 mg twice a day on the 2nd day and 300 mg incontinence, gastroenteritis, glaucoma, glycosuria,
3 times a day on the 3rd day; alternatively, 900 mg daily hearing loss, hematemesis, hematuria, hemiplegia,
in 3 divided doses; dose may increase in increments of heart block, hemorrhage, hepatitis, hepatomegaly,
300 mg every 2–3 days (maximum 3,600 mg daily). herpes zoster, hyperlipidemia, hypertension,
hyperthyroidism, hyponatremia, hypotension,
Dose Adjustment: hyperventilation, hypoventilation, hypothyroidism,
Geriatric: jaundice, leukocytosis, lymphadenopathy, joint swelling,
Dose reductions may be needed based on renal function. lymphocytosis, memory impairment, meningism,
migraine, movement disorder, myocardial infarction,
Renal Impairment: myoclonus (local), nerve palsy, nephrolithiasis,
Adjust doses for renal function. nephrosis, non-Hodgkin's lymphoma, palpitations,

460
NERVOUS SYSTEM

pancreatitis, ovarian failure, paresthesia, peptic ulcer, ATC Code: N03AX12

pericardial effusion, pericardial rub, pericarditis,
peripheral vascular disease, pneumonia, psychosis,
pulmonary thromboembolism, retinopathy, purpura, ANTIMIGRAINE PREPARATIONS
rhabdomyolysis, seasonal allergy, skin necrosis, status
epilepticus, Stevens-Johnson syndrome, subdural ERGOT ALKALOIDS
hematoma, suicidal ideation, suicidal tendencies,
syncope, tachycardia, thrombophlebitis, tumor growth,
thrombocytopenia, withdrawal syndrome. Rx ERGOTAMINE
Drug Interactions:
Monitor closely with: Oral: 1 mg tablet (as tartrate)
Enhances CNS Depressant effect of Gabapentin:
Brimonidine (Topical); Doxylamine; Dronabinol; Ergotamine is an ergot alkaloid with partial agonist and/or
Hydroxyzine; Minocycline; Nabilone antagonist activity against tryptaminergic, dopaminergic
and alpha-adrenergic receptors. It stimulates uterine
Enhances therapeutic effect of the following drugs: contraction, peripheral and cranial vasoconstriction and
Ethyl alcohol; Mirtazapine (CNS depressant effect); depression of central vasomotor center.
Pramipexole, Ropinirole, Rotigotine (sedative effect)
Indication: Management and prophylaxisof vascular
Increases risk of adverse or toxic effects of Gabapentin: headaches (e.g. migraine, migraine variants, or so-called
CNS Depressants [except Levocabastine, Nasal]; “histaminic cephalalgia”).
Rufinamide (sleepiness and dizziness)
Contraindications: Peripheral vascular disease; hepatic or
Increases risk of adverse or toxic effects of SSRIs e.g. renal impairment; coronary artery disease; hypertension;
Fluoxetine (psychomotor impairment) sepsis; concomitant use with strong CYP3A4 inhibitors;
pregnancy.
Avoid concomitant use with:

N
Decreases serum concentration of Gabapentin: Dose:
Antacids [administer gabapentin at least 2 hours after Vascular headache, by mouth, placed under the tongue,
antacid]; Magnesium Salts [administer gabapentin at ADULT, initially 2 mg at first sign of migraine, then 2 mg
least 2 hours after magnesium salts]; Mefloquine every 30 minutes if needed (maximum dose, 6 mg per
24 hours, or 10 mg per week).
Enhances therapeutic effect of Gabapentin:
Droperidol; Magneisum salts; Methotrimeprazine Dose Adjustment:
[reduce gabapentin dose by 50% with concomitant use]; Geriatric:
Perampanel; Sodium oxybate; Tapentadol [start Use is not recommended.
tapentadol at one-third to one-half of normal dose if used
concomitantly] (CNS depressant effect) Precautions:
WARNING: Concomitant use with CYP3A Inhibitors.
Enhances therapeutic effect of the following drugs: Serious and/or life-threatening peripheral
Azelastine, Nasal; Buprenorphine; Hydrocodone [start ischemia has been associated with concomitant
with a 20–30% lower hydrocodone dose when used use of potent CYP 3A4 inhibitors, including
concomitantly]; Methotrimeprazine [reduce gabapentin protease inhibitors e.g. Lopinavir and macrolide
dose by 50% with concomitant use]; Orphenadrine; antibiotics e.g. Erythromycin..Concomitant use of
Paraldehyde; Suvorexant; Thalidomide; Zolpidem (CNS these medications is contraindicated.
depressant effect)
Cardiac valvular fibrosis; cardiovascular effectse. g
Reduces therapeutic effect of Gabapentin: vasoconstriction, hypertension and direct myocardial
Mefloquine; Mianserin toxicity; anemia; ergotism; pleural or retroperitoneal
fibrosis.
TEST INTERACTION. May cause a false positive result with Elderly (may precipitate angina, MI, or aggravate
the Ames N-Multistix SG® dipstick test for urine protein. intermittent claudication).
Pregnancy (may cause prolonged constriction of the uterine
Administration: May be taken with or without food. vessels and/or increased myometrial tone leading to
Administer first dose on first day at bedtime to avoid reduced placental blood flow); lactation (excreted in
somnolence and dizziness. When given 3 times daily, the breastmilk; may cause vomiting, diarrhea, weak pulse,
maximum time between doses should not exceed 12 and unstable blood pressure in the nursing infant).
hours.
Adverse Drug Reactions:
Do NOT discontinue abruptly because of the possibility of Common and Less Common: Absence of pulse, bradycardia,
increasing seizure frequency. Withdraw gradually to cardiac valvular fibrosis, cyanosis, edema, ECG changes,
minimize the potential of increased seizure frequency, gangrene, hypertension, ischemia, tachycardia,
unless safety concerns require a more rapid withdrawal. vasospasm, vertigo, precordial distress and pain, itching,
nausea, vomiting, retroperitoneal fibrosis, muscle pain,
Pregnancy Category: C

461
 NERVOUS SYSTEM

paresthesia, weakness, cold extremities, SELECTIVE SEROTONIN (5HT1) AGONISTS

pleuropulmonary fibrosis.

Drug Interactions: Rx SUMATRIPTAN

Monitor closely with:
Enhances therapeutic effect of Ergotamine:
Oral: 50 mg tablet
5HT3 Antagonists e.g., Ondansetron, Antipsychotic
Agents, Tedizolid (serotonergic effect)
A selective serotonin agonist that acts at 5-HT1B/1D receptor,
causing vasoconstriction of meningeal vessels and/or
Increases risk of adverse or toxic effects of Ergotamine:
inhibition of neurogenic inflammatory processes in the
Antipsychotic Agents (possibly increasing the risk for
CNS. Its nociceptive effect is likely due to blocking the
neuroleptic malignant syndrome; serotonin syndrome)
pain transmission signals at trigeminal nerve terminals
Metoclopramide (serotonin syndrome; neuroleptic
and synapses of second-order neurons in trigeminal
malignant syndrome)
nucleus caudalis.
Tedizolid (serotonin syndrome)
Indication: Acute treatment of migraine with or without aura.
Avoid concomitant use with:
Enhances therapeutic effect of Ergotamine: NOTE: NOT for the prevention of migraine attacks
Beta Blockers e.g., Metoprolol, Serotonin 5­HT1D
Receptor Agonists (vasoconstricting effect) Contraindications: Hypersensitivity to sumatriptan or any
component of the formulation; Severe hepatic
Enhances therapeutic effect of the following drugs: impairment; ischemic coronary artery disease or
Alpha / Beta Agonists, Alpha1 Agonists (hypertensive; coronary artery vasospasm, including Prinzmetal’s
vasoconstricting effects) Serotonin 5­HT1D Receptor angina; uncontrolled hypertension; Wolff-Parkinson-
Agonists (vasoconstricting effect) White syndrome or arrhythmias associated with other
cardiac accessory conduction pathway disorders; history
Decreases serum concentration of Ergotamine: of stroke or transient ischemic attack; history of
Enzalutamide hemiplegic or basilar migraine; peripheral vascular
N

disease; ischemic bowel disease; recent use (within 24

Increases risk of adverse or toxic effects of Ergotamine: hours) of ergotamine-containing medication or another
Other Serotonin Modulators [except Tedizolid] (serotonin 5-HT1 agonist; concurrent or recent (within 2 weeks) use
syndrome) of a MAOA inhibitor.
Increases risk of adverse or toxic effects of Dapoxetine Dose:
Acute treatment of migraine, by mouth, ADULT >18 years,
Increases serum concentration of Ergotamine: initially a single dose 50 mg tablet; if the migraine has
Anti-hepaciviral Combination Products, Boceprevir, not resolved by 2 hours after administration, or returns
Clarithromycin, Cobicistat, Fusidic Acid (Systemic), after a transient improvement, administer a second dose
Itraconazole, Ketoconazole (Systemic), Macrolide at least 2 hours after the first dose (maximum daily dose,
Antibiotics [except Systemic Azithromycin, Fidaxomicin, 200 mg in a 24-hour period).
Spiramycin], Mifepristone [avoid ergotamine during and
2 weeks following mifepristone use], Nitroglycerin, Dose Adjustment:
Posaconazole, Protease Inhibitors, Voriconazole Geriatric:
Administer first dose at physician’s office, if needed.
Reduces therapeutic effect of Nitroglycerin (vasodilatory
effect) Hepatic Impairment:
Reduce doses, in mild-to-moderate hepatic impairment, the
FOOD INTERACTION. Grapefruit juice may cause increased
maximum single dose should not exceed 50 mg.
blood levels of ergotamine, leading to increased toxicity.
Precautions:
Administration: Administer sublingually, by placing under
Cardiac events (e.g., coronary artery vasospasm, transient
the tongue until it dissolves. Do NOT crush or swallow.
ischemia, MI, ventricular tachycardia or fibrillation,
cardiac arrest, and death); arrhythmias (life-
Discontinuation even after limited use may result in
threatening); elevated blood pressure (hypertensive
withdrawal symptoms, e.g., rebound headache, nausea,
crisis) Cerebrovascular events (e.g., cerebral
vomiting.
hemorrhage, subarachnoid hemorrhage, and stroke;
NOTE: Use for ≥10 days per month may lead to worsening some fatal); vasospasm reactions; CNS depression;
of headaches due to medication overuse headache. seizures; ocular effects.
Withdrawal treatment may be necessary in the setting of Serotonin syndrome; anaphylactic or anaphylactoid
overuse. reactions (may be fatal); hepatic impairment.
Elderly (may be at increased cardiovascular risk); children
Pregnancy Category: X (safety and effectiveness have not been established).
Pregnancy; (has been associated with embryolethality, fetal
ATC Code: N02CA02 abnormalities, and pup mortality in animal studies);
lactation (excreted in breastmilk; use with caution).

462
NERVOUS SYSTEM

SKILLED TASKS. May impair ability to perform tasks, which

require mental alertness, like driving or operating Rx ZOLMITRIPTAN
machinery.
Oral: 2.5 mg tablet
Adverse Drug Reactions:
Common: Hot and cold flashes, chest pain, chest pressure, Zolmitriptan is a selective 5-HT1B/1D/1F receptor agonist that
chest tightness, pain, sensation of pressure, causes vasoconstriction of cranial arteries and sensory
paresthesia, malaise, fatigue, feeling of heaviness, nerves of the trigeminal system. This causes
sensation of tightness, heaviness of chest, sore throat, vasoconstriction and reduces inflammation associated
jaw pain, jaw pressure, jaw tightness, pharyngeal edema, with relief of migraine.
neck pain, local pain
Less Common: Hypotension, palpitations, dystonia, tremor, Indication: Acute treatment of migraine with or without aura.
vertigo
Contraindications: Ischemic coronary artery disease;
Drug Interactions: coronary artery vasospasm, including Prinzmetal variant
Monitor closely with: angina, or other significant underlying cardiovascular
Enhances therapeutic effect of Sumatriptan: disease; Wolff-Parkinson-White syndrome or arrhythmias
Antipsychotic Agents (serotonergic effect) associated with other cardiac accessory conduction
pathway disorders; peripheral vascular disease;
Increases risk of adverse or toxic effects of Sumatriptan: ischemic bowel disease; uncontrolled hypertension;
Antipsychotic Agents (enhances dopamine blockade, recent use (within 24 hours) of other 5-HT1 agonist or an
possibly increasing the risk for neuroleptic malignant ergotamine-containing medication; history of stroke,
syndrome; serotonin syndrome) transient ischemic attack, or history of hemiplegic or
Metoclopramide (serotonin syndrome; neuroleptic basilar migraine; co-administration or use within 2 weeks
malignant syndrome) of MAOA inhibitor therapy

Avoid concomitant use with: Dose:

Enhances therapeutic effect of Sumatriptan: Migraine, by mouth, ADULT >18 years, 1.25–2.5 mg

N
Beta Blockers Ergot Derivatives [except Nicergoline] (maximum single dose, 5 mg), may repeat in 2 hours if
(vasoconstricting effect) the migraine headache has not resolved or returns after
Metaxalone, Methylene blue, Methylphenidate, Opioid transient improvement (maximum daily dose 10 mg).
Analgesics, Tramadol
(serotonergic effect) Dose Adjustment:
Other Serotonin 5­HT1D Receptor Agonists Geriatric:
Initiate therapy at the low end of the dosing range.
Enhances therapeutic effect of the following drugs:
Ergot Derivatives [except Nicergoline], Serotonin 5­HT1D Renal Impairment:
Receptor Agonists (vasoconstricting effect) Zolmitriptan clearance is reduced in patients with severe
renal impairment (CrCl 5–25 mL/min.)
Increases risk of adverse or toxic effects of Sumatriptan:
Other Serotonin Modulators [except Tedizolid] Hepatic Impairment:
Metaxalone, Methylene blue (serotonin syndrome) For moderate to severe impairment, initial dose is 1.25 mg.
Methylphenidate (serotonin toxicity) Maximum daily dose in severe impairment is 5 mg.
Opioid Analgesics, Tramadol
Precautions:
Increases risk of adverse or toxic effects of the following Cardiac events (coronary artery vasospasm, transient
drugs: ischemia, MI, ventricular tachycardia or fibrillation,
Dapoxetine cardiac arrest, and death have been reported within a
Tramadol (seizures) few hours’ administration); elevated blood pressure;
coronary artery disease (administer first dose in the
Increases serum concentration of Sumatriptan: healthcare provider's office).
MAO Inhibitors Cerebrovascular events (cerebral or subarachnoid
hemorrhage and stroke have been reported, some fatal);
Administration: Administer as soon as symptoms appear. visual effects; vasospasm-related events (have been
reported); hepatic impairment; serotonin syndrome.
Pregnancy Category: C Elderly, Pregnancy; lactation.

ATC Code: N02CC01 Adverse Drug Reactions:

Common: Chest pain, cardiac arrhythmia, syncope,
hypertension, tachycardia, dizziness, local alterations in
temperature sensations, vertigo, paresthesia,
drowsiness, sensation of pressure, hyperesthesia,
headache, agitation, amnesia, anxiety, depression,
emotional lability, insomnia, diaphoresis, pruritus,
urticaria, nausea, skin rash, xerostomia, dyspepsia,
vomiting, urinary frequency, urinary urgency, dysphagia,

463
 NERVOUS SYSTEM

local pain at the neck, throat, or jaw, hypersensitivity Withdrawal treatment may be necessary in the setting of
reaction, weakness, tinnitus, polyuria. overuse.
Less Common: Abnormal dreams, abnormality in thinking, If a patient does not respond to the first dose, the
altered sense of smell, amblyopia, anaphylactoid diagnosis of migraine should be reconsidered.
reaction, anaphylaxis, back pain, angina pectoris,
angioedema, apathy, ataxia, atrial fibrillation, Pregnancy Category: C
bradycardia, breast carcinoma, breast neoplasm, bruise,
cellulitis, cerebral ischemia, confusion, conjunctivitis, ATC Code: N02CC03
constipation, colitis, convulsions, coronary artery
vasospasm, cyanosis, cyst, cystitis, diarrhea,
dysmenorrhea, dry eye syndrome, eructation, erythema, OTHER ANTIMIGRAINE PREPARATIONS
eye pain, eczema, erythema multiforme, euphoria,
fibrocystic breast disease, flu­like symptoms, fever,
gastritis, GI carcinoma, GI infarction, GI necrosis, Rx FLUNARIZINE
genitourinary neoplasm, gingivitis, hallucination, hepatic
neoplasm, hiccups, hypertensive crisis, hyperthyroidism,
Oral: 5 mg capsule (as hydrochloride)
hypertonia, hyperventilation, increased appetite,
increased bronchial secretions, increased thirst,
Flunarizine is a selective calcium channel blocker that
infection, intestinal obstruction, irritability, ischemic
prevents cellular calcium overload by reducing excessive
colitis, ischemic heart disease, lacrimation, laryngitis,
transmembrane calcium influx. It has calmodulin binding
leukopenia, mania, menorrhagia, MI, neoplasm,
properties and histamine H1 blocking activity. It also
neuropathy, otalgia, photophobia, pneumonia,
appears to act by blocking dopamine D2 receptors in a
psychosis, pyelonephritis, renal pain, salivation, seizure,
manner similar to antipsychotics.
serotonin syndrome, sialadenitis, skin neoplasm, splenic
infarction, stomatitis, tardive dyskinesia, tenosynovitis,
Indication: Prophylactic treatment of migraine, with or
thrombophlebitis, thyroid edema, tongue edema, tremor,
without aura, in patients with frequent severe attacks
twitching, UTI, uterine hemorrhage, uterine fibroid
who have not responded satisfactorily to other
enlargement, vasodilatation, vaginitis, ventricular
treatments and/or do not tolerate other therapy.
N

fibrillation, ventricular tachycardia, visual field defect,

voice disorder, yawning.
Contraindications: History of depression, preexisting
symptoms of Parkinson’s disease or other
Drug Interactions:
extrapyramidal disorders.
Monitor closely with:
Enhances therapeutic effect of Zolmitriptan:
Dose:
5HT3 Antagonists e.g., Ondansetron, Antipsychotic
Migraine prophylaxis, by mouth, ADULT <65 years, 10 mg
Agents (serotonergic effect)
once daily.
Increases risk of adverse or toxic effects of Zolmitriptan
Dose Adjustment:
(serotonergic syndrome)
Hepatic Impairment:
5HT3 Antagonists e.g., Ondansetron, Antipsychotic
Use with caution. Undergoes hepatic metabolism.
Agents
Precautions:
Increases risk of adverse or toxic effects of the following
CNS effects e.g. (CNS depression); extrapyramidal
drugs:
symptoms,
Antipsychotic Agents (enhances dopamine blockade,
Endocrine effects e.g. mild but significant increase in
possibly increasing the risk for neuroleptic malignant
serum prolactin levels and menstrual irregularities;
syndrome) Metoclopramide (serotonin syndrome;
Elderly (risk of extrapyramidal symptoms is increased).
neuroleptic malignant syndrome)
Pregnancy (adverse events have been observed in animal
studies); lactation (not known if excreted in breastmilk).
Avoid concomitant use with:
Decreases metabolism of Zolmitriptan: SKILLED TASKS. May impair ability to perform tasks, which
MAO Inhibitors e.g Phenelzine require mental alertness, like driving or operating
machinery.
Enhances therapeutic effect of Zolmitriptan:
Ergot Derivatives (vasoconstricting effect) Adverse Drug Reactions:
Common and Less Common: Drowsiness, anxiety,
Increases risk of adverse or toxic effects of Zolmitriptan: depression, dizziness, extrapyramidal reaction, fatigue,
Dapoxetine, Other Serotonin Modulators [except insomnia, motor dysfunction, sedation, sleep disorder,
Tedizolid] (serotonin syndrome) vertigo, skin rash, weight gain, galactorrhea, menstrual
disease, heartburn, increased appetite, nausea,
Administration: Administer as soon as migraine headache stomach pain, vomiting, xerostomia, myalgia weakness.
starts. May be broken in half to achieve a smaller initial
dose. Drug Interactions:
Monitor closely with:
NOTE: Use for ≥10 days per month may lead to worsening Enhances CNS depressant effect of Flunarizine:
of headaches, e.g., medication overuse headache.

464
NERVOUS SYSTEM

Doxylamine, Dronabinol, Hydroxyzine, Magnesium Dose:

Sulfate, Minocycline, Mirtazapine, Nabilone Migraine headache prophylaxis, by mouth, ADULT, initially
80 mg daily divided every 6–8 hours, increase by 20–40
Enhances therapeutic effect (sedative effect) of the mg/dose every 3–4 weeks to a maximum of 160–240
following drugs: mg daily given in divided doses every 6–8 hours; if
Ethyl Alcohol Pramipexole, Ropinirole, Rotigotine satisfactory response is not achieved within 6 weeks of
starting therapy, withdraw drug gradually over several
Increases risk of adverse or toxic effects of Flunarizine: weeks; CHILD >12 years, initially, 40 mg twice or thrice
CNS Depressants, Rufinamide (sleepiness and daily, increase to weekly intervals up to 160 mg daily
dizziness) (maximum, 240 mg daily); CHILD ≤12 years, 10–20 mg
twice or thrice daily.
Increases risk of adverse or toxic effects of SSRIs
(psychomotor impairment) Precautions:
WARNING: Do NOT withdraw abruptly, particularly in
Avoid concomitant use with: patients with CAD. Gradually taper dose to avoid
Enhances therapeutic effect of Flunarizine: acute tachycardia, hypertension, and/or ischemia.
Droperidol, Methotrimeprazine [reduce flunarizine dose
by 50% with concomitant use] (CNS depressant effect)
Administration: To be taken on an empty stomach.
Enhances therapeutic effect of the following drugs:
Hydrocodone [consider starting at a 20–30% lower See Propranolol under Cardiac Therapy – Antiarrhythmics
hydrocodone dose when used concomitantly], (Class II Antiarrhythmics) in Chapter 3: Cardiovascular
Methotrimeprazine [reduce flunarizine dose by 50% with System for other information.
concomitant use], Orphenadrine, Paraldehyde,
Perampanel, Sodium Oxybate, Tapentadol [start Pregnancy Category: C
tapentadol at one-third to one-half of the normal dose
when used concomitantly], Thalidomide Zolpidem (CNS ATC Code: Not available
depressant effect)

N
Increases risk of adverse or toxic effects of the following ANTIEPILEPTICS
drugs:
Alvimopan [administer at least 7 days apart], Azelastine
(Nasal) (CNS depressant effect) Buprenorphine BARBITURATES AND DERIVATIVES
Administration: Take with water at bedtime.
Rx PHENOBARBITAL
Allow 2 consecutive medication-free days each week to
decrease incidence of adverse effects. Discontinue use
if no significant improvement is seen after 3 months of Oral: 15 mg, 30 mg, 60 mg, and 90 mg tablet
therapy. Inj.: 120 mg/mL (130 mg/mL) (as sodium salt), 1 mL
ampule (IM, IV)
Pregnancy Category: C
Phenobarbital is a long-acting barbiturate with sedative,
ATC Code: N07CA03 hypnotic, and anticonvulsant properties. It depresses the
sensory cortex, decrease motor activity, alter cerebellar
function, and produce drowsiness, sedation, and
hypnosis. In high doses, barbiturates exhibit
Rx PROPRANOLOL anticonvulsant activity.

Indications: Management of generalized tonic-clonic (grand

Oral: 10 mg and 40 mg tablet (as hydrochloride)
mal), status epilepticus, and partial seizures.
Propranolol is a non-selective beta-adrenergic blocker that
Contraindications: Marked hepatic impairment; dyspnea or
competitively blocks response to beta1­ and
airway obstruction; porphyria (manifest and latent); intra-
beta2­adrenergic stimulation. These result in decrease in
arterial and SC administration; history of sedative /
heart rate, myocardial contractility, blood pressure, and
hypnotic addiction; nephritic patients (large doses).
myocardial oxygen demand.
Dose:
Indication: Prophylaxis for migraine headache.
NOTE: Individualize doses based on clinical response and
serum concentration. Once daily doses are usually
Contraindications: BP <50/30 mmHg; uncompensated CHF
administered at bedtime in children and adolescents.
(unless the failure is due to tachyarrhythmias being
treated with propranolol); cardiogenic shock; severe Status epilepticus, by IV infusion, ADULT, 20 mg/kg at 50 to
sinus bradycardia; sick sinus syndrome or heart block 100 mg/minute, may repeat once after 10 minutes with
greater than first degree (except in the presence of a an additional 5–10 mg/kg if needed; may administer
functioning artificial pacemaker) ; heart rate <80 bpm; additional boluses if in ICU [NOTE: Additional respiratory
bronchial asthma; bronchospasm. support may be required particularly when maximizing

465
 NERVOUS SYSTEM

loading dose or if on concurrent sedative therapy. Repeat hallucinations, “hangover” effect, headache,
doses administered sooner than 10–15 minutes may hyperkinesia, impaired judgment, insomnia, lethargy,
not allow adequate time for peak CNS concentrations to nervousness, nightmares, somnolence, exfoliative
be achieved and may lead to CNS depression]; dermatitis, rash, Stevens-Johnson syndrome, nausea,
ADOLESCENT, CHILD, and INFANT, 20 mg/kg over 10 vomiting, constipation, agranulocytosis, megaloblastic
minutes or 50–100 mg/minute (maximum dose, 1,000 anemia, thrombocytopenia, pain at injection site,
mg), may repeat dose after 15 minutes if needed thrombophlebitis (IV), oliguria, laryngospasm, respiratory
(maximum total dose, 40 mg/kg); or may administer an depression, hypoventilation, apnea (rapid IV), gangrene.
additional 5–10 mg/kg once after 10 minutes.
Seizures, maintenance, by mouth, ADULT, 50–100 mg 2–3 Drug Interactions:
times daily; ADOLESCENT, CHILD, and INFANT, 3–6 Monitor closely with:
mg/kg daily; or Enhances therapeutic effect (CNS depressant effect) of
by mouth or IV injection, ADOLESCENT, 1–3 mg/kg daily Phenobarbital:
in 1–2 divided doses; CHILD >5 years, 2–3 mg/kg daily Antihistamines, Brimonidin (Topical), Doxylamine,
in 1–2 divided doses; CHILD ≤5 years and INFANT, 3–5 Dronabinol, Fosphenytoin, Magnesium Sulfate,
mg/kg daily in 1–2 divided doses. Minocycline, Nabilone, Phenytoin, Sedative / Hypnotics

Dose Adjustment: Enhances therapeutic effect of the following drugs:

Geriatric: Ethyl Alcohol, Meperidin (CNS depressant effect)
Initiate at the lowest recommended dose. Hypotensive Agents (hypotensive effect)
Pramipexole, Rotigotine (sedative effect)
Renal Impairment:
In CrCl <10 mL/minute, administer ever 12–16 hours. Increases metabolism of Phenobarbital:
In patients under hemodialysis, administer dose before Pyridoxine, Rifamycin Derivatives
dialysis and 50% of the dose after dialysis.
In patients under peritoneal dialysis, administer 50% of Increases metabolism of the following drugs:
normal dose. Paracetamol, Propacetamol
N

Hepatic Impairment: Increases risk of adverse or toxic effects of Phenobarbital:

Reduce doses. Phenobarbital exposure is increased with CNS Depressants
hepatic impairment. Use with caution. Cosyntropin (hepatotoxic effect)
Dapsone (Topical), Primidone
Precautions:
NOTE: Phenobarbital requires an S-2 license for physicians Increases risk of adverse or toxic effects of the following
to be able to prescribe it and an S-1 license with a drugs:
triplicate prescription for pharmacists to dispense it. To Paracetamol, Propacetamol (liver damage)
be prescribed and dispensed through Yellow Rx. Only one Nitric Oxide, Prilocaine, Sodium Nitrite
(1) drug preparation shall be prescribed in one single (methemoglobinemia)
prescription form. Partial filling allowed. STRICTLY NO Quinidine (hepatotoxic effect)
REFILL. SSRIs (psychomotor impairment),
Thiazide Diuretics (orthostatic hypotensive effect)
CNS depression; paradoxical stimulatory response (e.g.,
agitation and hyperactivity); depression; suicidal Reduces therapeutic effect of the following drugs:
tendencies; Hypotension; Respiratory depression; Paracetamol, Propacetamol
Hepatic and Renal impairment; hypoadrenalism;
Substance abuse (e.g., drug dependence; tolerance) Avoid concomitant use with:
Decreases metabolism of Phenobarbital:
Use with caution in Chloramphenicol
Debilitated patients; Elderly (at risk of overdose at low
doses; increased risk of developing tolerance to sleep Decreases serum concentration of Phenobarbital:
effects; increased risk of physical dependence; may Cholestyramine Resin [administer phenobarbital at least
induce paradoxical stimulation, cause or aggravate 1 hour before or 4­6 hours after cholestyramine],
depression and confusion); Children (increased risk for Mefloquine.
paradoxical stimulatory response).
Pregnancy (Incidence of fetal abnormalities), lactation Decreases serum concentration of the following drugs:
(infantile spasms and other withdrawal symptoms may Abiraterone Acetate, Afatinib [increase dose by 10mg as
occur) tolerated then reduce to original dose 2–3 days after
stopping phenobarbital], Anti-hepaciviral Combination
SKILLED TASKS. May impair ability to perform tasks, which Products, Apixaban, Aripiprazole [double oral dose and
require mental alertness, like driving or operating closely monitor clinical response then reduce dose to
machinery. 10–15 mg daily after discontinuing phenobarbital; avoid
concomitant use for more than 14 days with extended-
Adverse Drug Reactions: release injectable aripiprazole], Artemether
Common and Less Common: Bradycardia, syncope, [dihydroartemisinin], Axitinib, Bedaquiline, Boceprevir,
hypotension, agitation, anxiety, ataxia, CNS excitation or Bortezomib, Cabozantinib, Canagliflozin [increase dose
depression, confusion, dizziness, drowsiness, to 300 mg daily in GFR >60 mL/min/1.73 m2 who

466
NERVOUS SYSTEM

tolerate canagliflozin 100 mg daily and require greater Increases risk of adverse or toxic effects of the following
glycemic control; consider alternatives in GFR 45–60 drugs:
mL/min/1.73 m2], Ceritinib, Clarithromycin, Clozapine, Azelastine, Nasal (CNS depressant effect)
Cobicistat, Dabigatran Etexilate, Daclatasvir, Dasabuvir,
Dasatinib [consider increasing dose and monitor clinical Increases serum concentration of Phenobarbital:
response and toxicity closely], Deferasirox [consider a Clarithromycin, Felbamate [initiate at 1,200 mg daily in
50% increase in initial dose], Dexamethasone 3–4 divided doses and reduce phenobarbital dose by
(Systemic), Dienogest [avoid use within 28 days of 20%], Oxcarbazepine, Quinine
phenobarbital], Dolutegravir, Doxorubicin
(Conventional), Doxycycline, Enzalutamide, Erlotinib [If Increases serum concentration of Clarithromycin
concomitant use cannot be avoided, increase dose by 50
mg increments every 2 weeks as tolerated, to a Reduces therapeutic effect of Phenobarbital:
maximum of 450 mg daily], Etoposide, Everolimus Mefloquine
[consider gradually increasing dose in 5 mg increments
from 10 mg daily to 20 mg daily], Exemestane [consider Reduces therapeutic effect of the following drugs:
using an increased dose of 50 mg daily when used Contraceptives [Estrogens, Progestins], Steroidal
concomitantly], Felbamate [initiate at 1,200 mg daily in Hormones
3–4 divided doses and reduce phenobarbital dose by
20%], Gefitinib [increase dose to 500 mg daily when TEST INTERACTION. Interferes with assay of LDH.
used concomitantly, then resume 250 mg dose 7 days
after discontinuation of phenobarbital], Imatinib Administration:
[increase dose by at least 50% and closely monitor For oral administration, may be taken with or without
clinical response], Irinotecan, Itraconazole, Ivabradine, food.
Ivacaftor, Ixabepilone [if concomitant use cannot be
avoided, gradually increase dose from 40 mg/m2 to 60 For IM administration, inject deep into muscle. Do NOT
mg/m2 given as a 4-hour infusion] exceed 5 mL per injection site due to potential for tissue
irritation.
Decreases serum concentration of the following drugs:

N
Lamotrigine, Lapatinib [if concomitant use cannot be For IV administration, administer at 50–100 mg/minute
avoided, titrate lapatinib gradually from 1,250 mg daily Avoid rapid IV administration at >60 mg/minute in adults
up to 4,500 mg daily for HER2 positive metastatic breast and >30 mg/minute in children.
cancer, or 1,500 mg daily up to 5,500 mg daily for HER2
positive breast cancer], Ledipasvir, Linagliptin, Avoid extravasation.
Lopinavir, Lumefantrine, Macitentan,
Methylprednisolone, Mifepristone, Netupitant, Do NOT administer by SC or intra-arterial injection.
Nifedipine, Nilotinib, Nimodipine, Nintedanib,
Nisoldipine, Olaparib, Oxcarbazepine, Palbociclib, Do NOT discontinue abruptly because of the possibility of
Paliperidone, Pazopanib, Perampanel [increase starting increasing seizure frequency. Withdraw therapy
dose to 4 mg daily], Praziquantel, Quetiapine, Quinine, gradually to minimize the potential of increased seizure
Ranolazine, Regorafenib, Rilpivirine, Ritonavir, frequency, unless safety concerns require a more rapid
Rivaroxaban, Roflumilast, Simeprevir, Sofosbuvir, withdrawal.
Sorafenib, Sunitinib, Tadalafil, Ticagrelor, Tofacitinib,
Tolvaptan, Ulipristal, Vemurafenib, Vincristine NOTE: May cause loss in vitamin D due to malabsorption.
(Liposomal), Voriconazole, Vortioxetine [consider Increase intake of food rich in vitamin D. Vitamin D
increasing dose to not more than 3 times the original and/or calcium supplementation may be necessary.
dose when used concomitantly for >14 days, return dose
to normal within 14 days of stopping phenobarbital] Pregnancy Category: B / D (product-specific)

Enhances therapeutic effect of Phenobarbital: ATC Code: N03AA02

Droperidol Hydroxyzine, Sodium Oxybate, Tapentadol
[start at one-third to one-half of the normal dose] (CNS
depressant effect) HYDANTOIN DERIVATIVES

Enhances therapeutic effect of the following drugs:

Buprenorphine, Hydrocodone [consider starting with a Rx PHENYTOIN
20–30% lower dose when used concomitantly],
Orphenadrine, Paraldehyde, Thalidomide, Zolpidem Oral: 100 mg capsule (as sodium salt)
(CNS depressant effect) 30 mg/5 mL suspension, 120 mL (as sodium salt)
125 mg/5 mL suspension, 120 mL (as sodium salt)
Increases metabolism of the following drugs: Inj.: 50 mg/mL solution (as sodium salt), 2 mL and 5 mL
Chloramphenicol, Cyclosporine (Systemic), TCAs, Vitamin ampule (IV)
K Antagonists [e.g., Warfarin]
A hydantoin antiepileptic drug that works primarily through
Increases risk of adverse or toxic effects of Phenobarbital: the reduction of hyperexcitability on sodium channels. It
Somatostatin Acetate (sedative effects) stabilizes neuronal membranes and decreases seizure
activity.

467
 NERVOUS SYSTEM

Precautions:
Indications: Management of generalized tonic-clonic (grand
mal), complex partial seizures; prevention of seizures WARNING: Cardiovascular risk. The rate of IV
following neurosurgery. administration should not exceed 50 mg/min in
adults and 1–3 mg/kg per min (or 50 mg/min,
Contraindications: Concurrent use of delavirdine; sinus whichever is slower) in pediatric patients because
bradycardia, sinoatrial block, second­ and third-degree of the risk of severe hypotension and cardiac
heart block, Adams-Stokes syndrome (IV). arrhythmias. Careful cardiac monitoring is needed
during and after administering IV phenytoin.
Dose: Reduction in rate of administration or
Status epilepticus, by IV injection, ADULT, initially 10 to 15 discontinuation of dosing may be needed if
mg/kg loading dose at a maximum rate of 50 cardiovascular toxicities are observed below the
mg/minute, may give an additional 5–10 mg/kg 10 recommended infusion rate.
minutes after the loading dose; or 10–15 mg/kg at a
maximum rate of 50 mg/minute; Hazardous agent. Use appropriate precautions for
ADOLESCENT, CHILD, and INFANT, initially 15–20 mg/kg handling and disposal.
loading dose at a maximum rate of 1–3 mg/kg/minute
or 50 mg/minute, whichever is slower, may give an Blood dyscrasias (may be fatal); porphyria; bone effects
additional 5–10 mg/kg 10 minutes after the loading (e.g., decreased bone mineral density and bone
dose; or 15–20 mg/kg loading dose, followed by fractures); cardiovascular events (e.g., hypotension and
maintenance therapy. severe cardiac arrhythmias with rapid administration);
Anticonvulsant, by IV injection, ADULT, 20 mg/kg loading cardiovascular disease; dermatologic reactions;
dose at a maximum rate of 50 mg/minute, may give an hypersensitivity; suicidal ideation; hepatic impairment;
additional dose of 5–10 mg/kg 10 minutes after the hypoalbuminemia; hypothyroidism; Asian ancestry
loading dose; or 10 to 15 mg/kg at a max. rate of 50 (variant HLA-B*1502 may be at an increased risk of
mg/minute; developing SJS and/or TEN); debilitated patients.
Anticonvulsant, maintenance, by mouth or by IV injection, Elderly (higher incidence of adverse effects; avoid use in
ADULT and ADOLESCENT, 100 mg every 6–8 hours; older adults with a history of falls or fractures as it may
N

CHILD and INFANT, initially 5 mg/kg daily in 2–3 divided cause syncope, impaired psychomotor function, or
doses; usual dose range, 4–8 mg/kg daily (maximum ataxia).
daily dose, 300 mg or 8–10 mg/kg daily in divided Pregnancy (may cause fetal hydantoin syndrome; crosses
doses). the placenta; increased risk of congenital malformations
and adverse outcomes may occur following in utero
Dose Adjustment: phenytoin exposure); lactation (excreted in breastmilk;
NOTE: Phenytoin base (e.g., oral suspension) contains ~8% use with caution).
more drug than phenytoin sodium (~92 mg base is
equivalent to 100 mg phenytoin sodium). Dosage Adverse Drug Reactions:
adjustments and closer serum monitoring may be Common: Atrial conduction depression (IV), bradycardia (IV),
necessary when switching dosage forms. circulatory shock (IV), cardiac arrhythmia (IV),
hypotension (IV), periarteritis nodosa, ventricular
Geriatric: conduction depression (IV), ventricular fibrillation (IV),
Clearance is decreased in the elderly. Lower doses or lessen confusion, dizziness, ataxia, drowsiness, decreased
dosing frequency. coordination, nystagmus, headache, slurred speech,
mood changes, insomnia, nervousness, paresthesia,
Hepatic Impairment: peripheral neuropathy (chronic treatment), twitching,
In cirrhosis, clearance may be substantially reduced and vertigo, bullous dermatitis, exfoliative dermatitis,
plasma level monitoring with dose adjustment is hypertrichosis, morbilliform rash, scarlatiniform rash,
advisable. Free phenytoin levels should be monitored skin or other tissue necrosis (IV administration), skin
closely. rash, toxic epidermal necrolysis, hyperglycemia, vitamin
D deficiency (chronic treatment), constipation, dysgeusia
Obesity: (metallic taste), gingival hyperplasia, nausea,
Loading dose = 14 mg/kg IBW + 19 mg/kg weight in excess enlargement of facial features (lips), vomiting, Peyronie's
of IBW disease, granulocytopenia, Hodgkin lymphoma,
agranulocytosis, immunoglobulin abnormality,
leukopenia, lymphadenopathy, macrocytosis,
megaloblastic, anemia, malignant lymphoma,
pancytopenia, pseudolymphoma, purpuric dermatitis,
thrombocytopenia, acute hepatic failure, hepatitis,
anaphylaxis, DRESS syndrome, Injection site reaction
("purple glove syndrome"; edema, discoloration, and pain
distal to injection site), local inflammation, irritation,
tissue necrosis (IV), localized tenderness (IV), coarsening
of facial features, osteomalacia, systemic lupus
erythematosus, tremor, fever, tissue sloughing (IV)
Less Common: Dyskinesia, hepatotoxicity (idiosyncratic)

468
NERVOUS SYSTEM

Drug Interactions: Decreases serum concentration of the following drugs:

Monitor closely with: Everolimus [consider gradually increasing dose in 5 mg
Enhances therapeutic effect (CNS depressant effect) of increments from 10 mg daily to 20 mg daily],
Phenytoin: Exemestane [consider using an increased dose of 50 mg
Doxylamine, Dronabinol, Ethosuximide, Hydroxyzine, daily when used concomitantly], Felbamate [reduce
Magnesium Sulfate, Minocycline, Nabilone phenytoin dose by 20%], Gefitinib [increase dose to 500
mg daily when used concomitantly, then resume 250 mg
Enhances therapeutic effect of the following drugs: dose 7 days after discontinuation of phenytoin],
Ethyl Alcohol, Phenobarbital (CNS depressant effect) [consider increasing guanfacine dose by 2-fold when
Pramipexole, Ropinirole, Rotigotine (sedative effect) used concomitantly, titrate the guanfacine dose up to a
Neuromuscular-Blocking Agents, Nondepolarizing maximum of 8 mg daily], HMG-CoA Reductase Inhibitors
(neuromuscular-blocking effect) [except Pitavastatin, Rosuvastatin], Imatinib [increase
dose by at least 50% and closely monitor clinical
Increases metabolism of Phenytoin: response], Irinotecan, Itraconazole, Ivabradine,
Pyridoxine Ivacaftor, Ixabepilone [if concomitant use cannot be
avoided, gradually increase dose from 40 mg/m2 to 60
Increases metabolism of Primidone mg/m2 given as a 4-hour infusion], Lamotrigine,
Lapatinib [if concomitant use cannot be avoided, titrate
Increases risk of adverse or toxic effects of Phenytoin: gradually from 1,250 mg daily up to 4,500 mg daily for
Carbonic Anhydrase Inhibitors [except Brinzolamide] HER2 positive metastatic breast cancer, or 1,500 mg
(osteomalacia or rickets) daily up to 5,500 mg daily for hormone receptor/HER2
CNS Depressants, Dapsone (Topical), Dexketoprofen positive breast cancer], Ledipasvir, Linagliptin, Lopinavir,
Cosyntropin (hepatotoxic effect) Lumefantrine, Lurasidone, Macitentan, Maraviroc
[increase dose to 600 mg twice daily when used with
Increases risk of adverse or toxic effects of the following phenobarbital], Methylprednisolone, Metyrapone,
drugs: Mianserin, Mifepristone, Netupitant, Nifedipine,
Paracetamol, Propacetamol (hepatotoxicity) Lithium, Nilotinib, Nimodipine, Nintedanib, Nisoldipine, Olaparib,
Nitric Oxide, Prilocaine, Sodium Nitrite Oxcarbazepine, Palbociclib, Paliperidone, Panobinostat,

N
(methemoglobinemia) Paritaprevir, Pazopanib, Perampanel [increase starting
SSRIs (psychomotor impairment) dose to 4 mg daily], Ponatinib, Praziquantel, Quetiapine
[reduce dose within 7–14 days of phenytoin], Quinine,
Reduces therapeutic effect of Phenytoin: Ranolazine, Regorafenib, Rilpivirine, Ritonavir,
Ciprofloxacin (Systemic) Rivaroxaban, Roflumilast, Simeprevir, Sirolimus,
Sofosbuvir, Sorafenib, Sunitinib, Tadalafil, Temsirolimus
Avoid concomitant use with: [if concomitant use cannot be avoided, consider
Paracetamol, Levodopa, Loop Diuretics, Neuromuscular- increasing dose to 50 mg weekly], Teniposide,
Blocking Agents (Nondepolarizing), Propacetamol Theophylline Derivatives [except Dyphylline], Ticagrelor,
Tipranavir, Tofacitinib, Tolvaptan, Topotecan, Toremifene
Decreases serum concentration of Phenytoin:
Carbamazepine, Dexamethasone (Systemic), Decreases serum concentration of the following drugs:
Enzalutamide, Mefloquine, Rifampin, Ritonavir, Trimethoprim, Ulipristal, Vandetanib, Vemurafenib,
Theophylline Derivatives [except Dyphylline], Vincristine (Liposomal), Voriconazole, Vortioxetine
[consider increasing dose to no more than 3 times the
Decreases serum concentration of the following drugs: original dose when used concomitantly for more than 14
Abiraterone Acetate, Afatinib [increase dose by 10 mg as days, return dose to normal within 14 days of stopping
tolerated then reduce to original dose 2–3 days after phenobarbital]
stopping phenytoin], Antihepaciviral Combination
Products, Apixaban, Aripiprazole [double oral dose and Enhances therapeutic effect of Phenytoin:
closely monitor clinical response then reduce the dose to Droperidol, Sodium Oxybate, Tapentadol [start at one-
10–15 mg daily after discontinuing phenytoin; avoid third to one-half of the normal dose] (CNS depressant
concomitant use for >14 days with extended-release effect)
injectable aripiprazole], Artemether, Axitinib,
Bedaquiline, Boceprevir, Bortezomib, Cabozantinib, Enhances therapeutic effect of the following drugs:
Canagliflozin [increase dose to 300 mg daily in GFR >60 Buprenorphine Hydrocodone [consider starting with a
mL/min/1.73 m2 who tolerate canagliflozin 100 mg daily 20–30% lower dose when used concomitantly], Metho
and require greater glycemic control; consider [reduce codeine dose by 50% with concomitant use],
alternatives in GFR 45–60 mL/min/1.73 m2], Orphenadrine, Paraldehyde, Thalidomide, Vitamin K
Carbamazepine, Caspofungin, Ceritinib, Clarithromycin, Antagonists e.g., Warfarin (anticoagulant effect),
Clozapine, Cobicistat, Crizotinib, Dabigatran Etexilate, Zolpidem (CNS depressant effect)
Daclatasvir, Dasabuvir, Dasatinib [consider increasing
dose and monitor clinical response and toxicity closely], Increases metabolism of Cyclosporine (Systemic)
Deferasirox [consider a 50% increase in initial dose],
Dexamethasone (Systemic), Dienogest [avoid use within Increases risk of adverse or toxic effects of Phenytoin:
28 days of phenobarbital], Disulfiram, Dolutegravir, Cimetidine
Doxorubicin (Conventional)

469
 NERVOUS SYSTEM

Increases risk of adverse or toxic effects of the following

drugs: Avoid extravasation. Ensure proper needle or catheter
Azelastine, Nasal (CNS depressant effect) placement prior to and during IV infusion. Following IV
administration, inject NS through the same needle or IV
Increases serum concentration of Phenytoin: catheter to prevent irritation.
Capecitabine, Cimetidine, Clarithromycin,
Dexamethasone (Systemic), Efavirenz, Felbamate If extravasation occurs, stop infusion immediately and
[reduce phenytoin dose by 20%], Fluconazole, disconnect. Leave needle or cannula in place. Gently
Fluorouracil (Systemic), Isoniazid, Nifedipine, aspirate extravasated solution. Do NOT flush the line.
Oxcarbazepine, Sulfamethoxazole, Tegafur, Remove needle or cannula and elevate the extremity
Trimethoprim, Vitamin K Antagonists [e.g., Warfarin]
Pregnancy Category: D
Increases serum concentration of Clarithromycin
ATC Code: N03AB02
Reduces therapeutic effect of Phenytoin:
Mefloquine
BENZODIAZEPINE DERIVATIVES
Reduces therapeutic effect of the following drugs:
Contraceptives [Estrogens, Progestins]
Rx CLONAZEPAM
FOOD INTERACTION
Ethanol. Inhibits metabolism of phenytoin and may also
increase CNS depression. Chronic ethanol use Oral: 500 mcg and 2 mg tablet
stimulates metabolism of phenytoin.
A benzodiazepine derivative that suppresses the spike-and-
Folic acid. May decrease mucosal uptake of folic acid. wave discharge in absence seizures by depressing nerve
Administer prophylactic doses of folic acid and transmission in the motor cortex. It enhances the activity
cyanocobalamin to avoid folic acid deficiency and of GABA in the CNS.
N

megaloblastic anemia. 0.5 mg folic acid daily has been

shown to reduce the incidence of phenytoin-induced Indications: Monotherapy or adjunct therapy in the
gingival overgrowth in children. However, folate treatment of Lennox-Gastaut syndrome (petit mal
supplementation may increase seizures in some patients variant), akinetic, and myoclonic seizures; absence
(dose dependent). seizures (petit mal) unresponsive to succinimides.

Calcium. Hypocalcemia has been reported in patients Contraindications: Significant liver disease; acute narrow-
taking prolonged high-dose therapy. administer an angle glaucoma.
additional 4000 units/week of vitamin D to prevent
hypocalcemia. Dose:
Seizure disorders, by mouth, ADULT, ADOLESCENT, and
Vitamin D. Phenytoin interferes with vitamin D CHILD >10 years or ≥30 kg, initially 1.5 mg daily in 3
metabolism and osteomalacia. Consider vitamin D divided doses, may increase by 0.5–1 mg every third day
supplementation. until seizures are controlled or adverse effects seen
(maximum, 20 mg daily); usual maintenance dose, 2–8
mg daily in 1–2 divided doses (maximum, 20 mg daily);
Administration:
CHILD <10 years or <30 kg, initially 0.01–0.03 mg/kg
For oral administration, preferably take on an empty
daily in 3 divided doses (maximum: 0.2 mg/kg daily).
stomach. Taking with food may decrease phenytoin
serum concentrations. For oral suspension, shake well
Dose Adjustment:
prior to use.
Geriatric:
Initiate with low doses and observe closely.
Tube feedings decrease bioavailability. Absorption is
impaired when given concurrently to patients who are
Precautions:
receiving continuous nasogastric feedings. Hold tube
feedings 1–2 hours before and 1–2 hours after WARNING: Hazardous agent. Use appropriate
phenytoin. Divide daily dose and withhold administration precautions for handling and disposal.
of supplements for 1–2 hours before and after each
phenytoin dose to resolve this interaction.
Anterograde amnesia; CNS depression; paradoxical
reactions; suicidal ideation; depression; drug abuse;
For IV administration, may be administered by direct IV
Post-traumatic Stress Disorder.
injection. Administer by infusion pump either undiluted
Renal and hepatic impairment; respiratory disease (e.g.,
or diluted in normal saline as an IV piggyback (IVPB) to
prevent exceeding the maximum infusion rate. The respiratory depression and increase in salivation);
glaucoma.
maximum rate of IV administration is 50 mg/minute in
Debilitated patients; fall risk.
adults and 0.5 to 1 mg/minute in neonates. An in­line
Elderly (increased risk of impaired cognition, delirium, falls,
0.22 to 0.55-micron filter is recommended for IVPB
fractures, and motor vehicle accidents); children
solutions due to the potential for precipitation of the
solution. (increased risk for paradoxical reactions).

470
NERVOUS SYSTEM

Pregnancy (possible increased risk of birth defects when Avoid concomitant use with:
taken during pregnancy, especially during the first Decreases serum concentration of Clonazepam:
trimester; infants may experience withdrawal effects Dafrafenib, Deferasirox, Mitotane
when administered late in pregnancy; neonatal
flaccidity); lactation (excreted in breastmilk; drowsiness, Enhances therapeutic effect of the following drugs:
lethargy, or weight loss in nursing infants have been Buprenorphine, Hydrocodone [consider starting with a
observed following maternal use). 20–30% lower dose when used concomitantly],
Methadone, Orphenadrine, Paraldehyde, Perampanel,
SKILLED TASKS. May impair ability to perform tasks, which Sodium Oxybate, Thalidomide, Zolpidem (CNS
require mental alertness, like driving or operating depressant effect)
machinery.
Enhances therapeutic effect of Clonazepam:
Adverse Drug Reactions: Droperidol
Common: Edema (ankle or facial), palpitation, amnesia, Tapentadol (CNS depressant effect) [start at one-third to
ataxia, behavior problems, coma, confusion, impaired one-half of the normal dose]
coordination, depression, dizziness, drowsiness,
emotional lability, fatigue, fever, headache, hysteria, Increases risk of adverse or toxic effects of Clonazepam:
insomnia, reduced intellectual ability, hallucinations, Olanzapine
memory disturbance, nervousness, paradoxical
reactions (including agitation, anxiety, excitability, Increases risk of adverse or toxic effects of the following
hostility, aggressive behavior, irritability, nightmares, drugs:
sleep disturbance, vivid dreams), psychosis, slurred Azelastine (Nasal), Clozapine (CNS depressant effect)
speech, somnolence, vertigo, hair loss, hirsutism, skin
rash, dysmenorrhea, increased or decreased libido, Increases serum concentration of Clonazepam:
abdominal pain, anorexia, increased or decreased Fusidic Acid (Systemic), Idelalisib, Mifepristone
appetite, dehydration, constipation, diarrhea,
encopresis, coated tongue, gastritis, gum soreness, Reduces therapeutic effect of Clonazepam:
nausea, weight changes, xerostomia, Colpitis, dysuria, Theophylline Derivatives

N
delayed ejaculation, enuresis, micturition frequency,
nocturia, urinary retention, UTI, impotence, anemia, Administration: Swallow whole with water. Administer one
eosinophilia, leukopenia, thrombocytopenia, dose at bedtime to reduce somnolence.
hepatomegaly, Choreiform movements, dysarthria,
hypotonia, muscle weakness, myalgia, tremor, blurred Pregnancy Category: D
vision, diplopia, abnormal eye movements, nystagmus,
bronchitis, chest congestion, cough, hypersecretions, ATC Code: N03AE01
pharyngitis, respiratory depression, rhinitis, respiratory
tract infection, rhinorrhea, sinusitis, shortness of breath, NOTE: Clonazepam requires an S-2 license for physicians to
allergic reaction, dysdiadochokinesis, “glassy-eyed” be able to prescribe it and an S-1 license with a triplicate
appearance, lymphadenopathy, flu-like syndrome, prescription for pharmacists to dispense it.
aphonia, hemiparesis.
Less Common: Apathy, burning skin, chest pain,
depersonalization, hyperactivity, excessive dreaming, CARBOXAMIDE DERIVATIVES
dyspnea, hypoesthesia, increased oppositional behavior,
postural hypotension, infection, migraine, organic
disinhibition, pain, paresthesia, paresis, periorbital Rx CARBAMAZEPINE
edema, polyuria, suicidal attempt, suicide ideation, thick
tongue, twitching, visual disturbance, xerophthalmia. Oral: 200 mg tablet
200 mg and 400 mg MR tablet
Drug Interactions: 100 mg/5 mL syrup, 120 mL
Monitor closely with:
Enhances therapeutic effect of Clonazepam: Carbamazepine is an iminostilbene that limits the firing of
Brimonidine (Topical), Doxylamine, Dronabinol, action potentials evoked by a sustained depolarization in
Hydroxyzine, Magnesium Sulfate, Minocycline, Nabilone, cortical neurons. It acts by limiting influx of sodium ions
Vigabatrin (CNS depressant effect) or by slowing the rate of recovery of Na+ channels.
Enhances therapeutic effect of the following drugs: Indications: Management of epilepsy; complex or simple
Ethyl Alcohol, Mirtazapine (CNS depressant effect) partial seizures with or without secondary generalization;
Pramipexole, Ropinirole, Rotigotine (sedative effect) generalized tonic-clonic seizures; mixed forms of
seizures.
Increases risk of adverse or toxic effects of Clonazepam:
CNS Depressants NOTE: NOT effective in absence seizures (petit mal) and
Cosyntropin (hepatotoxic effect) myoclonic seizures.
Rufinamide (sleepiness and dizziness)
Contraindications: Atrioventricular block; bone marrow
Increases risk of adverse or toxic effects of SSRIs depression; acute intermittent porphyria; combination
(psychomotor impairment) with MAO Inhibitors e.g., Phenezline, Selegeline.

471
 NERVOUS SYSTEM

Dose: 29.1–39 kg 1,200 mg daily

NOTE: MR tablets are designed to be taken twice daily due >39 kg 1,800 mg daily
to the controlled release of the active substance. CHILD <20 kg, initiate at 16–20 mg/kg, titrate to the
maximum maintenance dose over 2–4 weeks, not to
Epilepsy, by mouth, ADULT, initially 100–200 mg once or
exceed 60 mg/kg daily twice daily.
twice daily, slowly raise until an optimal response is
Seizures, monotherapy, by mouth, ADULT, initially 600 mg
obtained (generally at 400 mg twice or thrice daily);
twice daily, may increase by 300 mg daily every third day
ADOLESCENT >12 years, 5–10 mg/kg daily divided every
to a dose of 1,200 mg daily;
12 hours then increase gradually to maintenance of 10– CHILD 4–16 years, initially 8–10 mg/kg daily twice daily,
30 mg/kg daily divided every 8 or 6 hours (maximum, 1 increase by 5 mg/kg daily every third day to the
g daily for 12–15 years old and 1.2 g daily if >16 years recommended daily dose as follows:
old); CHILD 6–12 years, initially 10 mg/kg daily in 2–4
divided doses, increase by 5 mg/kg weekly until
From dose To dose
therapeutic levels; CHILD <5 years, initially 5 mg/kg daily Weight in kg
(mg daily) (mg daily)
in 2–4 divided doses, increase every 5–7 days by 5
20 600 900
mg/kg based on response.
25 900 1,200
Administration: May be taken during, after, or between 30 900 1,200
meals. For the syrup formulation, shake well before use. 35 900 1,500
Administer tablets with little liquid. Swallow MR tablets 40 900 1,500
unchewed with a little liquid.
45 1,200 1,500
For existing anticonvulsant therapy, add carbamazepine 50 1,200 1,800
gradually while existing anticonvulsant is maintained or 55 1,200 1,800
gradually decreased, except with phenytoin, which may 60 1,200 2,100
need to be increased or decreased depending on 65 1,200 2,100
phenytoin serum levels.
70 1,500 2,100
N

See Carbamazepine under Analgesics – Other Analgesics

Dose Adjustment:
and Antipyretics: Drugs for Neuropathic Pain in Chapter
Renal Impairment:
10: Nervous System for other information.
In CrCl <30 mL/minute, initiate at ½ the usual starting dose
and increase slowly to achieve the desired clinical
Pregnancy Category: D
response.
ATC Code: N03AF01
Precautions:
Hyponatremia; anaphylactic reactions and angioedema
(eg., laryngeal edema can be fatal); serious
Rx OXCARBAZEPINE dermatological reactions (some fatal); bone metabolism.
Suicidal behavior and ideation; neuropsychiatric adverse
events; DRESS or multi-organ hypersensitivity (some
Oral: 300 mg and 600 mg tablet fatal); hematologic events; glaucoma; hyponatremia.
60 mg/mL, 100 mL and 250 mL suspension HLA-B*1502 allele carrier (e.g., SJS or toxic epidermal
necrolysis (SJS/TEN) during treatment).
Oxcarbazepine is a prodrug related to carbamazepine. It Elderly (increased incidence of adverse effects).
works by binding to the open channel conformation of Pregnancy (no adequate and well-controlled studies);
voltage-sensitive sodium channels at a site within the lactation (excreted in breastmilk).
channel itself at the α subunit.
Adverse Drug Reactions:
Indication: Management of partial-onset seizure in adults Common: Dizziness, somnolence, diplopia, fatigue, nausea,
and children and partial seizure with secondary vomiting, abdominal pain, abnormal vision, ataxia,
generalization. tremor, dyspepsia, abnormal gait, nystagmus,
maculopapular rash, convulsions, rash, status
Dose: epilepticus, fatigue, edema, weight gain, asthenia,
NOTE: Oral suspension and tablets may be interchanged at diarrhea, hypotension, hyponatremia, sprains, strains,
equal doses. muscle weakness, gastritis, constipation, acne,
headache, nervousness, agitation, dysmetria, abnormal
Seizures, adjunct therapy, by mouth, ADULT, initially 600 mg coordination, speech disorder, rhinitis, dry mouth,
twice daily, may increase up to a maximum of 600 mg toothache, lymphadenopathy, rectal hemorrhage,
daily at weekly intervals if clinically indicated; infection, thirst, emotional lability, hypoesthesia,
recommended daily dose is 1,200 mg; pharyngitis, purpura, earache, ear infection, vaginitis,
CHILD 2–16 years, initially 8–10 mg/kg twice daily, not micturition frequency.
to exceed 600 mg daily, titrate gradually over 2 weeks to
the target maintenance dose, as follows: Drug Interactions:
Monitor closely with:
Weight Target maintenance dose Enhances therapeutic effect of CNS Depressants
20–29 kg 900 mg daily

472
NERVOUS SYSTEM

Avoid concomitant use with: mg/kg daily [NOTE: In patients previously receiving
Decreases serum concentration of Hormonal valproic acid therapy, divalproex sodium is initiated at
contraceptives the same daily dose and dosing schedule].
Dose Adjustment:
Increases risk of adverse or toxic effects of the following Geriatric:
drugs: Lower initial dose and slower increase in dosage. Regularly
MAO Inhibitors (serotonin syndrome) monitor fluid and nutritional intake and increased
somnolence and other side effects.
Reduces therapeutic effect of Hormonal contraceptives
Renal Impairment:
Administration: May be taken with or without food. No dose adjustment necessary. May cause misleading
Administer in a twice-a-day regimen. results in therapeutic drug monitoring due to substantial
reduction of protein binding.
Keep out of sight and reach of children.
Hepatic Impairment:
Pregnancy Category: C Avoid if possible, hepatotoxicity and hepatic failure may
occasionally occur, usually in the first six months.
ATC Code: N03AF02
Precautions:
WARNING: Hepatotoxicity. Hepatic failure resulting in
FATTY ACID DERIVATIVES fatalities has occurred, usually during the first six
months of treatment. Increased risk for fatal
hepatotoxicity is seen in children <2 years old,
Rx VALPROIC ACID patients on multiple anticonvulsants, congenital
metabolic disorders, severe seizure disorders
Oral: 250 mg and 500 mg tablet (as divalproex sodium) accompanied by mental retardation, or organic
250 mg and 500 mg extended release tablet (as brain disease, hereditary neurometabolic
divalproex sodium) syndromes. Monitor for and immediately report

N
500 mg controlled release tablet (333 mg sodium non-specific symptoms such as malaise,
valproate + 145 mg valproic acid) weakness, lethargy, facial edema, anorexia, and
200 mg/5 mL syrup, 100 mL bottle (as sodium vomiting that may precede hepatotoxicity. Loss of
valproate) seizure control may also be seen. Discontinue
250 mg/5 mL syrup, 120 mL (as valproic acid) immediately in the presence of suspected or
Inj.: 500 mg/5 mL, 5 mL vial (IV infusion) (as valproic acid) apparent significant hepatic dysfunction.
Pancreatitis. May be life-threatening, some
Valproate is a simple branched-chain carboxylic acid that hemorrhagic and progressed rapidly from initial
inhibits sustained repetitive firing of cortical neurons by symptoms to death. Monitor for and immediately
prolonging recovery of voltage-activated Na+ channels report symptoms of abdominal pain, nausea,
from inactivation. Its activity is thought to be related to vomiting, and/or anorexia. Measure plasma
the elevated concentrations of gamma-aminobutyric amylase immediately if with abdominal pain.
acid (GABA) in the brain. Discontinue drug immediately.
Teratogenicity. May cause neural tube defects. Do
Indications: Management of status epilepticus and other NOT use in women of child-bearing age unless
epilepsies when oral dosage forms cannot be utilized or essential.
when IV anticonvulsants are warranted.
Hepatotoxicity (liver function tests, e.g., SGPT/ALT,
NOTE: It is an effective and safe alternative (less
prothrombin time, must be done pre-treatment and
hypotension, cardiac arrhythmia, sedation) for status
periodically especially within the first 6 months and in at-
epilepticus.
risk patients).
Urea cycle disorders (hyperammonemic encephalopathy,
Contraindications: Hepatic disease or significant hepatic
sometimes fatal)
dysfunction; urea cycle disorders; hereditary
Thrombocytopenia (platelet counts and coagulation tests,
neurometabolic syndromes caused by DNA mutations of
should be done before treatment and periodically
the mitochondrial DNA polymerase-gamma (POLG) gene
thereafter particularly during the first six months of
(e.g., Alpers Huttenlocher Syndrome); active pancreatitis.
therapy, and prior to surgery or anticoagulant therapy;
discontinue at first signs of hemorrhage, bruising, or
Dose:
disordered coagulation).
Epilepsy, by mouth, ADULT, initiate at 10–15 mg/kg daily
Suicidal thoughts and behavior (monitor and immediately
(give in 2–3 divided doses if total daily dose exceeds 250
report any unusual change in mood or behavior).
mg), gradually increase by 5–10 mg/kg per week to
Children (children <2 years are at increased risk for fatal
achieve optimal clinical response; usual maintenance
hepatotoxicity; use with extreme caution in this age
dose is 20–30 mg/kg daily; doses above 60 mg/kg daily
group and as a sole agent).
is not recommended (therapeutic serum range, 50 to
Pregnancy (may cause teratogenic effects, such as neural
100 micrograms/mL); ADULT and CHILD >12 years,
tube defects, e.g., spina bifida; must be considered in
maximum dose is 2.5 grams daily in divided doses;
women of child-bearing age only after the risks have
CHILD <12 years and >20 kg, maximum dose is 35

473
 NERVOUS SYSTEM

been carefully weighed against the benefits; immediately OTHER ANTIEPILEPTICS

refer to a specialist).

SKILLED TASKS. May impair ability to perform tasks, which Rx DIAZEPAM

require mental alertness, like driving or operating
machinery.
Oral: 5 mg tablet
Adverse Drug Reactions: Inj.: 5 mg/mL, 2 mL ampule (IM, IV)
NOTE: The frequency of adverse effects, particularly
elevated liver enzymes and thrombocytopenia, can be Diazepam is a long-acting benzodiazepine with
dose-related. anticonvulsant, anxiolytic, sedative, muscle relaxant and
amnestic properties. It increases neuronal membrane
Common: Nausea, vomiting, abdominal pain, diarrhea, permeability to Chloride ions by binding to
anorexia, dyspepsia, elevated AST or ALT, somnolence, benzodiazepine receptors on the postsynaptic GABA
dizziness, tremor, insomnia, nervousness, depression, neuron within the CNS and enhancing the GABA
anxiety, amnesia, mood changes, hallucinations, inhibitory effects resulting in hyperpolarization and
nystagmus, blurred vision, amblyopia, ataxia, vertigo, stabilization.
thrombocytopenia, increased bleeding time, petechiae
or ecchymosis, asthenia, flu syndrome infection, Indications: Management of initial and immediate
bronchitis, pharyngitis, rhinitis, headache, transient suppression of convulsive and non-convulsive status
alopecia, skin rash, increased appetite, weight gain, epilepticus prior to transfer to hospital; recurrent or
tinnitus. prolonged febrile convulsions; recurrent generalized or
Less Common: Irregular menses, secondary amenorrhea. grand mal seizures associated with poisoning and drug
Rare: Hepatic failure (may be fatal), pancreatitis, and acute alcohol withdrawal.
hyperammonemia, SJS, toxic epidermal necrolysis.
Contraindications: Respiratory depression; marked
Drug Interactions: neuromuscular respiratory weakness, including unstable
Monitor closely with: myasthenia gravis; acute pulmonary insufficiency; sleep
apnea syndrome; phobic or obsessional states;
N

Decreases metabolism of the following drugs:

Diazepam, Phenobarbital, Phenytoin hyperkinesis; severe hepatic impairment.

Decreases plasma clearance of the following drugs: NOTE: Oral diazepam is NOT recommended for chronic
Amitriptyline, Nortriptyline psychosis. NOT to be used alone in depression or in
anxiety with depression.
Increases plasma clearance of Valproate Disodium:
Rifampin Dose:
Status epilepticus, convulsive and non-convulsive, by slow
Increases risk of adverse or toxic effects of Phenobarbital IV injection, ADULT and CHILD >12 years, 5–10 mg at a
(neurologic toxicity, including CNS depression) rate not exceeding 2 mg/minute, repeated as necessary
every 5–10 minutes until seizures stop or up to a
Avoid concomitant use with: maximum total dose of 30 mg, may repeat in 2–4 hours
Reduces therapeutic effect of Valproate Disodium: if needed; CHILD up to 12 years and INFANT >1 month,
Carbapenem Antibiotics e.g., Imipenem, Meropenem, 300–400 micrograms/kg at a rate not exceeding 1
Ertapenem (loss of seizure control) mg/minute every 15–30 minutes up to a maximum total
dose of 5 mg in infants, and 10 mg for older children.
Administration: Swallow tablets whole. Do not chew or Prolonged or recurrent febrile convulsions, by slow IV
crush. Taken preferably after food intake. If dose is injection, CHILD and INFANT, 300–400 micrograms/kg
skipped, do not double the next dose. at a rate not exceeding 1 mg/minute every 15–30
minutes up to a maximum total dose of 5 mg in infants,
CONVERSION TO MONOTHERAPY. Reduce concomitant anti- and 10 mg for older children.
epilepsy drug dose by approximately 25% every 2 weeks. Seizures associated with poisoning, by slow IV injection,
Reduction may be started at initiation of therapy or ADULT, 100–150 micrograms/kg at a rate not exceeding
delayed by 1–2 weeks if there is a concern that seizures 2 mg/minute.
are likely to occur with a reduction.
Dose Adjustment:
AS ADJUNCT TO THERAPY. May be added to the regimen at Geriatric or Debilitated Patients:
an initial oral dose of 10–15 mg/kg daily (give in 2–3 Reduce dose.
divided doses if total daily dose exceeds 250 mg), may
increase dose 5–10 mg/kg daily at 1-week intervals to Renal Impairment:
achieve optimal clinical response (maximum 60 mg/kg Reduce dose in prolonged periods.
daily or less with a therapeutic serum range of 50 to 100
micrograms/mL). Hepatic Impairment:
Reduce maintenance dose.
Pregnancy Category: D

ATC Code: N03AG01

474
NERVOUS SYSTEM

Precautions: NOTE: Avoid extravasation, intra-arterial and IM injection.

Avoid dilution and infusion of injection, as diazepam has
WARNING: Overdose may produce coma and a low solubility and adsorbs to PVC-giving sets
respiratory depression.
Diazepam 5 mg requires an S-2 license for physicians to be
Agents for correcting hypotension and facilities for able to prescribe it and an S-1 license with a triplicate
supporting ventilation (e.g., AMBU bag, oxygen) in prescription for pharmacists to dispense it.
cases of respiratory depression should be
available. In such cases, the patient should be Pregnancy Category: D
referred to the nearest hospital immediately.
ATC Code: N05BA01

Hepatic impairment and renal impairment (can precipitate

coma in cases of severe hepatic and renal impairment);
avoid prolonged use and abrupt withdrawal; Rx GABAPENTIN
Respiratory disease (e.g., compromised respiratory drive
and sleep apnea may lead to hypoventilation and Oral: 100 mg and 300 mg capsule
hypoxemia); muscle weakness; (may worsen); history of
alcohol or drug abuse, marked personality disorder; use Gabapentin is a leucine analog of GABA. Its therapeutic
only if the indication is clear; porphyria. properties are due to its selective binding to α2δ subunits
Pregnancy (high doses during late pregnancy or labor may of voltage-sensitive calcium channels, causing closure of
cause neonatal hypothermia, hypotonia, and respiratory N and P/Q presynaptic calcium channels that diminishes
depression); lactation (monitor infant for drowsiness). excessive neuronal activity and neurotransmitter
release.
Adverse Drug Reactions:
Common: Coma or sensorial depression, hypotension, Indications: Adjunct therapy in the treatment of partial
respiratory depression. seizures with and without secondary generalization in
Rare: Allergic reactions (including anaphylaxis), jaundice. adults and pediatric patients 3 years and older.

N
Drug Interactions: Dose:
Monitor closely with: Seizures, partial onset, by mouth, ADULT or CHILD ≥12
Decreases metabolism of Diazepam: years, initially 300 mg on the 1st day, 300 mg twice a day
Azole Derivatives, e.g., Fluconazole on the 2nd day, and 300 mg 3 times a day on the 3rd day;
or 300 mg 3 times daily on the 1st day, increase dose
Enhances therapeutic effect of the following drugs: based on response and tolerability; usual dose range is
Amlodipine, Enalapril, Furosemide, Hydrochlorothiazide, 900–1,800 mg daily administered in 3 divided doses;
Methyldopa, Nitrates, e.g., Isosorbide Dinitrate CHILD 5–11 years, initially 10–15 mg/kg daily in 3
(hypotensive effect) divided doses, titrate to effective dose over
Chlorpromazine (sedative effect) approximately 3 days, increase dosage based on
CNS Depressants, e.g., Alcohol, Sedatives, Tranquilizers response and tolerability; usual dose range is 25–35
(CNS depression; sedative effect) mg/kg daily in 3 divided doses with maximum interval of
12 hours (maximum, 50 mg/kg daily); CHILD 3–4 years,
Increases risk of adverse or toxic effects of Diazepam: initially 10–15 mg/kg daily in 3 divided doses, titrate to
Azole Derivatives, e.g., Fluconazole effective dose over approximately 3 days, increase
dosage based on response and tolerability; usual dose
Increases risk of adverse or toxic effects of the following range is 40 mg/kg daily in 3 divided doses.
drugs:
Chlorphenamine (sedative effect) NOTE: If gabapentin is discontinued or if another
Seizure-inducing Drugs anticonvulsant is added to therapy, it should be done
slowly over a minimum of 1 week.
Reduces therapeutic effect of Diazepam:
Theophylline (sedative effects) Administration: May be taken with or without food.
Administer first dose on first day at bedtime to avoid
Avoid concomitant use with: somnolence and dizziness. When given 3 times daily, the
Decreases metabolism of Diazepam: maximum time between doses should not exceed 12
Isoniazid hours.

Reduces therapeutic effect of Diazepam due to decreased Do NOT discontinue abruptly because of the possibility of
serum concentration: increasing seizure frequency. Withdraw gradually to
Rifampicin (increases metabolism of Diazepam) minimize the potential of increased seizure frequency,
unless safety concerns require a more rapid withdrawal.
Administration: Give by slow IV injection at a rate not faster
than 2 mg/minute. See Gabapentin under Analgesics – Other Analgesics and
Antipyretics: Drugs for Neuropathic Pain in Chapter 10:
Nervous System for other information.

475
 NERVOUS SYSTEM

Pregnancy Category: C Multiorgan hypersensitivity reactions, i.e., drug reaction with

eosinophilia and systemic symptoms [DRESS];
ATC Code: N03AX12 photosensitivity; hepatic impairment; renal impairment.
Children (at increased risk for developing serious skin
rashes during therapy).
Pregnancy (weigh potential benefits to the mother against
Rx LAMOTRIGINE the risks to the fetus; increased risk of isolated cleft
palate or cleft lip deformity with first trimester exposure);
Oral: 50 mg and 100 mg tablet lactation (monitor infant for possible adverse effects).

Lamotrigine is a synthetic phenyltriazine anticonvulsant and SKILLED TASKS. May impair ability to perform tasks, which
mood stabilizer used in seizures and bipolar depression. require mental alertness, like driving or operating
It blocks the open channel conformation of voltage- machinery.
sensitive sodium channels and decreases the release of
glutamate and aspartate.
Adverse Drug Reactions:
Indication: Antiepileptic drug of choice for pregnant Common or Less Common: Aggression, ataxia, arthralgia,
patients. agitation, blurred vision, back pain, diarrhea, dizziness,
drowsiness, diplopia, dry mouthm, headache, nausea,
Dose: vomiting, insomnia, nystagmus.
Seizures, by mouth, ADULT and CHILD >12 years, weeks 1 Rare: conjunctivitis
and 2: initially 25 mg once daily at night; weeks 3 and 4:
50 mg once daily at night; week 5 onwards: increase by Drug Interactions:
50 mg daily every 1–2 weeks to a maintenance dose of Monitor closely with:
225–375 mg daily in 2 divided doses; CHILD 2–12 Enhances therapeutic effect of the following drugs:
years, weeks 1 and 2: 0.3 mg/kg daily in 1 or 2 divided CNS Depressants (central effects)
doses, rounded down to the nearest whole tablet; weeks Pramipexole, Ropinirole, Rotigotine (sedative effect)
3 and 4: 0.6 mg/kg daily in 2 divided doses, rounded
N

down to the nearest whole tablet; weeks 5 onwards: Increases metabolism of Lamotrigine:
increase dose every 1–2 weeks by 0.6 mg/kg daily, Carbamazepine, Rifampin
rounded to the nearest whole tablet to a maintenance
dose of 4.5–7.5 mg/kg daily (maximum daily dose, 300 Increases risk of adverse or toxic effects of Lamotrigine:
mg in 2 divided doses). [NOTE: In patients <30 kg, may Rufinamide (sleepiness and dizziness)
need to increase dose by as much as 50% based on Valproate (rash)
clinical response].
Increases risk of adverse or toxic effects of the following
Dose Adjustment: drugs:
Geriatric: Carbamazepine, Desmopressin
Select doses with caution. Start at the low end of the dosing SSRIs (psychomotor impairment)
range, reflecting greater frequency of decreased hepatic,
renal, or cardiac function, and of concomitant disease or Avoid concomitant use with:
other drug therapy. Decreases serum concentration of Lamotrigine:
Estrogen Derivatives, Estrogen-containing Products,
Renal Impairment: Mefloquine, UGT Inducers, UGT Substrates
Reduce maintenance dose in patients with significant
impairment. Decreases serum concentration of Progestins
(Contraceptive)
Hepatic Impairment:
In moderate and severe impairment without ascites, reduce Enhances therapeutic effect of Olanzapine (sedative effect)
maintenance doses by 25%.
In severe impairment with ascites, reduce maintenance Increases serum concentration of Lamotrigine:
dose by 50%. UGT Inhibitors

Precautions: Increases serum concentration of the following drugs:

Organic Cation Transporter 2 Substrates, Procainamide
WARNING: Serious skin rashes. Can cause serious
rashes requiring hospitalization and Reduces therapeutic effect of Lamotrigine:
discontinuation of treatment, including SJS. Nearly Mefloquine
all cases of life-threatening rashes occurred within
2–8 weeks of treatment initiation. Administration: May be taken with or without food.

Aseptic meningitis; blood dyscrasias (e.g., neutropenia, Pregnancy Category: C

leukopenia, thrombocytopenia, pancytopenia, and
anemias); CNS depression; seizures; suicidal ideation. ATC Code: N03AX09

476
NERVOUS SYSTEM

Rx MAGNESIUM SULFATE See Magnesium Sulfate under I.V. Solutions Additives in

Chapter 2: Blood and Blood Forming Organs for other
Inj.:250 mg/mL (as heptahydrate), 2 mL and 10 mL information.
ampule (IM, IV)
250 mg/mL (as heptahydrate), 10 mL, 20 mL, and 50 Pregnancy Category: D
mL vial (IV)
500 mg/mL (as heptahydrate), 2 mL and 10 mL ATC Code: Not available
ampule (IM, IV)
Magnesium sulfate decreases levels of acetylcholine in
motor nerve terminals. It also acts on the myocardium by
decreasing the rate of SA node impulse formation and
Rx MIDAZOLAM
prolonging the conduction time.
Oral: 15 mg tablet
Indication: Drug of choice for the prevention of seizures in Inj.: 1 mg/mL, 5 mL ampule/vial (IM, IV)
women with severe preeclampsia, and for controlling 5 mg/mL, 1 mL, 2 mL, 3 mL, 5 mL, and 10 mL ampule
seizures or preventing their recurrence among eclamptic (IM, IV)
patients.
Midazolam is a short-acting benzodiazepine that binds to
Contraindications: Heart block; myocardial infarction; stero-specific receptors on the postsynaptic GABA
hypermagnesemia; deranged renal function; myasthenia neuron at several sites within the CNS. This results to an
gravis. enhanced inhibitory effect of GABA on neuronal
excitability.
Dose:
Prevention of recurrent seizures, by IV injection, ADULT, 4 g Indications: Management of seizures and status
as loading dose over 5–15 minutes followed by an IV epilepticus.
infusion of 1 g/hour as maintenance dose for at least 24
hours after the last seizure or delivery, whichever occurs Contraindications: Intrathecal or epidural injection; acute

N
later; narrow-angle glaucoma; concurrent use of potent
by deep IM injection, ADULT (special situations; when IV inhibitors of CYP3A4 (e.g., amprenavir, atazanavir,
lines are not available), 5 g into each buttock, then 5 g ritonavir)
every 4 hours into alternate buttocks for at least 24 [Oral]: Severe respiratory insufficiency; severe hepatic
hours after the last seizure or delivery; treat recurrent insufficiency; sleep apnea syndrome; myasthenia gravis;
seizure by further IV bolus of 2 g, or 4 g if body weight is use in children and adolescents.
over 70 kg.
Dose:
NOTE: Continue therapy until paroxysms cease. A serum NOTE: Individualize dose based on patient’s age, underlying
magnesium level of 6 mg/100mL is considered optimal diseases, and concurrent medications. Initial dose for
for seizure control. NOT to exceed 30–40 g per 24 hours. sedation should not exceed 2.5 mg in a healthy adult.
Consider reducing dose by 20–50% in patients receiving
Administration: Administer at a concentration not exceeding opioids or other CNS depressants.
20%. Dilute according to manufacturer’s instructions.
Seizures, by IM injection, ADOLESCENT and CHILD, 0.2
For IM route, solutions may need dilution prior to mg/kg (maximum dose, 6 mg), may repeat every 10–15
administration. 25% or 50% for adults or ≤20% for minutes.
children. Status epilepticus, convulsions >5 minutes or convulsions
occurring after intermittent seizures without regaining
For IV route, solutions must be diluted to ≤20% for IV consciousness for >5 minutes, by IM injection, ADULT,
infusion and may be administered by IV push, IVPB, or ADOLESCENT, and CHILD >40 kg, 10 mg once; or 0.2
continuous IV infusion. mg/kg once (maximum dose, 10 mg); ADOLESCENT and
CHILD 13–40 kg, 5 mg once.
For IV push, dilute first and do not administer faster than Status epilepticus, refractory, by IV injection, ADULT,
150 mg/minute. ADOLESCENT, CHILD, and INFANT, 0.2 mg/kg as loading
dose followed by a continuous IV infusion, 0.05–2 mg/kg
May be administered over 1–2 minutes in patients with per hour (0.83–33.2 micrograms/kg per minute), titrate
persistent pulseless VT or VF with known to cessation of electrographic seizures or burst
hypomagnesemia. Administer over 15 minutes in suppression; if patient experiences breakthrough status
patients with torsade de pointes. epilepticus while on the continuous infusion, administer
a bolus of 0.1–0.2 mg/kg and increase infusion rate by
Maximum rate of infusion is 1 g/hour in asymptomatic 0.05–0.1 mg/kg per hour (0.83–1.66 micrograms/kg
patients. For doses <6 g, infuse over 8–12 hours. For per minute) every 3–4 hours. [NOTE: Withdraw
larger doses, infuse over 24 hours. continuous infusion after a period of at least 24–48
hours of electrographic control; withdraw gradually to
If patient is severely symptomatic or has conditions such prevent recurrent status epilepticus]; or
as preeclampsia or eclampsia, more aggressive therapy ADOLESCENT, CHILD, and INFANT, 0.15–0.2 mg/kg
(≤4 g over 4-5 minutes) may be required. followed by a continuous infusion of 1 microgram/kg per

477
 NERVOUS SYSTEM

minute, titrated every 15 minutes by increments of 1 be increased with use; neonatal withdrawal symptoms
microgram/kg per minute until the cessation of seizures may occur within days to weeks after birth; “floppy infant
(maximum dose, 5 micrograms/kg per minute). syndrome” has been reported); lactation.

Dose Adjustment: SKILLED TASKS. May impair ability to perform tasks, which
Geriatric, Chronically Ill, or Debilitated Patients: require mental alertness, like driving or operating
Consider reducing dose by 20–50%. Initial doses should be machinery.
conservative. Initiate treatment at the low end of the
dosing range. Titrate subsequent doses slowly. Adverse Drug Reactions:
Common: Hypotension, drowsiness, over-sedation,
Renal Impairment: headache, seizure-like activity (children), pain and local
Lower doses may be needed. Patients with renal failure reactions at injection site, nausea, vomiting, myoclonic
receiving continuous infusion cannot adequately jerks (preterm infants), nystagmus, decreased tidal
eliminate the active hydroxylated metabolites, which may volume and/or decreased respiratory rate, apnea,
cause prolonged sedation. cough, physical and psychological dependence
(prolonged use), hiccups, paradoxical reaction (children).
Hepatic Impairment: Less Common: Acid taste, agitation, amnesia, bigeminy,
Lower doses as needed. bronchospasm, confusion, dyspnea, bradycardia,
emergence delirium, euphoria, hallucinations,
Precautions: hyperventilation, laryngospasm, excessive salivation,
WARNING: Respiratory Depression. Has been PVC, rash, tachycardia, wheezing, respiratory arrest (life-
associated with respiratory depression and threatening), cardiac arrest (life-threatening).
respiratory arrest, especially when used for
sedation in noncritical care settings. The immediate Drug Interactions:
availability of specific reversal agents (e.g., Monitor closely with:
flumazenil) and size appropriate equipment for Enhances therapeutic effect (CNS depressant effect) of
intubation and ventilation is highly recommended. Midazolam:
Monitor vital signs continuously during the recovery Brimonidine (Topical), Doxylamine, Dronabinol,
N

period. For deeply sedated patients, a dedicated Hydroxyzine, Magnesium Sulfate, Minocycline, Nabilone
individual, other than the practitioner performing
the procedure, should monitor the patient Enhances therapeutic effect of the following drugs:
throughout the procedure. Ethyl Alcohol, Mirtazapine (CNS depressant effect)
Pramipexole, Ropinirole, Rotigotine (sedative effect)
Sedation precaution. Administer over at least 2
minutes and allow an additional 2 or more minutes Increases risk of adverse or toxic effects of Midazolam:
to fully evaluate the sedative effect. Use 1 mg/mL Other CNS Depressants
formulation or dilution of the 1 mg/mL or 5 mg/mL Rufinamide (sleepiness and dizziness)
formulation to facilitate slower injection. Doses of
sedative medications in pediatric patients must be Increases risk of adverse or toxic effects of SSRIs
calculated on a mg/kg basis. Initial pediatric dose (psychomotor impairment)
for sedation, anxiolysis, or amnesia is dependent
on age, procedure, and route. Avoid concomitant use with:
Decreases serum concentration of Midazolam:
Neonates [injection]. Do NOT administer by rapid Dabrafenib, Mitotane
injection in neonates. Rapid IV injection (<2
minutes) in neonates has been associated with Enhances therapeutic effect of Midazolam:
seizures and severe hypotension, particularly when Droperidol, Methotrimeprazine [reduce dose by 50%
used concomitantly with fentanyl. Severe when used concomitantly], Tapentadol (CNS depressant
hypotension has also been observed in neonates effect) [start at one-third to one-half of the normal dose]
receiving a continuous infusion of midazolam who
then receive a rapid IV injection of fentanyl. Enhances therapeutic effect of the following drugs:
Buprenorphine, Hydrocodone [consider starting with a
Anterograde amnesia; CNS depression; paradoxical 20–30% lower dose when used concomitantly],
reactions (e.g., hyperactive behavior, particularly in Methadone, Methotrimeprazine [reduce dose by 50%
adolescent and pediatric patients; consider treatment when used concomitantly], Orphenadrine, Paraldehyde,
with flumazenil). Perampanel, Sodium Oxybate, Thalidomide, Zolpidem
Hypotension; hemodynamic events are more common in (CNS depressant effect)
pediatric patients or patients with hemodynamic
instability); heart failure. Increases risk of adverse or toxic effects of Midazolam:
Impaired gag reflex; renal impairment (half-life may be Olanzapine
prolonged); respiratory disease; fall risk; obesity (may
have prolonged action when discontinued). Increases risk of adverse or toxic effects of the following
Elderly; neonates (e.g., severe hypotension and seizures; drugs:
risk may be increased with concomitant fentanyl use). Azelastine (Nasal), Clozapine (CNS depressant effect)
Pregnancy; (teratogenic effects have been observed;
incidence of premature birth and low birth weights may

478
NERVOUS SYSTEM

Increases serum concentration of Midazolam: Dose:

Anti-hepaciviral Combination Products, Boceprevir, Seizures, by IV injection, ADULT, 75–125 mg per dose as a
Cobicistat, Fusidic Acid (Systemic), Idelalisib, 2.5% solution, repeated as needed; convulsions
Itraconazole, Ketoconazole (Systemic), Macrolide following use of local anesthetic may require 125–
Antibiotics [except Systemic Azithromycin, Fidaxomicin, 250 mg given over 10 minutes; dose depends on the
Spiramycin], Mifepristone [avoid midazolam during and amount of local anesthetic given and its convulsant
2 weeks following use], Protease Inhibitors, Telaprevir properties.

Increases serum concentration of Amodiaquine Administration: Administer by IV infusion. Avoid intra-arterial

administration.
Reduces therapeutic effect of Midazolam:
Theophylline Derivatives Avoid extravasation.

FOOD INTERACTION. Grapefruit juice may increase serum The patient must always lie supine as even a small
concentrations of midazolam.
overdose can cause hypotension.
Administration: NOTE: IV infusion of concentrated solutions (e.g., 5%) may
For IM route, administer by deep IM injection into a large cause thrombophlebitis. Repeated doses may result
muscle. in prolonged drug effect because of accumulation.
For IV route, administer by slow IV injection over at least
2–5 minutes at a concentration of 1–5 mg/mL or by IV See Thiopental Sodium under Anesthetics, General –
infusion via an infusion pump. For induction of Barbiturates, Plain in Chapter 10: Nervous System for
anesthesia, administer IV bolus over 5–30 seconds. other information.
For oral administration, swallow tablet whole with Pregnancy Category: C
adequate fluid.
ATC Code: N05CA19
Rebound or withdrawal symptoms may occur following
abrupt discontinuation or large decreases in dose.

N
Decrease doses slowly and monitor for withdrawal
symptoms. Rx TOPIRAMATE
NOTE: Midazolam 15 mg requires an S-2 license for
physicians to be able to prescribe it and an S-1 license Oral: 25 mg, 50 mg, and 100 mg tablet
with a triplicate prescription for pharmacists to dispense
it. Topiramate is a sulfamate-substituted monosaccharide that
potentiates GABA action and inhibits glutamate release
Pregnancy Category: D through interfering with both calcium and sodium
channels.
ATC Code: N05CD08
Indications: Initial monotherapy or adjunct therapy in
patients ≥2 years with partial onset or primary
generalized tonic-clonic seizures.
Rx THIOPENTAL SODIUM
Rx Dose:
Partial-onset seizure and primary generalized tonic-clonic
Inj.: 500 mg vial (IV) seizure, monotherapy, by mouth, ADULT and CHILD ≥10
1 g vial + 50 mL diluent (IV) years, initially 25 mg twice daily, may increase weekly by
50 mg daily up to 100 mg twice daily (week 4 dose), may
Thipental is an ultrashort-acting thiobarbiturate with further increase weekly by 100 mg daily up to the
anesthetic activity. It acts by binding to the chloride recommended dose of 200 mg twice daily;
CHILD 2 to <10 years, initially 25 mg once daily in the
site of the GABAA/chloride receptor complex, thereby
enhancing the inhibitory actions of GABAA in the brain. evening, may increase to 25 mg twice daily in week 2,
This leads to synaptic inhibition, decreased neuronal may further increase by 25–50 mg daily at weekly
excitability and induction of anesthesia, as well as intervals over 5–7 weeks up to the minimum
decreased glutamate responses. recommended maintenance dose; if additional seizure
control is needed and therapy is tolerated, may further
Indication: Treatment of convulsive states. increase weekly by 25–50 mg daily up to the maximum
recommended maintenance dose:
Contraindications: Variegate or acute intermittent
porphyria; absence of suitable veins for IV Minimum
Maximum
administration; status asthmaticus; dyspnea or Maintenance
Maintenance
respiratory obstruction; severe cardiovascular Weight Dose
Dose (in 2
disease or hypotension; Addison’s disease; hepatic (in 2
divided doses)
dysfunction; myxedema. divided doses)
≤11 kg 150 mg daily 250 mg daily

479
 NERVOUS SYSTEM

12–22 kg 200 mg daily 300 mg daily weakness, muscle spasm, leg pain, nephrolithiasis,
23–31 kg 200 mg daily 350 mg daily rhinitis, bronchitis, sinusitis, epistaxis, dyspnea, fever,
32–38 kg 250 mg daily 350 mg daily upper respiratory tract infection.
Less Common: Abnormal electroencephalogram, abnormal
≥39 kg 250 mg daily 400 mg daily
dreams, abnormal hair texture, acute myopia with
secondary angle-closure glaucoma, albuminuria, alcohol
Partial-onset seizure, primary generalized tonic-clonic intolerance, altered sense of smell, angina pectoris,
seizure, or Lennox-Gastaut syndrome, adjunct therapy, apraxia, AV block, blepharoptosis, bone marrow
by mouth, ADULT, initially 25 mg once or twice daily for 1 depression, brain disease, bullous rash, cerebellar
week, may increase weekly by 25–50 mg daily until syndrome, chloasma, deep vein thrombosis,
response; usual maintenance dose, 100–200 mg twice dehydration, delirium, delusions, dyskinesia, dystonia,
daily for partial-onset seizures or 200 mg twice daily for diabetes mellitus, enlargement of abdomen, ejaculatory
primary generalized tonic-clonic seizures; ADOLESCENT disorder, erythema multiforme, hepatitis,
<17 years and CHILD ≥2 years, initially 25 mg once daily hyperchloremic metabolic acidosis (non-anion gap),
(1–3 mg/kg daily) in the evening for 1 week, may hepatic failure, hyperesthesia, hyperglycemia,
increase every 1–2 weeks in increments of 1–3 mg/kg hyperlipidemia, hypernatremia, hypocholesterolemia,
daily to the recommended dose of 5–9 mg/kg daily in 2 hypothermia (with valproic acid, with or without
divided doses. hyperammonemia), hyperthermia, hypohidrosis,
hypocalcemia, hyponatremia, hypotension, increased
Dose Adjustment: libido, impotence, iritis, lymphadenopathy,
Geriatric: lymphocytosis, maculopathy, lymphocytopenia, melena,
An initial dose of 25 mg daily may be recommended, mydriasis, manic reaction, neuropathy, nipple discharge,
followed by incremental increases of 25 mg at weekly oliguria, orthostatic hypotension, ostealgia, pancreatitis,
intervals until an effective dose is reached. pancytopenia, paranoia, pemphigus, phlebitis,
photophobia, polycythemia, polyuria, psychosis,
Renal Impairment: pulmonary embolism, renal pain, scotoma, skin
In CrCl <70 mL/minute, administer 50% of the dose and photosensitivity, SJS, stomatitis, strabismus, suicidal
titrate more slowly. ideation, suicidal tendencies, tongue edema, tongue
N

In hemodialysis, supplemental dose may be needed. paralysis, toxic epidermal necrolysis, upper motor
neuron lesion, urinary retention, urticaria, vasodilation,
Precautions: vasospasm, visual field defect, voice disorder,
WARNING: Hazardous agent. Use appropriate xerophthalmia.
precautions for handling and disposal.
Drug Interactions:
CNS effects (e.g., cognitive dysfunction, psychiatric Monitor closely with:
disturbances, and sedation); paresthesia, dizziness, and Decreases excretion of the following drugs:
ataxia); suicidal ideation; hyperammonemia or Memantine, Quinidine
encephalopathy; oligohidrosis or hyperthermia.
Metabolic acidosis (hyperchloremic non-anion gap Enhances therapeutic effect of Topiramate:
metabolic acidosis; metabolic acidosis); ophthalmic Brimonidine (Topical), Doxylamine, Dronabinol,
effects (acute myopia and secondary angle-closure Hydroxyzine, Magnesium Sulfate, Minocycline, Nabilone
glaucoma); visual field defects; renal calculus (e.g., (CNS depressant effect)
kidney stones); renal and hepatic impairment (clearance
may be reduced); eating disorders (may develop or Enhances therapeutic effect of the following drugs:
exacerbate anorexia nervosa and bulimia). Amitriptyline, Mirtazapine (CNS depressant effect)
Elderly (use with caution). Pramipexole, Ropinirole, Rotigotine (sedative effect)
Pregnancy (hypospadia cleft lip or palate with use during
pregnancy); lactation (use with caution). Increases risk of adverse or toxic effects of Topiramate:
Anticholinergics
SKILLED TASKS. May impair ability to perform tasks, which Loop Diuretics (hypokalemic effect)
require mental alertness, like driving or operating Other CNS Depressants
machinery. Rufinamide (sleepiness and dizziness)

Adverse Drug Reactions: Increases risk of adverse or toxic effects of the following
Common: Flushing, chest pain, paresthesia, memory drugs:
impairment, drowsiness, dizziness, lack of SSRIs (psychomotor impairment)
concentration, mood disorder, depression, ataxia, Primidone (osteomalacia and rickets)
insomnia, cognitive dysfunction, anxiety, hypoesthesia, Valproate Products
nervousness, UTI, psychomotor retardation, confusion,
behavioral problems, hypertonia, vertigo, alopecia, Avoid concomitant use with:
pruritus, skin rash, acne vulgaris, increased gamma- Decreases serum concentration of Topiramate:
glutamyl transferase, intermenstrual bleeding, weight Carbamazepine, Mefloquine
loss, dysgeusia, constipation, gastritis, xerostomia,
anorexia, diarrhea, GERD, decreased libido, urinary Decreases serum concentration of the following drugs:
frequency, vaginal hemorrhage, cystitis, urinary Aripiprazole [double dose when used concomitantly;
incontinence, dysuria, anemia, viral infection, infection, reduce dose to 10–15 mg daily when topiramate is

480
NERVOUS SYSTEM

discontinued], Contraceptives [Estrogens and

Progestins], Ulipristal ANTI-PARKINSON DRUGS

Enhances therapeutic effect (CNS depressant effect) of

Topiramate: ANTICHOLINERGICS
Droperidol, Ethyl Alcohol, Methotrimeprazine [reduce
midazolam dose by 50% when used concomitantly]
Tapentadol [start at one-third to one-half of the normal
Rx BIPERIDEN
dose]
Oral: 2 mg tablet (as hydrochloride)
Enhances therapeutic effect (CNS depressant effect) of the Inj.: 5 mg/mL (as lactate), 1 mL ampule (IM, IV)
following drugs:
Buprenorphine, Hydrocodone [consider starting with a A tertiary-amine, centrally-acting anticholinergic drug, used
20–30% lower dose when used concomitantly], in the management of Parkinsonism and is effective for
Methotrimeprazine [reduce midazolam dose by 50% the treatment of acute EPS.
when used concomitantly], Orphenadrine, Paraldehyde,
Perampanel, Sodium Oxybate, Thalidomide, Zolpidem Indication: Management of drug-induced extrapyramidal
symptoms (except tardive dyskinesia) by phenothiazines,
Increases risk of adverse or toxic effects of Topiramate: butyrophenones or reserpine; adjunctive treatment of
Other Carbonic Anhydrase Inhibitors (acid-base post-encephalitic, idiopathic or arteriosclerotic
disorders; kidney stones; metabolic acidosis) Parkinson’s disease.
Salicylates
Thiazide Diuretics (hypokalemic effect) Contraindications: Angle-closure glaucoma; untreated
urinary retention; prostatic hypertrophy; myasthenia
Increases risk of adverse or toxic effects of the following gravis; and GI obstruction or atony; toxic megacolon.
drugs:
Azelastine, Nasal (CNS depressant effect) Dose:
Metformin Parkinsonism, by mouth, ADULT, 2 mg every 8 or 6 hours,

N
Salicylates (salicylate toxicity) with initial dose of 0.5–1 mg daily, gradually increase by
0.5 mg every 5–6 days until optimum dose (maximum,
Increases serum concentration of Topiramate: 16 mg daily).
Ethyl Alcohol, Thiazide Diuretics Drug-induced extrapyramidal disorders, by mouth, ADULT,
1–4 mg daily, in single or 2 divided doses; CHILD >3
Reduces therapeutic effect of Topiramate: years, 0.02–0.05 mg/kg per dose every 8–12 hours; by
Mefloquine IM injection or slow IV infusion, ADULT, 10 to 20 mg once
daily.
Reduces therapeutic effect of the following drugs:
Contraceptives, Estrogens and Progestins (contraceptive Dose Adjustment:
failure is possible) Geriatric:
Methenamine Start with low dose and increase slowly to the lowest
effective dose.
FOOD INTERACTION. Ketogenic diet may increase the
possibility of acidosis and/or kidney stones. Hepatic Impairment:
For mild-to-moderate hepatic impairment, dose reduction is
Administration: May be taken with or without food. warranted.
Administer in divided doses. Do NOT crush, break, or For severe impairment, the patient should be referred to a
chew tablets due to bitter taste. specialist.

Do NOT abruptly discontinue therapy because of the Precautions:

possibility of increasing seizure frequency. Taper dosage Avoid abrupt withdrawal in Parkinson’s disease (to prevent
gradually to prevent rebound effects and to minimize the acute exacerbation); tardive dyskinesia; fever or high
potential of increased seizure frequency, unless safety ambient temperature (hyperthermia).
concerns require a more rapid withdrawal. Heart diseases e.g., arrhythmias, coronary heart disease,
and heart failure (may be exacerbated); hepatic
Pregnancy Category: D impairment.
Inflammatory bowel disease (paralytic ileus); dementia
ATC Code: N03AX11 (anticholinergics are best avoided; may worsen
symptoms and antagonize therapeutic effects of
anticholinesterases); GERD (may be aggravated).
Elderly (more sensitive to anticholinergic adverse effects;
confusion may be precipitated or worsened); children
(more susceptible to anticholinergic side effects).
Pregnancy; lactation (use with caution).

481
 NERVOUS SYSTEM

SKILLED TASKS. May impair ability to perform tasks, which DOPAMINERGIC AGENTS
require mental alertness, like driving or operating
machinery.
Rx BROMOCRIPTINE
Adverse Drug Reactions:
Common: Blurred vision, confusion, constipation,
Oral: 2.5 mg tablet (as mesilate)
decreased sweating, disorientation, dizziness,
drowsiness, flushing, lightheadedness, dryness of
Bromocriptine is a semisynthetic ergot alkaloid and
mouth, mydriasis, nausea, nervousness, reduced
dopamine agonist with high affinity for the D2 receptor
bronchial secretions, thirst, urinary hesitancy and
and weak α-agonist activity. The dopamine receptor
retention, vomiting.
agonist activity also causes inhibition of prolactin-
Less Common or Rare: Agitation, angle-closure glaucoma,
secreting cells in the anterior pituitary for the treatment
arrhythmias, delirium, delusions, diplopia, excitement,
of hyperprolactinemia and for reducing tumor sizes in
hallucinations, epigastric distress, hypotension, memory
prolactin- and growth hormone-secreting pituitary
impairment, muscular cramping and weakness,
adenomas.
palpitations, paralytic ileus, paresthesia, rash,
psychiatric disturbances, urticaria, bradycardia followed
Indication: Management of hyperprolactinemia.
by tachycardia.
Contraindications: Uncontrolled hypertension; eclampsia;
Drug Interactions:
preeclampsia; pregnancy-induced hypertension; post-
NOTE: Concomitant use of two or more drugs having
partum patients with coronary artery disease or other
antimuscarinic effects can increase side-effects, such as
severe cardiovascular conditions.
constipation, urine retention and dryness of mouth, and
can also lead to confusion especially in the elderly.
Dose:
Monitor closely with: Hyperprolactinemia, by mouth, ADULT, initially 0.5 to 2.5 mg
Enhances therapeutic effect of Fluphenazine once daily at bedtime to increase tolerance; slowly
(antimuscarinic effects) increase the daily dose by 1.25 to 2.5 mg every 1–2
weeks up to an average of 20–30 mg once daily
N

Increases risk of adverse or toxic effects of Biperiden: (maximum, 100 mg once daily).
Antipsychotic Drugs, e.g., Phenothiazines, Haloperidol
(masking of extrapyramidal symptoms; tardive Dose Adjustment:
dyskinesia; long-term therapy) Hepatic Impairment:
May require dose adjustment. Undergoes extensive hepatic
Reduces therapeutic effect of the following drugs: metabolism. Use with caution.
Isosorbide Dinitrate, Sublingual (failure to dissolve under
the tongue owing to dry mouth) Precautions:
Cardiac valvular fibrosis; cardiovascular effects (e.g.,
Avoid concomitant use with: symptomatic hypotension; seizures, hypertension, MI,
Decreases bioavailability of Levodopa and stroke).
Visual or auditory hallucinations; impulse control disorders;
Enhances therapeutic effect of Alcohol (CNS depression) sedation (e.g., sudden sleep onset and somnolence);
dementia; psychosis.
Increases risk of adverse or toxic effects of Biperiden: Melanoma; pleural or retroperitoneal fibrosis (prolonged
Anticholinergics (including central anticholinergic and high-dose daily use); peptic ulcer disease (severe GI
delirium) bleeding; may be fatal).
Drugs with Anticholinergic Effects (including central Acromegaly (digital vasospasm); diabetic ketoacidosis;
anticholinergic delirium) macroadenomas; pituitary irradiation; prolactin-
secreting adenomas.
Reduces therapeutic effect of Biperiden: Elderly (concomitant diseases or drug therapy may
Anticholinesterases, e.g., Neostigmine, Pyridostigmine complicate therapy).
Cisapride Pregnancy (a pregnancy test every 4 weeks is
recommended as long as no menses occur); lactation.
Reduces therapeutic effect of the following drugs:
Haloperidol Adverse Drug Reactions:
Metoclopramide Common: Hypotension, Raynaud’s phenomenon, syncope,
vasospasm (digital), dizziness, fatigue, headache,
Administration: Should be taken with food. drowsiness, hypoglycemia, nausea, lightheadedness,
constipation, anorexia, GI hemorrhage, abdominal
Do NOT discontinue abruptly to prevent acute cramps, dyspepsia, diarrhea, vomiting, xerostomia,
exacerbation. Gradually taper dose. increased susceptibility to infection weakness,
amblyopia, rhinitis, flu-like symptoms, nasal congestion,
Pregnancy Category: C sinusitis.
Less Common: Abdominal distress, acquired valvular heart
ATC Code: N04AA02 disease, alopecia, anxiety, ataxia, blepharospasm,
blurred vision, bradycardia, cardiac arrhythmia,
cerebrovascular accident (postpartum), cold extremities,

482
NERVOUS SYSTEM

cold intolerance, confusion, constrictive pericarditis, Dapoxetine, Other Serotonin Modulators [except
delusions, depression, dyskinesia, dysphagia, dyspnea, Tedizolid]
epileptiform seizures, ergot alkaloids toxicity,
erythromelalgia, GI ulcer, hallucination, heavy Increases risk of adverse or toxic effects of the following
headedness, MI (postpartum), hypersensitivity reaction, drugs:
hypertension (postpartum), increased cerebrospinal Dapoxetine, Tizanidine
fluid pressure, increased libido, insomnia, lassitude, Serotonin Modulators [except Tedizolid] (serotonin
lethargy, muscle cramps, narcolepsy, nervousness, syndrome)
nightmares, on­off phenomenon, pallor, paranoia,
paresthesia, pericardial effusion, peripheral edema, Increases serum concentration of Bromocriptine:
pleural effusion, psychomotor agitation, psychosis, Anti-hepaciviral Combination Products, CYP3A4
pulmonary fibrosis, retroperitoneal fibrosis, pleurisy, Inhibitors, Fusidic Acid (Systemic), Idelalisib, Macrolide
seizure (postpartum), skin mottling, skin rash, status Antibiotics [except Systemic Azithromycin, Fidaxomicin,
epilepticus (postpartum), sleep disorder, tachycardia, Spiramycin], Mifepristone [if concomitant use cannot be
tingling of the ears, tinnitus, transient blindness, urinary avoided, minimize Bromocriptine doses], Nitroglycerin,
frequency, urinary incontinence, vasodepressor syncope, Protease Inhibitors
urinary retention, ventricular tachycardia, vertigo, visual
disturbance. Increases serum concentration of the following drugs:
Tizanidine [if concomitant use cannot be avoided, initiate
Drug Interactions: at 2 mg and increase in 2–4 mg increments based on
Monitor closely with: patient response]
Enhances therapeutic effect (hypoglycemic effect) of
Bromocriptine: Reduces therapeutic effect of Bromocriptine:
Alpha-Lipoic Acid, Androgens [except Danazol], Amisulpride, Antipsychotic Agents (First Generation /
Hypoglycemia-Associated Agents, MAO Inhibitors Typical), Antipsychotic Agents (Second Generation /
[Linezolid, Tedizolid], Pegvisomant, Quinolone Antibiotics Atypical)
e.g., Ciprofloxacin, Salicylates e.g. Aspirin
Reduces therapeutic effect of the following drugs:

N
Enhances therapeutic effect of the following drugs: Amisulpride, Antipsychotic Agents (First Generation /
5HT3 Antagonists e.g., Ondansetron (serotonergic effect) Typical)
MAO Inhibitors [except Linezolid, Tedizolid] (hypotensive Nitroglycerin (vasodilatory effect)
effect)
Tedizolid (serotonergic effect) Administration: Administer with food to decrease GI
distress.
Increases risk of adverse or toxic effects of Bromocriptine:
Ethyl Alcohol, Methylphenidate Do NOT discontinue abruptly to prevent acute
Quinolone Antibiotics (loss of blood sugar control) exacerbation. Discontinue gradually over a period of 1
week.
Increases risk of adverse or toxic effects of the following
drugs: Pregnancy Category: B
5HT3 Antagonists (serotonin syndrome), Tedizolid
(serotonin syndrome) ATC Code: N04BC01
Bupropion, Ethyl Alcohol, Methylphenidate
MAO Inhibitors [Linezolid] (orthostatic hypotensive)
Metoclopramide (serotonin syndrome; neuroleptic
malignant syndrome) Rx LEVODOPA + CARBIDOPA

Reduces therapeutic effect of Bromocriptine: Oral: 100 mg levodopa + 25 mg carbidopa per tablet
Hyperglycemia-Associated Agents, Metoclopramide, 250 mg levodopa + 25 mg carbidopa per tablet
Thiazide Diuretics 200 mg levodopa + 50 mg carbidopa extended-
Quinolone Antibiotics (loss of blood sugar control) release tablet

Avoid concomitant use with: Levodopa is an aromatic amino acid and the naturally-
Enhances therapeutic effect of Bromocriptine: occurring form of dihydroxyphenylalanine. It is the
Beta Blockers e.g., Propranolol, Serotonin 5­HT1D immediate precursor to dopamine and can pass through
Receptor Agonists (vasoconstricting effect) the blood-brain barrier, where it is immediately taken up
by dopaminergic neurons and converted into dopamine.
Enhances therapeutic effect of the following drugs: It is administered with carbidopa, a peripheral
Alpha / Beta Agonists, Alpha1 Agonists (hypertensive decarboxylase inhibitor that prevents gut metabolism of
effect; vasoconstricting effect) levodopa, thereby increasing dopamine in the CNS.
Serotonin 5­HT1D Receptor Agonists (vasoconstricting
effect) Indication: Management of Parkinson’s disease, including
idiopathic parkinsonism, post-encephalitic
Increases risk of adverse or toxic effects of Bromocriptine: parkinsonism, and symptomatic parkinsonism.
Beta Blockers (vasoconstricting effect)

483
 NERVOUS SYSTEM

Contraindications: Narrow angle glaucoma; history of edema, reddish discoloration of the urine and other body
melanoma. fludis, weakness, weight changes.
Rare: Abdominal pain, activation of malignant melanoma,
Dose: agitation, alopecia, blurred vision.
Parkinson’s disease, by mouth, ADULT,
Immediate-release, initially 300 mg/75 mg daily in 3 Drug Interactions:
divided doses, may be increased by 100 mg/25 mg every Monitor closely with:
other day (maximum, 800 mg/200 mg daily in divided Enhances therapeutic effect of Blood Pressure Lowering
doses); Agents (hypotensive effect)
Extended-release, initially 400 mg/100 mg daily in 2
divided doses, may be increased by 100 mg/25 mg to Increases absorption of Levodopa + Carbidopa:
200 mg/50 mg every other day (maximum, 2,450 TCAs
mg/612.5 mg daily in divided doses).
Increases bioavailability of Levodopa + Carbidopa:
Precautions: Antacids, Anticholinergics, TCAs e.g., Amytriptylline
Abnormal thinking or behavioral changes e.g. aggresive
behavior, agitation, confusion, delirium, disorientation, Increases risk of adverse or toxic effects of Levodopa +
delusion, paranoid ideation and psychotic like behavior; Carbidopa:
hallucinations (typically presents shortly after initiation of Biperiden (choreic movements or dyskinesias),
therapy; may require dose reduction); psychotic Methylphenidate, Papaverine (hypotensive effect),
disorders (use with extreme caution; at risk of Sapropterin
exacerbating psychosis; depression with concomitant
suicidal tendencies). Increases risk of adverse or toxic effects of the following
Dyskinesias (may require dosage reduction); impulse drugs:
control disorders. Antihypertensives (orthostatic hypotension)
Leukopenia; melanoma (monitor closely; perform periodic Bupropion
skin examinations). Duloxetine (hypotensive effect)
Neuroleptic malignant syndrome (rapid dose reduction, or MAOIs (hypertensive reactions)
N

abrupt withdrawal; monitor closely for this reaction; Selegiline (severe orthostatic hypotension)
discontinue immediately if signs and symptoms arise);
peripheral neuropathy. Reduces diagnostic effect of Macimorelin
Cardiovascular disease (use with caution); orthostatic
hypotension (monitor closely for signs and symptoms of Reduces therapeutic effect of Levodopa + Carbidopa:
postural hypotension, especially during dose escalation). Benzodiazepines, Dopamine Receptor Antagonists,
Somnolence (evaluate for factors that may increase these Fosphenytoin, Isoniazid
risks such as concomitant sedating medications, and the Methionine [with large doses], Metoclopramide,
presence of sleep disorders; monitor for drowsiness or Multivitamins / Fluoride with ADE [pyridoxine when used
sleepiness). in the absence of a dopa decarboxylase inhibitor],
Endocrine disease (use with caution in patients with Multivitamins / Minerals e.g., ADEK, Folate, Iron, (Oral),
endocrine disease and when interpreting plasma or Multivitamins / Minerals with AE, no Iron [pyridoxine
urine catecholamine levels; falsely diagnosed when used in the absence of a dopa decarboxylase
pheochromocytoma). inhibitor], Papaverine, Phenytoin, Pyridoxine, Spiramycin
Glaucoma (use with caution; monitor IOP carefully);
respiratory disease. Reduces therapeutic effect of Antipsychotics
Peptic ulcer disease (use with caution); hepatic and renal
impairment.
Elderly (use with caution; may be more sensitive to CNS Avoid concomitant use with:
effects, e.g., hallucinations). Increases risk of adverse or toxic effects of Non-selective
Pregnancy (safety has not been established); lactation (can MAOIs (hypertensive crisis)
cause reduced serum prolactin levels, resulting in
reversible suppression of lactation). Administration: Should be taken on an empty stomach.

SKILLED TASKS. May impair ability to perform tasks, which Pregnancy Category: C
require mental alertness, like driving or operating
machinery. ATC Code: N04BA02

Adverse Drug Reactions:

Common: Abnormal dreams, anorexia, anxiety, arrhythmias,
chorea, confusion, dementia, depression, dizziness,
drowsiness, dry mouth, dyskinesia, dystonia, euphoria,
fatigue, insomnia, nausea, palpitations, postural
hypotension, psychosis, syncope, taste disturbances,
vomiting.
Less Common: Ataxia, chest pain, constipation, diarrhea,
dysphagia, flatulence, hand tremor, hoarseness,
hypersalivation, hypertension, malaise, muscle cramps,

484
NERVOUS SYSTEM

loss, diarrhea, xerostomia, abdominal pain, nausea,

Rx SELEGILINE dyspepsia, constipation, vomiting, dysgeusia, flatulence,
anorexia, gastroenteritis, urinary retention,
Oral: 5 mg tablet (as hydrochloride) dysmenorrhea, sexual disorder, UTI, urinary frequency,
uterine hemorrhage, bruise, leg cramps, myalgia,
Selegeline is a phenethylamine selective MAO-B inhibitor tinnitus, pharyngitis, sinusitis, bronchitis, cough.
used as an adjunct to levodopa in managing Parkinson’s Less Common: Agitation, ankle edema, arrthymias, anxiety,
disease. It increases dopaminergic activity by intervening dyspnea, angina, blurred vision, loss of appetite,
w/ the reuptake of dopamine at the synapse. It also palpitation, micturition difficulties, leukocytopenia,
irreversibly inhibits monoamine oxidase (MAO)-B which is postural hypotension, skin reactions, thrombocytopenia,
involved in the metabolism of dopamine in the brain. supraventricular tachycardia.
Rare: Activation of suicidal ideation and behavior.
Indication: Adjunctive therapy for the symptomatic
treatment of parkinsonian syndrome. Drug Interactions:
Monitor closely with:
Contraindications: Pheochromocytoma; elective surgery Enhances therapeutic effect of Selegiline:
requiring general anesthesia; active duodenal Dihydrocodeine, Fentanyl, Metaxalone, Opioids,
ulceration, active gastric ulceration, avoid or use with Oxycodone, Tapentadol, Oxcarbazepine (serotonergic
great caution in postural hypotension (when used in effect)
combination with levodopa). Diphenoxylate (hypertensive effect)
Pheniramine (anticholinergic effect)
Dose: Spinal Anesthesia (combined hypotensive effects)
Parkinson’s disease, by mouth, ADULT, initially 2.5 mg twice
daily; slowly increase to 5 mg twice daily and reduce the Enhances therapeutic effect of the following drugs:
dose of levodopa after 2–3 days; avoid doses greater Alpha / Beta Agonists (Indirect-Acting), Alpha1 Agonists,
than 10 mg daily. Amphetamines, Dopamine, Epinephrine, Bupropion,
Norepinephrine (hypertensive effect)
Dose Adjustment: Anticholinergics, Pizotifen (anticholinergic effects)

N
Geriatric: Blood Glucose Lowering Agents (hypoglycemic effect)
Increase doses with caution. Blood Pressure Lowering Agents, Pindolol (hypotensive
effect)
Renal Impairment: CNS depressants (sedation and hypotension)
Use with caution. May require a lower dose to prevent Mequitazine (anticholinergic effect)
accumulation in the plasma. SSRIs, Serotonin Modulators, SNRIs, TCAs (serotonergic
effect)
Hepatic Impairment:
May require a lower dose. Increases risk of adverse or toxic effects of Selegiline:
Antipsychotics (serotonin syndrome)
Precautions:
Increases risk of adverse or toxic effects of Selegiline:
WARNING: Antidepressants increase the risk of
Antipsychotics, Second Generation / Atypical, Spinal
suicidal thoughts and behaviors in pediatric and
Anesthesia, Blood Pressure Lowering Agents (Topical)
young adult patients. Closely monitor for clinical
(hypotensive effect)
worsening and for emergence of suicidal thoughts
Buprenorphine, Cerebrolysin, Chlorphenesin,
and behaviors.
Carbamate, COMT Inhibitors, Dapoxetine, Ethyl Alcohol,
Oxymorphone, Tryptophan, Heroin, Hydrocodone,
Blood pressure effects (e.g., hypertension and orthostatic Hydromorphone
hypotension); CNS depression; dyskinesia; impulse Buspirone (blood pressure elevations)
control disorders. Fentanyl, Opioids, Oxycodone (serotonin syndrome)
Melanoma; psychosis; serotonin syndrome; hepatic and Disulfiram (acute delirium)
renal impairment; hypoglycemia; surgery patients. L-tryptophan, L–tyrosine, Phenylalanine (hypertensive
Elderly (orthostatic hypotension when titrating dose); crisis)
children (monitor for activation of suicidal ideation). Levodopa (hypertensive reactions)
Pregnancy (use is not recommended, especially during the Tapentadol (adverse cardiovascular effects; serotonin
first trimester); lactation. syndrome)
SKILLED TASKS. May impair ability to perform tasks, which Increases risk of adverse or toxic effects of the following
require mental alertness, like driving or operating drugs:
machinery. Antipsychotics (neuroleptic malignant syndrome)
Atomoxetine (neurotoxic / central effect)
Adverse Drug Reactions: Atropine (Ophthalmic), Methylphenidate,
Common: hypertension, hypotension, chest pain, Tetrahydrozoline (Nasal) (hypertensive effect)
peripheral edema, body pain, confusion, hallucination, Beta2 Agonists, Codeine, Domperidone, Lithium,
vivid dream, lethargy, abnormality in thinking, agitation, Methyldopa, Moclobemide, Morphine, Serotonin
amnesia, paresthesia, headache, dizziness, insomnia, Reuptake Inhibitor or Antagonists
skin rash, acne vulgaris, diaphoresis, pruritus, weight Hypotension-Associated Agents (hypotensive effect)

485
 NERVOUS SYSTEM

Iohexol, Iomeprol, Iopamidol (seizures) OTHER DRUGS FOR PARKINSONISM

Metoclopramide (serotonin syndrome; neuroleptic
malignant syndrome)
Mirtazapine (neurotoxic effect)
Rx DIPHENHYDRAMINE
Reserpine (paradoxical effects, e.g., excitation,
hypertension) Oral: 25 mg and 50 mg capsule (as hydrochloride)
SSRIs, Serotonin Modulators, SNRIs, TCAs (serotonin 12.5 mg/5 mL, 30 mL and 60 mL syrup
syndrome) Inj.: 50 mg/mL (as hydrochloride), 1 mL ampule (IM, IV)

Reduces diagnostic effect of I123 Diphenhydramine is a monoethanolamine-derived, first-

generation H1 receptor antagonist, which exhibits anti-
Reduces therapeutic effect of Selegiline: muscarinic and pronounced sedative property, with low
Domperidone incidence of GI side effects.

Reduces therapeutic effect of Domperidone Indications: Management of Parkinsonism; drug-induced

dystonic reaction (Extrapyramidal Syndrome).
Avoid concomitant use with:
Enhances therapeutic effect of Selegiline: Contraindications: Acute asthma; neonates or premature
Alcohol (central effects) infants (increased susceptibility to antimuscarinic
Tyramine (additive sympathomimetic effects) effects); breastfeeding; use of the parenteral form as a
local anesthetic.
Increases risk of adverse or toxic effects of Selegiline:
Alcohol, Carbamazepine Dose:
Antidepressants, Ginseng, Linezolid, MAOB Inhibitors, Parkinsonism, by mouth, ADULT, 25–50 mg 3 or 4 times
Methadone, Methylene Blue, Sibutramine, daily and reassess need for continued administration
Propoxyphene (serotonin syndrome) after 1–2 weeks;
Dextromethorphan, Meperidine, Non-selective MAOIs by IV infusion, ADULT, 10–50 mg per dose at a rate not
(severe agitation, stupor, muscle rigidity, elevated exceeding 25 mg/minute, may use doses up to 100
N

temperatures, hallucinations, death) mg/dose (maximum, 400 mg daily); CHILD ≥12 years, 5
Sympathomimetics (severe agitation, stupor, muscle mg/kg every 24 hours; or 150 mg every 24 hours at a
rigidity, elevated temperatures, hallucinations, rate not exceeding 25 mg/minute (maximum daily dose,
hypertensive crisis, death) 300 mg divided into 4 doses);
Tramadol (serotonin syndrome; seizures) by deep intramuscular injection, ADULT, 10–50 mg per
dose (maximum daily dose, 400 mg); CHILD ≥12 years,
Increases risk of adverse or toxic effects of the following 5 mg/kg every 24 hours; or 150 mg every 24 hours
drugs: (maximum daily dose, 300 mg divided into 4 doses).
Diuretics, Guanethidine (combined hypotensive effects) Drug-induced dystonic reaction (extrapyramidal syndrome),
by IM or IV injection, ADULT, 25–50 mg single dose, may
Increases serum concentration of Selegiline: repeat in 20–30 minutes if necessary; CHILD, 0.5–1
Carbamazepine mg/kg per dose.

Administration: Should be taken with food. Dose Adjustment:

Geriatric:
Do NOT discontinue abruptly. Gradually taper dose. If used, consider lower doses.
Use only smallest effective dose, 25 mg oral or IV every 8–
When discontinuing selegiline, wait 2 weeks (wash-out 12 hours due to usual association with reduced
period) before starting another antidepressant to allow clearance of drug.
enough time for the body to regenerate MAO enzyme.
Hepatic Impairment:
NOTE: Abrupt discontinuation or interruption of In severe impairment, refer patient to a specialist.
antidepressant therapy has been associated with a
discontinuation syndrome, which may resemble Precautions:
neuroleptic malignant syndrome; symptoms may include WARNING: May cause sedation. Serious adverse drug
elevated temperature, muscular rigidity, altered interactions are quite common, potentially fatal in
consciousness and autonomic instability. some. Antihistamines can cause hypersensitivity
reactions themselves.
Pregnancy Category: C
CNS depression (caution in performing tasks requiring
ATC Code: N04BD01 mental alertness); prostatic hypertrophy, urinary
retention, susceptibility to angle-closure glaucoma, and
pyloroduodenal obstruction; asthma; thyroid
dysfunction; cardiovascular disease; epilepsy.
Elderly (associated with reduced drug clearance, and
increased risk of confusion, dryness of mouth,
constipation or other anticholinergic effects, and

486
NERVOUS SYSTEM

toxicity); children (may cause excitation; more disorder; bipolar disorder; autism-related irritability;
susceptible to side-effects). Tourette syndrome.
Pregnancy (use during the latter part of third trimester may
cause irritability, paradoxical excitability, and tremor in Dose:
neonates). Acute mania or mixed mania, by mouth, ADULT, initially 10–
15 mg once daily, slowly titrate dose based on efficacy
Adverse Drug Reactions: and tolerability (maximum, 30 mg once daily), CHILD ≥10
Common: Anxiety, blurred vision, constipation, cough, years, initially 2 mg once daily for 2 days, increase to 5
diarrhea, dizziness, dryness of mouth, nose and throat, mg once daily for 2 days, further increase to a target dose
epigastric discomfort, euphoria, incoordination, of 10 mg once daily, slowly titrate dose in 5 mg
insomnia, nausea, nervousness, psychomotor increments based on efficacy and tolerability (maximum,
impairment, sedation, sleepiness, thickening of 30 mg once daily).
bronchial secretions, tinnitus, tremor, vomiting. Autism-related irritability, by mouth, CHILD ≥6 years, initially
Less Common: Hallucinations, hypotension, headache, 2 mg once daily for 7 days, then increase to 5 mg once
palpitations, psychosis, restlessness, urinary retention, daily, slowly titrate dose in 5 mg increments at intervals
vertigo. of ≥1 week based on efficacy and tolerability (maximum,
Rare: Agranulocytosis, arrhythmias, blood dyscrasias, 15 mg once daily).
convulsions, EPS, hemolytic anemia, hepatitis, Major depressive disorder, adjunct, by mouth, ADULT,
hypersensitivity reactions, leukopenia, liver disorders, initially 2–5 mg once daily, may increase by 5 mg daily at
excitation, hallucination, seizures, paralysis. intervals of ≥1 week based on efficacy and tolerability
(maximum, 15 mg once daily).
Drug Interactions: Schizophrenia, by mouth, ADULT, initially 10–15 mg once
Monitor closely with: daily, slowly titrate dose based on efficacy and
Enhances therapeutic effect of Diphenhydramine: tolerability (maximum, 30 mg once daily); CHILD ≥13
CNS Depressants, e.g., Alcohol, Anxiolytic Sedatives, years, initially 2 mg once daily, slowly titrate dose based
Barbiturates, Hypnotics, Neuroleptics, Opioid Analgesics on efficacy and tolerability (maximum, 30 mg once daily).
(sedative effect) Tourette syndrome, by mouth, CHILD ≥6 years or <50 kg,
initially 2 mg once daily for 2 days, then increase to a

N
Enhances therapeutic effect of the following drugs: target dose of 5 mg once daily, slowly titrate dose at
Beta Blockers, e.g., Labetalol, Metoprolol, Propranolol intervals of no less than 1 week based on efficacy and
(cardiovascular effects) tolerability (maximum, 10 mg once daily); assess the
need for ongoing treatment periodically; CHILD ≥50 kg,
Administration: initially 2 mg once daily for 2 days, then increase to 5 mg
For oral administration, may be taken with or without once daily for 5 days with a target dose of 10 mg once
food. daily on day 8, slowly titrate dose in 5 mg increments at
intervals of no less than 1 week based on efficacy and
For IV administration, do NOT exceed a rate of 25 tolerability (maximum, 20 mg once daily).
mg/minute.
Dose Adjustment:
IM administration must be deep. Local necrosis may Geriatric:
result with SC or intradermal use. May tolerate lower doses better. Antipsychotics are
considered potentially inappropriate in in the elderly.
Pregnancy Category: B Avoid in patients 65 years and older with dementia due
to an increased risk of mortality, cerebrovascular
ATC Code: Not available accidents (stroke), a greater rate of cognitive decline with
use, and potential to cause or exacerbate or
hyponatremia unless all nonpharmacologic options have
failed or are not possible or the patient is threatening
PSYCHOLEPTICS substantial harm to self or to others.

Precautions:
ANTIPSYCHOTICS
WARNING: Elderly patients with dementia-related
psychosis are at an increased risk of death.
Rx ARIPIPRAZOLE Aripiprazole is NOT approved for the treatment of
dementia-related psychosis.
Oral: 10 mg, 15 mg, 20 mg, and 30 mg tablet
10 mg and 15 mg orally disintegrating tablet (ODT) Closely monitor for clinical worsening and for the
emergence of suicidal thoughts and behaviors.
Aripiprazole is a quinolinone derivative and an atypical
antipsychotic agent, which acts as a partial agonist at Cardiovascular disease; Parkinson disease (may aggravate
dopamine D2 and serotonin 5-HT21A receptors and as an motor disturbances); seizures.
antagonist at 5-HT22A receptors. Elderly (may be at increased risk of seizures; increased risk
of mortality and cerebrovascular accidents; potential to
Indications: Management of Schizophrenia; acute mania or cause or exacerbate SIADH or hyponatremia); children
mixed mania; adjunct treatment of major depressive

487
 NERVOUS SYSTEM

(increased risk of suicidal thoughts and behavior; safety swollen tongue, syncope, tardive dyskinesia,
and efficacy have not been established). thrombocytopenia, tongue spasm, tonic-clonic seizures,
Pregnancy (risk of abnormal muscle movements and torsades de pointes, transient ischemic attacks, trismus,
withdrawal symptoms in newborns with use during the uncontrolled diabetes mellitus, urinary retention,
third trimester); lactation (excreted in breastmilk; urticaria, venous thromboembolism, ventricular
monitor infant for possible adverse effects). tachycardia.
Rare: Neuroleptic malignant syndrome, seizures, theoretical
SKILLED TASKS. May impair ability to perform tasks, which risk of tardive dyskinesia, dysphagia, blood dyscrasias
require mental alertness, like driving or operating (leukopenia, neutropenia, agranulocytosis), increased
machinery. risk of death and cerebrovascular events (elderly with
dementia-related psychosis).
TEST INTERACTION. May give false positive urine
immunoassay screening tests for amphetamines. Drug Interactions:
Monitor closely with:
Adverse Drug Reactions: Enhances therapeutic effect of Aripiprazole:
Common: Malaise, hypersalivation, peripheral edema, Antidepressants (serotonergic effect)
headache, dizziness, insomnia, drowsiness, sedation Antihypertensives
(dose-related), lethargy, fatigue (dose-related), CNS Depressants (central effects)
extrapyramidal reaction (dose-related), akathisia (dose-
related), agitation, activation, anxiety, restlessness, pain, Increases risk of adverse or toxic effects of Aripiprazole:
dystonia, irritability, ataxia, tremor (dose-related), Lithium (neurotoxic effect)
anorexia, weight gain, weight loss, decreased HDL Methylphenidate, Metoclopramide
cholesterol, nausea, vomiting, constipation, dyspepsia, (sleepiness; dizziness)
decreased or increased appetite, xerostomia,
toothache, diarrhea, gastric distress, stomach Increases risk of adverse or toxic effects of the following
discomfort, upper abdominal pain, abdominal distress, drugs:
urinary incontinence, dysmenorrhea, arthralgia, limb Acetylcholinesterase Inhibitors (extrapyramidal
pain, myalgia, stiffness, muscle cramps, muscle rigidity, symptoms)
N

weakness, asthenia, muscle spasm, dyskinesia, blurred Antidepressants (serotonin syndrome; neuroleptic
vision, nasopharyngitis, upper respiratory tract infection, malignant syndrome)
cough, pharyngolaryngeal pain, epistaxis, aspiration Iohexol, Iomeprol, Iopamidol (seizures)
pneumonia, dyspnea, fever. Mequitazine (arrhythmogenic effect)
Less Common: Depression, dry mouth, anticholinergic Serotonin Modulators (serotonin syndrome; neuroleptic
effects, hypersomnia, orthostatic hypotension, nasal malignant syndrome)
congestion, changes in body thermoregulation, SSRIs (psychomotor impairment)
aggressive behavior, agranulocytosis, akinesia, Methylphenidate
alopeciaamenorrhea, anaphylaxis, angina pectoris,
angioedema, anorgasmia, atrial fibrillation, atrial flutter, Reduces therapeutic effect of the following drugs:
AV block, altered serum glucose, bradycardia, Amphetamines, CNS Stimulants (stimulant effect)
bradykinesia, bruxism, cardiac arrhythmia, catatonia, Antidiabetics, Dopamine Agonists
cerebrovascular accident, change in libido, chest Guanethidine (antihypertensive effect)
discomfort, chest pain, choreoathetosis, cogwheel
rigidity, delayed ejaculation, delirium, depression, Avoid concomitant use with:
diabetes mellitus, diabetic ketoacidosis, diplopia, drug- Increases risk of adverse or toxic effects of Aripiprazole:
induced Parkinson disease, dysgeusia, dysphagia, Other Antipsychotics (increased side effect burden, high
dystonia (oromandibular), edema, erectile dysfunction, dose prescribing, increased hospitalization rates and
esophagitis, extrasystoles, eyelid edema, facial edema, length of stay, higher treatment costs, and increased
falling, GERD, glycosuria, gynecomastia, heatstroke, mortality)
hepatotoxicity, hepatic failure, hepatitis, hirsutism,
homicidal ideation, hostility, hyperglycemia, Administration: May be taken with or without food
hyperhidrosis, hyperinsulinism, hyperlipidemia,
hypersensitivity reaction, hypertension, hypertonia, Orally disintegrating tablets must be removed from the
hypokalemia, hypoglycemia, hypokinesia, hypothermia, foil blister by peeling back. Do NOT push the tablet
joint stiffness, hyponatremia, hypotonia, impulse control through the foil. Place tablet in mouth immediately upon
disorder, MI, panic attack, intentional injury, ischemic removal. Tablet dissolves rapidly in saliva and may be
heart disease, jaundice, laryngospasm, skin swallowed without liquid. If needed, can be taken with
photosensitivity, leukopenia, mastalgia, memory liquid. Do NOT split the tablet.
impairment, mobility disorder, muscle twitching,
myasthenia, menstrual disease, myoclonus, nocturia, NOTE: Do NOT discontinue abruptly because of the
obesity, oropharyngeal spasm, oculogyric crisis, possibility of withdrawal and rebound psychosis.
palpitations, pancreatitis, photophobia, photopsia, Discontinue gradually to avoid physical withdrawal
pollakiuria, polydipsia, polyuria, presyncope, priapism, symptoms, including anorexia, anxiety, diaphoresis,
prolonged QT interval, pruritus, psychosis, diarrhea, dizziness, dyskinesia, headache, myalgia,
rhabdomyolysis, seizure, sleep apnea syndrome nausea, paresthesia, restlessness, tremulousness, and
(obstructive), sleep talking, somnambulism, SVT, speech vomiting.
disturbance, suicidal tendencies, tics, suicidal ideation,

488
NERVOUS SYSTEM

Pregnancy Category: C by slow IV infusion, ADULT, if refractory to IM treatment,

25–50 mg in 500–1,000 mL normal saline; CHILD 1–12
ATC Code: N05AX12 years, 500 micrograms/kg every 4–6 hours (maximum
daily dose, 75 mg if 5 years old, 40 mg if 1–5 years old).
Nausea and vomiting, non-CINV (chemotherapy-induced
nausea and vomiting), by mouth, ADULT, 10–25 mg
Rx CHLORPROMAZINE every 4–6 hours as needed;
by IM injection, ADULT, initially 25 mg; if no hypotension
Oral: 50 mg, 100 mg, and 200 mg tablet (as hydrochloride) occurs, 25–50 mg every 3–4 hours may be given until
Inj.: 25 mg/mL (as hydrochloride), 1 mL ampule (IM, IV) vomiting stops; during surgery, initially administer 12.5
mg and repeat in 30 minutes if necessary and if no
Chlorpromazine is a dimethylamine derivative of hypotension occurs;
phenothiazine. It has weak anticholinergic and strong by IV injection, ADULT, during surgery, 2 mg per fractional
antiadrenergic activity and possesses slight ganglionic, injection at 2-minute intervals using a 1 mg/mL solution,
antihistaminic, and anti-serotonin activity. It blocks at not to exceed 25 mg;
least 60% of D2 receptors in the mesolimbic pathway of by mouth, IM or IV injection, CHILD ≥5 years or >22.7 kg
the brain to produce a therapeutic effect on the positive but <45.5 kg, initially 0.55 mg/kg every 6–8 hour as
symptoms of schizophrenia. needed; in severe cases, higher doses may be needed
up to a maximum of 75 mg once daily; CHILD <5 years or
Indications: Management of schizophrenia; bipolar mania; <22.7 kg and INFANT ≥6 months, initially 0.55 mg/kg
nausea; vomiting; restlessness and apprehension before every 6 to 8 hours as needed; in severe cases, higher
surgery; acute intermittent porphyria; manifestations of doses may be needed up to a maximum of 40 mg once
manic type of manic-depressive illness; tetanus daily; CHILD ≥45.5 kg, initially 25 mg; if no hypotension
(adjunct); intractable hiccups; combativeness and/or occurs, administer 25–50 mg every 4–6 hours as
explosive hyperexcitable behavior (children); hyperactive needed.
children who show excessive motor activity with Schizophrenia, by mouth, ADULT (outpatient), 10 mg 3–4
accompanying conduct disorders consisting impulsivity, times daily, or 25 mg 3 times daily; for more severe
difficulty sustaining attention, aggressivity, mood lability, cases, may increase the initial dose after 1–2 days by

N
poor frustration tolerance, and/or psychosis. 20–50 mg at semi-weekly intervals until patient
becomes calm and cooperative;
Contraindications: Hypersensitivity to chlorpromazine, other ADULT (hospitalized), 25 mg 3 times daily, increase
phenothiazines, sulfites, or any component of the gradually until effective dose is reached (usually 400 mg
formulation; comatose states; Reye’s syndrome; blood daily); for patients in acute schizophrenic state, once
dyscrasias; bone marrow suppression; subcortical brain patient is quiet and cooperative, oral doses may be
injury, CNS depression, pheochromocytoma, substituted for IM and increased, usually to 500 mg
hypothyroidism. daily, may gradually increase to 2,000 mg daily may be
needed, although doses greater than 1,000 mg daily for
Dose: extended periods generally do not provide therapeutic
Acute intermittent porphyria, by mouth, ADULT, 25–50 mg gain.
3 or 4 times daily; by IM injection, ADULT, initially 25 mg, a second 25-mg
by IM injection, ADULT, 25 mg 3 or 4 times daily until to 50-mg dose may be administered after 1 hour; slowly
patient can tolerate oral administration. titrate dose based on efficacy and tolerability until
Behavior problems, severe, by mouth, CHILD ≤45.5 kg and patient is controlled, usually within 24–48 hours at
INFANT ≥6 months, initially 0.55 mg/kg every 4–6 hours which time oral doses may be substituted (maximum,
as needed, slowly titrate dose based on efficacy and 400 mg every 4–6 hours).
tolerability (maximum, 500 mg once daily); CHILD ≥45.5 Tetanus adjunct, by IM injection, ADULT, usually in
kg, initially 30–40 mg daily in 3–4 divided doses or 50– combination with barbiturates, initially 25–50 mg 3 or 4
75 mg daily in 2–3 divided doses, slowly titrate dose times daily, slowly titrate dose to response;
based on efficacy and tolerability; usual dose is 200 mg by IV injection, ADULT, usually in conjunction with
once daily. barbiturates, 25–50 mg at a rate of 1 mg/minute, initiate
Bipolar mania, by mouth, ADULT, initially 30–40 mg daily in with low dose and gradually increase;
3–4 divided doses or 50–75 mg daily in 2–3 divided by IM or IV injection, CHILD ≥5 years or >22.7 kg but
doses; an initial dose of 100–200 mg once daily is <45.5 kg, initially 0.55 mg/kg every 6–8 hour as needed;
reserved for severe inpatient cases, slowly titrate dose in severe cases, higher doses may be needed up to a
based on efficacy and tolerability (maximum, 1,000 mg maximum of 75 mg once daily; CHILD <5 years or <22.7
once daily); kg and INFANT ≥6 months, initially 0.55 mg/kg every 6–
by IM injection, ADULT, initially 25 mg, a second 25-mg 8 hour as needed; in severe cases, higher doses may be
or 50-mg dose may be administered after 1 hour, slowly needed up to a maximum of 40 mg once daily; CHILD
titrate dose based on efficacy and tolerability (maximum, ≥45.5 kg, initially 25 mg; if no hypotension occurs, 25–
400 mg every 4–6 hours). 50 mg 3 or 4 times daily, slowly titrate dose to response.
Intractable hiccups, by mouth, ADULT, 25–50 mg 3 or 4
times daily for 2–3 days, if symptoms are persistent Dose Adjustment:
beyond 2–3 days, administer parenterally; Geriatric:
by IM injection, ADULT, if refractory to oral treatment, Start with small doses in severe renal impairment because
25–50 mg; of increased cerebral sensitivity.

489
 NERVOUS SYSTEM

Hepatic Impairment: Methylphenidate, Metoclopramide, Lithium (neurotoxic

Can precipitate coma; phenothiazines are hepatotoxic. effect)

Precautions: Increases risk of adverse or toxic effects of the following

drugs:
WARNING: Elderly patients with dementia-related
Diuretics, Hypotension-associated Agents (hypotension)
psychosis are at an increased risk of death.
Glucagon (GI adverse effects)
Closely monitor for clinical worsening and for the Iohexol, Iomeprol, Iopamidol (seizures)
emergence of suicidal thoughts and behaviors. Mequitazine (arrhythmogenic effect)
Methylphenidate, Mirabegron
Photosensitizing Agents (photosensitizing effect)
Cardiovascular disease; anticholinergic effects (e.g.,
QTc-prolonging Agents (torsades de pointes)
constipation, xerostomia, blurred vision, urinary
Serotonin Modulators (neuroleptic malignant syndrome;
retention); blood dyscrasias (e.g., leukopenia,
serotonin syndrome)
neutropenia, and agranulocytosis, some fatal); seizures.
SSRIs (psychomotor impairment)
Hepatic impairment; masking (may mask signs of other
Topiramate (hyperthermia)
disorders or overdose); renal impairment; respiratory
disease; Reye syndrome; ocular effects (pigmentary
Reduces absorption of Chlorpromazine:
retinopathy, and lenticular and corneal deposits);
Antacids
photosensitivity (mild urticarial-type rash or
photosensitivity); glaucoma.
Reduces absorption of Nitroglycerin (decreases dissolution
Elderly (tardive dyskinesia; mortality and cerebrovascular
of sublingual nitroglycerin tablets)
accidents; SIADH or hyponatremia); children (suicidal
thoughts and behavior; safety and efficacy have not
Reduces therapeutic effect of Chlorpromazine:
been established).
Anticholinergics (anticholinergic effect)
Pregnancy (abnormal muscle movements and withdrawal
Methylphenidate (inhibits antipsychotic and mood-
symptoms in newborns with use during the third
stabilizing activity)
trimester); lactation (monitor infant for possible adverse
effects).
N

Reduces therapeutic effect of the following drugs:

Anticoagulants, Dopamine Agonists, Prokinetics,
SKILLED TASKS. May impair ability to perform tasks, which
Secretin
require mental alertness, like driving or operating
Amphetamines (stimulant effect)
machinery.
Guanethidine (antihypertensive effects)
Adverse Drug Reactions: Methylphenidate (inhibits stimulatory effects)
Common: Neuroleptic-induced deficit syndrome, akathisia,
priapism, extrapyramidal symptoms, parkinsonism, Avoid concomitant use with:
acute dystonia, galactorrhea, dry mouth, amenorrhea, Decreases serum concentration of Tamoxifen
gynecomastia, dizziness, sedation, impaired memory,
constipation, urinary retention, blurred vision, decreased Delayed gastric emptying with Potassium Salts (Oral)
sweating, sexual dysfunction, hypotension, tachycardia,
syncope, tardive dyskinesia, maculopapular rash, weight Increases risk of adverse or toxic effects of the following
gain, erythema multiforme, urticaria, photosensitivity drugs:
reactions, urine discoloration (red to red-brown), Nilotinib (QTc prolongation; torsades de pointes)
photosensitivity, cholestatic jaundice, long-term skin Other Antipsychotics (increased hospitalization rates
pigmentation changes. and length of stay; increased mortality; QTc
Less Common: Jaundice, changes in body prolongation; torsades de pointes)
thermoregulation.
Rare: Cornea and lens pigmentation, retinitis pigmentosa, Administration:
blood dyscrasias (leukocytosis or leukopenia, For oral administration, may be taken with or without
eosinophilia, thrombocytopenia, agranulocytosis), food. May be taken with meals to reduce GI discomfort.
seizures, increased risk of death and cerebrovascular
events (elderly with dementia-related psychosis), For direct IV injection, admqinister diluted solution by
neuroleptic malignant syndrome. slow IV at a rate not to exceed 0.5 mg/minute in children
and 1 mg/minute in adults. Patients must remain lying
Drug Interactions: down during and for 30 minutes after administration to
Monitor closely with: reduce the risk of hypotension.
Decreases metabolism of Phenytoin
For IM administration, inject slowly, deep into the upper
Enhances therapeutic effect of the following drugs: outer quadrant of buttock.
Antihypertensives [except Guanethidine]
Beta Blockers [except Atenolol, Nadolol] Do NOT administer by SC injection to prevent tissue
CNS Depressants (central effects) damage and irritation. Avoid skin contact with solution to
Vasopressors, e.g. Epinephrine (lowers blood pressure) prevent contact dermatitis.
Thiopental (hypotensive effect; CNS excitatory effect)
NOTE: Do NOT discontinue abruptly because of the
Increases risk of adverse or toxic effects of Chlorpromazine: possibility of withdrawal and rebound psychosis.

490
NERVOUS SYSTEM

Discontinue gradually to avoid physical withdrawal Dose Adjustment:

symptoms, including anorexia, anxiety, diaphoresis, Geriatric:
diarrhea, dizziness, dyskinesia, headache, myalgia, May tolerate lower doses better. Initiate with 12.5 mg once
nausea, paresthesia, restlessness, tremulousness, and daily for 3 days, then increase to 25 mg once daily for 3
vomiting. days as tolerated, may further increase, as tolerated, in
increments of 12.5–25 mg daily every 3 days to desired
For the treatment of intractable hiccups, infuse as a slow response, up to a maximum of 700 mg daily.
IV infusion.
Renal Impairment:
Pregnancy Category: C Avoid in severe impairment.

ATC Code: N05AA01 Hepatic Impairment:

Avoid in symptomatic liver disease, progressive liver disease
and hepatic failure. Monitor hepatic function regularly.
Rx CLOZAPINE Precautions:
WARNING: Agranulocytosis. Associated with a
Oral: 25 mg and 100 mg tablet significant risk of potentially life-threatening
agranulocytosis. Reserved use in the treatment of
Clozapine is a tricyclic dibenzodiazepine and an atypical
severely-ill patients with schizophrenia who fail to
antipsychotic with weak D2 blocking action. It is the only
show an acceptable response to adequate courses
antipsychotic documented to reduce suicide risk in
of standard antipsychotic drug treatment, or for
patients with schizophrenia. It has 5-HT2A antagonism
reducing the risk of recurrent suicidal behavior in
which gives it little to no EPS and tardive dyskinesia risk,
patients with schizophrenia and schizoaffective
and dose not elevate prolactin. It is often reserved as a
disorder who are judged to be at risk of re-
last-line option due to the risk of developing life-
experiencing suicidal behavior. Patients must have
threatening and occasionally fatal agranulocytosis, as
a baseline absolute neutrophil count (ANC) before
well as an increased risk of seizures.
initiation of treatment, as well as regular ANCs

N
during treatment and for at least 4 weeks after
Indications: Management of clozapine-resistant
discontinuation of treatment.
schizophrenia; for reducing the risk of recurrent suicidal
behavior in patients with schizophrenia and
schizoaffective disorder. Seizures. Use caution when administering to
patients with a history of seizures or other
Contraindications: Uncontrolled epilepsy, paralytic ileus, predisposing factors. Advise patients not to engage
myoproliferative disorders, history of clozapine-induced in any activity where sudden loss of consciousness
agranulocytosis or severe granulocytopenia; severe CNS could cause serious risk to themselves or others.
depression; coma, bone-marrow disorders, alcoholic and
toxic psychoses, severe cardiac disorders (e.g., Fatal myocarditis and cardiomyopathy.
myocarditis), history of circulatory collapse. Discontinue immediately when myocarditis is
suspected. Re-challenge with clozapine patients
Dose: with clozapine-related myocarditis or
Treatment-resistant schizophrenia and for reducing risk of cardiomyopathy.
recurrent suicidal behavior in patients with
schizophrenia and schizoaffective disorder, by mouth,
ADULT, initially 25 mg daily in 2 divided doses, slowly Orthostatic hypotension, with or without
increase by 25–50 mg daily each day to a target dose of syncope, can occur. Rarely, collapse can be
300–450 mg daily in divided doses by the end of 2 profound and be accompanied by respiratory
weeks; administer doses above 300 mg once daily in and/or cardiac arrest. In case of a brief interval off
divided doses; dose increases beyond 450 mg once daily clozapine, i.e. 2 or more days since the last dose,
should be done no more frequently than once or twice resume treatment with 12.5 mg once or twice daily.
weekly in increments not exceeding 100 mg daily up to a
maximum dose of 900 mg once daily; if dosing is Use with caution when administered concurrently
interrupted for ≥48 hours, re-initiate therapy at 12.5 mg with benzodiazepine or any other psychotropic drug
once or twice daily to minimize the risk of hypotension, since collapse, respiratory arrest and cardiac arrest
bradycardia, and syncope. has occurred in this combination.

NOTE: Recommended dose is between 300–800 mg once Elderly patients with dementia-related psychosis
daily for at least 8 weeks as an adequate trial in treated with antipsychotic drugs are at an
treatment-resistant schizophrenia. If despite adequate increased risk of death. Clozapine is not approved
dosing and adherence there is no adequate response, for use in patients with dementia-related
perform therapeutic drug monitoring. Plasma levels psychosis.
above 350 nanograms/mL have been associated with
treatment response.
Anticholinergic effects (e.g., constipation, xerostomia,
blurred vision, urinary retention; use is associated with

491
 NERVOUS SYSTEM

increased risk of paralytic ileus, bowel obstruction, fecal dysphagia, enlargement of salivary glands, erythema
impaction, bowel perforation, and in rare cases death); multiforme, fecal impaction, gastroenteritis,
fever (benign transient temperature elevation >38°C or granulocytopenia, esophageal dysmotility, hepatic
100.4°F); neuroleptic malignant syndrome; impared cirrhosis, hepatic fibrosis, hepatic insufficiency, hepatic
temperature regulation. necrosis, hepatitis, hypersensitivity reaction,
CNS depression; extrapyramidal symptoms e.g. acute hepatotoxicity, hyperglycemia associated with
dystonic reactions, pseudoparkinsonism, akathisia, and ketoacidosis or hyperosmolar coma or death,
tardive dyskinesia; risk of dystonia may be greater with hyperuricemia, hyponatremia, interstitial nephritis
increased doses); falls; suicidal ideation; QT prolongation (acute), intestinal obstruction, jaundice, ketoacidosis,
(ventricular arrhythmias; cardiac arrest and sudden leukocytosis, liver injury, liver steatosis, lower respiratory
death). tract infection, mitral valve insufficiency, myasthenia
Dyslipidemia; eosinophilia; hyperglycemia (associated with syndrome, myocardial infarction, myocarditis,
ketoacidosis, hyperosmolar coma, or death); sialorrhea myoclonus, neuroleptic malignant syndrome, nocturnal
(drooling, skin irritation and infections, aspiration enuresis, obsessive compulsive disorder, obstructive
pneumonia, chronic sleep disturbances with daytime orthostatic hypotension, palpitations, sleep apnea,
fatigue and somnolence, painful swelling of the salivary pancreatitis (acute), paralytic ileus, paresthesia,
glands, and symptomatic aerophagia with resultant gas pheochromocytoma (pseudo), periorbital edema, pleural
bloating, pain, and flatus may also develop); effusion, pneumonia, priapism, pulmonary embolism,
thromboembolism (deep vein thrombosis and pulmonary prolonged QT interval (dose-dependent), renal failure,
embolism, some fatal). psychosis (exacerbated), retrograde ejaculation,
Esophageal dysmotility or aspiration; hepatotoxicity (severe, rhabdomyolysis, sepsis, skin photosensitivity,
life-threatening, sometimes fatal, including hepatic sialadenitis, status epilepticus, SJS, systemic lupus
failure, hepatic necrosis, and hepatitis); weight gain. erythematosus, syncope, tardive dyskinesia,
Acute infectious or inflammatory processes; benign ethnic thrombocytopenia, thrombocytosis, torsade de pointes,
neutropenia; cardiovascular disease; glaucoma; vasculitis, weight loss.
prostate; renal impairment. Rare: Changes in body thermoregulation.
Smokers (decreases clozapine concentration; may require
twice the daily dose to obtain an equivalent Drug Interactions:
N

concentration; smoking cessation may cause toxicity in Monitor closely with:

patients stabilized on clozapine; monitor change in Enhances therapeutic effect of the following drugs:
smoking patterns). Antihypertensives
Elderly (more susceptible to adverse effects; potentially CNS Depressants (central effects)
inappropriate in the elderly; avoid use in patients ≥65
years with dementia due to an increased risk of mortality Increases risk of adverse or toxic effects of Clozapine:
and cerebrovascular accidents, a greater rate of Methylphenidate, Metoclopramide (sleepiness and
cognitive decline, and potential to cause or exacerbate dizziness)
SIADH or hyponatremia, unless all non-pharmacologic Lithium (neurotoxic effect)
options have failed or are not possible or the patient is
threatening substantial harm to self or to others). Increases risk of adverse or toxic effects of the following
Pregnancy (risk of abnormal muscle movements and drugs:
withdrawal symptoms in newborns with fetal exposure Acetylcholinesterase Inhibitors (extrapyramidal
during the third trimester); lactation (monitor infant for symptoms), Antihypertensives (hypotension)
possible adverse effects). Glucagon (GI adverse effects)
Iohexol, Iomeprol, Iopamidol (seizures)
SKILLED TASKS. May impair ability to perform tasks, which Mequitazine (arrhythmogenic effect)
require mental alertness, like driving or operating Mirabegron, Topiramate, Myelosuppressive Agents
machinery. (bone marrow suppression)
QTc-prolonging Agents (torsades de pointes) Saquinavir
Adverse Drug Reactions: (arrhythmogenic effect)
Common: Tachycardia, hypotension, hypertension, syncope, Serotonin Modulators (neuroleptic malignant syndrome;
drowsiness, sedation, dizziness, insomnia, headache, serotonin syndrome)
agitation, restlessness, vertigo, akinesia, disturbed SSRIs (psychomotor impairment)
sleep, nightmares, akathisia, confusion, seizure (dose
related), fatigue, tremor, hypersalivation (can be severe), Reduces absorption of Nitroglycerin (decreases dissolution
diaphoresis, skin rashweight gain, sialorrhea, weight of sublingual nitroglycerin tablets)
gain, constipation, nausea, vomiting, dyspepsia,
xerostomia, abdominal distress, heartburn, diarrhea, Reduces therapeutic effect of the following drugs:
leukopenia, neutropenia, eosinophilia, urine Antidiabetics, Phenylephrine, Prokinetics, Secretin
abnormality, hypokinesia, muscle rigidity, visual Amphetamines (stimulant effect)
disturbance. Anticholinergics (anticholinergic effect)
Less Common: Agranulocytosis, abnormal Epinephrine (reverses pressor effect)
electrocephalogram, angioedema, aspiration, Guanethidine (antihypertensive effects)
bradycardia, cardiac arrhythmia, cardiac failure,
cardiomyopathy (usually dilated), cataplexy, Avoid concomitant use with:
cerebrovascular accident, cholestasis, colitis, deep vein Increases risk of adverse or toxic effects of the following
thrombosis, delirium, diabetes mellitus, dyschromia, drugs:

492
NERVOUS SYSTEM

Agranulocytosis-inducing Drugs (agranulocytosis) Slowly titrate dose at maximum increments of ≤20 mg

Other Antipsychotics (increased hospitalization rates based on efficacy and tolerability up to a maximum
and length of stay; increased mortality; QTc maintenance dose of 200 mg every 1–4 weeks.
prolongation; torsades de pointes)
Dose Adjustment:
Administration: May be taken with or without food. Geriatric:
Initially 5 mg by IM injection into the gluteal muscle.
Do NOT discontinue abruptly because of the possibility of Recommended maintenance dose is 10–20 mg every 15
withdrawal and rebound psychosis. Perform days.
discontinuation or cross-titration gradually over 1–2
weeks to minimize the potential of withdrawal, rebound Renal Impairment:
psychosis, extrapyramidal side effects, cholinergic Recommended maintenance dose is 10–20 mg every 15
rebound, rebound insomnia, and unwanted pregnancy, days.
unless safety concerns require a more rapid withdrawal.
Hepatic Impairment:
Pregnancy Category: B Can precipitate coma. Consider serum-flupentixol
concentration monitoring
ATC Code: N05AH02
Precautions:
WARNING: Neuroleptic malignant syndrome. Has been
Rx FLUPENTIXOL associated with use. Monitor for mental status
changes, fever, muscle rigidity and/or autonomic
instability, elevated creatine phosphokinase (CPK),
Inj.: 20 mg/mL (as decanoate), 1 mL ampule and 10 mL myoglobinuria, and/or acute renal failure.
vial (IM) Discontinue treatment immediately with onset of
NMS. Recurrence has been reported when re-
Flupentixol is a thioxanthene typical antipsychotic that challenged with antipsychotic therapy.
inhibits dopamine-mediated effects by blocking

N
postsynaptic dopamine receptors in the CNS. It was Elderly patients with dementia-related psychosis
formulated as a long-acting injectable for use in patients treated with antipsychotic drugs are at an increased
with schizophrenia who have difficulty with adherence to risk of death.
oral medications.
Anticholinergic effects (e.g., constipation, xerostomia,
Indication: Management of chronic schizophrenia whose blurred vision, urinary retention; use is associated with
main manifestations do not include excitement, agitation increased risk of paralytic ileus, bowel obstruction, fecal
or hyperactivity; bipolar disorder impaction, bowel perforation, and in rare cases death);
Impaired temperature regulation
Contraindications: Acute intoxication with ethanol, CNS depression; extrapyramidal symptoms (e.g., acute
barbiturate, or opioid; psychoneurotic patients or dystonic reactions, pseudoparkinsonism, akathisia, and
geriatric patients with confusion and/or agitation; tardive dyskinesia; risk of dystonia may be greater with
suspected or established subcortical brain damage; CNS increased doses); dementia; Parkinson disease; seizure
depression; blood dyscrasias; comatose or brain disorder; ocular effects (lens opacity has been reported
damage; pheochromocytoma; liver damage; severe rarely).
cardiovascular disorder; cerebrovascular insufficiency; Esophageal dysmotility or aspiration; masking of toxicity of
renal insufficiency. other drugs or conditions; diabetic ketoacidosis
Altered cardiac conduction (life-threatening arrhythmias);
Dose: cardiovascular disease; orthostatic hypotension; blood
Maintenance therapy of schizophrenia and reduces dyscrasias (agranulocytosis, neutropenia, leukopenia,
symptoms of acute psychotic mania but not proven as a and granulocytopenia); venous thromboembolism.
mood stabilizer or as an effective maintenance Glaucoma; hepatic impairment; renal impairment; prolactin-
treatment in bipolar disorder, by IM injection, ADULT dependent tumors.
(stabilized on oral flupentixol), 20 mg into the gluteal Surgical patients (monitor closely for hypotension).
muscle; continue oral flupentixol until 1 week after first Elderly (increased risk of tardive dyskinesia, especially
injection while slowly tapering; administer second 20 mg among women; potentially inappropriate in the elderly;
dose not earlier than 4–10 days after the first injection, avoid use in patients ≥65 years with dementia due to an
followed by 20–40 mg every 2–3 weeks maintenance increased risk of mortality and cerebrovascular
dose; maximum of 200 mg every 1-4 weeks accidents, a greater rate of cognitive decline, and
potential to cause or exacerbate SIADH or hyponatremia,
NOTE: Conversion of oral flupentixol to long-acting injectable unless all nonpharmacologic options have failed or are
maintenance dose: not possible or the patient is threatening substantial
harm to self or to others).
x mg once daily is equivalent to Pregnancy (risk of abnormal muscle movements and
4x mg decanoate every 2 weeks; or withdrawal symptoms in newborns with fetal exposure
8x mg decanoate every 4 weeks during the third trimester); lactation (excreted in
breastmilk; tardive dyskinesia, dystonia, and sedation
have been observed in nursing infants).

493
 NERVOUS SYSTEM

SKILLED TASKS. May impair ability to perform tasks, which Reduces absorption of Nitroglycerin (decreases dissolution
require mental alertness, like driving or operating of sublingual nitroglycerin tablets)
machinery.
Reduces therapeutic effect of the following drugs:
Adverse Drug Reactions: Antidiabetics, Dopamine Agonists, Prokinetics, Secretin
Common: Neuroleptic-induced deficit syndrome, Amphetamines (stimulant effect) Anticholinergics
extrapyramidal symptoms, Parkinsonism, tardive (anticholinergic effect) Epinephrine (reverses pressor
dyskinesia (duration and dose dependent), acute effect)
dystonia, insomnia, restlessness, agitation, Guanethidine (antihypertensive effects)
galactorrhea, gynecomastia, amenorrhea, weight gain,
sedation, tachycardia, hypomania, photosensitivity, long- Avoid concomitant use with:
term skin pigmentation changes. Enhances therapeutic effect of CNS Depressants [high
Less Common: ECG changes (broadened, flattened T waves, dose] (CNS depression)
QT and PR interval prolongation, ST segment
depression), palpitations, syncope, depression, Increases risk of adverse or toxic effects of the following
dizziness, drowsiness, headache, hyperreflexia, drugs:
hypertonia, hypomania, insomnia, opisthotonos, Other Antipsychotics (increased hospitalization rates
psychomotor agitation, contact dermatitis, diaphoresis, and length of stay; increased mortality; QTc
eczema, erythema, exfoliative dermatitis, pruritus, prolongation; torsades de pointes)
seborrhea, skin rash, urticaria, amenorrhea, decreased
libido, hyperprolactinemia, increased libido, fatigue, Administration: Administer by deep IM injection into the
weight changes, constipation, nausea, paralytic ileus, gluteal muscle or deltoid muscle.
sialorrhea, xerostomia, impotence, urination disorder,
eosinophilia, jaundice, tremor, blurred vision, cataract, Do NOT discontinue abruptly because of the possibility of
oculogyric crisis, accommodation disturbance, withdrawal and rebound psychosis. Discontinue or cross-
abdominal pain, confusion, diarrhea, dyspepsia, titrate gradually to minimize the potential of withdrawal,
dyspnea, ejaculation failure, erectile dysfunction, rebound psychosis, extrapyramidal side effects,
flatulence, hot flash, hyperglycemia, impaired glucose cholinergic rebound, rebound insomnia, and unwanted
N

tolerance, increased appetite, muscle rigidity, myalgia, pregnancy, unless safety concerns require a more rapid
nervousness, prolonged QT interval, priapism, speech withdrawal.
disturbance, torsades de pointes, urinary retention,
ventricular arrhythmia, ventricular fibrillation, ventricular Pregnancy Category: C
tachycardia, vomiting, weakness.
Rare: Cholestatic jaundice, jaundice, neuroleptic malignant ATC Code: N05AF01
syndrome, seizures, changes in body thermoregulation,
blood dyscrasias (eosinophilia, leukocytosis or
leukopenia, granulocytopenia, agranulocytosis,
thrombocytopenia).
Rx FLUPHENAZINE

NOTE: Patients taking this drug may experience weight gain Inj.: 25 mg/mL (as decanoate), 1 mL ampule and 10 mL
and/or sedation. vial (IM)

Drug Interactions: Fluphenazine is a phenothiazine typical antipsychotic

Monitor closely with: formulated as a long-acting injectable for use in patients
Enhances therapeutic effect of the following drugs: with schizophrenia who have difficulty with adherence to
Antihypertensives oral medications. It blocks brain dopamine (D2) receptors
CNS Depressants (central effects) in the mesolimbic system and decreases the release of
hypothalamic and hypophyseal hormones.
Increases risk of adverse or toxic effects of Flupentixol:
Methylphenidate, Metoclopramide (sleepiness and Indication: Management of psychotic disorders.
dizziness)
Lithium (neurotoxic effect) Contraindications: Comatose state; CNS depression;
children <12 years; hepatic disease; blood dyscrasias;
Increases risk of adverse or toxic effects of the following bone marrow suppression; subcortical brain injury with
drugs: or without hypothalamic damage; marked cerebral
Acetylcholinesterase Inhibitors (extrapyramidal atherosclerosis; pheochromocytoma; pregnancy (third
symptoms) trimester); lactation.
Antihypertensives (hypotension)
Glucagon (GI adverse effects) Dose:
Iohexol, Iomeprol, Iopamidol (seizures) Psychotic disorders, by IM injection, ADULT (stabilized on
Mequitazine (arrhythmogenic effect), Mirabegron, oral fluphenazine), 12.5 mg/0.5 mL to 25 mg/1 mL into
Topiramate the deltoid or gluteal muscle; determine subsequent
QTc-prolonging Agents (torsades de pointes) Serotonin doses and intervals based on patient’s response;
Modulators (neuroleptic malignant syndrome; serotonin average dosing is usually 6.25–25 mg every 2 weeks or
syndrome) 50 mg/2 mL not longer than every 4 weeks; if doses >50
SSRIs (psychomotor impairment)

494
NERVOUS SYSTEM

mg are needed, increase cautiously in 12.5 mg up to a Adverse Drug Reactions:

maximum of 100 mg per dose. Common: Neuroleptic-induced deficit syndrome, akathisia,
priapism, extrapyramidal symptoms, parkinsonism,
Dose Adjustment: tardive dyskinesia, tardive dystonia, galactorrhea,
Geriatric: amenorrhea, sedation, dry mouth, urinary retention,
Use with caution and initiate with lower dose decreased sweating, sexual dysfunction, syncope, red to
red-brown urine, photosensitivity, long-term skin
Renal Impairment: pigmentation changes.
Use with caution and titrate slower. Monitoring is Less Common: Jaundice, cardiac arrhythmia, edema,
recommended. hypertension, hypotension, tachycardia, variable blood
pressure, akathisia, bizarre dream, cerebral edema,
Hepatic Impairment: depression, disruption of body temperature regulation,
Avoid in hepatic failure. Can precipitate coma. dizziness, drowsiness, dystonia, excitement, headache,
Phenothiazines are hepatotoxic. hyperreflexia, lethargy, Parkinsonian-like syndrome,
tardive dyskinesia, restlessness, dermatitis, eczema,
Precautions: erythema, pruritus, skin photosensitivity, seborrhea, skin
pigmentation, skin rash, urticaria, amenorrhea, change
WARNING: NOT approved for the treatment of
in libido, galactorrhea, gynecomastia, menstrual
patients with dementia-related psychosis. Elderly
disease, SIADH (syndrome of inappropriate antidiuretic
patients with dementia-related psychosis treated
hormone secretion), weight gain anorexia, constipation,
with antipsychotic drugs are at an increased risk
paralytic ileus, salivation, xerostomia, bladder paralysis,
of death, mostly associated with cardiovascular
ejaculatory disorder, impotence, mastalgia,
diseases (e.g. heart failure, sudden death) or
agranulocytosis, eosinophilia, leukopenia, lens disease,
infections (e.g. pneumonia).
nonthrombocytopenic purpura, urinary incontinence,
pancytopenia, thrombocytopenia hepatotoxicity muscle
Altered cardiac conduction (life-threatening arrhythmias); spasm (neck), systemic lupus erythematosus, tremor
orthostatic hypotension; cardiovascular disease; (fingers), blurred vision, corneal changes, glaucoma,
respiratory disorder; blood dyscrasias (agranulocytosis, retinitis pigmentosa, polyuria, asthma, laryngeal edema,

N
neutropenia, and leukopenia, some fatal). nasal congestion.
Anticholinergic effects (e.g., constipation, xerostomia, Rare: Cholestatic jaundice, cornea and lens pigmentation,
blurred vision, urinary retention); pheochromocytoma; blood dyscrasias (leukocytosis or leukopenia,
hyperprolactinemia; temperature regulation (impaired eosinophilia, thrombocytopenia, agranulocytosis),
core body temperature regulation); neuroleptic seizures, changes in body thermoregulation, neuroleptic
malignant syndrome. malignant syndrome.
CNS depression; extrapyramidal symptoms
(pseudoparkinsonism, acute dystonic reactions, NOTE: Patients taking this drug may experience weight gain
akathisia, and tardive dyskinesia; risk of dystonia may be and/or sedation.
greater with increased doses); Parkinson’s disease;
seizure disorder; ocular effects (cause pigmentary Drug Interactions:
retinopathy, and lenticular and corneal deposits); Monitor closely with:
glaucoma. Additive effect of drugs with:
Esophageal dysmotility or aspiration; hepatic effects (liver CNS depressants
damage and jaundice of the cholestatic type of
hepatitis); hepatic impairment; renal impairment; Additive cholinergic effects with:
masking. Atropine or related compounds
Elderly (increased risk of tardive dyskinesia, especially
among women; potentially inappropriate in the elderly; Enhances therapeutic effect of Fluphenazine:
avoid use in patients ≥65 years with dementia due to an Anticholinergics (anticholinergic effects)
increased risk of mortality and cerebrovascular
accidents, a greater rate of cognitive decline, and Enhances therapeutic effect of the following drugs:
potential to cause or exacerbate SIADH or hyponatremia, Antihypertensives [except Guanethidine], Beta Blockers
unless all nonpharmacologic options have failed or are [except Atenolol, Nadolol]
not possible or the patient is threatening substantial Vasopressors, e.g. Epinephrine (lowers blood pressure)
harm to self or to others). Thiopental (hypotensive effect; CNS excitatory effect)
Pregnancy (risk of abnormal muscle movements and
withdrawal symptoms in newborns with fetal exposure Increases risk of adverse or toxic effects of Fluphenazine:
during the third trimester); lactation (tardive dyskinesia, Diuretics (hypotension)
dystonia, and sedation have been observed in nursing Epinephrine (low blood pressure)
infants). Methylphenidate, Metoclopramide (sleepiness and
dizziness)
SKILLED TASKS. May impair ability to perform tasks, which Lithium (neurotoxic effect)
require mental alertness, like driving or operating
machinery. Increases risk of adverse or toxic effects of the following
drugs:
Diuretics (hypotension)
Glucagon (GI adverse effects)

495
 NERVOUS SYSTEM

Hypotension-associated Agents (hypotension) Iohexol,

Iomeprol, Iopamidol (seizures) Mequitazine Rx HALOPERIDOL
(arrhythmogenic effect) Methylphenidate, Mirabegron
Photosensitizing Agents (photosensitizing effect) Oral: 2 mg, 5 mg, and 10 mg tablet
QTc-prolonging Agents (torsades de pointes) Serotonin Inj.: 5 mg/mL, 1 mL ampule (IM)
Modulators (neuroleptic malignant syndrome; serotonin 50 mg/mL (as decanoate), 1 mL (oily) ampule (IM)
syndrome)
SSRIs (psychomotor impairment) Haloperidol is a butyrophenone typical antipsychotic that
Topiramate (hyperthermia) blocks postsynaptic dopamine D1 and D2 receptors in the
Reduces absorption of Fluphenazine: mesolimbic system and decreases the release of
Antacids hypothalamic and hypophyseal hormones. It has the
lowest relative risk for sedation, anticholinergic effects,
Reduces absorption of Nitroglycerin (decreases dissolution and hypotension, but conversely a very high relative risk
of sublingual nitroglycerin tablets) for extrapyramidal symptoms. It is also formulated as a
long-acting injectable in the form of its decanoate salt.
Reduces therapeutic effect of the following drugs:
Amphetamines (stimulant effect) Indications: Management of manifestations of psychotic
Guanethidine (antihypertensive effects) disorders; tics and vocal utterances in Tourette
Methylphenidate (inhibits stimulatory effects) Levodopa, syndrome; second-line treatment of severe behavior
Dopamine Agonists, Prokinetics, Secretin problems in children of combative, explosive
hyperexcitability; second-line short-term treatment of
Reduces therapeutic effect of Fluphenazine: hyperactive children; treatment of schizophrenic
Methylphenidate (inhibits antipsychotic and mood- patients who require prolonged parenteral antipsychotic
stabilizing activity) therapy.

Avoid concomitant use with: Contraindications: Comatose state, CNS depression,

Delayed gastric emptying with Potassium Salts (Oral) Parkinson’s disease, blood dyscrasias, bone marrow
suppression, subcortical brain injury, IV administration,
N

Enhances therapeutic effect of Fluphenazine: significant depressive states, previous spastic diseases,
CNS Depressant [high dose] (CNS depression) young children.

Increases risk of adverse or toxic effects of the following Dose:

drugs: Behavior disorders, by mouth, CHILD 3–12 years and 15–
Other Antipsychotics (increased hospitalization rates 40 kg, initially 0.5 mg daily in 2–3 divided doses, slowly
and length of stay; increased mortality; QTc increase by 0.5 mg once daily every 5–7 days to an
prolongation; torsades de pointes) average maintenance dose of 0.05–0.075 mg/kg daily
in 2–3 divided doses; no benefit is seen with doses
Administration: Administer by IM injection using a dry greater than 6 mg once daily.
syringe and needle of ≥21 gauge. A wet needle or syringe Manifestations of psychotic disorders, by mouth, ADULT,
may cause the solution to become cloudy. Z-track initially 1–6 mg daily in 2–3 divided doses for moderate
injection techniques are recommended to limit leakage cases or 6–15 mg daily in 2 to 3 divided doses for severe
after injections. cases, slowly titrate dose based on efficacy and
tolerability up to a maximum of 100 mg once daily; usual
Do NOT discontinue abruptly because of the possibility of maintenance is 3–10 mg daily; CHILD 3–12 years and
withdrawal and rebound psychosis. Discontinue or cross- 15–40 kg, initially 0.5 mg daily in 2–3 divided doses,
titrate gradually to minimize the potential of withdrawal, slowly increase by 0.5 mg once daily every 5–7 days to
rebound psychosis, extrapyramidal side effects, an average maintenance dose of 0.05–0.15 mg/kg daily
cholinergic rebound, rebound insomnia, and unwanted in 2–3 divided doses; no benefit is seen with doses >6
pregnancy, unless safety concerns require a more rapid mg once daily;
withdrawal. by IM injection (immediate-release), ADULT, initially 2–5
mg every hour, may administer subsequent doses as
Pregnancy Category: C often as every 60 minutes, although 4- to 8-hour
intervals may be satisfactory until symptoms are
ATC Code: N05AB02 controlled (maximum, 18 mg daily) switch to oral
formulation as soon as possible.
Schizophrenia requiring prolonged parenteral antipsychotic
therapy, by IM injection (long-acting), ADULT (stabilized
on oral haloperidol), 10–15 times the oral daily dose
(oral haloperidol ≤10 mg daily for elderly or debilitated)
or 20 times the oral daily dose (oral haloperidol >10 mg
daily for high risk of relapse) into the deltoid or gluteal
muscle, not exceeding 100 mg every 4 weeks; if dose
conversion exceeds 100 mg, administer a second
injection in 3–7 days; following initial dose, taper the oral
dose and discontinue following the subsequent 2 or 3

496
NERVOUS SYSTEM

injections; administer the total dose every 4 weeks with Rare: Cholestatic jaundice, blood dyscrasias (leukocytosis
a maximum dose of 450 mg. or leukopenia, eosinophilia, thrombocytopenia,
Tourette syndrome, by mouth, ADULT, initially 0.5 mg 2 or 3 agranulocytosis), neuroleptic malignant syndrome,
times daily, slowly titrate dose based on efficacy and seizures, changes in body thermoregulation.
tolerability up to a maintenance dose of 0.5–3 mg daily
or 0.25–15 mg daily, up to a maximum of 100 mg once NOTE: Patients taking this drug may experience weight gain
daily, CHILD 3-12 years, initially 0.5 mg daily in 2–3 and/or sedation.
divided doses, slowly increase by 0.5 mg once daily every
5–7 days to an average maintenance dose of 0.05 to Drug Interactions:
0.075 mg/kg daily in 2–3 divided doses; no benefit is Monitor closely with:
seen with doses >6 mg once daily. Enhances therapeutic effect of Haloperidol:
Anticholinergics (anticholinergic effects)
Dose Adjustment:
Geriatric: Enhances therapeutic effect of the following drugs:
Use with caution and initiate with lower dose. Antihypertensives [except Guanethidine], Beta Blockers
[except Atenolol, Nadolol] (antihypertensive effect)
Precautions: CNS Depressants (central effects)
WARNING: Elderly patients with dementia-related Vasopressors, e.g. Epinephrine (lowers blood pressure)
psychosis treated with antipsychotic drugs are at
an increased risk of death. Increases risk of adverse or toxic effects of Haloperidol:
Methylphenidate, Metoclopramide, NSAIDs
Lithium (encephalopathic syndrome)
Altered cardiac conduction (cases of sudden death, QT
prolongation, and torsades de pointes); orthostatic
Increases risk of adverse or toxic effects of the following
hypotension; cardiovascular disease; respiratory
drugs:
disorder; blood dyscrasias; some fatal)
Diuretics, Hypotension-associated Agents (hypotension)
Anticholinergic effects (e.g., constipation, xerostomia,
Glucagon (GI adverse effects)
blurred vision, urinary retention); hyperprolactinemia;
Iohexol, Iomeprol, Iopamidol (seizures)
neuroleptic malignant syndrome; temperature regulation

N
Mequitazine (arrhythmogenic effect)
(impaired core body temperature regulation); thyroid
Methylphenidate, Mirabegron
dysfunction.
Photosensitizing Agents (photosensitizing effect)
CNS depression; extrapyramidal symptoms (e.g.,
QTc-prolonging Agents (torsades de pointes)
pseudoparkinsonism, acute dystonic reactions,
Serotonin Modulators (neuroleptic malignant syndrome;
akathisia, and tardive dyskinesia; risk of dystonia may be
serotonin syndrome)
greater with increased doses); falls; bipolar disorder;
SSRIs (psychomotor impairment)
Parkinson disease; seizure disorder; glaucoma.
Topiramate (hyperthermia)
Esophageal dysmotility or aspiration.
Elderly (tardive dyskinesia, especially among women;
Reduces absorption of Nitroglycerin
potentially inappropriate; avoid use in patients ≥65 years
with dementia (mortality and cerebrovascular accidents,
Reduces therapeutic effect of Haloperidol:
cognitive decline, and SIADH or hyponatremia, unless all
Methylphenidate (inhibits antipsychotic and mood-
nonpharmacologic options have failed or are not
stabilizing activity)
possible or the patient is threatening substantial harm to
self or to others).
Reduces therapeutic effect of the following drugs:
Pregnancy (abnormal muscle movements and withdrawal
Prokinetics, Secretin
symptoms in newborns with fetal exposure during the
Amphetamines (stimulant effect)
third trimester); lactation (tardive dyskinesia, dystonia,
Dopamine Agonists (antagonism)
and sedation).
Guanethidine (antihypertensive effect)
SKILLED TASKS. May impair ability to perform tasks, which Methylphenidate (stimulatory effect)
require mental alertness, like driving or operating Urea Cycle Disorder Agents (increases plasma ammonia
machinery. concentrations)

Adverse Drug Reactions: Avoid concomitant use with:

Delayed gastric emptying with Potassium Salts (Oral)
Common: Syncope, extrapyramidal reaction, parkinsonian-
like syndrome, dystonia, dry mouth, hypertonia, Increases risk of adverse or toxic effects of the following
drowsiness, akathisia, headache, dizziness, neuroleptic- drugs:
induced deficit syndrome, decreased sweating, Nilotinib (QT prolongation; torsades de pointes)
galactorrhea, amenorrhea, constipation, abdominal Other Antipsychotics (increased hospitalization rates
pain, xerostomia, sialorrhea, constipation, urinary and length of stay; increased mortality; QTc
retention, hyperkinesia, tremor, bradykinesia, oculogyric prolongation; torsades de pointes)
crisis, long-term skin pigmentation changes, depression,
weight loss, tardive dyskinesia (long term use, Administration:
irreversible). For oral administration, may be taken with or without
Less Common: Dyspnea, edema food, but preferably taken with meals to minimize GI
irritation.

497
 NERVOUS SYSTEM

In End-stage renal disease (ESRD) with hemodialysis,

For IM injection as decanoate formulation, administer by administer dose after dialysis.
IM only, using a 21-gauge needle. Do NOT administer by
IV injection. The maximum volume per injection site is 3 Precautions:
mL. Z-track injection techniques are recommended to
limit leakage after injections.
WARNING: Lithium toxicity is closely related to serum
lithium levels and can occur at doses close to
Do NOT discontinue abruptly because of the possibility of
therapeutic levels. Facilities for prompt and
withdrawal and rebound psychosis. Discontinue or cross-
accurate serum lithium determinations should be
titrate gradually to minimize the potential of withdrawal,
available before initiating therapy. Monitor trough
rebound psychosis, extrapyramidal side effects,
lithium plasma levels frequently (1.0 and 1.5
cholinergic rebound, rebound insomnia, and unwanted
mEq/L for acute treatment and 0.6 and 1.2 mEq/L
pregnancy, unless safety concerns require a more rapid
for chronic treatment)
withdrawal.

Pregnancy Category: C CNS depression; depression; suicidal ideation;

heart failure, e.g., reversible myocardial toxicity;
ATC Code: N05AB02 cardiovascular disease; hypercalcemia; hypothyroidism;
thyroid disease; renal effects e.g. renal impairment,
dehydration.

Rx LITHIUM CARBONATE Debilitated patients and Elderly (lithium toxicity); women

(hypothyroidism).
Oral: 450 mg MR tablet
SKILLED TASKS. May impair ability to perform tasks, which
require mental alertness, like driving or operating
The mechanism of action of Lithium Carbonate is unclear,
machinery.
but is effective in managing mania, bipolar disorder, and
recurrent unipolar depression.
N

Adverse Drug Reactions:

Common: AV block or other conduction issues,
Indications: First-line treatment of manic episodes of bipolar
bradyarrhythmia, ECG changes, arrhythmias, QTc
disorder; maintenance treatment for bipolar disorder
prolongation, ataxia, dysarthria, delirium, tremor,
with a history of mania; maintenance treatment for
memory problems, diarrhea, acne, psoriasis, alopecia,
manic-depressive patients with a history of mania; manic
hypothyroidism, weight gain, nausea, dry mouth,
episodes of manic-depressive illness.
polyuria, benign leukocytosis.
Less Common: End stage renal disease, hypothyroidism
Contraindications: Severe kidney disease; severe
(children, adolescents), abnormal T waves, bradycardia,
cardiovascular disease; Brugada syndrome; severe
chest tightness, circulatory shock, cold extremities,
debilitation; severe dehydration; sodium depletion.
edema, hypotension, myxedema, startled response,
sinus node dysfunction, syncope, ataxia, blackout spells,
Dose:
cogwheel rigidity, coma, confusion, dizziness,
Treatment for bipolar disorder I (acute mania, acute
drowsiness, dystonia, EEG pattern changes,
depression),, by mouth, ADULT, initially 450 mg twice
extrapyramidal reaction, fatigue, hallucination,
daily, slowly titrate dose based on efficacy, tolerability,
headache, hyperactive deep tendon reflex, hypertonia,
and serum lithium concentrations to an average of 900–
involuntary choreoathetoid movements, lethargy,
1,800 mg daily in 2 divided doses; maintenance
memory impairment, local anesthesia, loss of
treatment of bipolar disorders I and II, initially 500 mg
consciousness, metallic taste, pseudotumor cerebri,
daily, increase gradually every 7 days until target blood
psychomotor retardation, reduced intellectual ability,
level is reached; maximum of 600-1200 mg daily.
restlessness, salty taste, sedation, seizure, slowed
Manic episodes of bipolar disorder, by mouth, ADULT,
intellectual functioning, slurred speech, stupor, tics,
initially 450 mg twice daily, slowly titrate dose based on
vertigo, worsening of organic brain syndromes, blue-gray
efficacy, tolerability, and serum lithium concentrations to
skin pigmentation, dermal ulcer, exacerbation of
an average of 1,800 mg daily in 2 divided doses; CHILD
psoriasis, folliculitis, pruritus, skin rash, xerosis,
≥12 years, initially 1.8 g daily in 2–3 divided doses.
albuminuria, dehydration, diabetes insipidus, euthyroid
goiter, glycosuria, hypercalcemia, hyperparathyroidism,
Dose Adjustment:
increased radioactive iodine uptake, hyperthyroidism,
Geriatric:
polydipsia, weight loss, abdominal pain, anorexia, dental
Lower doses and lower serum lithium concentrations are
caries, diarrhea, dysgeusia, dyspepsia, excessive
often adequate and advisable.
salivation, flatulence, gastritis, vomiting, sialadenitis,
sialorrhea, swelling of lips, xerostomia, impotence,
Renal Impairment:
incontinence, leukocytosis, angioedema, joint swelling,
Not recommended for use in patients with severe renal
muscle hyperirritability, neuromuscular excitability,
impairment.
polyarthralgia, tremor, blurred vision, exophthalmos,
In CrCl 10–50 mL/minute and in patients on continuous
nystagmus, transient scotoma, tinnitus, oliguria,
renal replacement therapy (CRRT), administer 50–75%
polyuria, fever.
of dose.
In CrCl <10 mL/minute, administer 25–50% of dose.

498
NERVOUS SYSTEM

Rare: Lithium toxicity, renal impairment (interstitial Indications: Management of schizophrenia; maintaining
nephritis), nephrogenic diabetes insipidus, acute tubular response in schizophrenia, acute phase schizophrenia;
necrosis, cardiovascular changes, sick sinus syndrome, acute agitation associated with schizophrenia, acute
bradycardia, hypotension, nephrotic syndrome, T wave mania or mixed mania; bipolar maintenance; acute
flattening and inversion, pseudotumor cerebri, seizures, agitation associated with bipolar I mania, bipolar
chronic kidney disease, syndrome of irreversible lithium- depression; treatment-resistant depression (in
effectuated neurotoxicity (SILENT), myasthenia gravis. combination with fluoxetine).

NOTE: Patients taking this drug may experience weight gain and/or Contraindications: Psychosis in Parkinson’s disease.
sedation.
Drug Interactions: Dose:
Monitor closely with: Acute mania or mixed mania, by mouth, ADULT and CHILD
Enhances therapeutic effect of the following drugs: ≥13 years, as monotherapy, initially 10 to 15 mg once
Linezolid, Methylene Blue, Opioids, SSRIs e.g., Fluoxetine daily, increase by 5 mg once daily at intervals of not less
(serotonergic effect) than 1 week until desired efficacy is reached (maximum
Neuromuscular Blockers (prolonged effects) Potassium dose, 20 mg once daily).
Iodide (hypothyroid effect) Acute mania/mixed mania, by mouth, ADULT and CHILD
QTc-prolonging Agents ≥13 years, as adjunct to lithium or valproate, initially 10
mg once daily, increase by 5 mg once daily at intervals of
Increases risk of adverse or toxic effects of lithium not less than 1 week until desired efficacy is reached
carbonate (maximum dose, 20 mg once daily).
Antipsychotics, CCBs e.g., Amlodipine, Carbamazepine, Bipolar I disorder maintenance, by mouth, ADULT, continue
Fosphenytoin, MAOIs [except Moclobemide], therapy at the lowest effective dose and adjust dose
Methyldopa, Phenytoin, Metronidazole, Sargramostim depending on clinical response and tolerability.
(myeloproliferative effects) Depression associated with bipolar 1 disorder, by mouth,
ADULT, in combination with fluoxetine, initially 5 mg once
Increases risk of adverse or toxic effects of the following daily in the evening, slowly titrate dose based on efficacy
drugs: and tolerability up to a maximum of 12.5 mg once daily

N
Dapoxetine, Haloperidol (encephalopathic syndrome), in the evening; CHILD ≥10 years, initially 2.5 mg once
Linezolid, Opioids, daily in the evening, slowly titrate dose based on efficacy
Serotonin Modulators [except Nicergoline, Tedizolid] and tolerability.
(serotonin syndrome) Schizophrenia, by mouth, ADULT and CHILD ≥13 years,
Methylphenidate, SSRIs e.g. Fluoxetine (serotonin initially 5–10 mg once daily, increase by 5 mg once daily
syndrome) Metoclopramide (serotonin syndrome; once a week until desired efficacy is reached (maximum
neuroleptic malignant syndrome) dose, 20 mg once daily).
TCAs e.g., Amytriptylline (neurotoxic effect) Treatment-resistant depression, by mouth, ADULT, in
Tramadol (seizures) combination with fluoxetine, initially 5 mg once daily in
the evening, slowly titrate dose based on efficacy and
Reduces therapeutic effect of the following drugs: tolerability (maximum, 12.5 mg once daily in the
Amphetamines (stimulatory effect) evening).
Desmopressin
Dose Adjustment:
Administration: Should be taken with food. Geriatric:
May tolerate lower doses better.
Maintain normal fluid and salt intake during therapy.
Hepatic Impairment:
Pregnancy Category: D For moderate to severe hepatic impairment, consider initial
dose of 5 mg daily. When used in combination with
ATC Code: N05AN01 fluoxetine, limit initial dose to 2.5–5 mg once daily.
Increase dose with caution.

Rx OLANZAPINE Debilitated Patients with a predisposition to Hypotensive

reactions, who exhibit a combination of factors that may
result in slower metabolism, e.g., nonsmoking female
Oral: 5 mg and 10 mg tablet patients ≥65 years), or who may be more
10 mg orodispersible tablet (ODT) pharmacodynamically sensitive to olanzapine:
Initiate at 5 mg once daily, increase dose with caution as
Olanzapine is a thienobenzodiazepine structurally related to clinically indicated.
clozapine. It is more potent and less sedating than
clozapine. It also has low risk for extrapyramidal Precautions:
symptoms, even at high doses. However, it has the
greatest known cardiometabolic risks, because it WARNING: NOT approved for treatment of dementia-
increases triglyceride levels and promotes insulin related psychosis (increased risk of death)
resistance.
Altered cardiac conduction, e.g., life-threatening
arrhythmias; orthostatic hypotension; cardiovascular

499
 NERVOUS SYSTEM

disease; blood dyscrasias, e.g., leukopenia, neutropenia, Serotonin Modulators (neuroleptic malignant syndrome;
and agranulocytosis; dyslipidemia; hyperglycemia; serotonin syndrome)
hyperprolactinemia (dose-related); Anticholinergic SSRIs (psychomotor impairment)
effects, e.g., constipation, xerostomia, blurred vision, Topiramate (hyperthermia)
urinary retention; esophageal dysmotility or aspiration;
multiorgan hypersensitivity reactions (drug reaction with Reduces absorption of Nitroglycerin (decreases dissolution
eosinophilia and systemic symptoms [DRESS]); of sublingual nitroglycerin tablets)
neuroleptic malignant syndrome; temperature
regulation, e.g., impaired core body temperature Reduces therapeutic effect of Olanzapine:
regulation; cerebrovascular effects; CNS depression; Methylphenidate (antipsychotic and mood- stabilizing
extrapyramidal symptoms, e.g., dystonic reactions, actions)
pseudoparkinsonism, akathisia, and tardive dyskinesia;
greater risk for dystonia with increased doses; greater Reduces therapeutic effect of the following drugs:
risk for falls; suicidal ideation; Parkinson disease; Phenylephrine, Prokinetics, Secretin, Antidiabetics,
seizures; weight gain; hepatic impairment; renal Anticholinergics
impairment Methylphenidate (stimulant effect)
Dopamine Agonists (antagonism)
Smokers (decreases olanzapine concentration; may require Guanethidine (antihypertensive effects)
daily doses 30% higher to obtain an equivalent
concentration); Elderly (more susceptible to adverse Avoid concomitant use with:
effects; potentially inappropriate in the elderly; avoid use Increases risk of adverse or toxic effects of the following
in patients ≥65 years with dementia due to an increased drugs:
risk of mortality and cerebrovascular accidents, a greater Other Antipsychotics (increased hospitalization rates
rate of cognitive decline, and potential to cause or and length of stay; increased mortality; QTc
exacerbate SIADH or hyponatremia, unless all non- prolongation; torsades de pointes)
pharmacologic options have failed or are not possible or
the patient is threatening substantial harm to self or to Administration:
others); children (safety of doses >12 mg in combination Olanzapine orodispersible tablet may be placed on the
N

with doses >50 mg of fluoxetine has not been studied; tongue and allowed to dissolve, or dispersed in water,
use in adolescents ≥13 years of age may result in orange juice, apple juice, milk or coffee. May be taken
increased weight gain, sedation, and increases in LDL with or without food.
cholesterol, total cholesterol, triglycerides, prolactin, and
liver transaminase levels). Do NOT discontinue abruptly because of the possibility of
withdrawal and rebound psychosis. Perform
SKILLED TASKS. May impair ability to perform tasks, which discontinuation or cross-titration gradually to minimize
require mental alertness, like driving or operating the potential of withdrawal, rebound psychosis,
machinery. extrapyramidal side effects, cholinergic rebound,
rebound insomnia, and unwanted pregnancy, unless
Adverse Drug Reactions: safety concerns require a more rapid withdrawal.
Common: Arthralgia, hypercholesterolemia,
hypertriglyceridemia, increased appetite, malaise, Pregnancy Category: C
edema.
Less Common: Alopecia, amnesia, bradycardia, epistaxis. ATC Code: N05AH03
Rare: Hepatitis, pancreatitis, rhabdomyolysis.

NOTE: Patients taking this drug may experience weight gain

and/or sedation. Rx PALIPERIDONE

Drug Interactions: Inj.: 50 mg/0.5 mL, 75 mg/0.75 mL, 100 mg/mL, and
Monitor closely with: 150 mg/1.5 mL prolonged-release suspension for
Enhances therapeutic effect of the following drugs: injection (IM)
Antihypertensives [except Guanethidine], CNS
Depressants (sedative effect), QTc-prolonging Agents Paliperidone is a benzisoxazole atypical antipsychotic, and
(QTc-prolonging effect) a metabolite of risperidone. It is an antagonist at
dopamine (D2), serotonin (5-HT2A), adrenergic (α1 and
Increases risk of adverse or toxic effects of Olanzapine: α2), and histamine (H1) receptors. Paliperidone is not
Methylphenidate, Metoclopramide hepatically metabolized and is eliminated via the urine,
giving it less drug interactions.
Increases risk of adverse or toxic effects of the following
drugs: Indications: Maintenance in schizophrenia; maintaining
Glucagon (GI adverse effects) stability in schizophrenia; schizoaffective disorder;
Hypotension- associated Agents (hypotension)
Iohexol, Iomeprol, Iopamidol (seizures) Contraindications: History of QTc prolongation or cardiac
Mequitazine (arrhythmogenic effect) arrhythmia; recent acute myocardial infarction;
Methylphenidate, Mirabegron uncompensated heart failure; preexisting severe GI
Potassium Chloride (ulcerogenic effect) narrowing.

500
NERVOUS SYSTEM

Administer second dose of

Dose: 100 mg by intramuscular
Maintaining stability in schizophrenia, by intramuscular injection into the deltoid
injection, ADULT, stabilize service user/patient on oral muscle as soon as possible,
paliperidone. Initially, 150 mg injected into the deltoid 4-7 weeks since first followed by another 100 mg
muscle, followed after 1 week (±4 days) by 100 mg injection by intramuscular injection
injected into the deltoid muscle. Monthly maintenance into the deltoid muscle one
doses (±7 days) may be administered after the second week after the second dose.
loading dose in the gluteal muscle or the deltoid muscle Resume regular monthly
and dosed based on the oral dose the service dosing after.
user/patient is stabilized on: >7 weeks since first Restart with recommended
12 mg by mouth once daily = 150 mg by intramuscular injection initiation dosing schedule.
injection once a month Missed Doses – Maintenance Dose
9 mg by mouth once daily = 100 mg by intramuscular Resume previous schedule
injection once a month 4-6 weeks since last
and dose as soon as
6 mg by mouth once daily = 75 mg by intramuscular dose
possible.
injection once a month If maintenance dose <150
3 mg by mouth once daily = 25-50 mg by intramuscular mg, administer the dose by
injection once a month. intramuscular injection into
Schizoaffective disorder, by intramuscular injection, ADULT, the deltoid muscle as soon
stabilize service user/patient on oral paliperidone. as possible and administer a
Initially, 150 mg injected into the deltoid muscle, second previously stabilized
followed after 1 week (±4 days) by 100 mg injected into dose after 1 week
the deltoid muscle. Monthly maintenance doses (±7
days) ranging from 25-150 mg may be administered >6 weeks and ≤6 If maintenance dose is 150
after the second loading dose in the gluteal muscle or months since last mg, administer a 100 mg
the deltoid muscle and dosed based on the oral dose the injection dose by intramuscular
service user/patient is stabilized on: injection into the deltoid

N
12 mg by mouth once daily = 150 mg by intramuscular muscle as soon as possible
injection once a month and administer a second 100
9 mg by mouth once daily = 100 mg by intramuscular mg dose after 1 week
injection once a month
6 mg by mouth once daily = 75 mg by intramuscular Continue with the previously
injection once a month stabilized dose 1 week after
3 mg by mouth once daily = 25-50 mg by intramuscular the second injection.
injection once a month. Restart with the
Schizophrenia, by intramuscular injection, >6 months since last
recommended initiation
ADULT/CHILD≥12 years, stabilize service user/patient injection
dosing schedule.
on oral paliperidone. Initially, 150 mg injected into the
deltoid muscle, followed after 1 week (±4 days) by 100 NOTE: Antipsychotics should not be discontinued abruptly because of
mg injected into the deltoid muscle. Monthly the possibility of withdrawal and rebound psychosis;
maintenance doses (±7 days) may be administered after discontinuation or cross-titration should be done gradually to
the second loading dose in the gluteal muscle or the minimize the potential of withdrawal, rebound psychosis and
deltoid muscle and dosed based on the oral dose the extrapyramidal side effects, cholinergic rebound, rebound
insomnia, and unwanted pregnancy, unless safety concerns
service user/patient is stabilized on:
require a more rapid withdrawal.
12 mg by mouth once daily = 150 mg by intramuscular
injection once a month Dose Adjustment:
9 mg by mouth once daily = 100 mg by intramuscular Geriatric:
injection once a month Some patients may tolerate lower doses better;
6 mg by mouth once daily = 75 mg by intramuscular antipsychotics are considered to be potentially
injection once a month inappropriate in in the elderly. and to be avoided in
3 mg by mouth once daily = 25-50 mg by intramuscular service patients 65 years and older with dementia due to
injection once a month. an increased risk of mortality, cerebrovascular accidents
(stroke), a greater rate of cognitive decline with use, and
Missed Doses – Second Initiation Dose potential to cause or exacerbate or hyponatremia unless
Administer second dose of all nonpharmacologic options have failed or are not
100 mg by intramuscular possible or the service user/patient is threatening
injection into the deltoid substantial harm to self or to others. It may be
muscle as soon as possible, appropriate for use in schizophrenia.
<4 weeks since first followed by a third dose of
injection 75 mg by intramuscular Renal Impairment:
injection into the deltoid or For mild renal impairment (CrCl≥50 mL/min and <80
gluteal muscle 5 weeks after mL/min), reduce initiation doses to 100 mg by
the first injection (regardless intramuscular injection on day 1 and 75 mg by
of timing of second dose) intramuscular injection after 1 week. Administer a

501
 NERVOUS SYSTEM

maintenance dose of 50 mg by intramuscular injection

once a month. Do not mix with any other product or diluent. Prior to
Not recommended for use in service patients with moderate injection, shake syringe for at least 10 seconds to ensure
to severe renal impairment (CrCl<50 mL/min). a homogenous suspension. Administer using only the
needles that are provided in the kit. The 2 initial
Hepatic Impairment: injections should be administered in the deltoid muscle
No dose adjustment necessary in mild to moderate hepatic using a 11/2 inch, 22-gauge needle for service patients
impairment. Not studied in severe hepatic impairment. ≥90 kg, and a 1 inch, 23-gauge needle for service
patients <90 kg. The 2 initial deltoid intramuscular
Precautions: injections help attain therapeutic concentrations rapidly.
Alternate deltoid injections (right and left deltoid
WARNING: NOT approved for treatment of dementia-
muscle). The second dose may be administered 4 days
related psychosis (increased risk of death)
before or after the weekly time point. Monthly
maintenance doses can be administered in either the
STORAGE AND STABILITY: Store between 20-25°C. deltoid or gluteal muscle. Administer injections in the
Excursions permitted to 15-30°C. Protect from moisture. gluteal muscle using a 11/2 inch, 22-gauge needle
(regardless of service user/patient weight) in the upper-
Adverse Drug Reactions: outer quadrant of the gluteal area. Alternate gluteal
Common: Dose-dependent extrapyramidal symptoms, injections (right and left gluteal muscle). The monthly
hyperprolactinemia, anxiety, appetite changes, maintenance dose may be administered 7 days before
arthralgia, depression, epistaxis, hypertension, infection, or after the monthly time point.
malaise, myalgia, edema, respiratory disorders, sleep
disorders, toothache, urinary disorders; may increase Pregnancy Category: C
risk for diabetes and dyslipidemia.
Less Common: Alopecia, hypoesthesia, paresthesia, taste ATC Code: N05AX13
disturbances, tinnitus, visual disorders.
Rare: Inappropriate antidiuretic hormone secretion-
obstruction, intra-operative floppy iris syndrome,
QUETIAPINE
N

pancreatitis, pulmonary embolism, rhabdomyolysis. Rx

NOTE: Patients taking this drug may experience weight gain Oral: 25 mg, 100 mg, 200 mg, and 300 mg tablet (as
and/or sedation. fumarate)
Drug Interactions: Quetiapine is dibenzothiazepine atypical antipsychotic
Monitor closely with: structurally related to clozapine. It is a dopamine D1,
Reduces the therapeutic effects of the following drugs: dopamine D2, 5-HT2 alpha1-adrenoceptor, and
Amphetamines, Antidiabetics, Dopamine agonists, histamine-1 receptor antagonist.
Levodopa
Indications: Management of acute schizophrenia,
Enhances the therapeutic effects of CNS depressants e.g. schizophrenia maintenance, acute bipolar mania,
Alcohol bipolar maintenance, bipolar depression, bipolar
maintenance, depression (as an adjunct only)
Increases risk adverse/toxic effect of Paliperidone:
Metoclopramide
Dose:
Acute bipolar mania, by mouth, ADULT, monotherapy and
Increases risk of adverse or toxic effects of the following
adjunct to lithium/valproate: initially 50 mg twice daily.
drugs:
Increase by 50 mg twice daily each day up to 200 mg
Iohexol, Iomeprol, Iopamidol (seizures)
twice daily. Further dose increases up to a maximum of
QTc-prolonging agents, Methylphenidate
400 mg twice daily should be done in increments of no
Mequitazine (arrhythmogenic effect)
greater than 100 mg twice daily, CHILD≥10 years,
Serotonin modulators (neuroleptic malignant syndrome;
monotherapy: initially 25 mg twice daily. Increase to 50
serotonin syndrome)
mg twice daily on day 2, then increase by 50 mg twice
SSRIs (psychomotor impairment)
daily each day up to 200 mg twice daily on day 5. Further
Acetylcholinesterase inhibitors (neurotoxic effect; severe
dose adjustments may be done in increments of ≤100
extrapyramidal symptoms)
mg/day up to a maximum of 600 mg/day in 2-3 divided
Avoid concomitant use with: doses.
Increases risk of adverse or toxic effects of the following Acute schizophrenia, by mouth, ADULT, initially 25 mg twice
drugs: daily. Increase in increments of 25-50 mg/day twice or
Other Antipsychotics (increased hospitalization rates thrice daily each day until an average of 300-400
mg/day in 2-3 divided doses on day 4. Further dose
and length of stay; increased mortality; QTc
adjustments should be done at intervals of no less than
prolongation; torsades de pointes)
2 days in increments of 25-50 mg twice daily up to a
Administration: Administer by IM route only as a single maximum dose of 400 mg twice daily, CHILD≥13 years,
initially 25 mg twice daily. Increase to 50 mg twice daily
injection (do not divide); do not administer by any other
on day 2 then further increase by 100 mg/day divided
route. Avoid inadvertent injection into vasculature.
into 2 doses until 400 mg/day divided into 2 doses is

502
NERVOUS SYSTEM

reached on day 5. Further dose increases may be done Reduced drug clearance with:
in increments of ≤100 mg/day up to a maximum of 800 Lorazepam (by 20%)
mg/day in 2-3 divided doses.
Bipolar depression, by mouth, ADULT, initially 50 mg once Enhances the therapeutic effects of the following drugs:
daily at bedtime. Increase to 100 mg once daily at CNS depressants, Antihypertensives [except
bedtime on day 2. Increase by 100 mg/day as needed guanethidine]
up to a maximum of 300 mg once daily at bedtime on
day 4. Increases risk adverse/toxic effect of Quetiapine:
Bipolar maintenance, by mouth, ADULT, continue therapy at Metoclopramide
the lowest effective dose and adjust dose depending on
clinical response and tolerability. Increases risk of adverse or toxic effects of the following
Schizophrenia maintenance, by mouth, 150–750 mg/day drugs:
(in divided doses) Iohexol, Iomeprol, Iopamidol (seizures)
Depression, adjunct to any antidepressant, by mouth, 25 Mequitazine (arrhythmogenic effect)
mg once daily Serotonin modulators (neuroleptic malignant syndrome)
SSRIs (psychomotor impairment)

NOTE: Antipsychotics should not be discontinued abruptly Lorazepam – quetiapine may reduce the clearance of
because of the possibility of withdrawal and rebound lorazepam by 20%
psychosis; discontinuation or cross-titration should be Serotonin modulators – may enhance the risk of
done gradually to minimize the potential of withdrawal, neuroleptic malignant syndrome and serotonin
rebound psychosis and extrapyramidal side effects, syndrome with antipsychotics
cholinergic rebound, rebound insomnia, and unwanted
pregnancy, unless safety concerns require a more rapid Avoid concomitant use with:
withdrawal. Increases risk of adverse or toxic effects of other
Antipsychotics (increased hospitalization rates and
Dose Adjustment: length of stay; increased mortality)
Geriatric:

N
Lower doses are generally used, but higher doses may be Administration: May be taken with or without food.
used if tolerated; initially 50 mg once daily and may
increase in increments of 50 mg/day to an effective dose Pregnancy Category: C
based on efficacy and tolerability
ATC Code: N05AH04
Hepatic Impairment:
Initially 25 mg once daily or in 2 divided doses. Slowly
increase by 25-50 mg once daily to effective dose. Rx RISPERIDONE
Precautions:
WARNING: NOT approved for treatment of dementia- Oral: 1 mg, 2 mg, 3 mg, and 4 mg tablet
related psychosis (increased risk of death) 1 mg and 2 mg orodispersible tablet
1 mg/mL oral solution, 100 mL
Cerebrovascular disease; elderly patients at risk of Inj.: 25 mg and 37.5 mg MR powder for suspension, vial
aspiration pneumonia; treatment of depression in + 2 mL diluent in pre-filled syringe (IM)
patients under 25 years (increased risk of suicide) 50 mg prolonged-release powder for suspension for
injection (IM) + 2 mL diluent

STORAGE AND STABILITY: Store between 20-25°C. Risperidone is a benzisoxazole atypical antipsychotic that
Excursions permitted to 15-30°C. gains typical properties such as extrapyramidal
symptoms when given in higher doses. It has a moderate
Adverse Drug Reactions: risk of inducing weight gain and dyslipidemia.
Common: Asthenia, dysarthria, dyspnea, increased
appetite, irritability, peripheral edema, sleep disorders, Indications: Treatment of schizophrenia; delaying relapse in
dizziness, increased risk for diabetes and dyslipidemia schizophrenia; other psychotic disorders; treatment of
Less Common: Hyponatremia, hypothyroidism, restless legs acute and long term mania/mixed mania (monotherapy
syndrome, rhinitis. and adjunct to lithium or valproate); autism-related
Rare: Angioedema, inappropriate secretion of antidiuretic irritability in children; bipolar maintenance (monotherapy
hormone, rhabdomyolysis, SJS. and adjunct to lithium or valproate)

NOTE: Patients taking this drug may experience weight gain and/or Dose:
sedation. Acute mania/mixed mania, monotherapy and adjunct to
lithium or valproate, by mouth, ADULT, initially 2-3 mg
Drug Interactions: once daily or in two divided doses. Slowly increase by 1
Monitor closely with: mg once daily each day until desired efficacy is reached
Reduces the therapeutic effects of the following drugs: up to a maximum of 6 mg once daily, CHILD≥10 years,
Amphetamines, Guanethidine initially 0.5 mg once daily or in two divided doses. Slowly
increase by 0.5-1 mg once daily each day until desired

503
 NERVOUS SYSTEM

efficacy is reached up to a maximum of 6 mg once daily, >5 mg by mouth once daily = 50 mg by intramuscular
with doses >2.5 mg daily not conferring additional injection every 2 weeks.
benefit and are associated with increased adverse Continue therapy at the lowest effective dose and adjust
events. dose depending on clinical response and tolerability at
Autism-related irritability, by mouth, CHILD≥5 years (15 to intervals of no more than 4 weeks.
<20 kg), initially 0.25 mg once daily or in two divided NOTE: Antipsychotics should not be discontinued abruptly
doses. Increase dose to 0.5 mg once daily after at least because of the possibility of withdrawal and rebound
4 days and maintain dose for at least 14 days. If psychosis; discontinuation or cross-titration should be
response is insufficient, slowly increase dose by 0.25 mg done gradually to minimize the potential of withdrawal,
once daily not earlier than every 2 weeks up to a rebound psychosis and extrapyramidal side effects,
maximum of 3 mg once daily or in two divided doses, cholinergic rebound, rebound insomnia, and unwanted
CHILD≥5 years (≥20 kg), initially 0.5 mg once daily or in pregnancy, unless safety concerns require a more rapid
two divided doses. Increase dose to 1 mg once daily after withdrawal.
at least 4 days and maintain dose for at least 14 days. If
response is insufficient, slowly increase dose by 0.5 mg Dose Adjustment:
once daily not earlier than every 2 weeks up to a Geriatric:
maximum of 3 mg once daily or in two divided doses. Initially 0.5 mg twice daily. Slowly increase by 0.5 mg twice
Bipolar maintenance, monotherapy and adjunct to lithium daily and increase dose not more than once a week for
or valproate, by intramuscular injection, ADULT, initially doses above 1.5 mg twice daily.
stabilize service user/patient on oral risperidone.
Administer 12.5-25 mg into the deltoid or gluteal muscle. Renal Impairment:
Continue oral risperidone for 3 weeks before Initially 0.5 mg by mouth twice daily for the first week.
discontinuing and administer maintenance doses based Increase to 1 mg by mouth twice daily on the second
on the oral dose the service user/patient is stabilized on: week. Slowly increase doses beyond 1.5 mg by mouth
≤3 mg by mouth once daily = 25 mg by intramuscular twice daily at intervals of 1 week or longer.
injection every 2 weeks For long-acting injectable formulation, do not administer
3-≤5 mg by mouth once daily = 37.5 mg by intramuscular unless service user/patient has demonstrated
injection every 2 weeks tolerability to at least 2 mg by mouth once daily or in
N

>5 mg by mouth once daily = 50 mg by intramuscular divided doses. An initial dose of 12.5 mg may be more
injection every 2 weeks. appropriate. Maintenance doses should be 25 mg every
Continue therapy at the lowest effective dose and adjust two weeks, with oral risperidone being continued for 3
dose depending on clinical response and tolerability at weeks after the first injection.
intervals of no more than 4 weeks.
Delaying relapse in schizophrenia, by mouth, ADULT, initially Hepatic Impairment:
1 mg/day in two divided doses. Slowly increase by 1 mg Initially 0.5 mg by mouth twice daily for the first week.
once daily each day until desired efficacy is reached up Increase to 1 mg by mouth twice daily on the second
to a maximum of 6 mg once daily. Clinical benefit and week. Slowly increase doses beyond 1.5 mg by mouth
risk of EPS beyond 6 mg usually does not warrant twice daily at intervals of 1 week or longer.
exceeding 6 mg once daily up to 16 mg once daily. For long-acting injectable formulation, do not administer
Psychosis, by mouth, initialy 1 mg daily, gradually increase unless service user/patient has demonstrated
to 2-6 mg daily; for a maximum of 10 mg. tolerability to at least 2 mg by mouth once daily or in
Other psychotic disorders, by mouth, ADULT, initially 1 divided doses. An initial dose of 12.5 mg may be more
mg/day in two divided doses. Slowly increase by 1 mg appropriate. Maintenance doses should be 25 mg every
once daily each day until desired efficacy is reached up two weeks, with oral risperidone being continued for 3
to a maximum of 6 mg once daily. Clinical benefit and weeks after the first injection.
risk of EPS beyond 6 mg usually does not warrant
exceeding 6 mg once daily up to 16 mg once daily. Precautions:
Schizophrenia, by mouth, ADULT, initially 1 mg/day in two WARNING: NOT approved for treatment of dementia-
divided doses. Slowly increase by 1 mg once daily each related psychosis (high risk of cardiovascular and
day until desired efficacy is reached up to a maximum of infectious-related deaths).
6 mg once daily. Clinical benefit and risk of EPS beyond
6 mg usually does not warrant exceeding 6 mg once daily Pregnancy: There is a risk of abnormal muscle movements
up to 16 mg once daily, CHILD≥13 years, initially 0.5 mg and withdrawal symptoms in newborns during the third
once daily or in two divided doses. Slowly increase by 0.5- trimester.
1 mg once daily each day until desired efficacy is reached Hypersensitivity
up to a maximum of 6 mg once daily, by intramuscular
injection, ADULT, initially stabilize service patient on oral STORAGE AND STABILITY: Tablet: store between 20-25°C.
risperidone. Administer 12.5-25 mg into the deltoid or Excursions permitted to 15-30°C. Protect from light and
gluteal muscle. Continue oral risperidone for 3 weeks moisture. Orodispersible tablet: No special storage
before discontinuing and administer maintenance doses conditions. Oral solution: store between 15-25°C.
based on the oral dose the service user/patient is Excursions permitted to 15-30°C. Protect from light and
stabilized on: freezing. Long-acting injectable: The entire dose pack
≤3 mg by mouth once daily = 25 mg by intramuscular should be stored in the refrigerator between 2–8°C and
injection every 2 weeks protected from light. If refrigeration is unavailable, it can
3-≤5 mg by mouth once daily = 37.5 mg by intramuscular be stored at temperatures not exceeding 25°C for no
injection every 2 weeks

504
NERVOUS SYSTEM

more than 7 days prior to administration. Do not expose ANXIOLYTICS

unrefrigerated product to temperatures above 25°C.

Adverse Drug Reactions: Rx ALPRAZOLAM

Common: Anxiety, appetite changes, arthralgia, depression,
dose-dependent extrapyramidal symptoms, dose-related
Oral: 250 micrograms, 500 micrograms, and 1 mg tablet
hyperprolactinemia, dose-dependent dizziness,
insomnia, anxiety, sedation, epistaxis, hypertension,
Alprazolam is a short-acting benzodiazepine which causes a
infection, malaise, myalgia, edema, respiratory
dose-related CNS depressant activity varying from mild
disorders, sleep disorders, toothache, urinary disorders,
impairment of task performance to hypnosis.
weight gain, sedation, dizziness, hypotension, motor side
Indications: Acute treatment of generalized anxiety disorder,
effect, dose-dependent extrapyramidal symptoms, dose-
acute treatment of panic disorder with or without
dependent hyperprolactinemia
agoraphobia. Adjunct for acute mania and acute
Less Common: Alopecia, hypoesthesia, paresthesia, taste
psychosis, generalized anxiety disorder, panic disorder.
disturbances, tinnitus, visual disorders.
Rare: Inappropriate antidiuretic hormone secretion,
NOTE: Alprazolam does not have analgesic, antidepressant,
intestinal obstruction, intra-operative floppy iris
or antipsychotic properties.
syndrome, pancreatitis, pulmonary embolism,
rhabdomyolysis.
Contraindications: Narrow-angle glaucoma, myasthenia
gravis, history of substance use disorder, respiratory
NOTE: Patients taking this drug may experience weight gain
disorders (e.g. chronic obstructive pulmonary disease,
and/or sedation.
sleep apnea), significant hepatic disease, pregnancy,
labor, lactation.
Drug Interactions:
Monitor closely with:
Dose:
Reduces the therapeutic effects of the following drugs:
NOTE: Treatment >4 weeks should be reevaluated to
Amphetamines, Dopamine agonists, Levodopa
determine the service user/patient's continued need for
the drug.

N
Enhances the therapeutic effects of the following drugs:
Antihypertensives [except Guanethidine]
Generalized anxiety disorder, by mouth, ADULT, Immediate
Increases therapeutic effects of Risperidone:
release: initially 0.75-1.5 mg/day in 3 divided doses.
Anticholinergics
Slowly titrate dose every 3-4 days until desired efficacy is
reached with a maximum dose of 4 mg/day. Assess need
Increases risk adverse/toxic effect of Risperidone:
for continued treatment regularly as benzodiazepines
Acetylcholinesterase inhibitors, Metoclopramide,
should generally be used for not more than 4 weeks for
Valproate (increase the risk of generalized edema with
anxiety disorders.
and the clearance of risperidone)
Panic disorder, by mouth, ADULT:
Increases risk of adverse or toxic effects of the following
Immediate release: initially 1.5 mg/day in 3 divided
drugs:
doses. Slowly increase by ≤1 mg/day every 3-4 days until
CNS depressants, Methylphenidate
desired efficacy is reached. Slowly increase by small
Iohexol, Iomeprol, Iopamidol (seizures)
amounts for dosages beyond 4mg/day. Doses as high as
Mequitazine (arrhythmogenic effect)
10 mg/day may be required for difficult cases. Assess
QTc-prolonging agents
need for continued treatment regularly as
SSRIs (psychomotor impairment)
benzodiazepines should generally be used for not more
than 4 weeks for anxiety disorders.
Avoid concomitant use with:
Increases risk of adverse or toxic effects of the following
Extended release: initially 0.5-1 mg once daily in the
drugs:
morning. Slowly increase by ≤1 mg/day every 3-4 days
Other Antipsychotics (increased hospitalization rates
until desired efficacy is reached up to a maximum dose
and length of stay; increased mortality)
of 10 mg once daily. Assess need for continued
treatment regularly as benzodiazepines should generally
Administration: May be taken with or without food.
be used for not more than 4 weeks for anxiety disorders.
Intramuscular injection into the deltoid or gluteal muscle.
Switching from immediate release to extended release:
Pregnancy Category: C
Service patients may be switched to extended release
tablets by taking the total daily dose of the immediate
ATC Code: N05AX08
release tablets and giving it once daily using the
extended release preparation.

Adjunct for acute mania and acute psychosis in patients

who are in acute agitation, by mouth, 250 mcg-1mg
every hour (maximum of 3 doses) provided that vital
signs are monitored

505
 NERVOUS SYSTEM

NOTE: Dose reduction: Abrupt discontinuation should be NOTE: Patients taking this drug may experience sedation.
avoided. Generally, the dose is reduced by 25% per week
until 50% of the dose is reached, then the dose is Drug Interactions:
reduced by one-eighth every 4-7 days. If therapy is >8 Monitor closely with:
weeks, slowly taper over 2-3 weeks. If therapy is >6 Enhances the therapeutic effects of CNS Depressants e.g.,
months, slowly taper over 4-8 weeks. If therapy is >1 Alcohol
year, slowly taper over 2-4 months.
Increases risk of adverse or toxic effects of SSRIs e.g.
Dose Adjustment: Fluoxetine (psychomotor impairment)
Geriatric:
Immediate release: Initial 0.25 mg twice or thrice daily. Avoid concomitant use with:
Extended release: Initial: 0.5 mg once daily. Increases the serum concentration of Alprazolam:
Itraconazole, Ketoconazole (Systemic), Estrogen-
NOTE: Elderly service patients may be more sensitive to the containing hormonal contraceptives
effects of alprazolam including ataxia and oversedation.
The elderly may also have impaired renal function Administration:
leading to decreased clearance. Titrate gradually, if NOTE: May be administered with or without food. If drug
needed and tolerated. upsets stomach, take with food.

Renal Impairment: Immediate release preparations: Can be administered

Start with small doses in severe impairment. sublingually if oral administration is not possible;
absorption and onset of effect are comparable to oral
Hepatic Impairment: administration.
For service patients with advanced liver disease: Extended release tablet: Should be taken once daily in the
Immediate release: 0.25 mg twice or thrice daily; titrate morning; do not crush, break, or chew.
slowly if needed and tolerated. Orally disintegrating tablets: Do not remove tablets from the
Extended release: 0.5 mg once daily; titrate slowly if needed container until just prior to administration. Do not push
and tolerated. the tablet out of the foil when opening. Using dry hands,
N

place tablet on top of tongue and allow to disintegrate. If

Precautions: using one half of tablet, immediately discard remaining
NOTE: half (may not remain stable). Administration with water
Muscle weakness; is not necessary. Do not swallow it whole. Do not chew,
Organic brain changes break, or crush it. Discard any cotton included in the
Personality disorder (within the fearful group) dependent, container and reseal the container tightly after opening
avoidant, obsessive-compulsive) to prevent introduction of moisture.
Patients may develop dependence/tolerance with long-term
use. Pregnancy Category: D
Pregnancy (not recommended as treatment for anxiety
during pregnancy, especially during the first trimester). BREAST-FEEDING CONSIDERATIONS: Benzodiazepines are
present in milk, and should be avoided if possible during-
MONITORING PARAMETERS: Respiratory and breast feeding.
cardiovascular status.
PATIENT ADVICE: May impair judgement and increase
STORAGE AND STABILITY: Immediate release tablets: Store reaction time, and so affect ability to drive or operate
at 20°C to 25°C (68°F to 77°F). Extended release machinery; they increase the effects of alcohol.
tablets: Store at 25°C (77°F); excursions permitted to Moreover, the hangover effects of a night dose may
15°C to 30°C (59°F to 86°F). Orally disintegrating impair driving on the following day. Take only as
tablet: Store at room temperature of 20°C to 25°C prescribed; do not increase dosage or duration of
(68°F to 77°F). Protect from moisture. Seal bottle tightly therapy unless otherwise instructed by a clinician. Do
and discard any cotton packaged inside bottle. not abruptly discontinue therapy. For women, inform
clinicians if they are or planning to become pregnant or
Adverse Drug Reactions: plan to breast-feed. Inform clinicians of any concomitant
Common: Amnesia, ataxia (especially in the elderly), illness, particularly depression; behavioral or mental
confusion (especially in the elderly), dependence, changes, memory impairment, tolerance, or
depression, drowsiness the next day, fatigue, dependence/withdrawal symptoms.
forgetfulness, hyperexcitability, lightheadedness the
next day, muscle, nervousness, weakness, paradoxical SPECIAL CONSIDERATIONS: In adolescent with psychotic or
increase in aggression, slurred speech. bipolar disorder, Risperidone can be offered as a
Less Common: Changes in libido, dizziness, dysarthria, treatment option only under supervision of a specialist,
gastrointestinal disturbances, gynecomastia, headache, if treatment with Risperidone is not feasible,
hypotension, incontinence, salivation changes, slurred Haloperidol or Chlopromazine may be used only under
speech, tremor, urinary retention, vertigo, visual supervision of a specialist.
disturbances.
Rare: Apnea, blood disorders, jaundice, respiratory ATC Code: N05BA12
depression, skin reactions.

506
NERVOUS SYSTEM

Elderly (impaired cognition, delirium, falls, fractures, and

Rx BROMAZEPAM motor vehicle accidents. (avoid use for treatment of
insomnia, agitation, or delirium);
Oral: 1.5 mg tablet Pregnancy (not recommended as treatment for anxiety
during pregnancy, especially during the first trimester;
Bromazepam is a benzodiazepine. It has been used in the drug should be tapered if discontinued); Lactation (use
short-term treatment of anxiety disorders occurring while breastfeeding is not recommended).
alone or associated with insomnia.
MONITORING PARAMETERS: Respiratory, cardiovascular,
Indications: Short-term relief of symptoms of excessive and mental status; periodic CBC and liver function tests.
anxiety.
STORAGE AND STABILITY: Store at room temperature of
NOTE: Bromazepam does not have analgesic, 15°C to 30°C (59°F to 86°F).
antidepressant, or antipsychotic properties.
Adverse Drug Reactions:
Contraindications: Myasthenia gravis; narrow-angle Common: Cardiac arrest, hypotension, palpitations,
glaucoma; severe hepatic or respiratory disease; sleep tachycardia; Ataxia, confusion, depression, dizziness,
apnea; history of substance use disorder; pregnancy, drowsiness, emotional lability, euphoria, fatigue,
labor, or lactation headache, impaired consciousness, myasthenia,
seizure, Pruritus, skin rash, change in libido,
Dose: Gastrointestinal distress, nausea, vomiting, xerostomia;
Anxiety, by mouth, ADULT, Initial: 6 to 18 mg/day in equally urinary incontinence, muscle spasm, Blurred vision,
divided doses. Initial course of treatment should not last diplopia, respiratory depression.
longer than 1 week without reassessment of the need for
a limited extension. Optimal dosage range: 6 to 30 Drug Interactions:
mg/day. Limited experience with doses up to 60 mg/day. Monitor closely with:
For debilitated service patients: Initial dose: 3 mg/day in Reduces the therapeutic effect of Bromazepam:
divided doses; may adjust dose cautiously based on Theophylline Derivatives e.g., Aminophylline

N
response and tolerance.
Enhances the therapeutic effects of CNS depressants e.g.
Dose Adjustment: Alcohol
Geriatric:
Anxiety, by mouth, Initial dose: 3 mg/day in divided doses; Increases risk of adverse or toxic effects of the following
may adjust dose cautiously based on response and drugs:
tolerance. Flumazenil (precipitate seizures)
Pramipexole, Ropinirole, Rotigotine (sedative effect)
Renal Impairment: SSRIs (psychomotor impairment)
No dosage adjustments; initiate therapy conservatively and
titrate cautiously. Administration: May be administered with or without food.

Hepatic Impairment: Pregnancy Category: C

Mild to moderate impairment: No dosage adjustments;
initiate therapy conservatively and titrate cautiously. NOTE: Bromazepam requires an S-2 license for physicians
Severe impairment: Use of bromazepam is contraindicated. to be able to prescribe it and an S-1 license with a
triplicate prescription for pharmacists to dispense it.
Precautions:
WARNING: Patients must be cautioned about performing ATC Code: N05BA08
tasks which require mental alertness (e.g., operating
machinery or driving).

Concerns related to adverse effects: Rx CLONAZEPAM

Anterograde amnesia; CNS depression; paradoxical
reactions (e.g., hyperactive or aggressive behavior); Oral: 500 micrograms and 2 mg tablet
sleep-related activities.
A benzodiazepine derivative that is used both as an
Use with caution in: anticonvulsant and for the short-term treatment of panic
Depression (not recommended in patients with depressive disorder with or without agoraphobia.
disorders or psychosis);
Drug abuse (dependence and tolerance); Withdrawal (use Indication: Second-line treatment for panic disorder, with or
caution when reducing dose or withdrawing therapy; without agoraphobia; Lennox-Gastaut syndrome (petit
decrease slowly and monitor for withdrawal symptoms); mal variance); akinetic seizure; myoclonic seizure;
Post-traumatic Stress Disorder; absence seizure (petit mal)
Hepatic and renal impairment;
Respiratory depression; NOTE: Clonazepam does not have analgesic,
antidepressant, or antipsychotic properties. Worsening
of seizures may occur when added to service patients

507
 NERVOUS SYSTEM

with multiple seizure types. Periodically re-evaluate the Elderly (Increase the risk of impaired cognition, delirium,
long-term usefulness of clonazepam for the individual falls, fractures, and motor vehicle accidents (avoid use
service user/patient. for treatment of insomnia, agitation, or delirium) though
use may be appropriate for seizure disorders, rapid eye
Contraindications: Severe liver disease, angle-closure movement sleep disorders, benzodiazepine withdrawal,
glaucoma, myasthenia gravis, current alcohol abuse and ethanol withdrawal, severe generalized anxiety disorder,
drug abuse, respiratory depression, coma. and periprocedural anesthesia.)
Pregnancy (Not recommended as treatment for anxiety
Dose: during pregnancy, especially during the first trimester.
Panic disorder with or without agoraphoia, by mouth, Drug should be tapered if discontinued.)
ADULT, initially 0.25 mg/day in 2 divided doses. Slowly Breastfeeding (should be avoided if possible during breast-
increase in increments of 0.25 to 0.5 mg/day in 2 feeding.)
divided doses every 3 days until an average dose of 1
mg/day in 2 divided doses daily is reached or the desired Other precautions:
efficacy is reached, whichever comes first, with a Opioids and skeletal muscle relaxants
maximum dose of 4 mg/day. Discontinuation of Tolerance (The effectiveness of clonazepam may decrease
treatment: To discontinue, treatment should be significantly after weeks or months of continuous
withdrawn gradually. Decrease dose by 0.25 mg/day in therapy.)
2 divided doses every 3 days until medication is Withdrawal
completely withdrawn.
Seizures, by mouth, 1.5 mg into three divided doses, raise MONITORING PARAMETERS: CBC, liver and renal function
by 0.5 mg every 3 days until desired effect is reached; tests (periodically with long-term therapy) suicidality
divide into three even doses or else give largest dose at (e.g., suicidal thoughts, depression, behavioral changes).
bedtime; maximum dose generally 20 mg/day.
STORAGE AND STABILITY: Tablets: Store at 20°C to 25°C
Panic disorder, by mouth, 0.25 mg twice daily; increase in (68°F to 77°F). Orally disintegrating tablets: Store at
increments of 0.125 to 0.25 mg twice daily every 3 days; 25°C (77°F) ; excursions permitted between 15°C and
target dose: 1 mg daily (maximum: 4 mg daily). 30°C (59°F and 80°F).
N

Discontinuation of treatment: To discontinue, treatment

should be withdrawn gradually. Decrease dose by 0.125 Adverse Drug Reactions:
mg twice daily every 3 days until medication is Common: Amnesia, bronchial hypersecretion and salivary
completely withdrawn. hypersecretion in infants and small children,
coordination disturbances, confusion, dependence,
Dose Adjustment: dizziness, drowsiness, fatigue, muscle hypotonia,
Geriatric: nystagmus, poor concentration, restlessness, withdrawal
Refer to adult dosing. Initiate with low doses and observe syptoms (in children).
closely for signs of CNS and pulmonary toxicity. Rare: Aggression, anxiety, blood disorders, dysrthria,
gastrointestinal symptoms, headache, paradoxical
Renal Impairment: effects, pruritus, respiratory depression.
Start with small doses in severe impairment.
Drug Interactions:
Hepatic Impairment: Monitor closely with:
Start with smaller initial doses or reduce dose. Can Increases risk adverse/toxic effect of Clonazepam:
precipitate coma. Avoid in severe impairment. (sleepiness and dizziness)

Precautions: Decreases the therapeutic effects of Clonazepam:

Theophylline derivatives, Yohimbine, CNS Depressants
WARNING: Concomitant use of benzodiazepines and
opioids may result in profound sedation,
Increases risk of adverse or toxic effects of the following
respiratory depression (monitor), coma, and
drugs:
death. Reserve concomitant prescribing of these
Flumazenil (precipitate seizures)
drugs for use in service patients for whom
Ropinirole, Pramipexole, Rotigotine (sedative effect)
alternative treatment options are inadequate.
SSRIs (psychomotor impairment)
Limit dosages and durations to the minimum
required.
Increases plasma concentration of Clonazepam:
Disulfiram (reduce Clonazepam dosage as necessary)
Acute porphyrias, airways obstruction, brain damage,
cerebellar ataxia, depression, spinal ataxia, suicidal Decreases plasma concentration of Clonazepam:
ideation. Propantheline

Disease-related concerns: Administration: Administer in 3 equally divided doses for the

Drug abuse treatment of seizure disorders; if doses are not equally
Post-traumatic Stress Disorder divided, give the largest dose at bedtime. Administer in 2
equally divided doses for the management of panic
Special populations: disorder; alternatively, administer the entire dosage at
bedtime to reduce the inconvenience of somnolence.

508
NERVOUS SYSTEM

Orally disintegrating tablet: Just prior to administration, Indications: Short-term management of anxiety disorders,
remove blister from aluminum pouch. Open pouch and symptoms of anxiety, ethanol withdrawal symptoms,
peel back foil on the blister; do not push tablet through skeletal muscle relaxant, convulsive disorders (adjunct),
foil. Use dry hands to remove tablet and place in mouth. preoperative or preprocedural sedation and amnesia or
May be swallowed with or without water. Use perioperative anxiety (injection only), anxiety during
immediately after removing from package. endoscopic procedures (adjunct, injection only), anxiety
relief prior to cardioversion (IV), acute agitation, tremor,
Tablet: Swallow whole with water. impending or acute delirium tremens, hallucinosis in acute
alcohol withdrawal, skeletal muscle spasm due to reflex
See Clonazepam under Benzodiazepine Derivatives in spasm to local pathology, spasticity caused by upper motor
Chapter 10: Antiepileptics for other information. neuron disorder, athethosis, Stiffman syndrome, initial
treatment of status epilepticus
Pregnancy Category: D
NOTE: Diazepam does not have analgesic, antidepressant,
PREGNANCY or antipsychotic properties.

BREAST-FEEDING: Present in milk, and should be avoided if Contraindications: Myasthenia gravis; severe respiratory
possible during breast-feeding. All infants should be insufficiency; severe hepatic insufficiency; sleep apnea
monitored for sedation, feeding difficulties, adequate syndrome; acute narrow-angle glaucoma; not for use in
weight gain, and developmental milestones. infants <6 months of age (oral).

PATIENT ADVICE: Inform clinicians and pharmacists of Dose:

existing or contemplated concomitant therapy, including NOTE: Oral absorption is more reliable than IM.
prescription and OTC drugs, and alcohol consumption.
Inform clinician of any of these health problems: Acute ethanol withdrawal, by mouth, ADULT, 10 mg 3 to 4
glaucoma or very bad liver disease. Take only as times during first 24 hours, then decrease to 5 mg 3 to
prescribed; do not increase dosage or duration of 4 times daily and continue treatment as needed, by
therapy unless otherwise instructed by a clinician. Do intravenous infusion, ADULT, initially administer 10 mg

N
not abruptly discontinue therapy, this could cause at a rate of 5 mg/minute, followed by 5-10 mg 3-4 hours
seizures. If the drug has been taken for a long time or at later at a rate of 5 mg/minute, if needed, by
high doses, it may not work as well and higher doses may intramuscular injection, ADULT, initially administer 10
be needed to get the same effect—this is known as mg, followed by 5-10 mg 3-4 hours later, if needed.
tolerance, inform the clinician it the drug stops working Anxiety (symptoms/disorders), by mouth, ADULT, 2 to 10 mg
well. 2-4 times daily if needed, by intravenous infusion,
Avoid driving and doing other tasks or actions that needs ADULT, initially administer 2-10 mg at a rate of
alertness. Avoid alcohol or other drugs and natural 5mg/minute. Repeat in 3-4 hours at a rate of 5
products that slow down actions. Inform the clinician of mg/minute, if needed, by intramuscular injection,
any side effect (e.g., behavioral or mental changes, ADULT, initially administer 2-10 mg. Repeat in 3-4 hours,
memory impairment, tolerance, or if needed.
dependence/withdrawal symptoms) experienced with Conscious sedation for procedures, by mouth, CHILD, 0.2 to
taking the drug. If seizures have been experienced in the 0.3 mg/kg (maximum dose: 10 mg) 45 to 60 minutes
past, the drug may cause you to pass out. Do not do prior to procedure; Adolescents: 10 mg. by intravenous
activities that may be unsafe to you or others if you pass infusion, Adolescents: 5 mg; may repeat with 2.5 mg if
out, like driving or swimming. For women, inform needed.
clinicians if they are or planning to become pregnant or Perioperative anxiety, by intramuscular injection, ADULT,
plan to breast-feed. Do not breast-feed while taking this administer 10 mg prior to surgery.
drug. Rapid tranquilization of agitated service user/patient
(administer every 30 to 60 minutes), by mouth, ADULT,
ATC Code: N03AE01 5 to 10 mg; average total dose for tranquilization: 20-60
Clonazepam requires an S-2 license for physicians to be mg; by iInjection:5 mg per mL, 0.5 mL-1 mL every 30-60
able to prescribe it and an S-1 license with a triplicate minutes provided that the vital signs are monitored
prescription for pharmacists to dispense it. Sedation or muscle relaxation or anxiety, by mouth, CHILD,
0.12 to 0.8 mg/kg/day in divided doses every 6 to 8
hours. IV or IM, CHILD, 0.04 to 0.3 mg/kg/dose every 2
to 4 hours to a maximum of 0.6 mg/kg within an 8-hour
Rx DIAZEPAM period if needed.
Sedation in the ICU service user/patient, by intravenous
Oral: 5 mg tablet infusion, ADULT, Loading dose: 5 to 10 mg; Maintenance
Inj.: 5 mg/mL, 2 mL ampule (IM, IV) dose: 0.03 to 0.1 mg/kg every 30 minutes to 6 hours.
Skeletal muscle relaxant (adjunct therapy), by mouth,
Diazepam is a benzodiazepine that exerts anxiolytic, ADULT, 2-10 mg 3-4 times daily.
sedative, muscle- relaxant, anticonvulsant and
amnestic effects due to its facilitation of the action of Dose Adjustment:
gamma aminobutyric acid (GABA), an inhibitory Debilitated Patients/Geriatric:
neurotransmitter in the central nervous system. Oral: Initially 2-2.5 mg once or twice daily. Slowly increase
as needed and tolerated.

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 NERVOUS SYSTEM

NOTE: Due to its long-acting metabolite, diazepam is not discontinued. Women who have seizures in the second
considered a drug of choice in the elderly. Long-acting half of pregnancy should be assessed for eclampsia
benzodiazepines have been associated with falls in the before any change is made to antiepileptic treatment.
elderly. Lactation (Because diazepam and its metabolites may be
present in breast milk for prolonged periods following
Renal Impairment: administration, it is recommended to discontinue breast-
Initially 2-2.5 mg once or twice daily. Slowly increase as feeding for an appropriate period of time.).
needed and tolerated. Benzyl alcohol and derivatives (potentially fatal toxicity
“gasping syndrome” in neonates).
NOTE: Hemodialysis – Not dialyzable (0%-5%); supplemental dose is
not necessary.
MONITORING PARAMETERS: Respiratory, cardiovascular,
and mental status; check for orthostasis. /For critically ill
Hepatic Impairment: mechanically-ventilated service patients: Monitor depth
Initially 2-2.5 mg once or twice daily and slowly increase as of sedation with either the Richmond Agitation Sedation
needed and tolerated for mild to moderate hepatic Scale (RASS) or Sedation-Agitation Scale (SAS).
impairment. Contraindicated in severe hepatic
impairment. If treatment is necessary, benzodiazepines STORAGE AND STABILITY: Injection: Store at 20°C to 25°C
with shorter half lives are safer, such as temazepam or (68°F to 77°F) ; excursions permitted to 15°C to 30°C
oxazepam. (59°F to 86°F). Protect from light. Potency is retained for
up to 3 months when kept at room temperature. Most
Precautions: stable at pH 48; hydrolysis occurs at pH <3. Tablet: Store
WARNING: Concomitant use of benzodiazepines and at 15°C to 30°C (59°F to 86°F).
opioids may result in profound sedation, respiratory
depression, coma, and death. Reserve concomitant Adverse Drug Reactions:
prescribing of these drugs for use in patients for NOTE: Adverse reactions may vary by route of
whom alternative treatment options are administration.
inadequate. Limit dosages and durations to the
minimum required. Follow patients for signs and Common: Localized phlebitis, vasodilatation, amnesia,
N

symptoms of respiratory depression and sedation. ataxia, confusion, depression, drowsiness the next day,
When given IV, there is a risk of propylene glycol lightheadedness the next day, dysarthria, muscle
toxicity; monitor closely if using for prolonged weakness, constipation, diarrhea, nausea, pain at
periods or at high doses. injection site; tremor, asthma, bradypnea; paradoxical
To be prescribed and dispensed through Yellow Rx. increase in aggression.
Only one (1) drug preparation shall be prescribed in Less common: Changes in libido (in adults), dizziness,
one single prescription form. Partial filling allowed. dysarthria, gastro-intestinal disturbances, gynecomastia,
STRICTLY NO REFILL. headache, hypotension (in adults), incontinence,
Diazepam 5 mg requires an S-2 license for physicians salivation changes, slurred speech, tremor, urinary
to be able to prescribe it and an S-1 license with a retention, vertigo, visual disturbances.
triplicate prescription for pharmacists to dispense Rare: Apnea, changes in libido (in children) respiratory
it. depression (overdose), hepatic dysfunction, renal
dysfunction, blood disorders, hallucinations, mania,
hypotension (in children), jaundice, skin reactions.
Anterograde amnesia;
CNS depression; Drug Interactions:
Opioids–should be reduced by approximately one third Monitor closely with:
when diazepam is added; Enhances the toxic/adverse effects of SSRIs (psychomotor
Psychiatric and paradoxical reactions (discontinue if impairment)
reactions occur);
Convulsive disorders (abrupt withdrawal - seizures); Enhances the toxic/adverse effects of diazepam:
Depression; Cosyntropin (hepatotoxic)
Drug abuse; tolerance, psychological and physical CNS depressants (central effects)
dependence may occur with prolonged used (generally Flumazenil (precipitate seizures)
>10 days);
Hepatic and renal impairment; Enhances the sedative effect of the following drugs:
Impaired gag reflex; Pramipexole, Ropinirole, Rotigotine
Post-traumatic Stress Disorder;
Respiratory disease (lower dose is recommended for Decreases therapeutic effect of diazepam:
chronic insufficiency). Theophylline derivatives e.g. Aminophylline

Special populations: FOOD INTERACTIONS: Diazepam serum concentrations may

Debilitated/elderly patients; Obese patients (prolonged be decreased if taken with food. Grapefruit juice may
action when discontinued). increase diazepam serum concentrations. Avoid
Psychotic patients (use of diazepam is not recommended in concurrent use of grapefruit juice. Maintain adequate
place of appropriate therapy. hydration, unless instructed to restrict fluid intake.
Pregnancy (not recommended during pregnancy, especially
during the first trimester. Drug should be tapered if

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NERVOUS SYSTEM

TEST INTERACTIONS: False-negative urinary glucose HYPNOTICS AND SEDATIVES

determinations when using Clinistix® or Diastix®.

Administration: Rx MIDAZOLAM
Note: Do not mix IV product with other medications. When
given intravenously, continuous infusion is not
Oral: 15 mg tablet
recommended because of precipitation in IV fluids and
Inj.: 1 mg/mL, 5 mL ampule / vial (IM, IV)
absorption of drug into infusion bags and tubing. In
5 mg/mL, 1 mL, 2 mL, 3 mL, 5 mL, and 10 mL ampule
children, do not exceed 1 to 2 mg/minute IVP; in adults
(IM, IV)
5 mg/minute.
Midazolam is a short-acting benzodiazepine with general
WARNING: Parenterally administered diazepam may properties similar to those of diazepam, except that it
cause hypotension and/or respiratory depression, has a more potent amnestic action. It is mainly used for
particularly if the drug is administered too rapidly sedation in minor surgical or investigative procedures
IV. and in intensive care, for premedication, and for
induction of general anaesthesia.
When given IV, diazepam should be administered directly
into a large vein to avoid thrombosis; if this is not Indications: Sedation in minor surgical or investigative
feasible, the drug should be given into the tubing of a procedures; ICU sedation (continuous infusion);
flowing IV solution as close as possible to the vein preoperative sedation, conscious prior to short
insertion. Small veins such as those of the wrist or the diagnostics or endoscopic procedures; preoperative
dorsum of the hand should not be used. Care should be anxiolytic; drug-induced amnesia premedication and
taken to avoid intra-arterial administration or sedation, and for induction and maintenance of general
extravasation. Alternatively, some clinicians have anesthesia; moderate sedation prior to diagnostic or
suggested IV administration of dilute solutions of the radiographic procedures. Sedation in pediatric patients
drug to avoid extravasation; however, the drug may
precipitate when diluted and the manufacturers do not WARNING: Use only when adequate treatment

N
recommend this method of administration. facilities for appropriate management of therapy
and complications are available.
Although diazepam may also be given by deep IM injection,
this route of administration of the drug is rarely justified NOTE: Midazolam does not have analgesic, antidepressant,
because absorption is slow and erratic. or antipsychotic properties. Does not protect against
increases in heart rate or blood pressure during
Therapy with oral diazepam should replace parenteral intubation. Should not be used in shock, coma, or acute
administration as soon as possible. alcohol intoxication.

Contraindications: Intrathecal or epidural injection of

WARNING: Diazepam is a vesicant; ensure proper parenteral forms containing preservatives (i.e., benzyl
needle or catheter placement prior to and during alcohol); acute narrow angle glaucoma; Severe
infusion; avoid extravasation. Extravasation respiratory depression; severe hepatic insufficiency;
management: If extravasation occurs, stop IV sleep apnea syndrome; myasthenia gravis, CNS
administration immediately and disconnect (leave depression.
cannula/needle in place) ; gently aspirate
extravasated solution (do NOT flush the line) ; Dose:
remove needle/cannula; elevate extremity. Apply NOTE: The dose of midazolam needs to be individualized
dry cold compresses. based on the patient's age, underlying diseases, and
concurrent medications. Consider reducing dose by 20%-
See Diazepam under Other Antiepileptics in Chapter 10: 50% in elderly, chronically ill, or debilitated patients and
Antiepileptics for other information. those receiving opioids or other CNS depressants.

Pregnancy Category: D Preoperative/preprocedural sedation, by mouth,

ADULT<60 years, 7.5-15 mg 30-60 minutes prior to
ATC Code: N05BA01 surgery/procedure, by intramuscular injection,
ADULT<60 years, 0.07 to 0.08 mg/kg 30-60 minutes
prior to surgery/procedure; usual dose: 5 mg, by
intravenous infusion, ADULT<60 years, 0.02 to 0.04
mg/kg; repeat every 5 minutes as needed to desired
effect or up to 0.1 to 0.2 mg/kg.
Conscious sedation, by intravenous infusion, ADULT<60
years, Initial: Some service patients respond to doses as
low as 1 mg; no more than 2.5 mg should be
administered over a period of 2 minutes. Additional
doses of midazolam may be administered after a 2
minute waiting period and evaluation of sedation after
each dose increment. A total dose >5 mg is generally not

511
 NERVOUS SYSTEM

needed. Maintenance: 25% of dose used to reach intramuscular injection, 0.1-0.15 mg/kg 30 to 60
sedative effect. ADULT ≥60 years, debilitated, or minutes before surgery or procedure; range: 0.05-0.15
chronically ill, Refer to geriatric dosing. Alternate mg/kg; doses up to 0.5 mg/kg have been used in more
recommendations (American Society for anxious patients; maximum total dose: 10 mg.
Gastrointestinal Endoscopy): Initial: 0.5 to 2 mg slow IV
over at least 2 minutes; slowly titrate to effect by Conscious sedation for procedures or preoperative
repeating doses every 2 to 3 minutes if needed; usual sedation, by intravenous infusion, CHILD<6 months,
total dose: 2.5 to 5 mg. Limited information is available in nonintubated infants;
Anesthesia, by intravenous infusion, ADULTS<55 years, dosing recommendations not clear; infants <6 months
Induction: Unpremedicated service patients: 0.3 to 0.35 are at higher risk for airway obstruction and
mg/kg over 20-30 seconds; after 2 minutes, may repeat hypoventilation; titrate dose in small increments to
if necessary at 25% of initial dose every 2 minutes, up to desired effect. CHILD 6 months-5 years, Initial: 0.05-0.1
a total dose of 0.6 mg/kg in resistant cases. mg/kg; total dose of 0.6 mg/kg may be required;
Premedicated patients: Usual dosage range: 0.05-0.2 maximum total dose: 6 mg, CHILD 6-12 years: Initial:
mg/kg. Use of 0.2 mg/kg administered over 5 to 10 0.025 to 0.05 mg/kg; total doses of 0.4 mg/kg may be
seconds has been shown to safely produce anesthesia required; maximum total dose: 10 mg, CHILD 12-16
within 30 seconds and is recommended for ASA physical years: Dose as adults; maximum total dose: 10 mg.
status P1 and P2 patients. When used with other Conscious sedation during mechanical ventilation, by
anesthetic drugs (i.e., coinduction), the dose is <0.1 intravenous infusion, CHILD<18 years, Loading dose:
mg/kg. ASA physical status >P3 or debilitation: Reduce 0.05 to 0.2 mg/kg, followed by initial continuous
dose by at least 20%. Maintenance: 0.05 mg/kg as infusion: 0.06 to 0.12 mg/kg/hour (1 to 2
needed, or continuous infusion 0.015 to 0.06 mcg/kg/minute).
mg/kg/hour (0.25 to 1 mcg/kg/minute).
Sedation in mechanically-ventilated service patients, by USUAL INFUSION CONCENTRATIONS: Adult: IV infusion: 100
intravenous infusion, ADULT, Initial dose: 0.01 to 0.05 mg in 100 mL (concentration: 1 mg/mL) of D5W or NS.
mg/kg (~0.5 to 4 mg); may repeat at 5-15 minute Pediatric: IV infusion: 0.5 mg/mL or 1 mg/mL.
intervals until adequate sedation achieved; maintenance
infusion: 0.02 to 0.1 mg/kg/hour (0.3 to 1.7 WARNING: Calculate pediatric dosage on a mg/kg
N

mcg/kg/minute). Titrate to reach desired level of basis. Initial dose is dependent on age, procedure,
sedation. Titration to maintain a light rather than a deep and route; titrate subsequent dosages slowly.
level of sedation is recommended unless clinically
contraindicated. May consider a trial of daily awakening; Dose Adjustment:
if agitated after discontinuation of drip, then restart at Geriatric:
50% of the previous dose. NOTE: The dose of midazolam needs to be individualized
based on the patient's age, underlying diseases, and
WARNING: Initial IV dose for healthy adults should not concurrent medications. Consider reducing dose by 20%-
exceed 2.5 mg. Lower dosages are necessary in 50% in elderly, chronically ill, or debilitated patients and
patients >60 years of age, debilitated service those receiving opioids or other CNS depressants.
patients, and service patients receiving
concomitant opiates or other CNS depressants. Anesthesia, by intravenous infusion, ADULT >55 years,
Titrate initial and subsequent dosages slowly; Induction: Unpremedicated service patients: Initial dose:
administer the appropriate dose over ≥2 minutes 0.3 mg/kg; Premedicated service patients: Reduce dose
and wait an additional 2 or more minutes to fully by at least 20%. Maintenance: Refer to adult dosing.
evaluate the sedative effect. Conscious sedation, by intravenous infusion, ADULT, Initial:
0.5 mg slow IV; give no more than 1.5 mg in a 2 minute
NOTE: For pediatric patients: The dose of midazolam needs period; if additional titration is needed, give no more than
to be individualized based on the patient's age, 1 mg over 2 minutes, waiting another 2 or more minutes
underlying diseases, and concurrent medications. to evaluate sedative effect; a total dose of >3.5 mg is
Decrease dose (by ~30%) if opioids or other CNS rarely necessary.
depressants are administered concomitantly. Children Preoperative/pre-procedural sedation, ADULT >60 years
<6 years may require higher doses and closer monitoring (without concomitant opioid administration): by
than older children; in children with obesity, calculate intramuscular injection, 2 to 3 mg (or 0.02 to 0.05
dose based on ideal body weight. mg/kg) 30 to 60 minutes prior to surgery/procedure;
some may only require 1 mg (or 0.01 mg/kg) if
Conscious sedation for procedures or preoperative anticipated intensity and duration of sedation is less
sedation, CHILD≥6 months, Children, and Adolescents critical. By mouth, 7.5 mg 30 to 60 minutes prior to
≤16 years: oral (solution only), 0.25 to 0.5 mg/kg surgery/procedure.
(maximum: 20 mg) as a single dose 20 to 30 minutes
prior to procedure. Children <6 years or less cooperative Renal Impairment:
patients may require as much as 1 mg/kg as a single Oral: 7.5 mg; consider lower doses as needed.
dose; 0.25 mg/kg may suffice for children 6-16 years of IV, and Oral (Solution): There are no dosage adjustments
age or for cooperative patients. Doses of 0.5-0.75 mg/kg provided; however, patients with renal failure receiving a
administered 20-30 minutes prior to procedure have continuous infusion cannot adequately eliminate the
also been suggested; however, doses above 0.5 mg/kg active hydroxylated metabolites (e.g., 1-
typically do not improve the sedative and anxiolytic hydroxymidazolam) contributing to prolonged sedation
effects but increase side effects during recovery. by sometimes for days after discontinuation. Intermittent

512
NERVOUS SYSTEM

hemodialysis: Supplemental dose is not necessary. Opioids and skeletal muscle relaxants (CNS depression;
Continuous venovenous hemofiltration (CVVH): avoid)
Unconjugated 1-hydroxymidazolam not effectively Elderly/Debilitated patients (start at the lower end of dosing
removed; 1-hydroxymidazolamglucuronide effectively range); fall risk
removed; sieving coefficient = 0.45. Peritoneal dialysis: Obese patients (use with caution; may have prolonged
Significant drug removal is unlikely based on action when discontinued)
physiochemical characteristics. Neonates (do not administer by rapid IV injection in
neonates; increased risk with concomitant fentanyl use)
Hepatic Impairment: Benzyl alcohol and derivatives (potentially fatal toxicity
Oral: Mild to moderate impairment: 7.5 mg; consider lower (“gasping syndrome”) in neonates; avoid or use dosage
doses as needed. Severe impairment: Use is forms containing benzyl alcohol with caution in
contraindicated. neonates.)
IV, and Oral (solution): Severe hepatic impairment (e.g.,
cirrhosis): Note: Use with caution in patients with any MONITORING PARAMETERS: Respiratory and
degree of hepatic impairment; patients with hepatic cardiovascular status, blood pressure, blood pressure
encephalopathy likely to be more sensitive to monitor required during IV administration. For critically ill
midazolam. Single dose (e.g., induction): No dosage patients: Monitor depth of sedation with either the
adjustment recommended; patients with hepatic Richmond Agitation-Sedation Scale (RASS) or Sedation--
impairment may be more sensitive compared to patients Agitation Scale (SAS).
without hepatic impairment; anticipate longer duration of
action. Multiple dosing or continuous infusion: Expect STORAGE/STABILITY: Oral: Store at 25°C (77°F);
longer duration of action and accumulation; based on excursions permitted to 15°C to 30°C (59°F to 86°F).
patient response, dosage reduction likely to be Injection: Store at 20°C to 25°C (68°F to 77°F),
necessary. excursions permitted to 15°C to 30°C (59°F to 86°F).
The manufacturer states that midazolam, at a final
Precautions: concentration of 0.5 mg/mL, is stable for up to 24 hours
WARNING: Associated with respiratory depression when diluted with D5W or NS. A final concentration of 1
and respiratory arrest, especially when used for mg/mL in NS has been documented to be stable for up

N
sedation in noncritical-care settings. Death or to 10 days. Admixtures do not require protection from
hypoxic encephalopathy has resulted when light for short-term storage.
respiratory depression was not recognized
promptly and treated effectively. Adverse Drug Reactions:
Initial doses in debilitated and elderly patients should Common: Decreased tidal volume and/or respiratory rate
be conservative; start at the lower end of dosing decrease, apnea; hypotension; drowsiness,
range. oversedation, impaired recall, agitation, headache,
Do not administer by rapid IV injection in neonates; seizurelike activity; nausea, vomiting; pain and local
severe hypotension and seizures have been reactions at injection site; myoclonic jerks (preterm
reported; risk may be increased with concomitant infants); nystagmus; cough; physical and psychological
fentanyl use. dependence with prolonged use, hiccups, paradoxical
Midazolam 15 mg requires an S-2 license for reaction; vital sign fluctuations.
physicians to be able to prescribe it and an S-1 Less Common: Acid taste, agitation, amnesia, bigeminy,
license with a triplicate prescription for bradycardia, bronchospasm, confusion, dyspnea,
pharmacists to dispense it. emergence delirium, euphoria, excessive salivation,
hallucinations, hyperventilation, laryngospasm, PVC,
Cardiac disease; children (particularly if cardiovascular rash, tachycardia, wheezing, respiratory arrest, cardiac
impairment); concentration of midazolam in children arrest.
<15kg not to exceed 1 mg/mL.
Debilitated patients (reduce dose) (in children); Drug Interactions:
hypothermia; hypovolemia (hypotension); neonates; Monitor closely with:
airways obstruction and hypoventilation in children <6 Decrease therapeutic effect of Midazolam:
months (monitor respiratory rate and oxygen saturation); Aminophylline
vasocontriction. Anesthetic agents, inhalation (patients who have
Impaired gag reflex. received midazolam as an induction agent may require
Renal impairment (use with caution). reduced amounts of inhalation agents during
Respiratory disease (use with caution). maintenance of anesthesia)
Tolerance; withdrawal. Anticonvulsants e.g., carbamazepine, phenobarbital,
Pregnancy; Lactation (avoid breast-feeding for 24 hours phenytoin; Use with caution; consider dosage
after administration). adjustments, if necessary
CCBs e.g., diltiazem, nifedipine, verapamil); use oral or
Concurrent drug therapy issues: parenteral midazolam with caution; reduce oral
NOTE: See Drug Interactions Section for further information. midazolam dosage.
Clozapine (consider therapy modification; consider
CNS depressants/psychoactive medications decreasing the dose of (or possibly discontinuing)
CYP3A4 Inhibitors/Protease inhibitors (consider reducing benzodiazepines prior to initiating clozapine)
midazolam dose; is contraindicated with both oral and CNS Depressants
parenteral forms of midazolam) Ketamine

513
 NERVOUS SYSTEM

Opiates e.g., fentanyl (use with caution; adjust nitroglycerin, nitroprusside, norepinephrine,
midazolam dosage appropriately to avoid overdosage) palonosetron, pancuronium, piperacillin, ranitidine,
Quinupristin and Dalfopristin remifentanil, , theophylline, tirofiban, tobramycin,
SSRIs (psychomotor impairment) vancomycin, vecuronium. Incompatible: Albumin,
Thiopental (induction of anesthesia reduced by about amphotericin B cholesteryl sulfate complex, ampicillin,
15% in patients who received preoperative sedation with bumetanide, butorphanol, cefepime, ceftazidime,
IM midazolam) cefuroxime, dexamethasone sodium succinate,
drotrecogin alfa, foscarnet, fosphenytoin, furosemide,
Enchances the sedative effect of the following drugs: hydrocortisone sodium succinate, imipenem/cilastatin,
Pramipexole, Ropinirole, Rotigotine methotrexate, micafungin, nafcillin, sodium bicarbonate,
thiopental, trimethoprim/sulfamethoxazole. Variable
Decrease the therapeutic effect of midazolam: (consult detailed reference): Cefotaxime, clonidine,
Theophylline derivatives, Yohimbine dobutamine, haloperidol, methylprednisolone sodium
succinate, metoclopramide, pantoprazole, potassium
Avoid concomitant use with: chloride, propofol. Compatibility in syringe: Compatible:
FOOD INTERACTIONS: Grapefruit juice may increase serum Alfentanil, atracurium, atropine, buprenorphine,
concentrations of midazolam. Management: Avoid butorphanol, chlorpromazine, cimetidine,
concurrent use of grapefruit juice with oral midazolam diphenhydramine, dopamine, droperidol, fentanyl,
glycopyrrolate, hydromorphone, hydroxyzine, ketamine,
Administration: meperidine, metoclopramide, morphine, nalbuphine,
WARNING: For deeply sedated pediatric service ondansetron, promethazine, rocuronium, scopolamine,
patients, an individual other than the clinician trimethobenzamide. Incompatible: Dimenhydrinate,
performing the procedure should be dedicated to heparin, pantoprazole, pentobarbital, prochlorperazine
monitoring the service user/patient throughout edisylate, ranitidine. Variable (consult detailed
the procedure. reference): Dexamethasone sodium phosphate,
methylprednisolone sodium succinate.
IM: Give deep IM into large muscle.
IV: Administer by slow IV injection over at least 2 to 5 See Midazolam under Other Antiepileptics in Chapter 10:
N

minutes at a concentration of 1 to 5 mg/mL or by IV Antiepileptics for other information.

infusion. For induction of anesthesia, administer IV bolus
over 5to 30 seconds. Continuous infusions should be Pregnancy Category: D
administered via an infusion pump.
Oral: Swallow tablet whole with adequate fluid. PREGNANCY CONSIDERATIONS: Hypoglycemia and
respiratory problems in the neonate may occur following
Avoid intra-arterial injection or extravasation of the drug. Do exposure late in pregnancy. Neonatal withdrawal
not administer intrathecally or epidurally. It is advisable symptoms may occur within days to weeks after birth and
to keep the service user/patient supine during “floppy infant syndrome” (which also includes withdrawal
intravenous use and throughout the procedure. symptoms).

BREAST-FEEDING CONSIDERATIONS: Midazolam and

WARNING: Administer by direct IV injection as the 1-
hydroxymidazolam can be detected in breast milk. The
mg/mL solution or dilute the 1 or 5mg/mL
manufacturer recommends that caution be exercised
solution to facilitate slower administration. Rapid
when administering midazolam to nursing women.
IV administration may result in respiratory
depression, airway obstruction, and/or respiratory PATIENT ADVICE: Inform clinicians and pharmacists of
arrest. Do not administer by rapid IV injection in existing or contemplated concomitant therapy, including
neonates. Severe hypotension and seizures have prescription and OTC drugs, and alcohol consumption.
been reported following rapid IV administration, Inform clinician of any breathing problems experienced.
particularly with concomitant administration of Take only as prescribed; do not increase dosage or
fentanyl.
duration of therapy unless otherwise instructed by a
clinician.
DIETARY CONSIDERATIONS: Avoid grapefruit juice with oral Avoid driving and doing other tasks or actions that needs
syrup. alertness. Avoid alcohol or other drugs and natural
products that slow down actions. Inform the clinician of
COMPATIBILITY: Stable in D5NS, D5W, NS; incompatible any side effect (e.g., feeling sleepy, tired or weak, or
with LR. Y-site administration: Compatible: Abciximab, memory problems or loss) experienced with taking the
amikacin, amiodarone, anidulafungin, argatroban, drug. For women, inform clinicians if they are or planning
atracurium, bivalirudin, calcium gluconate, caspofungin, to become pregnant or plan to breast-feed.
cefazolin, cimetidine, ciprofloxacin, cisatracurium,
clindamycin, digoxin, diltiazem, doripenem, epinephrine, ATC Code: N05CD08
eptifibatide, erythromycin lactobionate, esmolol,
etomidate, famotidine, fenoldopam, fentanyl,
fluconazole, gentamicin, heparin, hetastarch in lactate
electrolyte injection (Hextend®), hydromorphone, insulin
(regular), labetalol, linezolid, lorazepam, methadone,
metronidazole, milrinone, morphine, nicardipine,

514
NERVOUS SYSTEM

Zolpidem requires an S-2 license for physicians to be

Rx ZOLPIDEM able to prescribe it and an S-1 license with a
triplicate prescription for pharmacists to dispense
Oral: 10 mg tablet it.

Zolpidem tartrate, a type A, γ-aminobutyric acid (GABAA) - Precautions:

receptor agonist of the imidazopyridine class, is a Avoid prolonged use (and abrupt withdrawal thereafter),
sedative and hypnotic agent. As conventional tablets, CNS depression, elderly, history of alcohol abuse, history
zolpidem tartrate is used as a hypnotic agent in the short- of drug abuse, muscle weakness, myasthenia gravis
term management of insomnia characterized by Hypersensitivity e.g., anaphylactic reactions
difficulties with sleep initiation. Behavior changes
Neuropsychiatric symptoms e.g., amnesia, anxiety
Indications: Short-term treatment of insomnia; as needed Temporary memory loss at doses >10 mg/night
for the treatment of insomnia when a middle-of the-night Insomnia may be a symptom of a primary disorder, rather
awakening is followed by a difficulty returning to sleep than a primary disorder itself.
and there are at least 4 hours of bedtime remaining Depression (suicide or suicidal ideation)
before planned time of wakening; short-term treatment History of drug dependence (abuse)
of insomnia. Elderly (dose adjustment; closely monitor elderly or
debilitated patients for impaired cognitive and/or motor
Contraindications: obstructive sleep apnea and acute performance, confusion, and potential for falling; avoid
and/or severe impairment of respiratory function; chronic use (>90 days) ; adverse events e.g., delirium,
unstable myasthenia gravis; severe hepatic impairment; falls, fractures.
personal or family history of sleepwalking, psychotic Females (dose adjustment)
illness Pregnancy (avoid regular use (neonatal withdrawal
symptoms); high doses during late pregnancy or labor
Dose: (neonatal hypothermia, hypotonia, respiratory
Short-term treatment of insomnia, by mouth, ADULT, depression); Lactation (avoid)
Sleep disturbance (failure of sleep disturbance to resolve

N
Note: The lowest effective dose should be used; higher after 7 to 10 days may indicate the need for psychiatric
doses may be more likely to impair next morning and/or medical illness reevaluation).
activities.
TEST INTERACTIONS: Increased aminotransferase
Immediate release tablet: 5 mg (females) or 5 to 10 mg [ALT/AST], bilirubin (S); decreased RAI uptake.
(males) immediately before bedtime for 7-10 days;
maximum dose: 10 mg daily. MONITORING PARAMETERS: Daytime alertness; fall risk,
Extended release tablet: 6.25 mg (females) or 6.25 to respiratory rate; behavior profile; tolerance, abuse, and
12.5 mg (males) immediately before bedtime; maximum dependence; reevaluate if insomnia persists after 7 to
dose: 12.5 mg daily. 10 days of use.
For debilitated patients:
STORAGE AND STABILITY: Store at 15°C to 25°C (59°F to
Immediate release tablet: 5 mg immediately before
77°F) ; limited excursions permitted up to 30°C (86°F).
bedtime.
Extended release tablet: 6.25 mg immediately before
bedtime. Adverse Drug Reactions:
Common: Agitation, amnesia, asthenia, ataxia, changes in
Dose Adjustment: libido, confusion, dependence, depression, diarrhea,
Geriatric: diplopia, dizziness, drowsiness, falls, hallucination,
Immediate release tablet: 5 mg immediately before headache.
bedtime. Less Common: Abnormal hepatic function tests, acute renal
Extended release tablet: 6.25 mg immediately before failure, aggressive behavior, agitation, anaphylaxis,
bedtime. anemia, angina pectoris, anorexia, arteritis, arthritis,
breast fibroadenosis, breast neoplasm, bronchitis,
Renal Impairment: cardiac arrhythmia, cerebrovascular disease, circulatory
No dosage adjustment necessary. Use with caution and shock, cognitive dysfunction, corneal ulcer, cough,
monitor cystitis, decreased libido, delusions, dementia,
dermatitis, diaphoresis, drug tolerance, dysarthria,
Hepatic Impairment: dysgeusia, dysphagia, dyspnea, edema, extrasystoles,
Immediate release tablet, 5 mg immediately before eye irritation, falling, glaucoma, hepatic insufficiency,
bedtime. hyperbilirubinemia, hyperlipidemia, hypertension,
Extended release tablet: 6.25 mg immediately before hypotension, hysteria, illusion, impotence, increased
bedtime. thirst, leg cramps, leukopenia, localized erythema,
lymphadenopathy, menstrual disease, migraine,
myocardial infarction, nervousness, neuralgia, neuritis,
WARNING: For severe hepatic impairment, use is neuropathy.
contraindicated. Rare: Hallucinations, angioedema

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 NERVOUS SYSTEM

Drug Interactions: OTHER PSYCHOLEPTIC AGENTS

Monitor closely with:
Chlorpromazine (additive effects)
Rx ATROPINE
Diminish the sedative effect of the zolpidem:
Flumazenil
Inj.: 500 micrograms/mL, 600 micrograms/mL and 1
mg/mL (as sulfate), 1 mL ampule (IM, IV, SC)
Enhances the sedative effect of the following drugs:
Pramipexole, Ropinirole, Rotigotine
An alkaloid from Atropa belladonna, that competitively
blocks acetylcholine action in central and peripheral
Enhances the toxic/adverse effects of SSRIs (psychomotor
muscarinic autonomic receptors.
impairment)
Indications: To relieve pylorospasm, hypertonicity of the
Avoid concomitant use with:
small intestine, and hypermotility of the colon; To relieve
biliary and ureteral colic; neuromuscular blockade
FOOD INTERACTIONS: Grapefruit juice may decrease the
reversal; bradycardia in children; antidote to overdosage
metabolism of zolpidem. Avoid grapefruit juice.
with cholinergic drugs, poisoning with organophosphate
and n-methyl carbamate pesticides, and mushroom
Administration: To be given orally, ingest immediately before
poisoning; as a pre-operative medication to reduce
bedtime due to rapid onset of action. Zolpidem tartrate
salivary, bronchial, gastric, pancreatic, and nasal
should be taken only once per night immediately before
secretions and to prevent bradycardia; Treatment of
bedtime and at least 7–8 hours before the planned time
symptomatic sinus bradycardia, syncope from Stokes-
of awakening; patients should be advised of the
Adams syndrome, and high-degree atrioventricular block
importance of only taking the drug at such time. In
with profound bradycardia, symptomatic sinus
addition, because food can reduce both the rate and
bradycardia.
extent of GI absorption of zolpidem tartrate, the drug
should not be administered with or immediately after a
Contraindications: Angle-closure glaucoma; severe
meal in order to facilitate the onset of sleep; should be
inflammatory GI disease or GI obstruction; prostatic
N

taken on an empty stomach. Swallow tablet as a whole.

hypertrophy; prostatism and urinary obstruction;
Do not chew, crush, or break tablet.
myasthenia gravis; thyrotoxicosis; organochlorine
poisoning; pyloric stenosis; poisoning caused by CNS
Pregnancy Category: B
adrenergic stimulants, phenothiazines, TCAs and other
anticholinergics.
PATIENT ADVICE: Inform clinicians and pharmacists of
existing or contemplated concomitant therapy, including NOTE: No contraindications exist in the treatment of life-
prescription and OTC drugs, and alcohol consumption. threatening organophosphate or carbamate
Take only as prescribed; do not start, stop, or change the insecticides, and nerve agent poisoning.
dose of any drug unless otherwise instructed by a
clinician. When sleep drugs are used nightly for more Dose:
than a few weeks, they may not work as well to help sleep
WARNING: Fatal dose of atropine in pediatric patients
problems. This is known as tolerance. Only use sleep
may be as low as 10 mg.
drugs for a short time. Do not take naps.
Avoid driving and doing other tasks or actions that needs
alertness. Avoid alcohol or other drugs and natural Bradyarrhythmia, IM or IV, ADULT, American Heart
products that slow down actions. To lower the chance of Association (AHA) recommendation: 0.5 mg every 3 to 5
feeling dizzy or passing out, rise slowly over a few minutes as needed, the total dose not to exceed 0.04
minutes when sitting or lying down. Be careful climbing mg/kg (3 mg). Use of shorting dose intervals (3 minutes)
stairs. Inform the clinician of any side effect (e.g., allergy, and higher maximum dose range (0.04 mg/kg) is
trouble swallowing, shortness of breath) experienced suggested in severe clinical conditions. Subsequent
with taking the drug. For women, inform clinicians if they doses of 0.5 to 1 mg may be given at 4- to 6-hour
are or planning to become pregnant or plan to breast- intervals. Doses under 0.5 mg may cause paradoxical
feed. slowing of HR, IV or IO, CHILD, 0.02 mg/kg with a
maximum single dose of 0.5 mg that may be repeated
ATC Code: N05CF02 once in 3-5 minutes and a maximum total dose of 1 mg.
Smooth muscle relaxation and suppression of secretions,
IM or IV or SC, ADULT, 0.4-0.6 mg 30-60 minutes
minutes preoperatively and repeat every 4 to 6 hours as
needed, CHILD<5 kg, 0.02 mg/kg 30-60 minutes
preoperatively and every 4-6 hours as needed. Usually
given SC., CHILD≥5 kg, 0.01-0.02 mg/kg 30-60 minutes
preoperatively and every 4-6 hours as needed with a
minimum dose of 0.1 mg and a maximum single dose of
0.4 mg.
Neuromuscular blockade reversal, by intravenous infusion,
ADULT, administer 15-30 mcg/kg of atropine with
neostigmine or 7-10 mcg/kg atropine with edrophonium.

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NERVOUS SYSTEM

Dose Adjustment:
Dose Adjustment: Geriatric:
Geriatric: Use with caution. Generally, lower dosages are started;
Reduced dose monitor sodium closely with initiation or dosage
adjustments in older adults.
Renal Impairment:
For mild-to-moderate renal impairment, dose reduction, or Renal Impairment:
less frequent doses, after initial atropinization is Use with caution; dose reduction in moderate to severe
warranted (since atropine may be eliminated more impairment. If GFR <10 mL/minute, administer 75% of
slowly); for severe impairment, the patient should be dose. For patients undergoing hemodialysis or peritoneal
referred to a specialist. dialysis, administer 75% of dose postdialysis. For
patients undergoing continuous renal replacement
Administration: therapy (CRRT), there are no dosage adjustment
Rate of administration - 1 mg or fraction thereof over 1 recommendation for adults; for children, administer 75%
minute. of dose.

See Atropine under Anticholinergics in Chapter 1: Drugs for Hepatic Impairment:

Functional Gastrointestinal Disorders, and Other Cardiac Metabolism impaired in advanced liver disease.
Preparations in Chapter 3: Cardiac Therapy for other
information. Precautions:
WARNING:
Pregnancy Category: C Serious dermatologic reactions and HLA-B*1502
allele: Serious and sometimes fatal dermatologic
ATC Code: Not available reactions, including toxic epidermal necrolysis
(TEN) and SJS. Studies in patients of Chinese
ancestry have found a strong association between
the risk of developing SJS/TEN and the presence
Rx CARBAMAZEPINE of HLA-B*1502, an inherited allelic variant of the

N
HLA-B gene. HLA-B*1502 is found almost
Oral: 200 mg tablet exclusively in patients with ancestry across broad
200 mg and 400 mg modified-release (MR) tablet areas of Asia. Test for HLA-B*1502 prior to
100 mg/5 mL syrup, 120 mL initiating treatment with carbamazepine in with an
increased likelihood of carrying this allele. Avoid
An iminostilbene that limits the firing of action potentials use of carbamazepine in patients testing positive
evoked by a sustained depolarization in cortical neurons for the allele unless the benefit clearly outweighs
mediated by a slowing of the rate of recovery of voltage- the risk. Discontinue carbamazepine if the patient
sensitive Na+ channels from inactivation. It stimulates is suspected of having a serious dermatologic
the release of antidiuretic hormone (ADH) and reaction.
potentiates its action in promoting reabsorption of water.
Aplastic anemia and agranulocytosis: Obtain
Indications: Second line treatment of acute and long term complete pretreatment hematological testing as a
mania. baseline and monitor complete blood cell count
periodically. If a patient in the course of treatment
Contraindications: AV conduction abnormalities (unless exhibits low or decreased WBC or platelet counts,
paced); history of bone marrow suppression; positive test monitor the patient closely. Consider
for HLA-B*1502 allele; acute porphyrias. discontinuation of the drug if any evidence of
significant bone marrow depression develops.
Dose:
NOTE: Dosage must be adjusted according to patients’ Patient w/ history of cardiac disease and haematological
response and serum concentrations. As a result of slow, reactions to other drugs; Not effective in absence,
controlled release of the active substance from the myoclonic, or akinetic seizures; Avoid abrupt withdrawal;
controlled-release (modified-release) tablets, these are Skin reactions; susceptibility to angle-closure glaucoma;
designed to be taken in a twice-daily dosage regimen. Hyponatremia (consider discontinuing therapy in
Administer suspension in 4 divided doses daily. patients with symptomatic hyponatremia); Multi-organ
hypersensitivity reactions (monitor for signs and
Acute mania/mixed mania, by mouth, ADULT/CHILD≥13 symptoms of possible disparate manifestations
years, start 200 mg daily (Increase by 200 mg weekly to associated with lymphatic, hepatic, renal, and/or
400 – 600 mg daily in 2 divided doses, maximum of hematologic organ systems; gradual discontinuation and
1200 mg daily). conversion to alternate therapy may be required);
Psychiatric effects; Anticholinergic sensitivity; Hepatic
NOTE: Anticonvulsants should not be discontinued abruptly and renal impairment (monitor renal function at baseline
because of the possibility of increasing seizure and periodically thereafter).
frequency; therapy should be withdrawn gradually to Pregnancy (doses should be adjusted on the basis of
minimize the potential of increased seizure frequency, plasma-drug concentration monitoring); Lactation.
unless safety concerns require a more rapid withdrawal. Elderly.

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 NERVOUS SYSTEM

SKILLED TASKS. May impair ability to perform tasks, which NOTE: Drug may cause GI upset, take with large amount of
require mental alertness, like driving or operating water or food to decrease GI upset. May need to split
machinery. doses to avoid GI upset. The suspension may contain
sorbitol; avoid use in service patients with hereditary
STORAGE AND STABILITY: Tablet: Store between 20-25°C. fructose intolerance.
Excursions permitted to 15-30°C. Protect from light and
moisture. Modified-release tablet: Store at 25°C. See Carbamazepine under Analgesics, and Antiepileptics in
Excursions permitted to 15-30°C. Protect from moisture. Chapter 10: Nervous System; for other information.
Syrup: Store between 20-25°C. Excursions permitted to
15-30°C. Protect from light. Pregnancy Category: D

Adverse Drug Reactions: ATC Code: N03AF01

NOTE: Particularly at the start of treatment, or if the initial
dose is too high, or in the elderly, certain adverse
reactions (e.g., central nervous system and
gastrointestinal symptoms, and allergy) commonly occur. Rx VALPROIC ACID

Common: Allergic skin reactions, urticaria, dermatitis, Oral: 250 mg and 500 mg tablet (as divalproex sodium)
vomiting, thrombocytopenia, leucopenia, nausea, 250 mg and 500 mg extended release tablet (as
edema, headache, hemolytic anemia, weakness, divalproex sodium)
eosinophilia, dry mouth, dizziness, drowsiness, blurring 500 mg controlled release tablet (333 mg sodium
of vision, blood disorders, ataxia, aplastic anemia. valproate + 145 mg valproic acid)
Less Common: involuntary movements e.g., nystagmus, 200 mg/5 mL syrup, 100 mL bottle (as sodium
exfoliative dermatitis, erythroderma, diarrhea, valproate)
constipation, visual disturbances. 250 mg/5 mL syrup, 120 mL (as valproic acid)
Rare: Abdominal pain, aggression, agitation, anorexia, Inj.: 500 mg/5 mL IV infusion, 5 mL vial (as valproic acid)
cardiac conduction disorders, confusion, delayed multi-
organ hypersensitivity disorder, depression, dysarthria, A simple branched-chain carboxylic acid with mood-
N

hallucinations, hepatitis, hypertension, hypotension, stabilizing properties that are hypothesized to be

jaundice, lymph node enlargement, muscle weakness, mediated by one or a combination of the following:
paresthesia, peripheral neuropathy, restlessness, SLE, reduction of excessive neurotransmission; GABA
vanishing bile duct syndrome. action enhancement; downstream actions on
complex signal transduction cascades, and activating
Drug Interactions: various signals that promote neuroprotection and
Monitor closely with: long-term plasticity.
Enhances the toxic/adverse effects of the following drugs:
Desmopressin (hyponatremia) Indication: First-line treatment for acute mania (divalproex),
Diuretics e.g., hydrochlorothiazide and furosemide mixed episodes (divalproex, divalproex ER).
(symptomatic hyponatremia)
Dipyrone, CNS depressants Contraindications: Family history of severe hepatic
Lacosamide (AV blocking effect) dysfunction; active liver disease; mitochondrial and
Lithium (neurotoxic effects) urea cycle disorders; pregnancy when used
MAOIs (serotonin syndrome; contraindicated within 14 exclusively for migraine prophylaxis;
days of MAOI use) thrombocytopenia; acute porphyrias; Hepatic
Adenosine (high degree heart block) impairment.
Anticonvulsants (thyroid function)
Hormonal contraceptives (bleeding and failure of Dose:
contraception; alternative or backup contraceptive Acute mania, by mouth, ADULT, immediate release: for less
methods are recommended) acute mania, initially 250-500 mg once daily on the
Warfarin (possibly requiring an increase in the dose of first day and slowly titrate dose based on efficacy and
warfarin; carefully monitor INR) tolerability. For more severe cases, initially 750-1000
Paracetamol (reduce bioavailability) mg/day in divided doses and increase dose rapidly to
desired clinical effect up to a maximum of 60
Avoid concomitant use with: mg/kg/day. Due to half-life, the immediate release
Liquid medications or diluents – may result in the formation formulation is ideally dosed as twice daily, while the
of a precipitate extended-release formulation may be given once daily
with a corresponding dose increase of about 8-20%
Administration: The tablets and the syrup (to be shaken when converting from the immediate release
before use) may be taken during, after, or between formulation due to decreased bioavailability
meals. Tablets should be taken with little liquid. The compared to the immediate release formulation,
modified-release tablets should be swallowed unchewed controlled release: initially 25 mg/kg once daily and
with a little liquid. Administer tablets in 2-3 divided doses increase dose rapidly to desired clinical effect up to a
daily and syrup in 4 divided doses daily. Avoid grapefruit maximum of 60 mg/kg/day.
juice.
Start 500 mg daily (Increase slowly to 1000 – 2000
mg daily, maximum of 60 mg/kg/day)

518
NERVOUS SYSTEM

Dose Adjustment:
Geriatric: PSYCHOANALEPTICS
Reduce initial dose and titrate slowly.

Renal Impairment: ANTIDEPRESSANTS

No dose adjustment necessary; may cause misleading
results in therapeutic drug monitoring due to substantial SELECTIVE SEROTONIN REUPTAKE
reduction of protein binding. INHIBITORS
Precautions: GENERAL PRECAUTIONS:
WARNING:
Liver toxicity; Liver dysfunction (including fatal hepatic Concerns related to adverse effects:
failure) especially in children <3 years and in those Bleeding risk (Use with caution in hemodynamically
with metabolic or degenerative disorders, organic unstable patients or if used concomitantly with aspirin,
brain disease or severe seizure disorders NSAIDs, warfarin, or other anticoagulants).
associated with mental retardation) usually in first Cardiovascular effects e.g., QTc prolongation (Use with
6 months and usually involving multiple caution in service users/patients with 1 or more risk
antiepileptic therapy. Raised liver enzymes are factors for torsades de pointes).
usually transient (patients should be reassessed CNS depression (Caution operating hazardous machinery or
clinically and liver function (including prothrombin driving).
time) monitored until return to normal – Fractures (Consider the possibility of a fragility fracture if an
discontinue if abnormally prolonged prothrombin antidepressant-treated patient presents with
time (particularly in association with other relevant unexplained bone pain, point tenderness, swelling, or
abnormalities). bruising).
Mitochondrial disease: valproate-induced acute liver Ocular effects e.g. mild pupillary dilation can lead to an
failure and resultant deaths. Valproate is episode of narrow-angle glaucoma. (Consider evaluating
contraindicated in patients known to have service users/patients who have not had an iridectomy
mitochondrial disorders caused by POLG for narrow-angle glaucoma risk factors).

N
mutations and children <2 years who are clinically Serotonin syndrome (Potentially life-threatening serotonin
suspected of having a mitochondrial disorder. In syndrome (SS) has occurred with serotonergic agents
patients >2 years who are clinically suspected of (e.g., SSRIs, SNRIs), particularly when used in
having a hereditary mitochondrial disease, only combination with other serotonergic agents (e.g.,
use after other anticonvulsants have failed. triptans, TCAs, fentanyl, lithium, tramadol, buspirone, St
Closely monitor this older group of patients during John's wort, tryptophan) or agents that impair
treatment for the development of acute liver injury metabolism of serotonin (e.g., MAO inhibitors intended to
with regular clinical assessments and serum liver treat psychiatric disorders, other MAO inhibitors [i.e.
testing. Perform POLG mutation screening in linezolid and intravenous methylene blue]). Monitor
accordance with current clinical practice. patients closely for signs of SS such as mental status
Pancreatitis: (life-threatening) Warn patients and changes (e.g. agitation, hallucinations, delirium, coma);
guardians that abdominal pain, nausea, vomiting, autonomic instability (e.g., tachycardia, labile blood
and/or anorexia can be symptoms of pancreatitis pressure, diaphoresis); neuromuscular changes (e.g.,
that require prompt medical evaluation. If tremor, rigidity, myoclonus); GI symptoms (e.g., nausea,
pancreatitis is diagnosed, ordinarily discontinue vomiting, diarrhea); and/or seizures. Discontinue
valproate. Initiate alternative treatment for the treatment (and any concomitant serotonergic agent)
underlying medical condition as clinically immediately if signs/symptoms arise.).
indicated. Sexual dysfunction: May cause or exacerbate sexual
dysfunction.
Administration: Take with food. Extended-release SIADH and hyponatremia: SSRIs and SNRIs have been
formulations should be taken whole and not crushed, associated with the development of SIADH and rarely,
chewed, or split. hyponatremia predominantly in the elderly.
Hyponatremia is reversible with discontinuation of
See Valproic Acid under Fatty Acid Derivatives in Chapter treatment.
10: Antiepileptics for other information.
Disease-related concerns:
Pregnancy Category: D Cardiovascular disease (Use with caution in patients with a
recent history of MI or unstable heart disease).
ATC Code: N03AG01 Hepatic impairment (Use with caution in service
users/patients with hepatic impairment; a lower dosage
may be needed.)
Mania/hypomania (May precipitate a shift to mania or
hypomania in patients with bipolar disorder.
Monotherapy in service users/patients with bipolar
disorder should be avoided. Patients presenting with
depressive symptoms should be screened for bipolar
disorder. Escitalopram is not FDA approved for the
treatment of bipolar depression.)

519
 NERVOUS SYSTEM

Metabolic disease (Use with caution patients with altered Major depressive disorder, by mouth, ADULT/CHILD> 12
metabolism.) years, initially 10 mg once daily. May increase to 20 mg
Renal impairment (Use with caution in service patients with once daily after at least 1 week (ADULT) or at least 3
severe renal impairment.) weeks (CHILD>12 years) if necessary. Continue
Seizure disorders (Use with caution in patients with a treatment for at least 6 months to 1 year.
previous seizure disorder or condition predisposing to
seizures such as brain damage or alcoholism.) NOTE: For all indications, allow a sufficient duration of
therapy for around 4-8 weeks on the maximum tolerable
Special populations: dose before switching the antidepressant.
Elderly (Bioavailability and half-life are increased by 50% in
the elderly; May also cause agitation, sleep disturbances Dose Adjustment:
and excessive CNS stimulation.) Geriatric:
Lactation: Must weigh benefits of breast feeding with risks 10 mg once daily; use with caution as per the Beers Criteria
and benefits of antidepressant treatment versus due to association of SSRIs with falls and fractures in
nontreatment to both the infant and the mother. service users/patients 65 years and older and should be
Pediatric: When treating children, carefully weigh the risks avoided such service users/patients who have a history
and benefits of pharmacological treatment against the of falls or fractures, as well as having the potential to
risks and benefits of nontreatment with antidepressants cause or exacerbate syndrome of inappropriate
and make sure to document this in the service antidiuretic hormone secretion (SIADH) or hyponatremia
user/patient’s chart. monitor sodium concentration closely when initiating or
Pregnancy: Not generally recommended for use during adjusting the dose in older adults.
pregnancy, especially during the first trimester;
nonetheless, continuous treatment during pregnancy Renal Impairment:
may be necessary and has not been proven to be harmful Use with caution
to the fetus; At delivery there may be more bleeding in
the mother and transient irritability or sedation in the Hepatic Impairment:
newborn; Must weigh the risk of treatment (first trimester Initially 5 mg once daily. Increase to 10 mg once daily after
fetal development, third trimester newborn delivery) to 2 weeks
N

the child against the risk of no treatment (recurrence of

depression, maternal health, infant bonding) to the Precautions:
mother and child; For many service users/patients this WARNING: Antidepressants increased the risk of
may mean continuing treatment during pregnancy. suicidal thinking and behavior (suicidality) in
children, adolescents, and young adults with major
Other warnings/precautions: depressive disorder (MDD) and other psychiatric
Discontinuation syndrome: Abrupt discontinuation or disorders. Balance the risk with the clinical need.
interruption of antidepressant therapy has been Appropriately monitor patients of all ages who are
associated with a discontinuation syndrome. Symptoms started on antidepressant therapy and closely
arising may vary with antidepressant however commonly observe for clinical worsening, suicidality, or
include nausea, vomiting, diarrhea, headaches, light- unusual changes in behavior. Advise families and
headedness, dizziness, diminished appetite, sweating, caregivers of the need for close observation and
chills, tremors, paresthesias, fatigue, somnolence, and communication with the health care provider.
sleep disturbances (e.g., vivid dreams, insomnia). Escitalopram is not approved for use in pediatric
service users/patients younger than 12 years.

Electroconvulsive therapy (ECT): Use with caution; no

Rx ESCITALOPRAM clinical studies have assessed the combined use of
escitalopram and electroconvulsive therapy; may
Oral: 10 mg tablet (as oxalate) increase the risks (e.g., cognitive adverse effects)
associated with electroconvulsive therapy; consider
Escitalopram is a furancarbonitrile and S-stereoisomer of discontinuing, when possible, prior to ECT treatment.
citalopram. It induces allosteric serotonin transporter Use with caution in patients with history of seizures.
(SERT) inhibition which results in a significant increase Use with caution in patients with bipolar disorder unless
of serotonin. treated with concomitant mood stabilizing agent.
Monitor patients for activation of suicidal ideation,
Indications: Management of major depressive disorder, especially children and adolescents.
generalized anxiety disorder. Do not use use if patients is taking a MAO inhibitor

Contraindications: Known QTc prolongation, congenital long STORAGE AND STABILITY: Store at 25°C. Excursions
QTc syndrome. permitted to 15-30°C. Protect from light.

Dose: See General Precautions under Selective Serotonin

Generalized anxiety disorder, by mouth, ADULT, initially 10 Reuptake Inhibitors in Chapter 10: Nervous System for
mg once daily. May increase to 20 mg once daily if other precautions.
necessary. Continue treatment for up to 12 months after
initial response.

520
NERVOUS SYSTEM

Adverse Drug Reactions: evening, CHILD≥10 years, initially 20 mg once daily in the
Common: Abnormal dreams, fatigue, paresthesia, pyrexia, evening or with the fixed-dose combination, 25 mg once
restlessness, sinusitis, yawning. daily in the evening. Slowly titrate dose based on efficacy
Less Common: Alopecia, bruxism, confusion, epistaxis, and tolerability. Safety of fluoxetine doses >50 mg in
menstrual disturbances, mydriasis, edema, pruritus, combination with doses >12 mg of olanzapine has not
syncope, tachycardia, taste disturbance, tinnitus. been studied in pediatrics.
Rare: Aggression, bradycardia, depersonalization. Major depressive disorder, by mouth, ADULT, initially 20 mg
once daily in the morning. Allow a few weeks to assess
Drug Interactions: effects before titrating dose slowly up to a maximum of
Monitor closely with: 80 mg once daily in the morning. Continue treatment for
Tramadol, buspirone, tryptophan (serotonin syndrome) up to 4 to 9 months, CHILD≥8 years, initially 10 mg once
NSAIDs (bleeding) daily in the morning. Allow at least 1 week to assess
Oral anticoagulants (altered anticoagulant effects) effects before titrating dose slowly up to a maximum of
Drug-induced hypokalaemia/hypomagnesaemia 20 mg once daily in the morning. Continue treatment for
(malignant arrhythmias) at least 4 to 9 months.
Concomitant administration or w/in 14 days of MAOIs Obsessive compulsive disorder, by mouth, ADULT, initially
withdrawal (serotonin syndrome; fatal) 20 mg once daily in the morning. Allow a few weeks to
QTc prolonging agents e.g., pimozide (additive effect; assess effects before titrating dose slowly up to a
fatal; monitor) maximum of 80 mg once daily in the morning. Continue
treatment for at least 1 to 2 years after initial response.
Avoid concomitant use with: Panic disorder with or without agoraphobia, by mouth,
Linezolid (may cause serotonin syndrome) ADULT, initially 10 mg once daily in the morning. Increase
MAOIs (may cause serotonin syndrome) to 20 mg once daily in the morning after 1 week. Allow a
Methylene blue (may cause serotonin syndrome) few weeks to assess effects before titrating dose slowly
Pimozide (may precipitate torsades de pointes) up to a maximum of 60 mg once daily in the morning.
Continue treatment for at least 12 months after initial
Administration: May be taken with or without food response.
Premenstrual dysphoric disorder, by mouth, ADULT, initially

N
Pregnancy Category: Category C 20 mg once daily in the morning through the menstrual
cycle or limited to the luteal phase.
ATC Code: N06AB10 Treatment-resistant depression, in combination with
olanzapine, by mouth, ADULT, initially 20 mg once daily
in the evening or with the fixed-dose combination, 25 mg
once daily in the evening. Slowly titrate dose based on
Rx FLUOXETINE efficacy and tolerability up to a maximum of 50 mg once
daily in the evening.
Oral: 20 mg dispersible tablet / capsule NOTE: For all indications, allow a sufficient duration of
therapy for around 4-8 weeks on the maximum tolerable
Fluoxetine is a propylamine with a long half-life that, in dose before switching the antidepressant.
addition to blocking SERT, also has antagonistic
properties at the 5-HT2C receptor and weak Dose Adjustment:
norepinephrine reuptake blockade. It blocks SERT and Geriatric:
possesses antagonistic properties at the 5-HT2C leading Decrease initial dose and increase dose intervals; some
to disinhibition of dopamine and norepinephrine release service users/patients may require an initial dose of 10
resulting to precognitive effects. mg/day with dosage increases of 10 mg and 20 mg every
several weeks as tolerated; should not be taken at night
Indications: Management of major depressive disorder, unless service user/patient experiences sedation.
depression associated with bipolar 1 disorder in
combination with olanzapine, treatment-resistant NOTE: Use with caution in patients >65 years, patients with
depression in combination with olanzapine, obsessive history of falls or fractures and patients with a potential
compulsive disorder, premenstrual dysphoric disorder, to cause SIADH or hyponatremia.
bulimia nervosa, panic disorder with or without
agoraphobia. Renal Impairment:
No dosage adjustment necessary. Accumulation of
Contraindications: Hypersensitivity to fluoxetine. fluoxetine or norfluoxetine is possible due to chronic
administration in patients with severely impaired renal
Dose: function.
Bulimia nervosa, by mouth, ADULT, initially 60 mg once daily
in the morning. Some patients may need to begin at Hepatic Impairment:
lower dose and titrate over several days Decrease initial dose and increase dose intervals; for
service users/patients with cirrhosis, administer a lower
Depression associated with bipolar 1 disorder, by mouth, dose or less frequent dosing interval; for service
ADULT, initially 20 mg once daily in the evening or with users/patients with compensated cirrhosis without
the fixed-dose combination, 25 mg once daily in the ascites, administer 50% of normal dose.
evening. Slowly titrate dose based on efficacy and
tolerability up to a maximum of 50 mg once daily in the

521
 NERVOUS SYSTEM

Precautions: equilibrium disturbance, erythema multiforme, erythema

WARNING: Antidepressants increased the risk nodosum, esophagitis, euphoria, exfoliative dermatitis,
compared with placebo of suicidal thinking and extrapyramidal reaction, gastritis, gastroenteritis,
behavior (suicidality). Appropriately monitor and gastrointestinal ulcer, glossitis, gout, gynecological
closely observe service users/patients of all ages gynecomastia, hallucination, hemolytic anemia, hepatic
who are started on antidepressant therapy for failure, hepatic necrosis, hepatitis, hiccups, hostility,
clinical worsening, suicidality, or unusual changes hypersensitivity reaction, hypertonia, hyperventilation,
in behavior. Advise families and caregivers of the hypoglycemia, hypokalemia, hypotension,
need for close observation and communication hypothyroidism, immune thrombocytopenia, laryngeal
with the prescriber edema, laryngospasm, leg cramps, lupus-like syndrome,
malaise, melena, memory impairment, migraine,
Fluoxetine should not be discontinued abruptly. mydriasis, myocardial infarction, myoclonus, neuroleptic
Therapy should be withdrawn gradually to malignant syndrome, optic neuritis, orthostatic
minimize unwanted effects. For long- term hypotension, ostealgia, pancreatitis, pancytopenia,
patients gradually taper the dose within 4- 6 paranoia, petechia, priapism, pulmonary embolism,
months. pulmonary fibrosis, pulmonary hypertension, purpuric
rash, renal failure, serotonin syndrome, sexual disorder
Caution operating hazardous machinery or driving. (may persist after discontinuation), skin photosensitivity,
Stevens-Johnson syndrome, syncope, tachycardia,
Monotherapy in service users/patients with bipolar
thrombocytopenia, toxic epidermal necrolysis, vasculitis,
disorder should be avoided. Patients presenting
ventricular tachycardia (including torsades de pointes),
with depressive symptoms should be screened for
violent behavior
bipolar disorder. Fluoxetine monotherapy is not
FDA approved for the treatment of bipolar
Drug Interactions:
depression.
Monitor closely with:
Enhances effect of the following:
Allergic events e.g., rash, lupus-like syndrome, larynospasm, Anti- platelet agents e.g. Aspirin, Glucosamine,
anaphylactoid reactions and pulmonary inflammatory Multivitamins/Minerals [with With Vitamins ADEK,
N

disease Folate, Iron], NSAID, Omega-3 Fatty Acids, Prostacyclin

analogues, Vitamin E (anti-platelet effect), Blood
See General Precaution under Selective Serotonin glucose- lowering agents
Reuptake Inhibitors in Chapter 10: Nervous System for Thiazide diuretics (hyponatremic effect), Anti-coagulants
other precautions. e.g. Vitamin K antagonists (anti- coagulant effect)

STORAGE AND STABILITY: Store between 20-25°C. Enhances effect of Fluoxetine:

Excursions permitted to 15-30°C. Protect from light. Anti-emetics, Anti- psychotic agents, Opioid analgesics,
(serotonin syndrome)
Adverse Drug Reactions:
Common: delayed ejaculation, erectile dysfunction; men Reduces the therapeutic effect of the following:
and women: anorgasmia, urinary frequency, urination Codeine, Thyroid products
disorder decreased/increased appetite, nausea, Reduces the therapeutic effect of Fluoxetine:
vomiting, diarrhea, constipation, flatulence, dry mouth, Cyproheptadine, Non-selective NSAID, Ioflupane I123
dyspepsia, dysgeusia, insomnia, sedation, drowsiness,
sleep disorder, agitation, personality disorder, Increases adverse effects of Fluoxetine:
abnormality in thinking, tremors, chills, emotional lability, Bupropion, CNS depressants e.g. Alcohol (psychomotor
headache, dizziness, headaches, anxiety, nervousness, impairment), Desmopressin
yawning, fatigue, anorexia, abnormal dreams, amnesia, Tositumomab (bleeding), Iodine I131
confusion, QTc prolongation, palpitations, vasodilation,
chest pain, hypertension, sweating, skin rash, pruritis, Increases adverse effects of the following drugs:
hypermenorrhea, increased thirst, weight loss, weight Antipsychotic agents (neuroleptic malignant syndrome);
gain, decreased sexual desire, bruising, pharyngitis, Metyrosine; Nifedipine, Obinituzumab (bleeding)
hyperkinesia, asthenia, weakness , visual disturbance,
otalgia, tinnitus, flu-like symptoms, sinusitis, epistaxis. Avoid concomitant use with:
Rare: bleeding, hyponatremia and SIADH, seizures, Increase serum concentration of the following:
induction of mania, suicidality, falls, fractures and Abiraterone acetate, Atomoxetine, Brexpiprazole
osteoporosis (long-term use), abnormal hepatic function Dabigatran etexilate, Dosulepin, Doxorubicin
tests, acne vulgaris, acute abdominal condition, Metoprolol, Mequitazine, Propafenone, Thioridazine,
akathisia, albuminuria, alopecia, amenorrhea, Tizanidine, Tricyclic anti- depressants e.g.
anaphylactoid reaction, anemia, angina pectoris, angle- Amytriptylline
closure glaucoma, aphthous stomatitis, aplastic anemia,
arthritis, asthma, ataxia, atrial fibrillation, bruise, Increase serum concentration of Fluoxetine:
bruxism, bursitis, cardiac arrhythmia, cataract, Fosphenytoin, Haloperidol, Pimozide (QTc prolonging
cerebrovascular accident, cholelithiasis, cholestatic effect), Darunavir
jaundice, colitis, congestive heart failure, dehydration,
delusions, depersonalization, dyskinesia, dysphagia, May enhance adverse effects of the following drugs:
dysuria, ecchymoses, edema, eosinophilic pneumonitis,

522
NERVOUS SYSTEM

Apixaban (bleeding), Aripiprazole, Metoclopramide Dose:

(neuroleptic malignant syndrome), Metoclopramide Major depressive disorder, by mouth, ADULT, initially 50 mg
(extrapyramidal symptoms) once daily. Allow a few weeks to assess effects before
increasing the dose, but may increase the dose by 25-50
Enhances the adverse effects of Fluoxetine: mg once a week. Slowly titrate to a maximum of 200 mg
Ethyl Alcohol (psychomotor impairment), Dapoxetine, once daily. Continue treatment for at least 4 to 9 months.
non-selective NSAID (anti- platelet effect); Serotonin Obsessive compulsive disorder, by mouth, ADULT and
modulators [except Tedizolid], Tedizolid, (serotonin CHILD≥13 years, initially 50 mg once daily. Allow a few
syndrome), Tricyclic anti- depressants e.g. weeks to assess effects before increasing the dose, but
Amaytriptylline may increase the dose by 25-50 mg once a week. Slowly
titrate to a maximum of 200 mg once daily. Continue
Enhances effects of the following drugs: treatment for up to 12 months after initial response,
Dextrometorphan (serotonin syndrome), Dabigatran CHILD 6-12 years, initially 25 mg once daily. Allow a few
etexeilate (anti-coagulant effect), Fosphenytoin, weeks to assess effects before increasing the dose, but
Haloperidol, Highest Risk QTc prolonging agents, may increase the dose by 25-50 mg once a week. Slowly
Ivabradine, Mifepristone, Moderate Risk QTc Prolonging titrate to a maximum of 200 mg once daily. Continue
agents, Pimozide, Thioridazine, Ziprasidone (QTc treatment for up to 12 months after initial response.
prolonging effect), Tramadol (neuroexcitatory effect), Panic disorder with or without agoraphobia, by mouth,
Urokinase (bleeding) ADULT, initially 25 mg once daily. Increase to 50 mg once
daily after 1 week. Allow a few weeks to assess effects
Enhances effects of Fluoxetine: before increasing the dose again, but may increase the
Antidepressants, Aripiprazole, Bupropion, Linezolid, dose by 25-50 mg once a week. Slowly titrate to a
Lithium, MAO inhibitors [except Linezolid, Methylene maximum of 200 mg once daily. Continue treatment for
blue and Tedizolid], Methylene blue, Metoclopramide, at least 12 months after initial response.
Tramadol, Tryptophan, Ziprasidone (serotonin Post-traumatic stress disorder, by mouth, ADULT, initially 25
syndrome) mg once daily. Increase to 50 mg once daily after 1 week.
Propafenone (QTc prolonging effect) Allow a few weeks to assess effects before increasing the
dose again, but may increase the dose by 25-50 mg once

N
Decreases the metabolism of the following drugs: a week. Slowly titrate to a maximum of 200 mg once
Bupropion, Carbamazepine, Cimetidine, Clopidogrel, daily. Continue treatment for at least 12 months after
Mexiletine initial response.
Premenstrual dysphoric disorder, by mouth, ADULT, initially
Increase the metabolism of Fluoxetine 50 mg once daily through the menstrual cycle or limited
Carbamazepine, Cobicistat to the luteal phase.
Social anxiety disorder, by mouth, ADULT, initially 25 mg
Decrease therapeutic effect of the following: once daily. Increase to 50 mg once daily after 1 week.
Iobenguane I123 Allow a few weeks to assess effects before increasing the
dose again, but may increase the dose by 25-50 mg once
Decreases effect of Fluoxetine a week. Slowly titrate to a maximum of 200 mg once
NSAID [non- selective] daily. Continue treatment for at least 12 months after
initial response.
Administration: May be taken with or without food.
NOTE: For all indications, allow a sufficient duration of
Pregnancy Category: Category C therapy for around 4-8 weeks on the maximum tolerable
dose before switching the antidepressant.
ATC Code: N06AB03
Dose Adjustment:
Geriatric:
No dose adjustment necessary
Rx SERTRALINE NOTE: Use with caution in patients >65 years, patients with history of
falls or fractures and patients with a potential to cause SIADH or
hyponatremia.
Oral: 50 mg tablet (as hydrochloride)
Renal Impairment:
Sertraline inhibits SERT and weak dopamine transporter No dose adjustment necessary; not removed by
that is necessary to create an antidepressant used in hemodialysis.
various types of psychiatric disorders.
Hepatic Impairment:
Indications: Major depressive disorder; premenstrual Decrease initial dose and increase dose intervals; for mild
dysphoric disorder; anxiety disorders (social anxiety hepatic impairment, reduce dose by 50% of the normal
disorder, panic disorder with or without agoraphobia); dose; for moderate to severe impairment, use is not
obsessive compulsive disorder; post-traumatic stress recommended.
disorder

Contraindications: Hypersensitivity to sertraline

523
 NERVOUS SYSTEM

osteoporosis, aggressive behavior, purpura, arthralgia,

Precautions: muscle twitching, epistaxis, fever, acute renal failure,
agranulocytosis, angioedema, angle-closure glaucoma,
WARNING:
aplastic anemia, atrial arrhythmia, atrioventricular block,
Suicidal risk
blindness, bradycardia, cataract, cerebrovascular
Antidepressants increased the risk of suicidal
spasms, coagulation time increased, diabetes mellitus,
thinking and
edema, extrapyramidal reaction, gynecomastia, hepatic
behavior (suicidality). Monitor and closely observe
failure, hepatitis, hyperglycemia, hyperprolactinemia,
service users/patients of all ages who are started on
hypersensitivity reaction, jaundice, leukopenia, lupus-
antidepressant therapy for clinical worsening
like syndrome, menstrual disease, neuroleptic malignant
suicidality, or unusual changes in behavior. Advise
syndrome nightmares, oculogyric crisis, optic neuritis,
families and caregivers of the need for close
pancreatitis, pancytopenia, prolonged Q-T interval on
observation and communication with the prescriber.
ECG, psychosis, pulmonary hypertension,
rhabdomyolysis, serotonin syndrome, serum sickness,
Withdrawal syndrome
skin photosensitivity, Stevens-Johnson syndrome,
Sertraline should not be discontinued abruptly.
thrombocytopenia, torsades de pointes, toxic epidermal
Therapy
necrolysis, trismus, vasculitis, ventricular tachycardia,
should be withdrawn gradually to minimize unwanted
withdrawal syndrome
effects. For long- term patients gradually taper the
dose
Drug Interactions:
within 4- 6 months.
Monitor closely with:
CNS Depression Enhances the effects of the following:
Caution operating hazardous machinery or driving. Anti-platelet agents e.g Aspirin, Glucosamine,
Multivitamins/Minerals, NSAIDs., COX-2 inhibitor,
Monotherapy Pentoxifylline, Prostacyclin analogues, Tipranavir,
Monotherapy in service users/patients with bipolar Vitamin E, Vitamin E, Oral (anti- platelet effect),
disorder Analgesics, Opioid, Anti- emetics, 5HT3 antagonists,
should be avoided. Patients presenting with Tedizolid (serotonin syndrome), Anticoagulants,
N

depressive symptoms should be screened for bipolar Dasatinib, Rivaroxaban, Thrombolytic agents, Vitamin K
disorder. Sertraline monotherapy is not FDA antagonists (anti- coagulant effect), Blood glucose
approved for the treatment of bipolar depression. lowering agents (hypoglycemic effect)
Limaprost, Propafenone (QTc prolonging effect)
Thiazide diuretics e.g Hydrochlorothiazide (hyponatremic
See General Precautions under Selective Serotonin effect), Tositumomab, Iodine I131 Tositumomab
Reuptake Inhibitors in Chapter 10: Nervous System for (bleeding)
other precautions.
Enhances the effects of Sertraline:
STORAGE AND STABILITY: Store between 20-25°C. Excursions Antipsychotic agents (serotonin syndrome)
permitted to 15-30°C.
Enhance adverse effects of the following:
Adverse Drug Reactions: Antipsychotic agents (neuroleptic malignant syndrome),
Common: CNS depressants e.g., Alcohol (psychomotor
Palpitations, edema, hypertension, syncope, tachycardia, impairment)
vasodilation, insomnia, sedation, drowsiness, lethargy, Collagenase, Systemic, Deoxycholic acid (injection site
psychomotor agitation, seizure, yawning, agitation, reaction), Desmopressi, Ibritumomab, Obinituzumab,
irritability, malaise, tremors, dizziness, headaches, Pentosan Polysulfate Sodium, Salicylates (bleeding),
anxiety, nervousness, fatigue, anorexia, abnormal gait, Ibrutinib, Metyrosine, Omega- 3 Fatty Acids
ataxia, coma, confusion, euphoria, hallucination,
hypertonia, hypoesthesia, impaired consciousness, Reduces the therapeutic effect of the following:
hyperhidrosis, sweating, alopecia, bullous dermatitis, Codeine, Cyproheptadine, Ioflupane I123
dermatitis, diaphoresis, erythematous rash, follicular Thyroid products
rash, maculopapular rash, pruritus, urticaria, weight loss,
weight gain, diabetes mellitus, galactorrhea, Decreases the metabolism of the following:
hypercholesterolemia, hypoglycemia, hypothyroidism, Risperidone
decreased sexual desire, decreased appetite, increased
appetite, nausea, vomiting, diarrhea, constipation, Decreases the metabolism of Sertraline:
dyspepsia, abdominal pain, dry mouth, bruxism, Macrolide antibiotics [except Azithromycin, Systemic,
hematochezia, melena, ejaculation failure, ejaculatory Fidaxomicin, Spiramycin]
disorder, erectile dysfunction, priapism, vaginal
haemorrhage, anorgasmia, hematuria, bruising, Avoid concomitant use with:
hemorrhage, rectal hemorrhage, anaphylaxis, Increases the serum concentration of the following:
hyperkinesia, muscle spasm, asthenia, visual Amodiaquine, Aripiprazole, Cilostazol, Citalopram,
disturbance, blurred vision, mydriasis, tinnitus, Clozapine, Dabigatran etexilate, Dextrometorphan,
bronchospasm. Dosulepin, Doxorubicin, Eliglustat, Metoprolol,
Rare: bleeding, hyponatremia and SIADH, induction of Thioridazine, Tizanidine
mania, hypotension, suicidality, falls, fractures and Tricyclic antidepressants e.g. Amytriptylline

524
NERVOUS SYSTEM

Decreases serum concentration of the following drugs: Contraindications: Extreme anxiety or agitation, motor tics
Clopidogrel, Tamoxifen or Tourette’s syndrome, family history of Tourette’s
syndrome or tics, glaucoma, structural cardiac
Decreases serum concentration of Sertraline: abnormalities, advanced atherosclerosis, symptomatic
Darunavir, Efavirenz, Phenytoin cardiovascular disease, moderate to severe
hypertension, cardiac arrhythmias, heart failure, recent
Enhances effects of the following drugs: myocardial infarction, hyperthyroidism and
Antidepressants, Dextrometorphan (serotonin thyrotoxicosis, gastrointestinal obstruction or severe GI
syndrome), Dabigatran etexilate, Urokinase (anti- narrowing (specific for Concerta formulation), history of
coagulant effect), QTc prolonging Agents (QTc prolonging substance use disorders.
effect), Mifepristone, non-selective NSAID (anti- platelet
effect) Dose:
Tramadol (neuroexcitatory effect) Attention deficit hyperactive disorder, by mouth, ADULT,
initially 18 mg once daily in the morning. Increase by 9-
Enhances the effects of Sertraline: 18 mg each week up to a maximum dose of 72 mg once
Buspirone, Linezolid, Lithium, MAO Inhibitors [except daily in the morning, CHILD 13-17 years, initially 18 mg
Linezolid, Methylene blue, Tedizolid], Methylene blue, once daily in the morning. Increase by 9-18 mg each
Tramadol, Tryptophan (serotonin syndrome) week up to a maximum dose (≥40 kg) of 54-72 mg once
daily in the morning, CHILD<13 years, initially 18 mg
Enhances adverse effects of the following: once daily in the morning. Increase by 9-18 mg each
Apixaban (bleeding), Aripiprazole, Pimozide week up to a maximum dose (≤40 kg) of 54 mg once
Tricyclic antidepressants daily in the morning.
Narcolepsy, by mouth, 20-60 mg/day in 2-3 divided doses.
Reduces the therapeutic effect of the following:
Iobenguane I123 Dose Adjustment:
Geriatric:
Enhances adverse effects of the Sertraline: Lower doses may be better tolerated.
Ethyl Alcohol (psychomotor impairment), Dapoxetine,

N
Disulfiram, Metoclopramide, Serotonin modulators Renal Impairment:
[except Tedizolid] (serotonin syndrome) No dose adjustment necessary.

Increases the metabolism of Sertraline: Hepatic Impairment:

Carbamazepine No dose adjustment necessary.

Decreases the metabolism of the following: Precautions:

Buspirone, Carbamazepine, Methadone WARNING: The use of methylphenidate-containing
products and amphetamines have a high potential
Decrease the metabolism of Sertraline: for abuse and dependence. Assess the risk of
Cimetidine abuse prior to prescribing, and monitor for signs
of abuse and dependence while on therapy. Long-
Administration: May be taken with or without food. term abusive use can lead to marked tolerance
and psychological dependence with varying
Pregnancy Category: Category C degrees of abnormal behavior. Frank psychotic
episodes can occur, especially with parenteral
ATC Code: N06AB06 abuse. Methylphenidate requires an S-2 license
for physicians to be able to prescribe it and an S-
1 license with a triplicate prescription for
PSYCHOTIMULANTS, AGENTS USED FOR ADHD AND pharmacists to dispense it.
NOOTROPICS Monotherapy in service users/patients with bipolar
disorder should be avoided. Patients presenting
with depressive symptoms should be screened for
Rx METHYLPHENIDATE bipolar disorder. Methylphenidate monotherapy is
not FDA approved for the treatment of bipolar
Oral: 10 mg tablet depression.
18 mg, 27 mg, and 36 mg modified release (MR) Caution operating hazardous machinery or driving.
tablet Take caution in switching formulations of
20 mg MR capsule methylphenidate, as bioequivalence does not
automatically translate into clinical equivalence.
Methylphenidate helps correct neurotransmitter levels for Not an appropriate first-line treatment for depression
norepinephrine and dopamine synapses in the prefrontal or for normal fatigue.
cortex, which brings prefrontal activity back to optimal
levels. Cardiovascular events (serious structural cardiac
abnormalities, cardiomyopathy, serious heart rhythm
Indications: Attention deficit hyperactive disorder (ADHD) abnormalities); Chemical leukoderma; Hypersensitivity
and narcolepsy. (angioedema and anaphylactic reactions); Peripheral

525
 NERVOUS SYSTEM

vasculopathy (Raynaud’s phenomenon, digital Drug Interactions:

ulceration); Priapism; Visual disturbance (difficulty in Monitor closely with:
accommodation and blurred vision); Adrenal tumors. Enhances the effects of the following:
Cardiovascular disorders; Hyperthyroidism; Psychiatric Atomoxetine (anti-hypertensive effects)
disorders; Seizure disorder; Tourette syndrome/tics.
Lactation; Children (appetite suppression, weight loss, Reduces therapeutic effect of the following:
slowing of growth rate); Pregnancy (infants whose Antihypertensives, Ioflupane I123
mothers took methylphenidate during pregnancy may
experience withdrawal symptoms); Neonates (Gasping Enhance adverse effects of the following:
syndrome may occur with benzyl alcohol and derivatives Anti-Parkinson’s agents e.g., Levodopa, Antipsychotic
containing preparation.) agents, Clonidine, Doxofylline
Sympathomimetics, Tricyclic anti- depressants
STORAGE AND STABILITY: Store between 20-25°C.
Excursions permitted to 15-30°C. Protect from light and Enhances the adverse effects of Methylphenidate:
moisture. Antipsychotic agents

Adverse Drug Reactions: Avoid concomitant use with:

Common: insomnia, sedation, headache, exacerbation of Increases the serum concentration of the following:
tics, nervousness, anxiety, restlessness, irritability, Methylphenidate
emotional lability (1%-, depressed mood, depression,
agitation, overstimulation, aggressive behavior, tremor, Enhance adverse effects of Methylphenidate:
dizziness, anorexia, hypertonia, lack of emotion, vertigo, Alcohol, Ethyl
confusion, tension, tension headache, paresthesia,
hyperhidrosis, excoriation, skin rash, weight loss, Enhances effects of the following:
decreased libido, temporary slowing of normal growth in Inhalational anaesthetic (anti-hypertensive effect)
children, nausea, vomiting, upper abdominal pain,
decreased appetite, dry mouth, bruxism, dyspepsia, Enhances effects of Methylphenidate:
motion sickness, constipation, blurred vision, eye pain, MAO Inhibitors (anti- hypertensive effects)
N

nasopharyngitis, cough, upper respiratory tract infection,

oropharyngeal pain, fever. Enhances adverse effects of the following:
Rare: Priapism; dysphoria; “zombie-like” state; psychotic Iobenguane I123
episodes; seizures; palpitations; tachycardia;
hypertension; neuroleptic malignant syndrome; Administration: May be taken with or without food. Swallow
activation of hypomania, mania, or suicidal ideation; whole and do not chew, divide, or crush.
cardiovascular adverse effects; Gilles de la Tourette
syndrome; hypervigilance; jitteriness; mood changes; Pregnancy Category: Category C
outbursts of anger; panic attack; psychomotor agitation;
sleep disorder; toxic psychosis; macular eruption; growth ATC Code: N06BA04
suppression; hot flash; increased thirst; abdominal
distress; diarrhea; erectile dysfunction; anemia;
leukopenia; muscle spasm; weakness; dry eye ANTI-DEMENTIA DRUGS
syndrome; dyspnea; sinusitis; accommodation
disturbance; allergic contact dermatitis; allergic contact ANTICHOLINESTERASES
sensitivity; alopecia; angina pectoris; application site
reaction; arthralgia; auditory hallucination; bradycardia;
cerebral arteritis; cerebrovascular occlusion; change in Rx DONEPEZIL
libido; chest discomfort; chest pain; decreased platelet
count; decreased therapeutic response; diplopia; Oral: 5 mg and 10 mg tablet/orodispersible tablet (ODT)
disorientation; drowsiness; dyskinesia; erythema;
extrasystoles; fatigue; hallucination; hepatic failure Donepezil inhibits acetylcholinesterase resulting in an
(acute); hepatic injury (severe); hyperpyrexia; increase of acetylcholine availability at the remaining
hypersensitivity reaction; immune thrombocytopenia; sites that slows the decline in function of dementia
lethargy; leukoderma; loss of scalp hair; muscle service users/patients without memory improvement to
twitching; myalgia; mydriasis; neuroleptic malignant enhanced memory.
syndrome; pancytopenia; peripheral vascular
insufficiency; priapism; Raynaud phenomenon; Indications: Management of Alzheimer dementia (mild,
rhabdomyolysis; seizure; supraventricular tachycardia; moderate, and severe)
talkativeness; thrombocytopenia; thrombotic
thrombocytopenic purpura; urticaria; ventricular Dose:
premature contractions; visual disturbance; sudden Alzheimer dementia (mild, moderate, severe), by mouth,
death in service users/patients with preexisting cardiac ADULT, mild to moderate: initially 5 mg by mouth once
structural abnormalities. daily at bedtime. May increase to 10 mg once daily at
bedtime after 4-6 weeks, moderate to severe: initially 5
mg by mouth once daily at bedtime. May increase to 10
mg once daily at bedtime after 4-6 weeks. May increase
further after ≥3 months to 23 mg once daily at bedtime.

526
NERVOUS SYSTEM

Dose Adjustment: epigastric distress, epistaxis, eructation, erythema,

Geriatric: erythrocytopenia, esophagitis, euphoria, extrapyramidal
Some service users/patients may tolerate lower doses reaction, facial edema, fasciculations, fibrocystic breast
better; for elderly women ≥85 years with low body weight, changes, first degree atrioventricular block, flatulence,
a maximum of 5 mg once daily at bedtime is fungal dermatitis, gastritis, gastric ulcer, gingivitis,
recommended. glaucoma, goiter, gout, hearing loss, heart block,
hemiplegia, hemolytic anemia, hemorrhoids, hepatitis,
Renal Impairment: hernia, herpes zoster, hiatal hernia, hirsutism,
Few data available; dose adjustment may not be necessary. hyperbilirubinemia, hyperglycemia, hyperkeratosis,
hypersensitivity reaction, hypertonia, hypokalemia,
Hepatic Impairment: hypokinesia, hyponatremia, hypoproteinemia, hypoxia,
Few data available; dose may need to be lowered. increased appetite, intestinal obstruction, intracranial
hemorrhage, iron deficiency anemia, irritable bowel
Precautions: syndrome, jaundice, leg cramps, leukocytosis, localized
Altered cardiac conduction (QTc prolongation and torsades coldness, malaise, mastitis, melena, motion sickness,
de pointes, bradycardia); Anorexia/weight loss; Bladder muscle spasm, myalgia, myasthenia, myocardial
obstruction; GI effects (dose-related diarrhea, nausea, infarction, neuralgia, neurodermatitis, neuroleptic
and/or vomiting); Neuroleptic malignant syndrome; malignant syndrome, night sweats, nystagmus,
Rhabdomyolysis. orthostatic hypotension, osteoporosis, otalgia, otitis
Peptic ulcer disease; Respiratory disease e.g. COPD and/or externa, otitis media, pacing, pancreatitis, paranoia,
asthma; Seizure disorder; Urinary tract obstruction. peptic ulcer disease, periodontal abscess, periodontitis,
Lactation; Low-weight service users/patients; Pregnancy periorbital edema, peripheral vascular disease,
(NOT recommended for use in pregnant women or pernicious anemia, pleurisy, polydipsia, post nasal drip,
women of childbearing potential). prolonged Q-T interval on ECG, psoriasis, pulmonary
congestion, pyelonephritis, pyuria, rectal hemorrhage,
STORAGE AND STABILITY: Store between 20-25°C. renal failure, retinal hemorrhage, rhabdomyolysis,
Excursions permitted to 15-30°C. rhinitis, seeing spots, sensation of cold, sepsis, severe
depression, sialorrhea, skin discoloration, sleep apnea,

N
Adverse Drug Reactions: snoring, supraventricular extrasystole, supraventricular
Common: hypertension, chest pain, syncope, atrial tachycardia, thrombocythemia, thrombocytopenia,
fibrillation, bradycardia, cardiac failure, ECG abnormality, tinnitus, tongue edema, tonic-clonic seizures, torsades
edema, hypotension, peripheral edema, vasodilation, de pointes, transient ischemic attacks, urinary urgency,
insomnia, dizziness, headache, pain, tremor, fatigue, uterine hemorrhage, vaginitis, vasodilation, ventricular
depression, abnormal dreams, hallucination, hostility, premature contractions, ventricular tachycardia, vertigo,
nervousness, confusion, drowsiness, emotional lability, vesiculobullous dermatitis, weight gain, wheezing,
personality disorder, abnormal gait, aggressive behavior, xeroderma, xerophthalmia, xerostomia.
agitation, anxiety, aphasia, ataxia, convulsions,
delusions, irritability, paresthesia, restlessness, vertigo, Drug Interactions:
wandering, anorexia, ecchymosis, eczema, dermal ulcer, Monitor closely with:
diaphoresis, pruritus, skin rash, urticaria, weight loss, Amifampridine – may enhance the therapeutic effect and
hyperlipidemia, dehydration, glycosuria, hot flash, side effects of acetylcholinesterase inhibitors;
increased libido, nausea, vomiting, diarrhea, appetite acetylcholinesterase inhibitors may enhance the
loss, increased gastric acid secretion, abdominal pain, therapeutic effect and side effects of amifampridine.
bloating, constipation, dyspepsia, epigastric pain, fecal Anesthetics – donepezil may enhance the effects of
incontinence, gastroenteritis, gastrointestinal anesthetics; donepezil should be discontinued before
hemorrhage, sore throat, toothache, urinary frequency, surgery.
cystitis, hematuria, nocturia, urinary tract infection, Anticholinergics – may decrease the efficacy of each other
bruise, hemorrhage, anemia, infection, fungal infection, due to opposite physiologic effects.
influenza, muscle cramps, back pain, arthritis, Benoxinate – acetylcholinesterase inhibitors may prolong
weakness, bone fracture blurred vision, cataract, eye the effects of benoxinate.
irritation bronchitis, dyspnea), flu-like symptoms, Beta-blockers – acetylcholinesterase inhibitors may
increased cough, pharyngitis , pneumonia, accidental enhance the bradycardic effect of beta-blockers except
injury (13%), fever (2%). for levobunolol and metipranolol.
Rare: seizures, syncope, bladder incontinence, abnormal Bradycardia-causing agents – may enhance the bradycardic
lacrimation, abnormal vision, abscess, acute rhinitis, effect of other bradycardia-causing agents.
albuminuria, alopecia, angina pectoris, apathy, arteritis, Bretylium – may enhance the bradycardic effect of other
arthralgia, arthropathy, asthma, atelectasis, atrophic bradycardia-causing agents; bretylium may also enhance
striae, benign prostatic hypertrophy, blepharitis, breast atrioventricular (AV) blockade in service users/patients
fibroadenosis, cachexia, cardiomegaly, cellulitis, receiving AV blocking agents.
cerebral hemorrhage, cerebral infarction, cerebral Ceritinib – may enhance the bradycardic effect of ceritinib.
ischemia, cerebrovascular accident, chills, cholecystitis, Cholinergics – may have a synergistic effect if administered
cholelithiasis, conjunctival hemorrhage, conjunctivitis, simultaneously.
convulsions, decreased libido, deep vein thrombosis, Corticosteroids (systemic) – may enhance the adverse/toxic
dementia, dermatitis, diabetes mellitus, diverticulitis, effect of acetylcholinesterase inhibitors; increased
duodenal ulcer, dysarthria, dysgeusia, dysphagia, muscular weakness may occur.
dysphoria, dysuria, emotional disturbance, eosinophilia,

527
 NERVOUS SYSTEM

Dipyridamole – may diminish the therapeutic effect of Dose Adjustment:

acetylcholinesterase Inhibitors. Geriatric:
Ivabradine – bradycardia-causing agents may enhance the Some service users/patients may tolerate lower doses
bradycardic effect of ivabradine. better.
Lacosamide – bradycardia-causing agents may enhance the
AV-blocking effect of lacosamide. Renal Impairment:
Levodopa – efficacy may be theoretically reduced by Dose adjustment not necessary; titrate to point of
donepezil. tolerability.
Neuromuscular-blocking agents (nondepolarizing) –
acetylcholinesterase inhibitors may diminish the Hepatic Impairment:
neuromuscular-blocking effect of neuromuscular- Dose adjustment not necessary; titrate to point of
blocking agents (nondepolarizing). tolerability.
QTc-prolonging agents – QTc-prolonging agents may
enhance the QTc-prolonging effect of QTc-prolonging Precautions:
agents. Caution operating hazardous machinery or driving.
Ruxolitinib – may enhance the bradycardic effect of
bradycardia-causing agents. Systemic exposure may be increased in service
Succinylcholine – acetylcholinesterase inhibitors may users/patients <50 kg and decreased in service
increase the serum concentration of succinylcholine. users/patients >100 kg
Terlipressin – may enhance the bradycardic effect of
bradycardia-causing agents. Concerns related to adverse effects:
Tofacitinib – may enhance the bradycardic effect of Allergic dermatitis; CNS depression; Extrapyramidal effects
bradycardia-causing agents. GI effects (nausea/vomiting/diarrhea or
anorexia/weight loss/decreased appetite); Vagotonic
Administration: May be taken with or without food. Allow effects (bradycardia and/or heart block with or without a
tablet to dissolve completely on tongue and follow with history of cardiac disease); Weight loss.
water. Peptic ulcer disease; Respiratory disease (use with caution
in service users/patients with COPD and/or asthma);
N

Pregnancy Category: Category C Seizure disorder; Urinary tract obstruction e.g. bladder
outlet obstruction or prostatic hyperplasia.
ATC Code: N06DA02 Lactation (not recommended for use in nursing women);
Pregnancy (not recommended for use in pregnant
women or women of childbearing potential).
Rx RIVASTIGMINE NOTE: Should be started at lowest dose and titrated; if
treatment is interrupted for >3 days, reinstate at the
Oral: 1.5 mg, 3 mg, and 6 mg capsule (as hydrogen lowest daily dose. Severe vomiting with esophageal
tartrate) rupture may occur if rivastigmine therapy is resumed
without retitrating the drug from the beginning (i.e. 1.5
A carbamate pseudoirreversible (self-reversing over hours), mg by mouth twice daily).
intermediate-acting agent that is selective for inhibiting
acetylcholinesterase over butyrylcholinesterase and for STORAGE AND STABILITY: Store between 20-25°C.
inhibiting acetylcholinesterase in the cortex and Excursions permitted to 15-30°C.
hippocampus over other areas of the brain. It also
inhibits butyrylcholinesterase in the glia, which may be Adverse Drug Reactions:
even more important when Alzheimer’s disease service Common: hypertension, syncope, nausea, vomiting,
users/patients develop gliosis when cortical neurons die. diarrhea, abdominal pain, appetite loss, weight loss,
dyspepsia, increased gastric acid secretion, upper
Indications: Alzheimer dementia (mild to moderate); abdominal pain, sialorrhea, anorexia, headache,
Parkinson’s disease dementia (mild to moderate) dizziness, falling, tremor, fatigue, insomnia, confusion,
depression, drowsiness, malaise, anxiety, hallucination,
Contraindications: hypersensitivity to rivastigmine or other aggressive behavior, exacerbation of Parkinson’s
carbamates disease, cogwheel rigidity, restlessness, drug-induced
Parkinson’s disease, diaphoresis, dehydration, urinary
Dose: tract infection, urinary incontinence, asthenia,
Alzheimer dementia, mild to moderate, by mouth, ADULT, weakness, bradykinesia, hypokinesia, dyskinesia
initially 1.5 mg twice daily. Increase by 3 mg every 2 Rare: seizures, syncope, severe vomiting with esophageal
weeks and titrate to tolerability with a maximum dose of rupture, rhinitis, urogenital infection, fever, injury,
6 mg twice daily. dyspnea, abnormal hepatic function tests, allergic
Parkinson’s disease dementia, mild to moderate, by mouth, dermatitis, atrial fibrillation, atrioventricular block,
ADULT, initially 1.5 mg twice daily. Increase by 3 mg every bradycardia, dystonia, edema, extrapyramidal reaction,
4 weeks and titrate to tolerability with a maximum dose gastrointestinal hemorrhage, hepatic failure, hepatitis,
of 6 mg twice daily. hyperacidity, hypersensitivity reaction, nightmares,
pancreatitis, sick-sinus syndrome, skin blister, Stevens-
Johnson syndrome, tachycardia, urticaria

528
NERVOUS SYSTEM

Drug Interactions: Dose:

Monitor closely with: NOTE: Pretreatment with atropine is recommended, and
Enhances the effect of the following: atropine should be available if a cholinergic reaction occurs.
Antipsychotic agents (severe extrapyramidal symptoms) Myasthenia gravis, diagnosis, by intramuscular injection,
Bradycardia-causing agents, Bretylium, Ivabradine ADULT, 0.022 mg/kg as a single dose. If test is
(bradycardic effect) Lacosamide (AV blockade effect) inconclusive, retesting can be done on a different day
with a single dose of 0.031 mg/kg, CHILD<2 years
Enhances effect of Rivastigmine: (limited data available), 0.04 mg/kg once. If results are
Ruxolitinib, Tofacitinib (bradycardic effect) equivocal or negative, may be repeated once in 4 hours.
Typical dose is 0.5-1.5 mg.
Enhances adverse effect of the following: Myasthenia gravis, treatment, by intramuscular or
Cholinergic agonists e.g., Betanechol intravenous or subcutaneous injection, ADULT, 0.5-2.5
mg. Dosing based on individual patient response, CHILD
Enhances adverse effects of Rivastigmine: AND ADOLESCENT (limited data available), 0.01-0.04
Corticosteroids, Systemic (muscular weakness) mg/kg every 2-6 hours.

Reduces the therapeutic effect of the following drugs: NOTE: An anticholinergic agent (atropine or glycopyrrolate)
Anticholinergic agents should be given intravenously prior to or in conjunction
Neuromuscular- blocking agents, Nondepolarizing with neostigmine; in the presence of bradycardia,
administer the anticholinergic prior to neostigmine.
Reduces the therapeutic of Rivastigmine: Peripheral nerve stimulation delivering train-of-four (TOF)
Dipyridamole stimulus must also be used to determine time of
neostigmine initiation and need for additional doses.
Avoid concomitant use with: Prior to administration, there must be a twitch response
Increases serum concentration of the following: to the first stimulus in the TOF of at least 10% of
Succinylcholine (neuromuscular blockade) baseline.

Enhances effect of the following: Reversal of nondepolarizing neuromuscular blockade after

N
Beta-blockers, Ceritinib (bradycardic effect) surgery, by intravenous injection, ADULT/CHILD,
Bioxiverz: The usual dose is 0.03-0.07 mg/kg, which
Enhances adverse effect of the following: generally achieves a TOF twitch ratio of 90% within 10-
Metoclopramide (extrapyramidal reactions) 20 minutes of administration. The maximum total dose
is 0.07 mg/kg or 5 mg, whichever is less. The 0.03
Administration: Take with food mg/kg dose is recommended for reversal of NMBAs with
shorter half-lives (e.g. rocuronium); or when the first
Pregnancy Category: Category B twitch response to the TOF stimulus is substantially
>10% of baseline or when a second twitch is present.
ATC Code: N06D The 0.07 mg/kg dose is recommended for NMBAs with
longer half-lives (e.g. vecuronium, pancuronium); or
when the first twitch response is relatively weak (i.e. not
substantially >10% of baseline); or rapid recovery is
OTHER NERVOUS SYSTEM DRUGS needed, NEONATE, Bloxiverz: Note: An anticholinergic
agent (atropine or glycopyrrolate) should be given prior
to or in conjunction with neostigmine; in the presence of
PARASYMPATHOMIMETICS bradycardia, administer the anticholinergic prior to
neostigmine. Peripheral nerve stimulation delivering
ANTICHOLINESTERASES train-of-four (TOF) stimulus must also be used to
determine time of neostigmine initiation and need for
additional doses.
Rx NEOSTIGMINE
Dose Adjustment:
Inj.: 500 micrograms/mL, 1 mL ampule and 10 mL vial Geriatric:
No dose adjustment necessary.
Neogstigmine inhibits the destruction of acetylcholine by
acetylcholinesterase. Renal Impairment:
ADULT, CrCl >50 mL/minute: No dosage adjustment
Indications: Management of myasthenia gravis, reversal of necessary.
non-depolarizing neuromuscular blockade after surgery; CrCl 10 to 50 mL/minute: Administer 50% of normal dose.
paralytic ileus and postoperative bladder CrCl <10 mL/minute: Administer 25% of normal dose.
distention/urinary retention and diagnosis of myasthenia Hemodialysis: No dosage adjustment necessary.
gravis. Peritoneal dialysis: No dosage adjustment necessary.
Continuous renal replacement therapy (CRRT): Administer
Contraindications: peritonitis or mechanical obstruction of 50% of normal dose.
the intestinal or urinary tract, hypersensitivity to
neostigmine or any component of the formulation. Hepatic Impairment:
Has not been studied

529
 NERVOUS SYSTEM

Precautions: Succinylcholine – acetylcholinesterase inhibitors may

Concerns related to adverse effects: increase the serum concentration of Succinylcholine.
Cardiovascular effects (bradycardia, hypotension, Management: Consider alternatives to this combination
dysrhythmias); Cholinergic crisis (extreme muscle due to a risk of prolonged neuromuscular blockade.
weakness and potentially fatal respiratory paralysis);
Hypersensitivity; Neuromuscular effects; Administration: Neostigmine Omega, Prostigmin: May be
Asthma; Cardiovascular disease; Hyperthyroidism; administered IM, IV, or SC. Bloxiverz: Administer by slow
Megacolon/GI dysfunction; Myasthenia gravis; Peptic IV injection over at least 1 minute.
ulcer disease; Seizure disorder; Vagotonia
Pediatric; Elderly (Elderly patients experience slower Pregnancy Category: Category
spontaneous recovery from neuromuscular blocking
agents.); ATC Code: N07AA01

NOTE: Adequate facilities should be available for

cardiopulmonary resuscitation when testing and
adjusting dose for myasthenia gravis. Rx PYRIDOSTIGMINE

STORAGE AND STABILITY: Store at 20-25°C. Excursions Oral: 60 mg tablet (as bromide)
permitted to 15-30°C. Protect from light. Store in carton
until time of use. Pyridostigmine is a quaternary pyridinium carbamate. It
inhibits destruction of acetylcholine by
Adverse Drug Reactions: acetylcholinesterase.
Atrioventricular block, cardiac arrhythmia (especially
bradycardia), flushing, hypotension, nodal arrhythmia, Indications: Management of myasthenia gravis; paralytic
syncope, tachycardia, thrombophlebitis (IV), dizziness, ileus; Soman nerve gas exposure, pretreatment (military
drowsiness, dysarthria, headache, loss of use)
consciousness, seizure, voice disorder, diaphoresis, skin
rash, urticaria, diarrhea, dysphagia, flatulence, Contraindications: Mechanical intestinal or urinary
N

increased peristalsis, nausea, salivation, stomach obstruction

cramps, vomiting, urinary urgency, anaphylaxis,
hypersensitivity reaction, arthralgia, fasciculations, Dose:
laryngospasm, muscle cramps, muscle spasm, Myasthenia gravis, by mouth, ADULT, highly individualized
weakness, lacrimation, miosis, bronchospasm, dyspnea, dosing ranges from 60-1500 mg/day. The usual dose is
exacerbation of asthma, increased bronchial secretions, 600 mg/day divided into 5-6 doses, spaced to provide
respiratory depression, respiratory paralysis maximum relief, CHILD 6-12 years, 60 mg, CHILD<6
years, initially 30 mg. Dosage should increase gradually,
Drug Interactions: in increments of 15-30 mg daily, until maximum
Monitor closely with: improvement is obtained. Total daily requirements are
Amifampridine – may enhance the therapeutic effect of usually in the range of 30-360 mg.
acetylcholinesterase inhibitors; acetylcholinesterase
inhibitor side effects may also be increased; NOTE: Do not administer pyridostigmine after Soman
acetylcholinesterase inhibitors may enhance the exposure; if taken immediately before exposure (e.g.
therapeutic effect of amifampridine; amifampridine side when gas attack alarm is given) or at the same time, it is
effects may also be increased. not expected to be effective and may exacerbate the
Anticholinergics – may diminish the therapeutic effect of effects of a sub-lethal exposure to Soman.
acetylcholinesterase inhibitors. acetylcholinesterase
inhibitors may diminish the therapeutic effect of Soman nerve gas exposure, pretreatment (military use), by
anticholinergics. mouth, ADULT, 30 mg every 8 hours beginning several
Benoxinate – acetylcholinesterase inhibitors may enhance hours prior to exposure. Discontinue at first sign of
the therapeutic effect of Benoxinate; specifically, the Soman exposure, then immediately begin atropine and
effects of benoxinate may be prolonged. pralidoxime.
Beta-blockers – acetylcholinesterase inhibitors may
enhance the bradycardic effect of beta-blockers except Dose Adjustment:
for levobunolol and metipranolol. Geriatric:
Cholinergic agonists – acetylcholinesterase inhibitors may No dose adjustment necessary.
enhance the adverse/toxic effect of cholinergic agonists.
Corticosteroids (systemic) – may enhance the adverse/toxic Renal Impairment:
effect of acetylcholinesterase inhibitors; increased Lower initial doses dosages may be required due to
muscular weakness may occur. prolonged elimination in renal impairment.
Dipyridamole – may diminish the therapeutic effect of
acetylcholinesterase inhibitors. Hepatic Impairment:
Neuromuscular-blocking agents (nondepolarizing) – No dose adjustment necessary.
acetylcholinesterase inhibitors may diminish the
neuromuscular-blocking effect of neuromuscular- Precautions:
blocking agents (nondepolarizing). Cholinergic effects; Hypersensitivity reactions;

530
NERVOUS SYSTEM

Cardiovascular disease; Glaucoma; Renal impairment; Beta-blockers – acetylcholinesterase inhibitors may

Respiratory disease (use with extreme caution in enhance the bradycardic effect of beta-blockers except
patients with asthma, bronchospastic disease, COPD) levobunolol and metipranolol.
Bromide sensitivity; Cholinergic agonists – acetylcholinesterase inhibitors may
Pediatrics (gasping syndrome due to benzyl alcohol and enhance the adverse/toxic effect of cholinergic agonists.
derivaitves); Corticosteroids (systemic) – may enhance the adverse/toxic
Military use (Only for pretreatment for exposure to Soman; effect of acetylcholinesterase inhibitors; increased
discontinue pyridostigmine at the first sign of Soman muscular weakness may occur.
exposure (do not administer pyridostigmine after Soman Dipyridamole – may diminish the therapeutic effect of
exposure); atropine and pralidoxime must be acetylcholinesterase inhibitors.
administered after Soman exposure. Use in conjunction Methocarbamol – may diminish the therapeutic effect of
with protective garments, including gas mask, hood and pyridostigmine.
overgarments.) Neuromuscular-blocking agents (nondepolarizing) –
acetylcholinesterase inhibitors may diminish the
NOTE: Must be administered by trained personnel; use of neuromuscular-blocking effect of neuromuscular-
peripheral nerve stimulation to monitor neuromuscular blocking agents (nondepolarizing).
function recovery and continuous patient observation. To Succinylcholine – acetylcholinesterase inhibitors may
counteract anticholinergic effects, use of glycopyrrolate increase the serum concentration of succinylcholine.
or atropine sulfate simultaneously with or prior to
administration is recommended until recovery of normal Administration: Should be taken with food.
respiration is recommended.
Inadequate reversal induced by nondepolarizing muscle Pregnancy Category: Category B/C (manufacturer
relaxants is possible; manage with manual or dependent)
mechanical ventilation until recovery is adequate
(additional doses not recommended). ATC Code: N07AA02
Pyridostigmine pretreatment offers no benefit against
Soman unless atropine and pralidoxime are
administered once symptoms of poisoning appear. DRUGS USED IN ADDICTIVE DISORDERS

N
STORAGE AND STABILITY: Store at 20-25°C. Excursions
permitted to 15-30°C. Dispense in original container. Rx NALTREXONE
Adverse Drug Reactions:
Oral: 50 mg tablet (as hydrochloride)
Common: twitching, hyperesthesia, xeroderma, abdominal
pain, diarrhea, dysmenorrhea, urinary frequency,
Naltrexone blocks mu opioid receptors, preventing
myalgia, neck pain, amblyopia, epistaxis
exogenous opioids from binding and thus preventing the
Rare: bradycardia (transient), chest tightness, decreased
pleasurable effects of opioid consumption. It also
heart rate, increased blood pressure, confusion,
reduces alcohol consumption through modulation of
depressed mood, disturbed sleep, drowsiness,
opioid systems, thereby reducing the reinforcing effects
headache, hypertonia, lack of concentration, lethargy,
of alcohol.
localized warm feeling, numbness of tongue, tingling of
extremities, vertigo, alopecia, diaphoresis, skin rash,
Indications: Management of alcohol dependence, blockade
abdominal cramps, bloating, borborygmi, flatulence,
of effects of exogenously administered opioids
increased peristalsis, nausea, salivation, vomiting,
fasciculations, muscle cramps, weakness, eye pain,
Contraindications: Concurrent opioid dependence or opiate
lacrimation, miosis, visual disturbance, acute bronchitis
withdrawal, failure in naloxone challenge test, positive
(exacerbation), exacerbation of asthma, increased
urine screening for opioids, acute hepatitis, liver failure
bronchial secretions, fecal incontinence, loss of
or liver function tests greater than 3 times the upper limit
consciousness, pallor (postsyncopal), stiffness (arms or
of normal, hypersensitivity to naltrexone
upper torso), thrombophlebitis, urinary incontinence
Dose:
Drug Interactions:
NOTE: Do not initiate therapy until service user/patient is
Monitor closely with:
opioid-free (including tramadol) for at least 7-10 days as
Amifampridine – may enhance the therapeutic effect of
determined by urinalysis; consider naloxone challenge
acetylcholinesterase inhibitors; acetylcholinesterase
test to confirm service user/patient is opioid-free if there
inhibitor side effects may also be increased;
is any suspicion since urinary opioid screen may not be
acetylcholinesterase inhibitors may enhance the
sufficient proof.
therapeutic effect of amifampridine; amifampridine side
effects may also be increased.
Alcohol dependence, by mouth, ADULT, 50 mg once daily.
Anticholinergics – may diminish the therapeutic effect of
Titration is not required. Alternative maintenance
acetylcholinesterase inhibitors. acetylcholinesterase
regimens may be used and include: 50 mg on weekdays
inhibitors may diminish the therapeutic effect of
with a 100 mg dose on Saturday; 100 mg every other
anticholinergics.
day; or 150 mg every 3 days (degree of blockade may be
Benoxinate – acetylcholinesterase inhibitors may enhance
reduced with extended dosing interval regimens and
the therapeutic effect of benoxinate; specifically, the
doses >50 mg may increase risk of hepatocellular injury).
effects of benoxinate may be prolonged.

531
 NERVOUS SYSTEM

Opioid dependence, by mouth, ADULT, initially 25 mg. If no neonates: shrill cry, failure to feed); Eosinophilic
withdrawal signs occur, administer 50 mg once daily pneumonia; Hepatocellular injury (dose-related
thereafter. Alternative maintenance regimens may be hepatocellular injury); Hypersensitivity; Injection site
used and include: 50 mg on weekdays with a 100 mg reactions (cellulitis, induration, hematoma, abscess,
dose on Saturday; 100 mg every other day; or 150 mg necrosis); Suicidal thoughts/depression.
every 3 days (degree of blockade may be reduced with Bleeding disorders; Hepatic and renal impairment;
extended dosing interval regimens and doses >50 mg Detoxified opioid addiction.
may increase risk of hepatocellular injury). Lactation.

Dose Adjustment: STORAGE AND STABILITY: Store at 20-25°C. Excursions

Geriatric: permitted to 15-30°C. Protect from light.
Some service users/patients may tolerate lower doses
better. Adverse Drug Reactions:
Common: Syncope, hypertension, headache, insomnia,
Renal Impairment: dizziness, anxiety, decreased energy, nervousness,
Dose adjustment not necessary for mild impairment; suicidal ideation, delayed ejaculation, depression,
drowsiness, fatigue, chills, depressed mood, increased
Hepatic Impairment: energy, irritability, skin rash, increased gamma-glutamyl
Dose adjustment not generally necessary for mild transferase, increased thirst, polydipsia, nausea,
impairment; has the potential to cause hepatocellular vomiting, decreased appetite, diarrhea, abdominal pain,
injury when given in excessive doses and is abdominal cramps, xerostomia, toothache, constipation,
contraindicated in acute hepatitis and liver failure. impotence, influenza, injection site reaction, arthralgia,
myalgia, muscle cramps, back pain, pharyngitis.
Precautions: Rare: Hepatocellular injury (excessive doses), dysphoria,
Patients who had been treated with naltrexone may abnormality in thinking, acne vulgaris, acute ischemic
respond to lower opioid doses than previously used. stroke, agitation, alopecia, altered blood pressure,
This could result in potentially life-threatening angina pectoris, anorexia, atrial fibrillation, blurred
opioid intoxication. Patients should be aware that vision, burning sensation of eyes, cardiac failure,
N

they may be more sensitive to lower doses of cerebral aneurysm, chest pain, chest tightness,
opioids after naltrexone treatment is discontinued. cholecystitis, cholelithiasis, chronic obstructive
Discontinue therapy if signs/symptoms of acute pulmonary disease, cold extremities, colitis, confusion,
hepatitis develop. Clinicians should note that cough, decreased libido, deep vein thrombosis,
elevated transaminases may be a result of pre- dehydration, delirium, diaphoresis, disorientation,
existing alcoholic liver disease, hepatitis B and/or C dyspnea, dysuria, ECG changes, edema, eosinophilia
infection, or concomitant use of other hepatotoxic (transient), eosinophilic pneumonitis, epistaxis,
drugs; abrupt opioid withdrawal may also lead to euphoria, eye pain, fever, flatulence, gastrointestinal
acute liver injury. hemorrhage, groin pain, hallucination, hemorrhoids,
hepatic insufficiency, hepatitis, herpes labialis,
Increase risk of suicidal thinking and behavior hoarseness, hot flash, hypercholesterolemia,
(suicidality).
hyperkinesia, hypersensitivity reaction, increased
Patients should be opioid-free (including tramadol) for appetite, increased bronchial secretions, increased
a minimum of 7-10 days; a naloxone challenge test libido, knee pain, leg pain, leukocytosis,
may be helpful to confirm service user/patient is lymphadenopathy, malaise, myocardial infarction, nasal
opioid-free prior to therapy if there is any suspicion congestion, nightmares, oily skin, opioid withdrawal
since urinary opioid screen may not be sufficient syndrome, otalgia, palpitations, pancreatitis, paralytic
proof. ileus, paranoia, perirectal abscess, photophobia,
Patients transitioning from buprenorphine or pneumonia, pulmonary embolism, restlessness,
methadone may be vulnerable to precipitation of rhinorrhea, rigors, seizure, shoulder pain, sinusitis,
withdrawal symptoms for as long as 2 weeks sneezing, sore throat, swelling of eye, tachycardia,
In naltrexone-treated service users/patients requiring thrombocytopenia, tinea pedis, tinnitus, tremor,
emergency pain management, consider twitching, ulcer, urinary frequency, urinary tract infection,
alternatives to opioid therapy. Seek direct care of a visual disturbance, weakness, weight gain, weight loss,
trained anesthesia provider yawning
For naltrexone- treated patients requiring surgery;
discontinue oral naltrexone at least 72 hours before NOTE: May cause cross- reactivity with some immunoassay
scheduled elective surgery if opioid use is methods
anticipated; extended-release IM naltrexone should
be discontinued at least 30 days prior to scheduled Drug Interactions:
surgery Monitor closely with:
Acamprosate – naltrexone may increase the serum
Naltrexone should be avoided in opioid- dependent
concentration of acamprosate.
patients as an acute withdrawal may be
Cannabinoids – naltrexone may enhance or diminish the
precipitated.
therapeutic effect of cannabinoids.
Codeine – naltrexone may block the effects of codeine.
Accidental opioid overdose, Acute opioid withdrawal (pain, Glyburide – may increase the serum concentration of
hypertension, sweating, agitation, and irritability; in naltrexone.

532
NERVOUS SYSTEM

Loperamide – naltrexone may block the effect of Renal Impairment:

loperamide. Has not been studied; use with caution.

Avoid concomitant use with: Hepatic Impairment:

Reduces therapeutic effect of the following: Has not been studied, but betahistine primarily undergoes
Analgesics, Opioid hepatic metabolism; use with caution.
Enhances adverse effects of Naltrexone:
Methylnaltrexone (increased risk of opioid withdrawal), Precautions:
Disulfiram (hepatotoxicity), Phenothiazines (lethargy) Disease-related concerns:
Buprenorphine – may precipitate withdrawal if used within Asthma; Cardiovascular disease (ventricular extrasystoles,
the last 14 days. hypotension, tachycardia); Hepatic impairment; Peptic
Methadone – may precipitate withdrawal if used within the ulcer;
last 14 days.
Methylnaltrexone – opioid antagonists may enhance the STORAGE AND STABILITY: Do not store above 25°C. Store
adverse/toxic effect of naloxegol; specifically, the risk for the tablets in the original package.
opioid withdrawal may be increased.
Naldemedine – opioid antagonists may enhance the Adverse Drug Reactions:
adverse/toxic effect of naloxegol; specifically, the risk for Common: headache, nausea, dyspepsia.
opioid withdrawal may be increased. Rare: confusion, convulsions, drowsiness, hallucination,
Naloxegol – opioid antagonists may enhance the paresthesia, hypotension, tachycardia, ventricular
adverse/toxic effect of naloxegol; specifically, the risk for premature contractions, pruritus, skin rash, Stevens-
opioid withdrawal may be increased. Johnson syndrome, urticaria, abdominal distension,
Opioid analgesics – may precipitate withdrawal if used abdominal pain, bloating, peptic ulcer, vomiting,
within the last 7 days except for buprenorphine or anaphylaxis, angioedema, hypersensitivity reaction,
methadone. dyspnea.

Administration: May be administered with or without food. Drug Interactions:

Administration with food or after meals may minimize Monitor closely with:

N
adverse gastrointestinal effects. Advise service Reduces therapeutic effect of the following:
user/patient not to self-administer opioids while Beta-2 agonists e.g. Salbutamol
receiving naltrexone therapy.
Reduces therapeutic effect of Betahistine:
Pregnancy Category: Category C Antihistamine [except Levocabastine]

ATC Code: N07BB04 Administration: Administer with or without meals;

administer with meals if adverse GI effects occur. Food
intake slows down absorption of betahistine.
ANTIVERTIGO PREPARATIONS
ATC Code: N07CA01

Rx BETAHISTINE
Rx CINNARIZINE
Oral: 8 mg, 16 mg, and 24 mg tablet (as hydrochloride/
dihydrochloride)
Oral: 25 mg tablet
Betahistine is a partial agonist of histamine at H1 receptors
and antagonist at H3 receptors. It produces excitatory Inhibits contractions of vascular smooth muscle cells by
effects on neuronal activity of cortical and subcortical blocking calcium channels. It also decreases the
structures agonism and decrease vestibular sensory contractile activity of vasoactive substances (e.g.
input and increases release of histamine from the norepinephrine and serotonin) by blocking receptor-
hypothalamus via H3-receptor antagonism. operated calcium channels.

Indications: Management of Ménière disease Indications: Cerebral circulatory disorders, migraine

prophylaxis, motion sickness, vestibular disorders
Contraindications: Presence or history of active peptic ulcer
disease, pheochromocytoma Contraindications: Hypersensitivity to cinnarizine or any
Dose: component of the formulation
Ménière disease (to decrease episodes of vertigo), by
mouth, ADULT, 8-16 mg thrice daily or 24 mg twice daily. Dose:
The usual dosage range is 24-48 mg daily in divided NOTE: Do not exceed 225 mg daily; suggested maximum
doses. daily doses for specific indications are noted, when
available.
Dose Adjustment:
Geriatric: Cerebral circulatory disorders, by mouth, ADULT, 25 mg
Use with caution due to likelihood of decreased thrice daily.
hepatic/renal function.

533
 NERVOUS SYSTEM

Migraine prophylaxis, by mouth, ADULT, 25-50 mg thrice Administration: Administer after meals to reduce gastric
daily with a maximum dose of 150 mg/day. irritation.
Motion sickness, by mouth, ADULT/CHILD>12 years, 25 mg
30 minutes before traveling. May repeat every 6 hours if Pregnancy Category: Not available
needed, CHILD 5-12 years, 12.5 mg about 30 minutes
before traveling. May repeat every 6 hours if needed. ATC Code: N07CA02
Vestibular disorders, by mouth, ADULT/CHILD>12 years,
25-30 mg thrice daily with a maximum dose of 90
mg/day, CHILD 5-12 years, 12.5-15 mg thrice daily with OTHER NERVOUS SYSTEM DRUGS
a maximum dose of 45 mg/day.
ADJUNCTS TO ANESTHETIC
Dose Adjustment:
Geriatric:
No dose adjustment necessary. Rx EPHEDRINE
Renal Impairment:
Has not been studied; use with caution. Inj.: 30 mg/mL, 1 mL ampule solution for injection
50 mg/mL (as sulfate), 1 mL ampule (IM, IV)
Hepatic Impairment:
Has not been studied; use with caution. Ephedrine is a phenethylamine alpha and beta adrenergic
agonist. It may also enhance the release of
Precautions: norepinephrine.
Caution operating hazardous machinery or driving.
Indications: Anesthesia-induced hypotension
Use with caution in patients with Parkinson’s disease
and/or when considering long-term therapy. Contraindications: Angle-closure glaucoma; co-
Prolonged therapy (>6 months) may increase risk administration with myocardial sensitizing anesthetics
and resolution of symptoms may take >1 year (cyclopropane or halothane)
after discontinuation or may not be reversible.
N

Dose:
CNS depression; Stomach discomfort; Hepatic impairment; Hypotension, anesthesia-induced, by slow intravenous
Hypotension push, ADULT/CHILD>15 years, 5-25 mg/dose. Repeat as
Parkinson’s disease (aggravation of parkinsonian needed to maintain blood pressure up to a maximum
symptoms); Porphyria; Renal impairment total dose of 50 mg.

STORAGE AND STABILITY: Store between 15-30°C. Dose Adjustment:

Geriatric:
Adverse Drug Reactions: No dose adjustment necessary.
Common: Drowsiness, weight gain, dyspepsia, nausea
Rare: Dyskinesia, extrapyramidal disorders, fatigue, Renal Impairment:
hyperhidrosis, hypersomnia, lethargy, lichenoid Use with caution.
keratosis, lichen planus, muscle rigidity, parkinsonism,
stomach discomfort, subacute cutaneous lupus Hepatic Impairment:
erythematosus, tremor, upper abdominal pain, vomiting No dose adjustment necessary.

Drug Interactions: Precautions:

Monitor closely with: Concerns related to adverse effects:
Enhances the effects of the following: Cardiovascular effects (may cause hypertension
Alcohol, Ethyl, Brimonidine, Topical, Cannabis, resulting in intracranial haemorrhage, anginal pain in
Doxylamine, Dronabinol, Magnesium sulfate, ischemic heart disease, fatal arrythmia); Decreased
Mirtazapine (CNS depression), Metyrosine, Ropinirole, urine output; Tolerance (Temporary cessation of therapy
Rotigotine, Rufinamide (sedative effect), SSRIs restores its effectiveness.)
(psychomotor impairment) Anxiety and symptoms of paranoid schizophrenia
(Repeated use).
Enhances the effects of Cinnarizine:
Hydroxyzine, Minocycline, Nabilone (CNS depression) Use caution in:
Cardiovascular disease e.g. Hypertension, angina
Avoid concomitant use with: pectoris (Ephedrine should not ordinarily be used.)
Enhances effects of the following: Diabetes Mellitus; Prostatic hyperplasia/urinary
Azelastine, Nasal, Buprenorphine, Droperidol, stricture; Renal impairment; Thyroid dysfunction;
Hydrocodone, Methotrimeprazine, Orphenadrine, Patients with unstable vasomotor symptoms; Elderly
Paraldehyde, Suvorexant, Thalidomide (CNS depression)
NOTE: Blood volume depletion should be corrected before
Enhances effects of Cinnarizine: IV therapy is instituted.
Perampanel, Sodium oxybate, Tapentadol, Thalidomide
(CNS depression)

534
NERVOUS SYSTEM

STORAGE AND STABILITY: Store at 20-25°C. Excursions Contraindications: Severe sinus bradycardia; heart block
permitted to 15-30°C. Protect from light. Store in carton greater than first degree (except in patients with a
until time of use. functioning artificial ventricular pacemaker); sick sinus
syndrome; cardiogenic shock; decompensated heart
Adverse Drug Reactions: failure; IV administration of calcium channel blockers
Angina pectoris, bradycardia, cardiac arrhythmia, (e.g. verapamil) in close proximity to esmolol (i.e. while
hypertension, palpitations, pulse irregularity, effects of other drug are still present); pulmonary
tachycardia, ventricular ectopy, visceral vasoconstriction hypertension; patients requiring inotropic agents and/or
(renal), anxiety, confusion, delirium, dizziness, vasopressors to maintain cardiac output and systolic
hallucination, headache, insomnia, intracranial blood pressure; hypotension; right ventricular failure
hemorrhage, nervousness, precordial pain, restlessness, secondary to pulmonary hypertension; untreated
tension, vertigo, diaphoresis, pallor, anorexia, nausea, pheochromocytoma; hypersensitivity to esmolol or any
vomiting, dysuria, oliguria, urinary retention (males with component of the formulation
prostatism), tremor, vesicle sphincter spasm, weakness,
dyspnea, tachyphylaxis Dose:
Intraoperative and postoperative tachycardia and/or
Drug Interactions: hypertension, by intravenous bolus and intravenous
Monitor closely with: infusion. ADULT, immediate control: initial bolus of 1000
May decrease therapeutic effect of the following drugs: mcg/kg over 30 seconds, followed by a 150
Alpha1-blockers (vasoconstricting effect), Iobenguane mcg/kg/minute infusion, if necessary. Adjust infusion
I123, Quinidine rate as needed to maintain desired heart rate and/or
blood pressure (up to 300 mcg/kg/minute). Gradual
May increase the therapeutic effect (hypertensive effect) of control: Initial bolus of 500 mcg/kg over 1 minute,
ephedrine followed by a 50 mcg/kg/minute infusion for 4 minutes.
Atomoxetine, Atropine (systemic), Beta-blockers e.g., Infusion may be continued at 50 mcg/kg/minute or, if
Metoprolol Chloroprocaine, Clonidine, Guanethidine, the response is inadequate, titrated upward in 50
Linezolid, Tedizolid, MAOi e.g., Phenelzine, Oxytocin, mcg/kg/minute increments (increased no more
Propofol, Ergot derivatives, SNRIs e.g., Duloxetine, TCA frequently than every 4 minutes) to a maximum of 300

N
e.g., Amytryptilline mcg/kg/minute; may administer an optional loading
dose equal to the initial bolus (500 mcg/kg over 1
May diminish the therapeutic effect of ephedrine: minute) prior to each increase in infusion rate.
Clozapine, Quinidine, Spironolactone
Dose Adjustment:
May enhance the adverse/toxic effect of Doxofylline Geriatric:
No dose adjustment necessary.
May enhance the effect of the following drugs:
Droxidopa, Rocuronium Renal Impairment:
No dose adjustment necessary; not removed by hemo- or
May enhance the adverse/toxic effect of Ephedrine: peritoneal dialysis. Supplemental dose is not necessary.
Guanethidine, Inhalational anesthetics (arrythmogenic
effects) Hepatic Impairment:
Other sympathomimetics No dose adjustment necessary.

Avoid concomitant use with: Precautions:

May enhance the adverse/toxic effect of Ephedrine: If hyperthyroidism is suspected, carefully manage
Cyclopropane, Halothane (arrythmogenic effects) and monitor; abrupt withdrawal may exacerbate
symptoms of hyperthyroidism or precipitate
Administration: Administer diluted solution as a slow IV thyroid storm.
push. Calcium channel blockers are contraindicated when
IV calcium channel blockers have been
Pregnancy Category: Category C administered in close proximity to esmolol
ATC Code: Not available Beta-blocker therapy should not be withdrawn
abruptly. Gradually taper the dose to prevent
exacerbation of withdrawal symptoms.

Concerns related to adverse effects:

Rx ESMOLOL Hyperkalemia (monitor serum potassium during
therapy), Hypotension (Close blood pressure monitoring
Inj.: 10 mg/mL (as hydrochloride), 10 mL vial (IV) needed. If an unacceptable drop in blood pressure
100 mg/mL (as hydrochloride), 10 mL vial (IV) occurs, reduction in dose or discontinuation may reverse
hypotension (usually within 30 minutes)).
Indications: Intraoperative and postoperative tachycardia
and/or hypertension Use with caution in:
History of severe anaphylaxis to allergens;
Bronchospastic disease; Conduction abnormality;

535
 NERVOUS SYSTEM

Diabetes; Heart failure; Myasthenia gravis; Peripheral Yohimbine

vascular disease (PVD) and Raynaud's disease;
Untreated pheochromocytoma (Adequate alpha- Reduces therapeutic effect of the following:
blockade is required prior to use of any beta-blocker.) Theophylline derivatives (bronchodilatory effect)
Renal impairment (monitor serum potassium), Thyroid
disease (If hyperthyroidism is suspected, carefully Decreases the metabolism of Esmolol:
manage and monitor; abrupt withdrawal may exacerbate Aminoquinolines, Anti-malarial
symptoms of hyperthyroidism or precipitate thyroid
storm.); Hypertension associated with hypothermia Avoid concomitant use with:
(monitor vital signs closely and titrate esmolol slowly), Increases serum concentration of Esmolol:
Hypovolemic patients (Avoid use; treat hypovolemia Dronedarone
first).
Enhance the effects of the following medicines:
Elderly (Bradycardia may be observed more frequently in Alpha/Beta Agonists, Direct- acting [except Dipivefrin]
elderly patients (>65 years of age); dosage reductions (vasopressor effect)
may be necessary. Alpha- 1 blockers (orthostatic hypotension)
Amifostine, Obinituzumab, Rituximab (hypotensive
STORAGE AND STABILITY: Store at 20-25°C. Excursions effect)
permitted to 15-30°C. Avoid excessive heat. Protect Ceritinib (bradycardic effect)
from freezing. Ergot derivatives (vasoconstricting effect)

Adverse Drug Reactions: Enhance the effect of Esmolol:

Common: Decreased blood pressure, asymptomatic Alpha- 2 agonists [except Apraclonidine] (AV blocking
hypotension, symptomatic hypotension, peripheral effect)
ischemia, dizziness, drowsiness, agitation, confusion, Dronedarone, Rivastigmine (bradycardic effect)
headache, nausea, vomiting, infusion site reaction
Rare: Abdominal distress, abnormality in thinking, Enhance adverse effects of the following:
angioedema, anorexia, anxiety, asystole (rare), Floctafenine
N

bradycardia, bronchospasm, cardiac failure Grass pollen allergen extract, 5 grass extract
(decompensated), constipation, coronary artery Methacholine
vasospasm, depression, dizziness, dyspepsia, flushing,
heart block, hyperkalemia, pallor, paresthesia, psoriasis, Administration: Loading doses may be administered over 30
renal tubular acidosis, seizure, severe bradycardia (rare), seconds to 1 minute depending on how urgent the need
syncope, urinary retention, urticaria, xerostomia for effect. Infusion into small veins or through a butterfly
catheter should be avoided (can cause
Drug Interactions: thrombophlebitis). Medication port of premixed bags
Monitor closely with: should be used to withdraw only the initial bolus, if
Enhance effects of Esmolol: necessary (not to be used for withdrawal of additional
Acetylcholinesterase inhibitors, Amiodarone, bolus doses). Ensure proper needle or catheter
Anilidopiperidine opiods, Bretylium, Dipyridamole, placement prior to and during infusion; avoid
Disopyramide, Regorafenib (bradycardic effect) extravasation. If extravasation occurs, stop infusion
Antihypertensives, Antipsychotic agents, Barbiturates, immediately and disconnect (leave cannula/needle in
Calcium channel blockers, Non- dihydropyridine [except place); gently aspirate extravasated solution (do NOT
Bepridil], Diazoxide, Ivabradine, Molsidomine, flush the line); remove needle/cannula; elevate
Nicorandil, Nifedipine, Pentoxifylline, Prostacyclin extremity.
analogues, Reserpine (hypotensive effect)
Bretylium, Lacosamide (AV blocking effect) Pregnancy Category: Category C
Brimonidine, Topical, Phosphodiesterase 5 inhibitors
(antihypertensive effect) ATC Code: Not available
Duloxetine, Levodopa, MAO Inhibitors [except Linezolid,
Tedizolid] (orthostatic hypotensive effect)
Nifedipine (negative inotropic effect)

Enhances effects of the following:

Disopyramide (negative inotropic effect)
Fingolimod, Midodrine (bradycardic effect)
Insulin, Sulfonylureas (hypoglycemic effect)
Risperidone, Tofacitinib (hypotensive effect)

Enhance the adverse effects of the following:

Cholinergic agonists (bronchoconstriction)

Reduces therapeutic effect of Esmolol:

Herbs, Hypertensive properties
Methylphenidate
Non- steroidal anti- inflammatory agents

536
NERVOUS SYSTEM

DRUGS TO REDUCE CEREBRAL EDEMA Corticosteroid use may cause psychiatric

disturbances, including depression, euphoria,
insomnia, mood swings, personality changes,
Rx DEXAMETHASONE severe depression to psychotic manifestations.
Preexisting psychiatric conditions may be
Oral: 500 micrograms, 750 micrograms, 3 mg, and 4 mg exacerbated by corticosteroid use.
tablet Long term use may lead to water retention, increased
Inj.: 4 mg/mL (as sodium phosphate), 1 mL and 2 mL bone loss, osteoporotic fractures
ampule / vial (IM, IV) Immunosuppressants may diminish the diagnostic
5 mg/mL (as sodium phosphate), 1 mL ampule (IM, effect of Coccidioides immitis skin test
IV)
Administration: Tablets should be taken with food. Ampules
Crosses cell membranes and binds with glucocorticoid are administered via intramuscular injection or
receptors, then bind to DNA glucocorticoid response intravenous infusion.
elements that in turn modify the protein synthesis
required for inflammation See Dexamethasone under Glucocorticoids in Chapter 6:
Systemic Hormonal Preparation for other information.
Indications: Cerebral edema associated with brain tumor or
craniotomy Pregnancy Category: Category C
Contraindications: Systemic fungal infections ATC Code: Not available
Dose:
Cerebral edema associated with brain tumor or craniotomy,
by mouth or by intramuscular injection or by intravenous Rx GLYCEROL (GLYCERIN)
infusion, ADULT, 10 mg intravenously immediately,
followed by 4 mg intramuscularly every 6 hours until
Oral: USP grade (liquid)
cerebral edema subsides, then switch to oral regimen.

N
Dosage may be reduced after 2-4 days and gradually
Elevates blood plasma osmolality, resulting in enhanced
discontinued over 5-7 days, CHILD, initially administer a
flow of water from extravascular spaces into plasma.
loading dose of 1-2 mg/kg/dose as a single dose. The
Reduction of intracranial pressure is attributed to the
maintenance dose is 1-1.5 mg/kg/day in divided doses
establishment of an osmotic gradient between blood,
every 4-6 hours up to a maximum dose of 16 mg/day.
cerebrospinal fluid (CSF), and brain, resulting in
withdrawal of fluid from the brain and CSF
Dose Adjustment:
Geriatric:
Indications: Management of cerebral edema
Use with caution and with the smallest possible dose.
Contraindications: Acute abdominal pain
Renal Impairment:
Use with caution; Supplemental doses are not necessary for
Dose:
patients undergoing hemodialysis or peritoneal dialysis.
Cerebral edema, by mouth, ADULT, 1-1.5 g/kg as a single
dose. Initial doses up to 2 g/kg have been used.
Hepatic Impairment:
Additional doses of 500 mg/kg may be administered at
No dose adjustment necessary.
approximately 6-hour intervals, if necessary, CHILD, 1-
1.5 g/kg or 40 g/m2 as a single dose. Dose may be
Precautions:
repeated in 4-8 hours, if necessary.
Withdrawal and discontinuation of a corticosteroid
should be done slowly and carefully. Particular Precautions:
care is required when patients are transferred Use with caution in:
from systemic corticosteroids to inhaled products Diabetes mellitus, type II (may increase risk of dehydration);
due to possible adrenal insufficiency or Confused mental states; heart disease; Kidney disease,
withdrawal from steroids, including an increase in Hypervolemia (circulatory overload).
allergic symptoms. Pregnancy and lactation (no adequate studies in women for
determining infant risk).
Corticosteroids should not be used for cerebral
malaria, fungal infections, or viral hepatitis. Close
observation is required in patients with latent Adverse Drug Reactions:
tuberculosis and/or TB reactivity; restrict use in Common: Headache, nausea, vomiting.
active TB Less Common: Confusion, diarrhea, dizziness, dryness of
Amebiasis should be ruled out in any patient with mouth, increased thirst
recent travel to tropic climates or unexplained Rare: Arrhythmias
diarrhea prior to initiation of corticosteroids. Use
with extreme caution in patients with Drug Interactions:
Strongyloides infections Monitor closely with:
Increases risk of adverse or toxic effects of Glycerol:

537
 NERVOUS SYSTEM

Tetracyclines Dose:
Intracranial pressure (ICP), reduction, by intravenous
Avoid concomitant use with: infusion, ADULT, 0.25 to 2 g/kg as a 15-20% solution
Enhances therapeutic effect of Glycerol: over at least 30 min administered not more frequently
ACE inhibitors e.g. Enalapril (additive effect), than every 6-8 hours, INFANT, CHILD, AND ADOLESCENT,
Acetazolamide, Bumetanide (potentiated effect), Other the usual range is 0.25-1 g/kg/dose infused over 20-30
Diuretics minutes. Repeat as needed to maintain serum osmolality
<300 to 320 mOsm/kg. The manufacturer's labeling
Enhances therapeutic effect of Diuretics (potentiated allows for higher single doses up to 2 g/kg/dose.
effect)
Dose Adjustment:
Increases risk of adverse or toxic effects of Glycerol: Geriatric:
ACE inhibitors (hypovolemia) Consider initiation at lower end of dosing range.
Acetazolamide, Bumetanide, Other diuretics (significant
loss of fluid and electrolytes), Carbamazepine Renal Impairment:
(hyponatremia), Drugs that prolong QT Interval Contraindicated in severe renal impairment. Use caution in
(electrolyte loss) patients with underlying renal disease. May be used to
reduce the incidence of acute tubular necrosis when
Increases risk of adverse or toxic effects of the following administered prior to revascularization during kidney
drugs: transplantation.
ACE inhibitors e.g. Enalapril (hypotension),
Corticosteroids (significant loss of electrolytes; Precautions:
hypokalemia), Digoxin (arrhythmias), QT prolonging Fluid/electrolyte loss (Watch for and correct electrolyte
drugs (torsade de pointes), Ondansetron (irregular heart disturbance; adjust dose to avoid dehydration);
rhythm) Nephrotoxicity;
Cerebral edema (rebound increases in intracranial
Administration: For use as an oral demulcent. Do NOT pressure);
swallow excessive amounts. Adequate renal function.
N

Mix it with a small amount of unsweetened lemon, lime, NOTE: Should not be administered until adequacy of renal
or orange juice, pour over cracked ice, and sip through a function and urine flow is established; use 1 to 2 test
straw to mask its unpleasant taste. Lie down when taking doses to assess renal response.
this medicine and for a short time after taking it to
prevent or relieve headaches. Adverse Drug Reactions:
Chest pain, cardiac failure, hypertension, hypotension,
NOTE: When used preoperatively, administer 60–90 local thrombophlebitis, peripheral edema, tachycardia,
minutes prior to surgery. Precautions should be taken to chills, dizziness, headache, seizure, bullous rash,
avoid acute urinary retention. urticaria, dehydration (secondary to rapid diuresis),
dilutional hyponatremia, electrolyte disturbance
Pregnancy Category: C (increased osmolar gap), fluid and electrolyte
disturbance, hypovolemia (secondary to rapid diuresis),
ATC Code: Not available hyperglycemia, hyperkalemia (hyperosmolality-induced),
hypernatremia, hypervolemia, metabolic acidosis
(dilutional), water intoxication, nausea, vomiting,
xerostomia, dysuria, hypersensitivity reaction, local pain,
Rx MANNITOL blurred vision, acute renal failure, tubular necrosis (adult
dose: >200 g/day; serum osmolality >320 mOsm/L),
Inj.: 20%, 250 mL and 500 mL bottle (IV) polyuria, pulmonary edema, rhinitis, fever, tissue
necrosis.
Mannitol is a naturally-occurring sugar alcohol. It reduces
ICP by reducing blood viscosity which transiently Drug Interactions:
increases cerebral blood flow and oxygen transport and Monitor closely with:
constricts pial arterioles which in turn reduces cerebral Aminoglycosides – mannitol (systemic) may enhance the
blood volume and ICP and withdraws water from the nephrotoxic effect of aminoglycosides.
brain parenchyma and excretes water in the urine. Diacerein – may enhance the therapeutic effect of diuretics;
specifically, the risk for dehydration or hypokalemia may
Indications: Reduction of intracranial pressure associated be increased.
with cerebral edema Opioid analgesics – may enhance the adverse/toxic effect
and diminish the therapeutic effect of diuretics.
Contraindications: Severe renal disease (anuria); severe Sodium phosphates – diuretics may enhance the
dehydration; active intracranial bleeding except during nephrotoxic effect of sodium phosphates; specifically,
craniotomy; progressive heart failure, pulmonary the risk of acute phosphate nephropathy may be
congestion, or renal dysfunction after mannitol enhanced.
administration; severe pulmonary edema or congestion Tobramycin (oral inhalation) – mannitol (systemic) may
enhance the nephrotoxic effect of tobramycin (oral
inhalation).

538
NERVOUS SYSTEM

Administration: Concentration and rate of administration

depends on indication/severity or may be adjusted to
urine flow. For cerebral edema or elevated ICP,
administer over 30-60 minutes. Inspect for crystals prior
to administration. If crystals are present, redissolve by
warming solution. Use filter-type administration set (≤5
micron) for infusion solutions containing mannitol ≥20%
(WHO 2011). Do not administer with blood. Crenation
and agglutination of red blood cells may occur if
administered with whole blood. Mannitol may act as a
vesicant at concentrations >5%. Ensure proper catheter
or needle position prior to and during IV infusion. Avoid
extravasation of IV infusions. If extravasation occurs,
stop infusion immediately and disconnect (leave
needle/cannula in place). Gently aspirate extravasated
solution (do NOT flush the line), initiate hyaluronidase
antidote, remove needle/cannula, apply dry cold
compresses, and elevate extremity.

See drug name under category name in Chapter number:

chapter title for other information.

Pregnancy Category: Category C

539
 ANTIPARASITIC PRODUCTS, INSECTICIDES, AND REPELLENTS

inadequate for reliable protection against malaria in the

ANTIPARASITIC PRODUCTS, breastfed infant; avoid breastfeeding when used for
INSECTICIDES, AND REPELLENTS rheumatic disease).

NOTE: If patient continues to deteriorate after chloroquine

ANTIPROTOZOALS medication – suspect resistance and administer quinine
IV as emergency measure.

AGENTS AGAINST AMOEBIASIS AND Adverse Drug Reactions:

OTHER PROTOZOAL DISEASES Common: GI disturbances, itch, lack of appetite, pruritus,
skin eruptions, weight loss
Less Common: Anxiety, confusion, dizziness, drowsiness,
Rx/OTC CHLOROQUINE headache, hypotension, irreversible retinopathy,
paresthesia, personality changes, psychotic episodes,
reversible corneal opacities, sleep disorders, vertigo,
Oral: 250 mg tablet (as phosphate or diphosphate) (150 visual disturbances
mg base) Rare: Hypersensitivity reactions, pancytopenia, porphyria,
Inj.: 50 mg/mL (as phosphate or diphosphate), 20 mL vial prolonged QT interval, psoriasis, neuromyopathy,
(IM, IV) seizure, rash, Steven-Johnsons Syndrome,
thrombocytopenia, tinnitus, toxic epidermal necrolysis,
An aminoquinoline antimalarial, found effective in extra CV collapse (potentially fatal); convulsions (potentially
intestinal amoebiasis fatal); coma (potentially fatal)
Indication: Treatment of extraintestinal amoebiasis Drug Interactions:
NOTE: Chloroquine has a long half-life; consequently, the
Contraindications: Presence of retinal or visual field potential for drug interactions may persist for weeks
changes either attributable to 4­aminoquinoline after it has been stopped.
compounds or to any other etiology; patients with
epilepsy Monitor closely with:
Reduces the absorption of Chloroquine: Antacids (e.g.
Dose: Aluminum or Magnesium Hydroxide)
P

Extraintestinal amoebiasis, by mouth, ADULT, 1 g (600 mg

base) on day 1, followed by 500 mg (300 mg base) after Avoid concomitant use with:
6 hours, 24 hours, and 48 hours following first dose, may Increases risk of adverse or toxic effects of the following
be combined with an intestinal amebicide. drugs:
Hepatic amoebiasis, by mouth, ADULT, 600 mg (as base) Artemether + Lumefantrine (potentially hazardous
daily for 2 days, then 300 mg daily for 2 or 3 weeks given interactions), Drugs which prolong QT Interval
with emetine or dehydroemetine; CHILD, up to 3 mg/kg (arrhythmia; prolonged QT interval), Other Antimalarials
daily (maximum daily dose, 300 mg). e.g. Mefloquine (arrhythmia; prolonged QT interval)
Dose Adjustment: Administration: To avoid nausea and vomiting, tablets
Renal Impairment: should be administered after meals.
For mild-to-moderate renal impairment, dose reduction is
warranted. NOTE: If part or all of a dose is vomited, re-administer the
For severe impairment, the patient should be referred to a same amount.
specialist.
Pregnancy Category: C
Precautions:
G6PD deficiency; Psoriasis may be worsened. ATC Code: P01BA01
Porphyria cutanea tarda
Epilepsy; May aggravate myasthenia gravis; neurological
disorders.
QT interval Rx DILOXANIDE
Renal impairment; hepatic impairment (avoid concurrent
therapy with hepatotoxic drugs); severe GI disorders.
Oral: 500 mg tablet (as furoate)
Pregnancy (in the first trimester of pregnancy, quinine in
125 mg/5 mL syrup / suspension (as furoate), 30 mL
combination with clindamycin for 7 days is the treatment
and 60 mL
of choice – this combination can be used throughout
pregnancy; in acute malaria and third trimester: benefit
A dichloroacetamide-derived luminal amoebicide acting
of prophylaxis and treatment outweighs risk).
mainly in the bowel lumen. It is given alone in
asymptomatic cyst passers. For patients with active
NOTE: If clindamycin is not available, then quinine should be
amoebic infections, it can be administered with a 5-
given as monotherapy.
nitroimidazole e.g. metronidazole or tinidazole.
Breastfeeding (at doses used for malaria prophylaxis;
amount in milk is probably too small to be harmful, and

540
ANTIPARASITIC PRODUCTS, INSECTICIDES, AND REPELLENTS

Indications: Second line agent for luminal infection; Liver abscess with positive amoeba serology, by mouth or
amebicide; intestinal amoebiasis; for hepatic abscess IV, ADULT, 750 mg 3 times daily for 10 days.
secondary to E. histolytica Trichomoniasis, first-line, by mouth, ADULT (women and
pregnant women), 2 g single dose; ADULT (women with
Dose: HIV infection), 500 mg 2 times daily for 7 days.
Asymptomatic and symptomatic amoebiasis, by mouth, Trichomoniasis, second-line, by mouth, ADULT, 500 mg 2
ADULT, 500 mg 3 times daily for 10 days (may repeat times daily for 7 days.
course if needed), CHILD, 20 mg/kg daily in 3 divided
doses for 10 days (may repeat if necessary). Administration:
For Oral: Tablets should be swallowed whole with water,
Dose Adjustment: No information found during or after a meal; oral suspension should be taken
one hour before a meal or on an empty stomach.
Precautions: For IV: Infuse intravenously over 30 to 60 minutes; Avoid
Pregnancy and lactation (use with caution). contact of drug solution with equipment containing
aluminum.
Adverse Drug Reactions:
Common: Flatulence See Metronidazole under Chapter 7: Anti-Infectives under
Less Common: Vomiting, pruritus, urticaria, anorexia other Antibacterials or other information

Drug Interactions: No information found Pregnancy Category: B

Administration: Swallow with water. ATC Code: P01AB01

Do NOT break, crush, or chew tablets.

ANTIMALARIALS
Pregnancy Category: Not classified
ARTEMETHER + LUMEFANTRINE
ATC Code: P01AC01 Rx
(AL)
Oral: 20 mg artemether + 120 mg lumefantrine per tablet

P
Rx METRONIDAZOLE
A fixed-dose, antimalarial combination of an oil-soluble,
artemisinin analog and a fluorene-derived aryl alcohol
Oral: 250 mg and 500 mg tablet (as base)
that is used for uncomplicated P. falciparum malaria.
125 mg base/5 mL (200 mg/5 mL (as benzoate)
suspension, 60 mL Indication: For acute, uncomplicated malaria caused by P.
5 mg/mL, 100 mL vial (IV infusion) falciparum, P. malariae, or P. knowlesi alone or with
Plasmodium spp. in areas with significant drug
A nitroimidazole, antiprotozoal drug, which has potent resistance; 2nd line drug for uncomplicated P. vivax or P.
antibacterial activity against anaerobes, including ovale infections.
Bacteroides and Clostridium spp.
Contraindications: Family history of sudden death or
Indications: Management of acute invasive amebic congenital prolongation of QT interval; history of
dysentery; trichomonal vaginitis; amoebiasis; giardiasis arrhythmias, clinically-relevant bradycardia, or CHF
accompanied by reduced left ventricular ejection
Contraindications: Chronic alcohol dependence
fraction; pregnancy (first trimester); breastfeeding
(during and for 1 week after stopping treatment; present
Dose:
in milk in animal studies)
Amoebiasis, by mouth, ADULT, 35–50 mg/kg per day in 3
divided doses for 7–10 days or 800 mg 3 times daily for Dose:
5 days (intestinal infection); 5–10 days (extra-intestinal Uncomplicated malaria due to P. falciparum or P. malariae
infection), (maximum, 2.4 g daily); CHILD 35 – 50 mg/ (in combination with primaquine tablet, 15 mg (0.24 mg
kg per day in 3 divided doses for 7 – 10 days. base per kg) on day 1; 3 tablets for adults >60 kg), by
Giardiasis, by mouth, ADULT, 15 mg/kg per day in 3 divided mouth,
doses for 5–7 days or 2 g once daily for 3 days, 400 mg
3 times daily for 5 days, or 500 mg twice daily for 7–10
days; CHILD 1–3 years, 500 mg once daily; CHILD 3–7 DAY 1 DAY 2 DAY 3
years, 600–800 mg once daily; CHILD 7–10 years, 1 g ADULT and 4 tablets followed
once daily; doses are given for 3 days. 4 tablets 2 times a
CHILD >35 by 4 tablets after 8
Suspected antibiotic-associated colitis presenting as severe day
kg hours
disease or with prolonged symptoms, by mouth, ADULT
and CHILD, 30 mg/kg per day in 4 divided doses for 10– 3 tablets followed
CHILD 25 3 tablets 2 times a
14 days. by 3 tablets after 8
to <35 kg day
Severe diarrhea due to Entamoeba histolytica, by mouth, hours
ADULT, 500–750 mg 3 times a day for 7–10 days.

541
 ANTIPARASITIC PRODUCTS, INSECTICIDES, AND REPELLENTS

2 tablets followed SKILLED TASKS. May cause dizziness. Avoid performing

CHILD 15 2 tablets 2 times a tasks, which require mental alertness, e.g., operating
by 2 tablets after 8
to <25 kg day machinery or driving.
hours
CHILD 5 to
<15 kg 1 tablet followed Adverse Drug Reactions:
1 tablet 2 times a Common: Abdominal pain, anorexia, arthralgia, asthenia,
and by 1 tablet after 8
day cough, diarrhea, dizziness, fatigue, headache, itch,
INFANT 6– hours
11 months myalgia, nausea, palpitations, prolonged QT interval,
pruritus, pyrexia, rash, sleep disorder, vomiting,
weakness
Uncomplicated malaria due to P. vivax or P. ovale (in
Less Common: Ataxia, clonus, hypesthesia, paresthesia
combination with primaquine tablet, 0.25 mg base per
Rare: Hepatitis, hypersensitivity reactions
kg starting on day 1), or Malaria due to P.
knowlesi (alone), plus primaquine tablet 0.25mg base
Drug Interactions:
per kg on day 1-14, by mouth,
Monitor closely with:
DAY 1 DAY 2 DAY 3 Increases risk of adverse or toxic effects
4 tablets followed Drugs which prolong QT Interval (arrhythmia), Other
4 tablets 2 times a Antimalarials (arrhythmia)
ADULT by 4 tablets after
day
8 hours
Reduces therapeutic effect of Hormonal Contraceptives
3 tablets followed
CHILD 25 3 tablets 2 times a
by 3 tablets after
to <35 kg day Avoid concomitant use with:
8 hours
Reduces therapeutic effect of Artemether + Lumefantrine:
2 tablets followed
CHILD 15 2 tablets 2 times a CYP3A4 Inducers (potential loss of antimalarial efficacy)
by 2 tablets after
to <25 kg day
8 hours
Increases risk of adverse or toxic effects of CYP2D6
CHILD 5 to Substrates (QT prolongation)
<15 kg 1 tablet followed
1 tablet 2 times a
and by 1 tablet after 8 Administration: Take the tablets with food or high-fat meal
day
INFANT 6– hours to increase absorption.
11 months
P

NOTE: If patient vomits out the dose within 1 to 2 hours, give

Mixed malarial infection due to P. falciparum and P. vivax another dose.
with or without P. malariae (in combination with
primaquine tablet, 0.25 mg base per kg on day 1–14), Pregnancy Category: C
by mouth,
DAY 1 DAY 2 DAY 3 ATC Code: P01BF01
4 tablets followed
4 tablets 2 times a
ADULT by 4 tablets after
day
8 hours Rx ARTESUNATE
3 tablets followed
CHILD 25 3 tablets 2 times a
by 3 tablets after
to <35 kg day Inj.: 60 mL vial
8 hours Rectal: 50 mg suppository
2 tablets followed
CHILD 15 2 tablets 2 times a
by 2 tablets after A potent artemisinin-derived, rapidly-acting blood
to <25 kg day
8 hours schizontocide effective against P. vivax and P. falciparum
1 tablet followed malaria.
CHILD 5 to 1 tablet 2 times a
by 1 tablet after 8
<15 kg day
hours Indication: For use by the National Malaria Program as pre-
referral drug for managing severe malaria cases both
Dose Adjustment: within the highly endemic and at-risk areas of the country
Renal and Impairment:
For mild-to-moderate impairment, use same dosage as in Dose:
patients with normal function. Severe malaria due to P. falciparum or P. malariae, by IV or
For severe impairment, refer patient to a specialist. IM injection, ADULT, 2.4 mg/kg per dose; give 3 IV or IM
doses 12 hours apart (shift to oral artemether-
Precautions: lumefantrine and primaquine once patient can tolerate;
Concomitant administration of drugs that prolong the QT by IV drip or IM injection into the anterior thigh, CHILD
interval; Acute porphyria and severe and/or complicated <20 kg, 3 mg/kg per dose, dissolved in 5% NaHCO3,
malaria (avoid use); Electrolyte disturbances; monitor diluted in 5 mL D5W.
patients unable to take; severe renal and hepatic Severe malaria due to P. falciparum or P. malariae, second-
impairment (monitor ECG and plasma potassium line (for pre-referral to hospital), by rectum, CHILD, 10
concentration) mg/kg
Pregnancy (avoid use in first trimester); lactation. Severe malaria due to P. vivax or P. ovale, first-line /
preferred treatment, by IV or IM injection, ADULT, 2.4

542
ANTIPARASITIC PRODUCTS, INSECTICIDES, AND REPELLENTS

mg/kg per dose for at least 24 hours (shift to oral Dose:

artemether-lumefantrine once patient can tolerate; by IV Prophylaxis of malaria, by mouth, ADULT, 300 mg as base,
drip or IM injection into the anterior thigh, CHILD <20 kg, once weekly, starting 1 week before exposure,
3 mg/kg per dose, dissolved in 5% NaHCO3, diluted in 5 continuing throughout on a weekly basis and for at least
mL D5W. 4 weeks after exposure; CHILD, 5 mg/kg weekly.
Uncomplicated malaria due to P. vivax or P. ovale, by mouth,
NOTE: Artesunate suppository is a last-resort drug ADULT, initially 600 mg as base, followed by 300 mg 6–
NOT recommended for older children and adults. 8 hours later on day 1, then single doses of 300 mg daily
on days 2 and 3; CHILD, initially 10 mg base/kg
Precautions: (maximum 600 mg base), followed by 5 mg base/kg after
Hepatic and renal impairment. 6 hours (maximum 300 mg base), then single doses of 5
Pregnancy and lactation (use with caution) mg base/kg on days 2 and 3.
Congenital and neonatal malaria, by mouth, CHILD, 10
Adverse Drug Reactions: mg/kg on day 1 and 2, and 5 mg/kg on day 3.
Common and Less Common: Drug fever, transient Relapse malaria, by mouth, ADULT and CHILD, 10 mg/kg on
reticulocytopaenia (reversible), bradycardia, rash, day 1 and 2, and 5 mg/kg on day 3.
transient first-degree heart block. Mixed malarial infection due to P. vivax and P. malariae, by
mouth, ADULT and CHILD, 10 mg/kg on day 1 and 2, and
Drug Interactions: 5 mg/kg on day 3 (in combination with primaquine 0.25
Avoid concomitant use with: mg (as base) per kg per day taken as a single dose for
Enhances therapeutic effect of Artesunate: day 1 to 14).
Chloroquine, Mefloquine, Primaquine, Tetracycline
Administration: Administer tablets after meals to avoid
Reduces therapeutic effect of Artesunate: nausea and vomiting.
Pyrimethamine, Sulfonamides
NOTE: If part or all of a dose is vomited, the same amount
Administration: When administering the rectal suppository, should be re-administered.
wash hands thoroughly. You may use a disposable glove
if desired. Remove the wrapper prior to insertion. Lie on See Chloroquine under Antiprotozoals – Agents against
your side with the lower leg straightened out and the ameobiasis and other protozoal diseases in this chapter
upper leg bent towards the torso. Lift the upper buttock for other information.

P
to expose rectal area. Insert the suppository, pointed end
first with your finger until it passes the muscular Pregnancy Category: C
sphincter of the rectum. Hold buttocks together for a few
seconds. Remain lying on your side for at least 5 ATC Code: P01BA01
minutes. Discard all used materials and wash hands
thoroughly.

Pregnancy Category: Not classified Rx MEFLOQUINE

ATC Code: P01BE03 Oral: 250 mg tablet (as hydrochloride)

A quinoline-methanol compound structurally similar to

quinine, capable of destroying the asexual blood forms
Rx CHLOROQUINE of Plasmodium falciparum and P. vivax.

Oral: 250 mg tablet (as phosphate or diphosphate) (150 Indication: Prophylaxis for chloroquine resistant malaria
mg base)
Inj.: 50 mg/mL (as phosphate or diphosphate), 20 mL vial NOTE: Not recommended for treatment of malaria acquired
(IM, IV) in Southeast Asia due to drug resistance

An aminoquinoline antimalarial, which has rapid Contraindications: Prophylactic use in patients with a history
schizontocidal activity against blood forms of of seizures or psychiatric disorder including active or
Plasmodium ovale and P. malariae, and against recent history of depression, generalized anxiety
susceptible strains of P. vivax and P. falciparum. It disorder, psychosis, schizophrenia, or other major
influences hemoglobin digestion by increasing psychiatric disorders; hypersensitivity to mefloquine,
intravesicular pH in malaria parasite cells and interferes related compounds, e.g., quinine and quinidine, or any
with the nucleoprotein synthesis of the patient. component of the formulation

Indications: Prophylaxis of malaria; treatment of non- Dose:

chloroquine-resistant acute malaria caused by P. vivax Malaria, chemoprophylaxis, by mouth, ADULT, 250 mg
and P. ovale (followed in P. vivax and P. ovale infections weekly starting 1 week before arrival in endemic area,
by primaquine to eliminate intrahepatic forms). continue weekly during travel and for 4 weeks after
leaving endemic area; CHILD, 5 mg/kg per dose weekly
Contraindications: In patients with history of epilepsy; starting 1 week before arrival in endemic area, continue
retinal damage or impaired visual field weekly during travel and for 4 weeks after leaving

543
 ANTIPARASITIC PRODUCTS, INSECTICIDES, AND REPELLENTS

endemic area [NOTE: Prophylaxis may begin 2­3 weeks Antimalarial Aminoquinolines e.g. Chloroquine (QTc-
prior to travel to ensure tolerance]. prolongation; convulsions) [if concomitant use cannot be
avoided, delay Mefloquine administration at least 12
Precautions: hours after the last dose of aminoquinoline antimalarial]
Agranulocytosis or aplastic anemia; Cardiovascular disease Artemether, Dapsone (hemolytic reactions),
(use with caution); Hypersensitivity reactions; Lumefantrine, Quinidine (QTc-prolongation; convulsions)
Neuropsychiatric effects (e.g. anxiety, paranoia, [if concomitant use cannot be avoided, delay Mefloquine
depression, hallucinations, and psychosis may develop administration at least 12 hours after the last dose of
early during therapy; suicidal ideation and suicide have Quinidine], Quinine (QTc-prolongation; convulsions) [if
been reported; dizziness or vertigo, tinnitus, and loss of concomitant use cannot be avoided, delay Mefloquine
balance); Seizure disorder; Hepatic impairment (use with administration at least 12 hours after the last dose of
caution) Quinidine]
Children (early vomiting leading to treatment failure has
been reported; consider alternate therapy if a second Increases risk of adverse or toxic effects of the following
dose is not tolerated). drugs:
Pregnancy (crosses the placenta); lactation (excreted in Halofantrine (QTc-prolonging effect), Highest Risk QTc-
breast milk in small quantities). prolonging Agents, Mifepristone (QTc-prolonging effect)

SKILLED TASKS. May cause drowsiness or blurred vision. Increases serum concentration of Mefloquine:
Avoid performing tasks, which require mental alertness, Conivaptan, Fusidic Acid, Idelalisib, Mifepristone,
e.g., operating machinery or driving. Warn patient not to Stiripentol
operate machinery nor drive during treatment or for 24
hours after treatment. Increases serum concentration of the following drugs:
Afatinib [if concomitant use cannot be avoided, reduce
Adverse Drug Reactions: Afatinib by 10 mg if not tolerated], Bosutinib, Colchicine
Common: Chills, dizziness, fatigue, fever, headache, rash, (enhances distribution to specific tissues, e.g., brain),
vomiting, abdominal pain, decreased appetite, diarrhea, Dabigatran Etexilate [active metabolite/s], Doxorubicin
nausea, myalgia, tinnitus (Conventional), Edoxaban, Everolimus, Pazopanib,
Less Common: Alopecia, bradycardia, emotional lability, Silodosin, Topotecan, Vincristine (Liposomal)
extra-systoles, pruritus, seizure, syncope, weakness,
abnormal dreams, abnormal T-waves, ataxia, aggressive Reduces therapeutic effect of Anticonvulsants
P

behavior, agitation, anxiety, arrhythmia, arthralgia, AV

block, cardiac arrest (with concomitant use of Administration: Administer with food and with at least 8 oz.
propranolol), chest pain, conduction abnormalities of water. Tablets may be crushed and suspended in a
(transient), confusion, depression, diaphoresis small amount of water, milk, or another beverage for
increased, dyspepsia, dyspnea, edema, encephalopathy, persons unable to swallow tablets.
erythema, erythema multiforme, exanthema, flushing,
forgetfulness, hallucinations, hearing impairment, When used for malaria prophylaxis, dose should be taken
hematocrit decreased, hypertension, hypotension, once weekly on the same day each week.
insomnia, irregular pulse, leukocytosis, leukopenia,
increased liver function tests, loss of balance, malaise, If vomiting occurs within 30 minutes after the dose,
mood changes, muscle cramps/weakness, palpitation, administer an additional full dose. If it occurs within 30–
panic attacks, paranoia, paresthesia, pneumonitis 60 minutes after dose, administer an additional half-
(allergic etiology), psychosis, QT prolongation, dose.
restlessness, somnolence, Stevens-Johnson syndrome,
suicidal ideation and behavior (causal relationship not Pregnancy Category: B
established), tachycardia, thrombocytopenia, tremor,
urticaria, vertigo, visual disturbances ATC Code: P01BC02

Drug Interactions:
Monitor closely with:
Increases risk of adverse or toxic effects of Mefloquine: Rx PRIMAQUINE
Amiodaquine (vision problems)
Oral: 26.3 mg tablet (as diphosphate) (15 mg base)
Increases risk of adverse or toxic effects of QTc-prolonging
agents (QTc-prolonging effect) An 8-aminoquinoline antimalarial used for the radical cure
and terminal prophylaxis of infections with P. vivax and
Avoid concomitant use with: P. ovale. It eliminates the exoerythrocytic form of malarial
Decreases serum concentration of Mefloquine: parasite by disrupting the mitochondria and binding to
Dabrafenib, Mitotane, DNA.

Decreases serum concentration of Anticonvulsants e.g. Indications: Radical cure in relapsing infections of P. vivax
Phenytoin, Barbiturates and P. ovale malaria; elimination of intrahepatic forms of
P. vivax and P. ovale (after standard chloroquine
Increases risk of adverse or toxic effects of Mefloquine: therapy); elimination of P. falciparum gametocytes (after
standard therapy with a blood schizontocide)

544
ANTIPARASITIC PRODUCTS, INSECTICIDES, AND REPELLENTS

Contraindications: G6PD deficiency in infants (risk of Rare: Agranulocytosis, anemia, arrhythmias,

hemolysis); infants <1 year (methemoglobinemia); granulocytopenia, hypertension, interference with visual
patients with conditions that predispose to accommodation, hemoglobinuria, leukopenia, pruritus
granulocytopenia, including active rheumatoid arthritis
and systemic lupus erythematosus; pregnancy (delay Drug Interactions:
treatment until after delivery; breastfeeding Monitor closely with:
Increases risk of hematological adverse effects of the
Dose: following drugs:
Uncomplicated malaria due to P. falciparum or P. malariae Bone Marrow Depressants, Hemolytics
(in combination with artemether-lumefantrine), ADULT
and CHILD, 0.25 mg base per kg per day as a single dose Administration: Take with food to avoid stomach upset and
per day 1. pain.
Uncomplicated malaria due to P. vivax or P. ovale, first-line
treatment (in combination with chloroquine 10 mg/kg on Do NOT give to patients with G6PD deficiency.
day 1–2, then 5 mg/kg on day 3), by mouth, ADULT and
CHILD, 0.25 mg base/kg per day as a single dose for day Pregnancy Category: C
1 to 14.
Relapse malaria due to hypnozoites of P. vivax (in ATC Code: P01BA03
combination with chloroquine 10 mg/kg on day 1–2,
then 5 mg/kg on day 3; or with artemether-lumefantrine),
by mouth, ADULT and CHILD, 0.75 mg/kg per day on day
1–14 (maximum dose, 30–45 mg/day). Rx PYRIMETHAMINE
Severe malaria due to P. vivax or P. ovale (in combination
with artemether-lumefantrine). Oral: 25 mg and 75 mg tablet
Mixed malarial infection due to P. falciparum and P. vivax
with or without P. malariae (in combination with A diaminopyrimidine that inhibits parasitic dihydrofolate
artemether-lumefantrine). reductase, resulting in inhibition of vital tetrahydrofolic
Mixed malarial infection due to P. vivax and P. malariae (in acid synthesis. It is active against pre-erythrocytic forms
combination with chloroquine tablet 10 mg/kg on day 1– and is also a slow-acting schizontocide.
2, then 5 mg/kg on day 3), by mouth, ADULT and CHILD,
0.25 mg base/kg per day as a single dose for day 1 to Indications: Treatment of toxoplasmosis or pneumocystosis

P
14. (in combination with sulfonamide)
Relapse malaria due to P. vivax (in combination with
chloroquine (150 mg base tablet), 2 tablets weekly for 8 Contraindications: Megaloblastic anemia secondary to
weeks, by mouth, ADULT (lactating women), 0.25 mg/kg folate deficiency; pregnancy; lactation
daily on day 1–14 (maximum, 30–45 mg daily).
Dose:
See National Antibiotic Guidelines for other dosing Toxoplasmosis treatment (in combination with a
information. sulfonamide and leucovorin calcium), by mouth, ADULT,
50–75 mg daily for 1–3 weeks depending on patient's
Dose Adjustment: tolerance and response, then dose may be reduced by
G6PD Deficiency: 50% and continue for 4–5 weeks, with 1–4 g
For mild deficiency, administer 0.75 mg/kg once a week for sulfadiazine daily; CHILD, initially 1 mg/kg daily divided
8 weeks. into 2 equal daily doses for 2 to 4 days, may decrease
dose to 0.5 mg/kg daily divided into 2 doses for 4 weeks,
Precautions: with usual pediatric dose of sulfadiazine.
G6PD deficiency (exclude before radical treatment for P.
vivax and P. ovale malaria; but, not necessary before Precautions:
single-dose gametocytocidal treatment); Concomitant Hematologic effects (most commonly with high doses;
use with other potentially hemolytic drugs that depress monitor CBC and platelets twice weekly in high-dose
myeloid elements of the bone marrow (monitor if either therapy); Folate deficiency (use with caution); G6PD
methemoglobinemia or hemolysis occurs, withdraw deficiency (use with caution); renal impairment; hepatic
treatment and consult a physician). impairment; Seizure disorders (use with caution).
Pregnancy (withhold during entire pregnancy; neonatal Pregnancy (adverse events have been observed in animal
hemolysis and methemoglobinemia have been reported reproduction studies; supplementation of folate is
with use during the third trimester); lactation (excreted strongly recommended); lactation (excreted in breast
in breast milk in amounts not harmful to the nursing milk; may result in significant systemic concentrations in
infant and in insufficient amounts to provide protection breast­fed infants).
against malaria).
Adverse Drug Reactions: Arrhythmias (large doses), rash,
Adverse Drug Reactions: anorexia, atrophic glossitis, vomiting, leukopenia,
Common: Abdominal pain, anorexia, dizziness, headache, megaloblastic anemia, pancytopenia, pulmonary
leukocytosis, nausea, vomiting eosinophilia, thrombocytopenia, hematuria, anaphylaxis
Less Common: Hemolytic anemia, methemoglobinemia Potentially Fatal: Cutaneous reactions (e.g., erythema
multiforme, Stevens-Johnson syndrome, toxic epidermal
necrolysis (with sulfadoxine at large doses)

545
 ANTIPARASITIC PRODUCTS, INSECTICIDES, AND REPELLENTS

Drug Interactions: mg/kg per hour), then 10 mg/kg for 4 hours every 8
Monitor closely with: hours as maintenance dose; CHILD ≤7 years, 10 mg/kg
Increases risk of adverse or toxic effects of the following for 4 hours as loading dose, then 10 mg/kg every 12
drugs: hours as maintenance dose.
Bone marrow suppression: Proguanil, Sulfonamides e.g.
Co-trimoxazole, Zidovudine, Cytostatic Agents See National Antibiotic Guidelines for other dosing
Co-trimoxazole (pancytopenia; megaloblastic anemia), information.
Lorazepam (hepatotoxicity)
Dose Adjustment:
Reduces therapeutic effect of Pyrimethamine: Renal Impairment:
Methylfolate For patients with severe chronic impairment but not on
dialysis, initiate dose at 648 mg, followed by 324 mg
Avoid concomitant use with: every 12 hours.
Increases risk of adverse or toxic effects of Pyrimethamine:
Artemether Hepatic Impairment:
For patients with mild-to-moderate impairment, no dosage
Increases risk of adverse or toxic effects of the following adjustment needed. Monitor closely.
drugs: For patients with severe impairment, avoid use or reduce
Dapsone (hemolytic reactions), Lumefantrine maintenance dose to 5–7 mg/kg of quinine salt every 8
hours.
Administration: Administer with meals to minimize GI
distress. Precautions:
Hypersensitivity reactions (discontinue following any signs
Pregnancy Category: C of sensitivity); Hypoglycemia; Thrombocytopenia (re-
exposure may result in increased severity of
ATC Code: Not available thrombocytopenia and faster onset); Altered cardiac
conduction (use with caution); Hepatic impairment (use
with caution); renal impairment (use with caution; dose
adjustment recommended in severe chronic
Rx QUININE impairment)
Elderly (use with caution).
P

Oral: 325 mg tablet (as sulfate) (300 mg base) Pregnancy (crosses the human placenta in amounts not
Inj.: 250 mg/mL (as dihydrochloride). 1 mL ampule (IV) therapeutic to the infant; teratogenic effects, optic nerve
300 mg/mL (as dihydrochloride). 1 mL ampule (IV) hypoplasia, and deafness have been reported in the
infant following maternal use of very high doses);
A methanolquinoline that intercalates into the DNA lactation.
structure of susceptible Plasmodium spp., disrupting the
parasite’s replication and transcription. Adverse Drug Reactions:
Common and Less Common: Atrial fibrillation,
Indications: 1st line treatment of uncomplicated atrioventricular block, bradycardia, cardiac arrest, chest
chloroquine-resistant P. falciparum malaria (in pain, hypotension, irregular rhythm, nodal escape beats,
conjunction with other antimalarial agents) in pregnant orthostatic hypotension, palpitation, QT prolongation,
and lactating women and infants less than 6 months old; syncope, tachycardia, torsade de pointes, unifocal
2nd line treatment of severe malaria. premature ventricular contractions, U waves,
vasodilation, ventricular fibrillation, ventricular
Contraindications: Prolonged QT interval; myasthenia tachycardia, aphasia, ataxia, chills, coma, confusion,
gravis; optic neuritis; G6PD deficiency; hypersensitivity to disorientation, dizziness, dystonic reaction, fever,
quinine, mefloquine, quinidine, or any component of the flushing, headache, mental status altered, restlessness,
formulation; seizure, suicide, vertigo, acral necrosis, allergic contact
dermatitis, bullous dermatitis, bruising, cutaneous rash,
Dose: cutaneous vasculitis, exfoliative dermatitis, erythema
Uncomplicated malaria due to P. falciparum or P. malariae multiforme, petechiae, photosensitivity, pruritus,
(in combination with clindamycin, 10 mg/kg twice daily Stevens-Johnson syndrome, toxic epidermal necrolysis,
for 7 days; and primaquine tablet, 15 mg (0.25 mg base hypoglycemia, abdominal pain, anorexia, diarrhea,
per kg) on day 1 and 3 tablets for adults >60 kg), by esophagitis, gastric irritation, nausea, vomiting,
mouth, ADULT (pregnant and lactating women), INFANT agranulocytosis, aplastic anemia, coagulopathy,
<6 months, 10 mg/kg every 8 hours for 7 days. disseminated intravascular coagulation, hemolytic
2nd line drug for severe malaria, by IV drip, ADULT, 20 anemia, hemolytic uremic syndrome, hemorrhage,
mg/kg in 500 mL D5W or 0.9 NaCl for 4 hours ass hypoprothrombinemia, immune thrombocytopenia,
loading dose (maximum total dose, 2,000 mg), then 10 leukopenia, neutropenia, pancytopenia,
mg/kg in 0.9 NaCl or D5W for 4 hours every 8 hours as thrombocytopenia, thrombotic thrombocytopenic
maintenance dose; shift to oral artemether-lumefantrine purpura, granulomatous hepatitis, hepatitis, jaundice,
plus clindamycin once patient can tolerate; CHILD 8–16 myalgia, tremor, weakness, blindness, blurred vision,
years (in combination with clindamycin, 10 mg/kg twice color vision disturbance, diminished visual fields,
daily for 7 days), 15 mg/kg for 4 hours in 10 mL/kg D5W diplopia, night blindness, optic neuritis, photophobia,
or 0.9 NaCl as loading dose (maximum infusion rate, 5 pupillary dilation, vision loss (sudden), deafness, hearing

546
ANTIPARASITIC PRODUCTS, INSECTICIDES, AND REPELLENTS

impaired, tinnitus, acute interstitial nephritis,, renal Pitavastatin, Pravastatin, Red Yeast Rice, Rosuvastatin],
failure, renal impairment, asthma, dyspnea, pulmonary Metoprolol, Pazopanib, Phenobarbital, Ritonavir,
edema, black water fever, diaphoresis, hypersensitivity Silodosin, Thioridazine, Topotecan, Vincristine
reaction, lupus anticoagulant, lupus-like syndrome (Liposomal)

Drug Interactions: Administration: Take with food to decrease incidence of

Monitor closely with: gastric upset. Swallow dose whole to avoid bitter taste.
Enhances therapeutic effect of the following drugs:
Antihypertensive Herbs, Vitamin K Antagonists [e.g., Avoid use of aluminum- or magnesium-containing
Warfarin (anticoagulant effect)] antacids because of drug absorption problems.

Increases risk of hypoglycemic adverse effects of Quinine: Pregnancy Category: C

Androgens [except Danazol], Antidiabetic Agents, Herbs
with Hypoglycemic Properties, MAO Inhibitors, Other ATC Code: P01BC01
hypoglycemia-associated Agents, Pegvisomant,
Salicylates, Selective Serotonin Reuptake Inhibitors
OTHER ANTIMALARIALS
Increases risk of the following drugs:
Herbs with Hypotensive Properties (excessive blood
pressure lowering), Rx DOXYCYCLINE
Significant methemoglobinemia: Nitric Oxide, Prilocaine,
Sodium Nitrite
Oral: 100 mg capsule (as hyclate)
Reduces therapeutic effect of the following drugs:
A broad-spectrum, long-acting tetracycline antibiotic used
Codeine, Tramadol
for infections caused by chlamydia, spirochetes and
other pathogens, and for malarial prophylaxis.
Avoid concomitant use with:
Decreases serum concentration of Quinine:
Indications: Prophylaxis and treatment (supplement to
Antacids [except Calcium Carbonate, Sodium
quinine or artesunate) of multi-drug-resistant P.
Bicarbonate], Carbamazepine, Dabrafenib,
falciparum malaria
Fosphenytoin, Lopinavir, Mitotane, Phenobarbital,

P
Phenytoin, Rifampin, Ritonavir,
Contraindications: Children <8 years (deposition of
tetracyclines in growing bones and teeth causes
Decreases serum concentration of Tamoxifen [active
deformation and inhibit bone growth) except for cholera
metabolite/s]
or leptospirosis but not to be given for > 7 days;
pregnancy (first trimester, effects on skeletal
Enhances therapeutic effect of Neuromuscular-blocking
development in animal studies; 2nd and 3rd trimesters,
Agents
dental discoloration; maternal hepatotoxicity with large
doses); breastfeeding; porphyria; SLE
Increases risk of adverse or toxic effects of Quinine:
Artemether, Dapsone (hemolytic reactions), Ivabradine
Dose:
(QTc-prolonging effect), Mifepristone (QTc-prolonging
2nd line treatment for Uncomplicated malaria due to P.
effect), QTc-prolonging Agents
falciparum or P. malariae, second-line treatment (in
combination with quinine sulfate, 10 mg/ kg every 8
Increases risk of adverse or toxic effects of the following
hours for 7 days and primaquine tablet, 15 mg (0.24 mg
drugs:
base per kg) on day 1; 3 tablets for adults >60 kg), by
Dapsone (hemolytic reactions), Halofantrine,
mouth, ADULT, 100 mg 2 times daily for 7 days.
Lumefantrine, Mefloquine (QTc-prolongation;
Prophylaxis of chloroquine-resistant malaria, beginning 1-2
convulsions)
days before travel to malarious area up to 4 weeks after
leaving, ADULT, 100 mg daily CHILD ≥ 8 years, 2.2 mg
Increases serum concentration of Quinine:
∙base/ kg daily.
Antihepatitis C viral Combination Products, Cimetidine,
Chloroquine-resistant falciparum malaria acute attack,
Conivaptan, CYP3A4 Inhibitors, Fusidic Acid, Idelalisib,
ADULT, 200 mg daily for at least 7 days, with or after
Macrolide Antibiotics e.g. Erythromycin [except
treatment with quinine.
Fidaxomicin], Mefloquine [delay Mefloquine
administration at least 12 hours after the last dose of
NOTE: Refer to DOH Public Health Program on Malaria for
Quinine], Stiripentol
more details.
Increases serum concentration of the following drugs:
Administration: Capsules should be swallowed whole with
Afatinib [if concomitant use cannot be avoided, reduce
plenty of fluid (a full glass of water). Remain sitting or
Afatinib dose by 10 mg if not tolerated], Amodiaquine,
standing (for at least 30 minutes) to prevent esophageal
Bosutinib, Carbamazepine, Colchicine (enhances
irritation or damage.
distribution into certain tissues, e.g., brain), Dabigatran
Etexilate [active metabolite/s], Doxorubicin
May be given with food to counter gastric irritation. Do NOT
(Conventional), Edoxaban, Everolimus, Halofantrine,
give with milk
HMG-CoA reductase inhibitors [except Fluvastatin,

547
 ANTIPARASITIC PRODUCTS, INSECTICIDES, AND REPELLENTS

See Doxycycline under Antibacterials for Systemic Use –

Tetracyclines in Chapter 7: Antiinfectives for Systemic ANTHELMINTICS
Use for other information.

Pregnancy Category: D ANTITREMATODALS

ATC Code: J01AA02 Rx PRAZIQUANTEL

Oral: 600 mg tablet (available under DOH program)
Rx TETRACYCLINE NOTE: Available at the DOH Central Office and government
health facilities in endemic areas.
Oral: 250 mg and 500 mg capsule
A quinoline-derived, broad-spectrum anthelmintic, which is
A tetracycline antibiotic that inhibits bacterial synthesis by effective, as a single dose, in the treatment of
binding with the 30s ribosomal subunit(s) of schistosome infections of all species, and other
susceptible microorganisms. trematode and cestode infections, including
cysticercosis. It increases the cell permeability to Ca in
Indication: For chloroquine-resistant falciparum malaria (in schistosomes, causing contractions and paralysis of
combination with other antimalarials) worm musculature leading to detachment of suckers
from the blood vessel walls and to dislodgement.
Dose:
2nd line treatment for uncomplicated malaria due to P. Indications: For fluke and tapeworm infections including
falciparum or P. malariae (in combination with quinine Cysticercus cellulosae; intestinal schistosomiasis;
sulfate, 10 mg/kg every 8 hours for 7 days; and urinary schistosomiasis
primaquine tablet, 15 mg (0.25 mg base per kg) on day
1 and 3 tablets for adults >60 kg), by mouth, ADULT, 3 Contraindications: Ocular cysticercosis
mg/kg once daily for 7 days.
Severe malaria due to P. falciparum or P. malariae, second- Dose:
line treatment (in combination with artemether- Schistosomiasis (selective treatment), by mouth, ADULT
lumefantrine), by mouth, ADULT, 3 mg/kg once daily for and CHILD >4 years, 40–60 mg/kg as a single dose; or
P

7 days. in 3 divided doses of 20 mg/kg at intervals of 4–6 hours.

Dose Adjustment: Dose Adjustment:

Renal Impairment: Hepatic Impairment:
If CrCl is 50–80 mL/minute, administer every 8–12 hours. Consider reducing dose due to increased concentration and
If CrCl is 10–50 mL/minute, administer every 12–24 hours. half-life.
If CrCl <10 mL/minute, administer every 24 hours.
Precautions:
Hepatic Impairment: Cardiovascular disease; cerebral cysticercosis (it is
Use with caution. Maximum dose is 1 g daily. recommended to hospitalize patients for the duration of
treatment)
Administration: Should be given on an empty stomach (1 Ocular cysticercosis (severe eye damage due to death of
hour prior to, or 2 hours after meals) to increase total parasites may occur)
absorption. Undiagnosed neurocysticercosis (seizures may result if
praziquantel is used to treat another systemic infection).
Administer at least 1–2 hours prior to, or 4 hours after Paragonimus infections (may have CNS involvement);
antacid because aluminum and magnesium cations may severe hepatic disease
chelate with tetracycline and reduce its total absorption. Areas endemic for cysticercosis (possible risk of edematous
reaction)
Administer around-the-clock to promote less variation in Reduced liver drug metabolism may result in higher and
peak and trough serum levels. longer lasting plasma concentration of unmetabolized
praziquantel.
See Tetracycline under Antibacterials for Systemic Use – Pregnancy (Taenia solium infections should be treated
Tetracyclines in Chapter 7: Antiinfectives for Systemic immediately; benefit of treatment in schistosomiasis
Use for other information. outweighs the risk; if treatment is not essential, it should
be delayed until after delivery); breastfeeding (low
Pregnancy Category: D excretion in breastmilk; avoid breastfeeding during, and
for 72 hours, after treatment; considered safe to
ATC Code: J01AA07 continue breastfeeding during treatment).

SKILLED TASKS. Avoid performing tasks, which require

mental alertness, e.g., operating machinery or driving.
Warn patient not to operate machinery or drive during
treatment or for 24 hours after treatment.

548
ANTIPARASITIC PRODUCTS, INSECTICIDES, AND REPELLENTS

Adverse Drug Reactions: Common and Less Common: Transient self-limiting biliary
Common: Abdominal pain, anorexia, appetite loss, colic, obstruction, gastrointestinal disturbance, abdominal
diarrhea, dizziness, drowsiness, fever, headache, cramps, diarrhea
malaise, myalgia, nausea, reversible rises in hepatic
aminotransferases, somnolence, urticaria, vertigo, Drug Interactions: No information found
vomiting
Rare: Arrhythmias, bloody diarrhea, hypersensitivity Administration: To be taken with fatty food to increase
reactions, rectal bleeding, seizures, eosinophilia, absorption.
pruritus
MISSED DOSE. Take missed dose as soon as remembered.
Drug Interactions: Do NOT take if near time for next dose. Do NOT take 2
Monitor closely with: doses at once.
Reduces therapeutic effect of Praziquantel:
Carbamazepine, Chloroquine, Dexamethasone, Pregnancy Category: D
Phenytoin
ATC Code: P02BX04
Avoid concomitant use with:
Reduces therapeutic effect of Praziquantel due to
decreased serum concentration of active metabolite/s: ANTINEMATODAL AGENTS
CYP450 Inducers (e.g., Rifampicin)

Increases serum concentration of Praziquantel: Rx ALBENDAZOLE

CYP Inhibitors (e.g., Cimetidine, Erythromycin,
Itraconazole) Oral: 400 mg chewable tablet
200 mg/5 mL suspension, 10 mL and 60 mL
Administration: Should be taken on a full stomach. Swallow
with water, without chewing, to lessen its bitter taste. A benzimidazole-derived, broad-spectrum, oral
anthelmintic, which is used for long-term treatment of
Pregnancy Category: B tissue helminth infections, including hydatid disease and
cysticercosis.
ATC Code: P02BA01

P
Indications: Management of filariasis; treatment of
intestinal helminths
Rx TRICLABENDAZOLE
Contraindications: Pregnancy (first trimester, avoid in
nematode infections); hepatic cirrhosis; cestode
Oral: 250 mg tablet infections due to Taenia solium occurring during
pregnancy; ocular cysticercosis (severe eye damage due
A benzimidazole compound that is active against immature to death of parasites may occur)
and adult Fasciola parasites.
Dose:
Indications: For the treatment of paragonimiasis; primary or Filariasis (selective treatment for patients positive for
alternate agent to praziquantel; for implementation of microfilariae in nocturnal blood examination, 12-day
the DPCB – Food and Waterborne Disease Program in treatment), by mouth, ADULT,
identified endemic areas in the Philippines Day 1, 400 mg albendazole and 6 mg/kg body weight
diethylcarbamazine citrate (DEC) in 3 divided doses;
Contraindications: Breastfeeding Day 2 to 12, 6 mg/kg body weight of DEC only, given in 3
divided doses daily.
Dose:
Fascioliasis, by mouth, ADULT and ADOLESCENT, 10 mg/kg NOTE: Refer to DOH National Filariasis Elimination Program
as a single dose, may be repeated after 2 weeks or 6 for more details
months if necessary; CHILD, 10 mg/kg as a single dose.
Fascioliasis, severe, by mouth, ADULT and ADOLESCENT, 20 Intestinal Helminths, by mouth, ADULT and CHILD> 2 years,
mg/kg in 2 divided doses 12 hours apart. 400 mg single dose.
Paragonimiasis, by mouth, ADULT and ADOLESCENT, 5
mg/kg once daily for 3 days; or 10 mg/kg as a single Dose Adjustment:
dose; CHILD, 10 mg/kg as a single dose; or 20 mg/kg in Hepatic Impairment:
2 divided doses for 1 day. Consider dose reduction during extended treatment.

Precautions: Precautions:
Pregnancy (studies in humans have not been conducted); Liver disease; Liver function tests, clinical signs of hepatic
lactation (excreted in breast milk). toxicity and blood count should be monitored twice
during each cycle before a longer-term treatment.
Adverse Drug Reactions: Pregnancy (exclude pregnancy before starting the
treatment; advise patients to use non-hormonal

549
 ANTIPARASITIC PRODUCTS, INSECTICIDES, AND REPELLENTS

contraception during and for one month after treatment); severe (especially in onchocerciasis and loiasis); Monitor
breastfeeding. for eye changes.

Adverse Drug Reactions: PATIENT ADVICE. Complete the prescribed course as

Common: Abdominal pain, headache, nausea, vomiting directed to minimize allergic reactions to dying parasites.
Less Common: Abnormal liver function tests, diarrhea,
dizziness, fever, increased intracranial pressure, Adverse Drug Reactions:
meningeal signs, vertigo Common: Allergic reactions
Rare: Agranulocytosis, allergic shock (if with cyst leakage), Less Common: Anorexia, asthmatic attacks, dizziness,
aplastic anemia, bone marrow suppression, jaundice, drowsiness, fever, headache, joint pain, malaise,
convulsions, erythema multiforme, hepatitis, transient hematuria, urticaria, vomiting
hypersensitivity reactions, proteinuria, Stevens-Johnson Rare: Convulsions, exacerbation of lymphedema, transient
syndrome lymphangitis

Drug Interactions: Drug Interactions: No information found.

Monitor closely with:
Reduces therapeutic effect of Albendazole due to Administration: To be taken after meals. Rigorous hygiene
decreased serum concentration of active metabolite/s: is essential.
Phenobarbital, Phenytoin
Total cumulative dose for W. bancrofti infections should be
Administration: To be taken with food. Oral absorption may 72 mg/kg. Treatment is best initiated with smaller doses
be increased 4–5 times with fatty meal for 2–3 days to avoid potential risk of immunological
reactions.
Pregnancy Category: C
NOTE: Before treatment with diethylcarbamazine citrate
ATC Code: P02CA03 (DEC), patients should be assessed for co-infection with
Loa loa and Onchocerca volvulus because DEC can
cause serious reactions in these patients.
May be co-administered with dexamethasone, 0.8
Rx DIETHYLCARBAMAZINE mg/kg daily to reduce intensity of Mazzotti reactions.
Administer prior to initiating diethylcarbamazine and
P

Oral: 50 mg and 100 mg tablet (available under DOH maintained for 5 days prior to gradual withdrawal.
program)
Pregnancy Category: X
NOTE: Refer to DOH National Filariasis Elimination Program
for more details ATC Code: P02CB02

A piperazine-derived, filarial medicine, which renders

microfilariae susceptible to destruction by the host’s
defense mechanism through parasite immobilization,
Rx MEBENDAZOLE
normal habitat dislocation and surface membrane
alteration. Oral: 100 mg tablet / capsule
500 mg tablet / chewable tablet
Indication: Management of filariasis 50 mg/mL suspension, 10 mL
100 mg/5 mL suspension, 30 mL and 60 mL
Contraindications: Pregnancy (delay medication until after
delivery) A benzimidazole derivative that inhibits the formation of
helminth microtubules. It selectively and irreversibly
Dose: blocks glucose uptake and other nutrients in susceptible
Filariasis (selective treatment for patients positive for adult intestine-dwelling helminths.
microfilariae in nocturnal blood examination, 12-day
treatment), by mouth, ADULT, Indication: Management of common roundworm infections
Day 1, 6 mg/kg body weight diethylcarbamazine citrate
(DEC) in 3 divided doses and 400 mg albendazole; Dose:
Day 2 to 12, 6 mg/kg body weight of DEC only, given in 3 Ascaris lumbricoides (roundworm), Strongyloides
divided doses daily. stercoralis (roundworm), mixed infection, by mouth,
ADULT, ADOLESCENT, and CHILD ≥2 years, 500 mg as
Dose Adjustment: single dose of 100 mg twice daily for 3 days, repeat in 3
Renal Impairment: weeks if not cured with initial treatment.
Consider reducing dose. Plasma half-life is prolonged, and
urinary excretion is considerably reduced. Precautions:
Bone marrow suppression; Hepatic impairment (undergoes
Precautions: extensive hepatic metabolism);
Cardiac disorders; other severe acute diseases (delay Children (experience with use in children <2 years of age is
treatment until after recovery); Treatment should be well limited)
supervised since allergic reaction is common and usually

550
ANTIPARASITIC PRODUCTS, INSECTICIDES, AND REPELLENTS

Pregnancy (use with caution; consider postponing therapy Administration: For external use only. Apply to intact skin
until the third trimester when possible). only. Do NOT apply to broken or irritated skin.

Adverse Drug Reactions: Dizziness, drowsiness, headache, Pregnancy Category: Not classified
seizure, alopecia, angioedema, exanthema, itching, rash,
Stevens-Johnson syndrome, toxic epidermal necrolysis, ATC Code: P03AX01
urticaria, abdominal pain, diarrhea, vomiting,
agranulocytosis, eosinophilia, decreased hemoglobin,
leukopenia, neutropenia, increased alkaline
phosphatase, hepatitis, cylindruria, glomerulonephritis, Rx CROTAMITON
hematuria, hypersensitivity reactions (anaphylactic,
anaphylactoid) Topical: 10% lotion, 60 mL bottle

Drug Interactions: A scabicidal and antipruritic agent for topical use only.
Avoid concomitant use with:
Increases risk of adverse or toxic effects Mebendazole: Indications: For eradication of scabies (Sarcoptes scabiei);
Metronidazole (Stevens-Johnson syndrome or toxic symptomatic treatment of pruritic skin
epidermal necrolysis)
Contraindications: Sensitive skin
Administration: May be administered with or without food.
Tablets may be chewed, swallowed whole, or crushed Dose:
and mixed with food. Scabies, by topical application, ADULT, CHILD >3 years,
thoroughly massage into the skin of the whole body from
Pregnancy Category: C the chin down, paying attention to all folds and creases,
re-apply after 24 hours, wash all clothing and bed linen
ATC Code: P02CA01 the next morning, take cleansing bath 48 hours after the
last application; CHILD <3 years, apply once daily with
medical supervision.
Pruritus, by topical application, ADULT, massage gently into
ECTOPARASITICIDES, INCLUDING SCABICIDES, affected areas until medication is completely absorbed,
INSECTICIDES, AND REPELLENTS repeat as needed; CHILD <3 years, apply once daily with

P
medical supervision.

ECTOPARASITICIDES, Dose Adjustment: No information found

INCLUDING SCABICIDES
Precautions:
WARNING: If severe irritation or sensitization
OTC BENZYL BENZOATE develops, treatment with this product should be
discontinued and appropriate therapy instituted.
Topical: 25% lotion, 60 mL and 120 mL bottle
Pregnancy (use with caution; use only when clearly needed).
An acaricide that is used in the treatment of scabies
Adverse Drug Reactions: Dermatitis, pruritus, rash, allergic
Indication: For the treatment of scabies sensitivity reactions

Contraindications: Broken or irritated skin; neonates; Administration: For external use only. Shake well before use.
pregnancy
Take a routine bath or shower. Thoroughly massage the
Dose: lotion into the skin from the chin to the toes including
Scabies, by topical application, ADULT, apply 3 times over folds and creases, as well as under fingernails after
the whole body once daily for 2 consecutive nights. May trimming the fingernails short. A toothbrush can be used
repeat 1 application at night 3 days later. to apply the lotion under the fingernails. Immediately
after use, the toothbrush should be wrapped in paper
Dose Adjustment: No information found and thrown away. Use of the same brush in the mouth
could lead to poisoning. One bottle is sufficient for 2
Precautions: applications. Clothing and bed linen should be changed
Prevent drug from entering the eyes. the next day. Contaminated clothing and bed linen may
Elderly (increased risk of drying effects). be dry-cleaned, or washed in the hot cycle of the washing
machine.
Adverse Drug Reactions: Irritant to eyes and mucous
membranes, allergic dermatitis reactions, drying effects Do NOT apply in the eyes or mouth because it may cause
(elderly) irritation. Do NOT apply to acutely inflamed skin or raw or
weeping surfaces until the acute inflammation has
Drug Interactions: No information found subsided.

551
 ANTIPARASITIC PRODUCTS, INSECTICIDES, AND REPELLENTS

Pregnancy Category: C Avoid contact with eyes, mucous membrane, and broken
skin.
ATC Code: Not available
Pregnancy Category: B

ATC Code: P03AC04

Rx PERMETHRIN

Topical: 1% lotion, 125 mL bottle

5% lotion, 30 mL and 60 mL bottle
OTC SULFUR
1% shampoo (crème rinse), 30 mL and 60 mL
bottle Topical: 10% cream / ointment, 15 g and 30 g tube

A topical scabicidal agent. It acts on the nerve cell A keratolytic, mild antiseptic, mild antifungal, and
membrane to disrupt the sodium channel current by parasiticide.
which the polarization of the membrane is regulated,
resulting to paralysis. Indication: Treatment of scabies

Indications: Treatment of scabies (Sarcoptes scabiei); head Contraindications: Children <2 years
pediculosis
Dose:
Dose: Scabies, by topical application, ADULT, apply a thin layer
For scabies, by topical application, ADULT and CHILD >2 uniformly and massage gently into all skin surfaces from
months, apply 5% lotion to entire skin from chin down to the neck to the toes (including the soles), leave on for 24
and including toes and under fingernails and toenails, hours before washing, repeat application for 2–3
leave on for 8–14 hours, repeat in 1–2 weeks. successive days, 30 g is sufficient for each application;
Pediculosis pubis, by topical application, ADULT and CHILD CHILD, use a smaller proportion of adult dose.
>2 months, apply 1% crème rinse to affected areas and
wash off after 10 minutes. Dose Adjustment: No information found

Dose Adjustment: No information found Precautions:

P

May stain the skin black and give off a foul smell when
Precautions: applied concomitantly with mercurial compounds.
Dermatological effects (may temporarily exacerbate
pruritus, edema, and erythema associated with scabies Adverse Drug Reactions: Skin irritation, dermatitis
infestation).
Children (safety and effectiveness in children <2 months Drug Interactions:
have not been established). Enhances therapeutic effect of Sulfur:
Lactation (excreted in breast milk; withhold drug while Resorcinol
mother is nursing)
Administration: For external use only.
Adverse Drug Reactions:
Common: Mild and transient burning and stinging, pruritus, Cleanse skin thoroughly. Cover the entire affected area with
erythema, numbness, tingling, rash, skin and scalp a thin layer and leave on for 24 hours. Thoroughly
irritation, eczema, localized edema remove with water.

Drug Interactions: No information found Avoid contact with eyes, mouth and other mucous
membranes. Do NOT use on broken skin.
Administration: Treat close contacts. Wash and dry linens to
prevent re-infection. Re-apply to hands after Do NOT use concurrently with other topical acne
handwashing. medications unless otherwise directed by physician.

Thoroughly massage the product into the skin from the head Pregnancy Category: Not classified
to the soles of the feet. Scabies rarely infests the scalp
of adults, although the hairline, neck, temple, and ATC Code: Not available
forehead may be infested in infants and geriatric
patients. Remove the product by washing (shower or
bath) after 8 to 14 hours. Infants should be treated on
the scalp, temple, and forehead. ONE APPLICATION IS
GENERALLY CURATIVE.

Patients may experience persistent pruritus after treatment.

This is rarely a sign of treatment failure and is NOT an
indication for retreatment. Demonstrable living mites
after 14 days indicate that retreatment is necessary.

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RESPIRATORY SYSTEM

Precautions:
RESPIRATORY SYSTEM WARNING: Discontinuation of Therapy. Withdraw
systemic therapy with gradual tapering of dose. There
have been reports of systemic corticosteroid
withdrawal symptoms (e.g., joint or muscle pain,
NASAL PREPARATIONS lassitude, depression) when withdrawing oral
inhalation therapy.

DECONGESTANTS AND OTHER NASAL Adrenal suppression; Bronchospasm (if this occurs, stop
PREPARATIONS FOR TOPICAL USE steroid and treat with a fast-acting bronchodilator);
Asthma (not to be used in status asthmaticus or for the
relief of acute bronchospasm); Immunosuppression (use
Rx BUDESONIDE is restricted in active TB); Local oral infections; Kaposi's
sarcoma (if noted, discontinue therapy); myopathy
Inhalation: (monitor creatine kinase; recovery may be delayed);
DPI: myasthenia gravis; Psychiatric disturbances; seizure
100 micrograms/dose x 200 doses with appropriate disorders; Cardiovascular disease (myocardial
accompanying dispenser infarction); Diabetes; gastrointestinal disease; Hepatic
200 micrograms/dose x 100 doses and 200 doses with impairment (long-term use has been associated with
appropriate accompanying dispenser fluid retention); renal impairment (fluid retention may
occur); Thyroid disease (changes in thyroid status may
MDI: necessitate dose adjustments); Ocular disease;
200 micrograms/dose x 120 actuations Osteoporosis; Elderly; children (routinely monitor
growth); lactation (excreted in breast milk).
Respiratory solution for nebulization:
250 micrograms/mL respiratory solution (for Adverse Drug Reactions:
nebulization), 2 mL (unite dose) Common: Syncope, headache, pain, hypertonia, insomnia,
voice disorder, weight gain, emotional lability, fatigue,
A corticosteroid with potent glucocorticoid activity and weak skin rash, contact dermatitis, eczema, pruritus, pustular
mineralocorticoid activity. It controls the rate of protein rash, dyspepsia, nausea, gastroenteritis, diarrhea,
synthesis, depresses the migration of vomiting, abdominal pain, dysgeusia, xerostomia,
polymorphonuclear leukocytes, fibroblasts, and reverses anorexia, cervical purpura, bruise, lymphadenopathy,
capillary permeability and lysosomal stabilization at the hypersensitivity reaction, candidiasis, viral infection,

R
cellular level to prevent or control inflammation. herpes simplex infection, infection, bone fracture,
hyperkinesia, myalgia, arthralgia, weakness, back pain,
Indications: For seasonal allergic and non-allergic perennial conjunctivitis, eye infection, otitis media, otic infection,
rhinitis; treatment of nasal polyps; prevention of nasal otalgia, otitis externa, cough, epistaxis, flu-like
polyps after polypectomy symptoms, stridor, nasopharyngitis, respiratory infection,
rhinitis, chest pain, sinusitis, nasal congestion,
Contraindications: Primary treatment of status asthmaticus, pharyngitis, fever
acute episodes of asthma Less Common: Adrenocortical insufficiency, aggressive
behavior, anxiety, avascular necrosis of femoral head,
NOTE: NOT for the relief of acute bronchospasm. bronchitis, bruise, cataract, depression, glaucoma,
growth suppression, headache, hypercorticolism,
Dose: hypersensitivity (including angioedema, bronchospasm,
NOTE: Dose should be individualized and tapered to the urticaria), increased intraocular pressure, irritability,
smallest dose maintaining symptom control. nervousness, osteoporosis, pain, pharyngitis, psychosis,
restlessness, skin irritation (facial), throat irritation,
Rhinitis, into the nostril, ADULT and CHILD ≥6 years, initially wheezing (patients with severe milk allergy)
256 micrograms daily once daily in the morning or in 2
divided doses (morning and evening). Drug Interactions:
Nasal polyps, into the nostril, ADULT, 64–100 micrograms Monitor closely with:
into each nostril twice daily for up to 3 months. Enhances therapeutic effect of Budesonide:
Trastuzumab (neutropenic effect)
Dose Adjustment:
Geriatric: Increases risk of adverse or toxic effects of Budesonide:
Administer the smallest possible effective dose for the Denosumab (serious infections)
shortest duration.
Increases risk of adverse or toxic effects of the following
Pediatric: drugs:
Titrate to lowest effective dose to minimize systemic effects. Amphotericin B (hypokalemic effect), Deferasirox (GI
ulceration, irritation, or bleeding), Loop Diuretics
(hypokalemic effect), Thiazide Diuretics (hypokalemic
effect)

Reduces therapeutic effect of the following drugs:

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 RESPIRATORY SYSTEM

Corticorelin, Sipuleucel-T
Dose Adjustment: No information found
Avoid concomitant use with:
Enhances therapeutic effect of Tofacitinib Precautions:
(immunosuppressive effect) Difficulty in urination secondary to prostate enlargement;
heart disease; high blood pressure; thyroid disease;
Increases risk of adverse or toxic effects of Budesonide: diabetes mellitus; Lactation
Pimecrolimus, Tacrolimus (Topical)
Adverse Drug Reactions:
Increases risk of adverse or toxic effects of the following Common and Less Common: Local stinging or burning,
drugs: sneezing, dryness of mouth and throat, rebound
Leflunomide (hematologic toxicity such as pancytopenia, congestion (prolonged use), headache, insomnia,
agranulocytosis, and/or thrombocytopenia), Loxapine, tachycardia, hypertension, nervousness, nausea,
Natalizumab (concurrent infection) dizziness, palpitation, arrhythmia

Increases serum concentration of Budesonide: Drug Interactions:

Conivaptan (CYP3A4 Inhibitors), Fusidic Acid (Systemic), Avoid concomitant use with:
Grapefruit Juice, Mifepristone, Stiripentol, Telaprevir Increases risk of adverse or toxic effects of MAO Inhibitors
e.g. Phenelzine (potentially fatal hypertensive crisis)
Reduces diagnostic effect of Coccidioides immitis Skin Test
Administration: Do NOT ingest. Keep out of reach of
Reduces therapeutic effect of the following drugs: children.
Aldesleukin (antineoplastic effect), BCG (Intravesical),
Hyaluronidase, Vaccines (Inactivated) [complete all age- Shake well before use. If using for the first time, remove
appropriate vaccinations at least 2 weeks prior to the protective cap from the tip and prime metered pump
starting budesonide; if vaccinated during budesonide by depressing the pump firmly several times. To spray,
therapy, revaccinate at least 3 months after hold bottle with thumb at base and nozzle between first
discontinuation] and second fingers. Without tilting your head, insert the
nozzle into nostril. Fully depress rim with a firm, even
Administration: Shake well before use. If using for the first stroke and sniff deeply. Wipe nozzle clean after use.
time, remove the protective cap from the tip and prime
metered pump by depressing the pump firmly several Administer each dose 10–12 hours apart. Do NOT
times. To spray, hold bottle with thumb at base and exceed 2 doses in any 24-hour period.
nozzle between first and second fingers. Without tilting For children under 6 years of age, ask a doctor prior to
R

your head, insert the nozzle into nostril. Fully depress rim administration.
with a firm, even stroke and sniff deeply. Wipe nozzle
clean after use. Use only as directed. Do NOT use more than directed. Do
NOT use for more than 3 days. Frequent or prolonged use
Pregnancy Category: B may cause nasal congestion to recur or worsen.

ATC Code: R01AD08 Do not share containers with other persons to prevent
the spread of infection

Pregnancy Category: C
OTC OXYMETAZOLINE
ATC Code: R01AB07
Topical: 0.05% nasal spray (as hydrochloride), 10 mL
and 15 mL bottle
0.025% nasal drops solution (as
hydrochloride), 10 mL bottle
THROAT PREPARATIONS

A direct-acting sympathomimetic with vasoconstrictor effect

on mucosal blood vessels when applied topically, OTC POVIDONE–IODINE
reducing edema of the nasal mucosa.
Oral: 1% antiseptic solution, 60 mL, 120 mL, and
Indications: Temporarily relieves nasal congestion due to
240 mL bottle
common cold, hay fever, upper respiratory allergies
An iodophore with a powerful broad-spectrum germicidal
Contraindications: Glaucoma; hyperthyroidism; heart
activity against a wide range of bacteria, viruses, fungi,
disease, including angina; hypertension; advanced
protozoa and spores.
arteriosclerotic conditions; children <6 years
Indications: oral hygiene; oral candidiasis
Dose:
Nasal congestion, into the nostril, ADULT and CHILD ≥6
years, spray 0.05% solution 1–3 times into each nostril
twice daily.

554
RESPIRATORY SYSTEM

Contraindications: prolonged use in patients with thyroid A short-acting, beta2-adrenergic agonist used in the
disorders or on lithium therapy; premature neonates or treatment or prevention of bronchospasm.
neonates weighing <1.5 kg
Indications: Prophylaxis and treatment of asthma;
Dose: bronchospasm in patients with reversible obstructive
Oral hygiene, by mouth or throat, ADULT and CHILD >6 airway disease; prevention of exercise-induced
years, rinse mouth with 10 mL 0.1% solution, undiluted bronchospasm
or diluted with an equal amount of warm water for 30
seconds 4 times daily for 14 days. Contraindications: Severe pre-eclampsia and eclampsia;
Oral candidiasis, by mouth or throat, ADULT, rinse with 1% intrauterine infection; intrauterine fetal death; ante-
solution. partum hemorrhage, placenta previa; cord compression;
threatened miscarriage; cardiac disease
Precautions:
Avoid contact with eyes; lactation; neonates. Dose:
Chronic asthma (as adjunct in stepped treatment), by
Adverse Drug Reactions: aerosol inhalation, ADULT, 100–200 micrograms (1–2
Rare: Local irritation, sensitivity puffs) up to 3–4 times daily; CHILD, 100 micrograms (1
puff) 3–4 times daily, increased to 200 micrograms (2
Drug Interactions: puffs) 3–4 times daily if necessary.
Monitor closely with: Prophylaxis of exercise-induced bronchospasm, by aerosol
Incompatible with the following products: inhalation, ADULT, 200 micrograms (2 puffs); CHILD,
Bupivacaine (Liposomal) [allow the site to dry completely 100 micrograms (1 puff) increased to 200 micrograms
before administering bupivacaine], Fibrin Sealant (2 puffs) if required.
(Human) [thoroughly rinse and dry prior to application of Relief of acute bronchospasm, by aerosol inhalation,
sealant] ADULT, 100–200 micrograms (1–2 puffs); CHILD, 100
micrograms (1 puff) increased to 200 micrograms (2
Avoid concomitant use with: puffs) if necessary.
Incompatible with the following products: Severe acute asthma, chronic bronchospasm
Benzalkonium Chloride, Collagenase (unresponsive to conventional treatment), by inhalation
of nebulized solution, ADULT and CHILD >18 months, 2.5
TEST INTERACTIONS. May interfere with thyroid function test mg repeated up to 4 times daily; may be increased to 5
results and interpretation if used for prolonged periods. mg if necessary (consider medical assessment since
alternative therapy may be indicated); CHILD <18
Administration: Do NOT ingest. Ensure to spit out the months, clinical efficacy uncertain (transient hypoxemia

R
solution after thorough rinsing. May color teeth and may occur – consider oxygen supplementation).
mucous membranes.
Dose Adjustment:
Pregnancy Category: D Geriatric:
Start with a lower dose than the usual adult dose. Gradually
ATC Code: R02AA15 increase if needed.

Precautions:
DRUGS FOR OBSTRUCTIVE AIRWAY WARNING: Excessive use and reliance on beta2-
DISEASE agonists for the treatment of asthma without an anti-
inflammatory agent have been associated with an
increased incidence of sudden deaths. Beta2-
ADRENERGICS, INHALANTS agonists inhalation can occasionally cause
paradoxical bronchospasm and hypoxemia.
Rx SALBUTAMOL
Paradoxical bronchospasm (should be treated immediately
with alternative therapy); discontinue treatment if the
Inhalation:
patient develops signs of pulmonary edema; Myocardial
DPI:
insufficiency, arrhythmias, susceptibility to QT-interval
200 micrograms per dose (as sulfate) with appropriate
prolongation, hypertension; Diabetes mellitus, especially
accompanying dispenser
IV administration (monitor blood glucose);
hyperthyroidism; renal and hepatic impairment (use with
MDI:
caution in high-dose treatments); Pregnancy (high doses
100 micrograms per dose (as sulfate) x 200 doses
should be given through inhalation only); lactation
(monitor breastfeeding infant).
Breath Actuated MDI:
100 micrograms per dose (as sulfate) x 200 doses
Adverse Drug Reactions:
Common: Cough, headache, musculoskeletal pain,
Respiratory solution for nebulization:
palpitations, throat irritation, tremor, upper respiratory
1 mg/mL (as sulfate), 2.5 mL (unit dose)
inflammation, viral respiratory infections
2 mg/mL (as sulfate), 2.5 mL (unit dose)

555
 RESPIRATORY SYSTEM

Less Common: Agitation, hyperactivity in children, Pregnancy Category: C

hyperglycemia (high doses), insomnia, tachycardia
Rare: Allergic reactions, hypokalemia, lactic acidosis, ATC Code: R03AC03
paradoxical bronchospasm

Drug Interactions:
Monitor closely with: Rx FORMOTEROL
Increases risk of adverse or toxic effects of Methyldopa
(acute hypotension) Inhalation:
DPI:
Avoid concomitant use with: 12 mcg dry powder for inhalation
Increases risk of adverse or toxic effects of Salbutamol:
Corticosteroids (serious hypokalemia), Diuretics (serious Formoterol is a long acting beta 2 agonist. It relaxes
hypokalemia), Drugs that increase blood glucose bronchial smooth muscle with little effect on heart rate.
concentration e.g., Glucocorticoids, Antipsychotics,
Calcineurin Inhibitors, high-dose Thiazide Diuretics, Indication: Maintenance treatment of chronic obstructive
Somatropin (hyperglycemia), Drugs that reduce pulmonary disease (COPD).
potassium concentration e.g., Amphotericin B, Diuretics
(hypokalemia), Theophylline (serious hypokalemia) Contraindications: Treatment of status asthmaticus or other
acute episodes of asthma or COPD; monotherapy
Increases risk of adverse or toxic effects of the following treatment in asthma; tachyarrhythmias.
drugs:
Sympathomimetic Amines e.g., Ephedrine, Dose:
Phenylephrine, Pseudoephedrine (sympathetic adverse Chronic obstructive pulmonary disease, by dry powder
effects e.g., tremor, tachycardia, headache) inhalation, ADULT and CHILD, 12 mcg every 12 hours
(maximum dose: 24 mcg/ day).
Reduces therapeutic effect of Beta Blockers e.g.,
Propranolol (may precipitate asthma) Dose Adjustment:
Renal and Hepatic impairment:
Administration: Multi-dose solution for nebulization may No dosage adjustments provided in the manufacturer’s
need dilution with 0.9% sodium chloride to obtain final labeling.
volume for the nebulizer.
Precautions:
Pregnancy Category: C
R

Asthma-related deaths, bronchospasm, hypersensitivity,

serious effects/fatalities;
ATC Code: R03AC02 Use in caution in patients with asthma, cardiovascular
disease, COPD, diabetes, exercise-induced
bronchospasm, hyperthyroidism, hypokalemia,
pheochromocytoma, and seizure disorders.
Rx TERBUTALINE
Adverse Drug Reactions:
Inhalation: Less Common: Chest pain, anxiety, dizziness, insomnia,
Respiratory solution for nebulization: voice disorder, headache, pruritus, skin rash, diarrhea,
2.5 mg/mL (as sulfate), 2 mL (unit dose) nausea, xerostomia, vomiting, abdominal pain,
dyspepsia, gastroenteritis, muscle cramps, tremor,
A direct acting sympathomimetic drug with beta-adrenergic respiratory infection, exacerbation of asthma, acute
activity, selectively on beta2 receptors. deterioration, bronchitis, pharyngitis, sinusitis, dyspnea,
tonsillitis, and fever.
Indications: Bronchodilator in reversible airway obstruction Rare: Agitation, anaphylaxis, angina pectoris, atrial
and bronchial asthma fibrillation, behavioral changes, cardiac arrhythmia,
cough, decreased glucose tolerance, dermatitis,
Contraindications: Acute or chronic use in the prevention, disturbed sleep, dysgeusia, fatigue, hyperglycemia,
treatment, or management of preterm labor hypertension, hypokalemia, malaise, metabolic acidosis,
muscle spasm, nervousness, palpitations, paradoxical
Dose: bronchospasm, prolonged Q-T interval on ECG,
Severe bronchospasm, by inhalation of nebulized solution, restlessness, tachycardia, urticarial, variable blood
as 1% solution, ADULT, 2.5–10 mg 2 to 4 times daily; pressure, and ventricular premature contractions.
CHILD ≥25 kg: 5 mg 2–4 times daily.
Drug Interactions:
Administration: Keep out of reach of children and pets. Monitor closely with:
Consult with pharmacist on discarding unused drugs. Decreases serum potassium when given with the following
drugs:
See Terbutaline under Other Gynecologicals – Salbutamol, Aspirin, Atenolol, Betaxolol, Bisoprolol,
Sympathomimetics, Labor Repressants in Chapter 5: Bumetanide, Ephedrine, Epinephrine, Esmolol,
Genito Urinary System and Sex Hormones for other Furosemide, Gentamicin, Hydrochlorothiazide,
information. Indapamide, Norepinephrine, Propranolol, Terbutaline

556
 RESPIRATORY SYSTEM

Decreases sedation: diabetes, hyperthyroidism, hypokalemia, and seizure

Salbutamol, Alprazolam, Aripiprazole, Caffeine, disorders.
Ephedrine, Epinephrine, Haloperidol, Hydroxyzine,
Norepinephrine, Risperidone, Terbutaline Adverse Drug Reactions:
Common: Nasopharyngitis
Increases QTc interval: Less Common: Skin rash, urinary tract infection, back pain,
Azithromycin, Fluoxetine, Goserelin, Levofloxacin, arthralgia, and bronchitis.
Ofloxacin, Quinine, Risperidone, Co-trimoxazole, Rare: Asthma-related death, constipation, cough,
Voriconazole depression of ST segment on ECG, diarrhea, dizziness,
fever, hypersensitivity reaction, hypokalemia, rhinorrhea,
Increases adrenergic effects of Formoterol: and upper respiratory tract infection.
Ephedrine, Epinephrine, Norepinephrine, Olodaterol,
Terbutaline, Salbutamol Drug Interactions:
Monitor closely with:
Decreases effects of Formoterol: Increases QTc interval:
Atenolol, Betaxolol, Bisoprolol, Carvedilol, Esmolol, Alfuzosin, Amiodarone, Artemether/Lumefantrine,
Metoprolol, Propranolol. Azithromycin, Chlorpromazine, Ciprofloxacin,
Clarithromycin, Erythromycin, Escitalopram, Fluconazole,
Avoid concomitant use with: Fluoxetine, Fluphenazine, Haloperidol, Levofloxacin,
Increases QTc interval: Moxifloxacin, Octreotide, Ofloxacin, Quetiapine, Quinine,
Amiodarone, Artemether/Lumefantrine, Risperidone, Tacrolimus, Voriconazole
Chlorpromazine, Clarithromycin, Epinephrine,
Erythromycin, Fluconazole, Fluphenazine, Haloperidol, Decreases serum potassium when given with the following
Ketoconazole, Moxifloxacin, Octreotide, Ondansetron drugs:
Betamethasone, Bumetanide, Dexamethasone,
Increases effect of Formoterol: Linezolid Furosemide, Hydrochlorothiazide, Hydrocortisone,
Prednisone
Administration: Remove capsule from foil blister
immediately before use. Capsules must not be Increases adrenergic effects:
swallowed whole; must only use the aerolizer inhaler. Dobutamine, Dopamine, Ephedrine, Epinephrine,
Formoterol, Indacaterol, Norepinephrine, Phenylephrine,
Pregnancy Category: C Terbutaline.

ATC Code: R03AC13 Antagonizes the effects of Olodaterol:

R
Carvedilol, Propranolol

Administration: For oral inhalation only; administer at the

Rx OLODATEROL same time each day. Prime inhaler prior to initial use or
if not used >21 days by pointing inhaler towards ground
Inhalation: 2.5 mcg/puff solution for inhalation, inhaler and actuating until aerosol cloud is seen, then repeat 3
with 4 mL cartridge x 60 puffs (equivalent to 30 additional times before use. If not used for >3 days,
medicinal doses) actuate once before use.

Oladeterol is long acting beta2-receptor agonist. It induces Pregnancy Category: C

bronchodilation by relaxation of airway smooth muscle
cells. ATC Code: R03AC19

Indication: Long term maintenance treatment of airflow

obstruction in chronic obstructive pulmonary disease
(COPD).

Contraindication: Monotherapy in the treatment of asthma

Dose:
Chronic obstructive pulmonary disease, by oral inhalation,
ADULT, 2 inhalations once daily.

Dose Adjustment:
Renal and Hepatic impairment:
No adjustment necessary.

Precautions:
May cause asthma-related deaths, bronchospasm,
hypersensitivity reactions, serious effects/fatalities; use
in caution in patients with cardiovascular disease, COPD,

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 RESPIRATORY SYSTEM

COPD (not use for acute episodes of COPD);

Rx BUDESONIDE + FORMOTEROL Hypersensitivity reactions; immunosuppression (restrict
use in active TB); lower respiratory infections (monitor
Inhalation: patients closely); oral candidiasis; Serious effects or
DPI: fatalities; Vasculitis; cardiovascular disease; Renal
80 micrograms budesonide + 4.5 micrograms formoterol impairment; hepatic impairment (monitor closely due to
(as fumarate dihydrate) x 60 doses with appropriate hepatic metabolism of both agents); Hypokalemia;
accompanying dispenser Ocular disease (consider routine eye exams in chronic
160 micrograms budesonide + 4.5 micrograms users); Seizure disorders; Thyroid disease (changes in
formoterol (as fumarate dihydrate) x 60 doses with thyroid status may necessitate dose adjustments;
appropriate accompanying dispenser metabolic clearance of corticosteroids increases in
320 micrograms budesonide + 9 micrograms formoterol hyperthyroid patients and decreases in hypothyroid
(as fumarate) x 60 doses with appropriate accompanying ones); Children (titrate to lowest effective dose to
dispenser minimize the systemic effects; growth should be
MDI: routinely monitored); Pregnancy and lactation (refer to
80 micrograms budesonide + 4.5 micrograms formoterol individual agents).
(as fumarate dihydrate) x 120 doses and 120 doses with
appropriate accompanying dispenser Adverse Drug Reactions:
160 micrograms budesonide + 4.5 micrograms Common: Headache, dizziness, abdominal distress, oral
formoterol (as fumarate dihydrate) x 120 doses with candidiasis, vomiting, influenza, back pain, upper and
appropriate accompanying dispenser lower respiratory tract infection, pharyngolaryngeal pain,
sinusitis, bronchitis, nasal congestion
A combination product containing a corticosteroid and a Less Common: Agitation, anaphylaxis, angina pectoris,
long-acting beta2-adrenergic agonist. angioedema, anxiety, atrial arrhythmia, behavioral
changes, bronchospasm, bruise, cataract, cough,
Indications: Treatment of asthma in patients ≥12 years of decreased linear skeletal growth rate (children),
age where combination therapy is indicated; depression, dermatitis, extrasystoles, glaucoma,
maintenance treatment of airflow obstruction associated hypercorticoidism signs and symptoms, hyperglycemia,
with chronic obstructive pulmonary disease (COPD), hypersensitivity reaction, hypertension, hypokalemia,
including chronic bronchitis and emphysema hypotension, immunosuppression, increased intraocular
pressure, insomnia, muscle cramps, nausea,
Contraindications: As primary treatment of status nervousness, palpitations, pruritus, restlessness, skin
asthmaticus, acute episodes of asthma or COPD rash, tachycardia, throat irritation, tremor, urticaria,
ventricular arrhythmia, voice disorder
R

requiring intensive measures, and potentially worsening

or rapidly deteriorating asthma or COPD.
Drug Interactions:
Dose: Monitor closely with:
NOTE: Recommended starting dose combination is Enhances therapeutic effect of Budesonide + Formoterol:
determined according to asthma severity. Consider Atomoxetine (tachycardia; hypertensive effect),
higher dose combination if not adequately controlled on Cannabinoid [except Cannabidiol] (tachycardia),
the lower combination dose following 1–2 weeks of Tedizolid (tachycardia; hypertensive effect)
therapy.
Increases risk of adverse or toxic effects of Budesonide +
Asthma, by aerosol inhalation, ADULT, 2 inhalations Formoterol:
(80/4.5mcg or 160/4.5mcg) twice daily (maximum, 4 Amphotericin B (hypokalemic effec), Caffeine
inhalations daily). (hypokalemic effect), Inhalational Anesthetics
COPD, by aerosol inhalation, ADULT, 2 inhalations (arrhythmogenic effect), MAO Inhibitors, Other
(160mcg/4.5mcg) twice daily (maximum, 4 inhalations Sympathomimetics, Tricyclic Antidepressants
daily).
Increases risk of adverse or toxic effects of the following
Precautions: drugs:
Atosiban (pulmonary edema and/or dyspnea), Ceritinib
WARNING: Long-acting beta2-adrenergic agonists (LABAs) (hyperglycemic effect), Deferasirox (GI ulceration,
increase the risk of asthma-related death and asthma- irritation, or bleeding), Doxofylline, Loop Diuretics
related hospitalization in pediatric and adolescent (hypokalemic effect), Moderate Risk QTc-prolonging
patients. Use only in patients not adequately controlled Agents (QTc-prolonging effect), Theophylline Derivatives
on a long-term asthma control medication or if disease (hypokalemic effect), Thiazide Diuretics (hypokalemic
severity clearly warrants treatment with both an inhaled effect)
corticosteroid and a LABA. Once asthma control is
achieved and maintained, assess the patient at regular Reduces therapeutic effect of Budesonide + Formoterol:
intervals and step-down therapy if possible without loss Beta1 Blockers (bronchodilator effect), Betahistine
of asthma control, and maintain the patient on a long-
term asthma control medication. Avoid concomitant use with:
Enhances therapeutic effect of Budesonide + Formoterol:
Adrenal suppression; diabetes; Bone density; osteoporosis; Linezolid (hypertensive effect) [reduce initial doses
Bronchospasm; asthma (not for acute bronchospasm); Budesonide + Formoterol]

558
RESPIRATORY SYSTEM

Increases risk of adverse or toxic effects of Budesonide + Dose:

Formoterol: Asthma, by aerosol inhalation, ADULT and CHILD ≥12 years,
Mifepristone (QTc-prolonging effect), Other Long-acting initially 2 puffs twice daily, titrated to the lowest effective
Beta2 Agonists dose; may be increased by switching to next highest
strength combination, depending on patient’s response.
Increases risk of adverse or toxic effects of the following
drugs: Dose Adjustment: No information found
Highest Risk QTc-prolonging Agents (QTc-prolonging
effect), Loxapine Precautions:
Patient with active or quiescent pulmonary TB, untreated
Increases serum concentration of Budesonide: Telaprevir systemic infections, ocular herpes simplex, or with
fungal, viral or airway infections, thyrotoxicosis,
Reduces therapeutic effect of Budesonide + Formoterol: pheochromocytoma, diabetes mellitus, hypokalemia,
Beta Blockers, Nonselective (bronchodilator effect) cardiovascular disorders; hepatic impairment;
Pregnancy and lactation.
Reduces therapeutic effect of the following drugs:
Aldesleukin (antineoplastic effect), Hyaluronidase, Adverse Drug Reactions: Hypokalemia, paradoxical
Iobenguane I 123 bronchospasm, increased wheezing, shortness of
breath, QTc interval prolongation, insomnia, headache,
Administration: Prior to first use, “load” the inhaler by tremor, dizziness, abnormal dreams, agitation, asthenia,
turning the grip on the inhaler as far as it will move in 1 palpitations, ventricular extra-systoles, angina pectoris,
direction, then turning in the opposite direction as far as tachycardia, hypertension, peripheral edema, oral
it will go. The inhaler is “loaded” with a dose, indicated candidiasis or fungal infections, hoarseness, stomatitis,
by a “click”. Loading procedure should be done twice. It dry mouth, diarrhea, dyspepsia, nausea, asthma
does not need to be repeated with subsequent uses even exacerbation, dysphonia, throat irritation, sinusitis,
when not used regularly. hyperglycemia, increased blood lactate levels, decrease
BMD, cataract, glaucoma, rash, pruritus, contusion, skin
Place mouthpiece gently between teeth, closing lips atrophy, anaphylaxis reactions, arrhythmia (potentially
around inhaler. Inhale deeply and hold breath for 5–10 fatal), cardiac arrest (potentially fatal)
seconds. The amount of drug delivered is small, and the
individual will not sense the medication as it is inhaled. Drug Interactions:
Remove mouthpiece prior to exhalation. Do NOT breathe Avoid concomitant use with:
out through the mouthpiece. After use of the inhaler, Increases risk of adverse or toxic effects of Fluticasone +
rinse mouth or oropharynx with water and spit out rinse Formoterol:

R
solution. Alcohol (impaired cardiac tolerance)
Antihistamines e.g. Diphenhydramine (prolonged QTc-
Withdrawal and discontinuation of a corticosteroid interval)
should be done slowly and carefully. Use with caution Antipsyschotic Agents (prolonged QTc-interval)
when transferring from systemic to inhaled Digitalis Glycoside e.g. Digoxin (ventricular arrhythmias)
corticosteroids. Disopyramide (prolonged QTc-interval)
Halogenated Hydrocarbon Anesthetics (ventricular
Pregnancy Category: B arrhythmias)
L-dopa (impaired cardiac tolerance)
ATC Code: R03AK07 L-thyroxine (impaired cardiac tolerance)
MAO Inhibitors e.g. Phenelzine (prolonged QTc-interval)
Oxytocin (impaired cardiac tolerance)
Procainamide (prolonged QTc-interval)
Rx FLUTICASONE + FORMOTEROL Quinidine (prolonged QTc-interval)
Tricyclic Antidepressants (prolonged QTc-interval)
Inhalation:
MDI: Increases risk of adverse or toxic effects of the following
50 micrograms (as propionate) + 5 micrograms (as drugs:
fumarate) x 120 actuations Diuretics (hypokalemia)
125 micrograms (as propionate) + 5 micrograms (as Steroids (hypokalemia)
fumarate) x 120 actuations Xanthine Derivatives e.g. Theophylline (hypokalemia)
250 micrograms (as propionate) + 10 micrograms (as
fumarate) x 120 actuations Increases serum concentration of Fluticasone:
CYP3A4 Inhibitors e.g., Ketoconazole, HIV Protease
A combination product containing a corticosteroid with Inhibitors, Clarithromycin, Ketoconazole
glucocorticoid activity and a long-acting beta2-adrenergic
agonist. Reduces therapeutic effect of Fluticasone + Formoterol:
Beta Blockers e.g. Propranolol
Indication: Management of adult asthma
Administration: Rinse mouth thoroughly every after
Contraindication: acute asthma attack inhalation.

559
 RESPIRATORY SYSTEM

Avoid abrupt withdrawal. cataracts; Metabolic effects (be alert to eosinophilic

conditions, hypokalemia and hyperglycemia); Patients
Pregnancy Category: C with convulsive disorders, thyrotoxicosis, diabetes
mellitus and ketoacidosis.
ATC Code: R03AK11
Adverse Drug Reactions:
Common: Dizziness, dysphonia, headache, nausea,
palpitations, throat irritation, upper respiratory tract
Rx FLUTICASONE + SALMETEROL infection and inflammation, tremor, vomiting
Less Common: Agitation, hyperactivity in children,
Inhalation: hyperglycemia (high doses), insomnia, tachycardia
DPI: Rare: Allergic reactions (including urticaria, angioedema,
100 micrograms fluticasone (as propionate) + 50 anaphylaxis), hypokalemia, lactic acidosis, paradoxical
micrograms salmeterol (as xinafoate) x 28 doses and 60 bronchospasm
doses with appropriate accompanying dispenser
250 micrograms fluticasone (as propionate) + 50 Drug Interactions:
micrograms salmeterol (as xinafoate) x 28 doses and 60 Avoid concomitant use with:
doses with appropriate accompanying dispenser Enhances therapeutic effect of Fluticasone + Salmeterol:
500 micrograms fluticasone (as propionate) + 50 CYP450 3A4 Inhibitors e.g. Ritonavir (may cause
micrograms salmeterol (as xinafoate) x 28 doses and 60 systemic corticosteroid and cardiovascular effects)
doses with appropriate accompanying dispenser
Increases risk of adverse or toxic effects of Fluticasone +
MDI: Salmeterol:
50 micrograms fluticasone (as propionate) + 25 Corticosteroids (serious hypokalemia), Diuretics e.g.,
micrograms salmeterol (as xinafoate) x 120 actuations Furosemide, Hydrochlorothiazide (serious hypokalemia),
(with dose counter*) Drugs that increase blood glucose concentration e.g.,
125 micrograms fluticasone (as propionate) + 25 Glucocorticoids, Antipsychotics, Calcineurin Inhibitors
micrograms salmeterol (as xinafoate) x 120 actuations e.g., Tacrolimus, high-dose Thiazide Diuretics e.g.
(*) Hydrochlorothiazide, Somatropin (hyperglycemia), Drugs
250 micrograms fluticasone (as propionate) + 25 that reduce potassium concentration e.g., Amphotericin
micrograms salmeterol (as xinafoate) x 120 actuations B, Theophylline (serious hypokalemia)
(*)
Increases risk of adverse or toxic effects of the following
drugs:
R

A combination product containing an inhaled corticosteroid,

and a long-acting beta2-adrenoceptor agonist, which is Sympathomimetic Amines e.g., Ephedrine,
used for controlling the symptoms of asthma. Phenylephrine, Pseudoephedrine (sympathetic adverse
effects e.g., tremor, tachycardia, headache)
Indications: For asthma patients aged 4 years and older;
maintenance treatment of airflow obstruction, and Increases serum concentration of Fluticasone + Salmeterol:
reduction of exacerbations in patients with COPD CYP450 3A4 Inhibitors e.g. Ritonavir

NOTE: This should be used only if the asthma is deemed to Reduces therapeutic effect of Beta Blockers (may
be not well-controlled with a long-term asthma control precipitate asthma)
medicine (e.g., inhaled corticosteroids).
Administration: Should be administered twice daily every
Contraindications: As primary treatment of status day by the orally inhaled route only. After inhalation, the
asthmaticus, acute episodes of asthma or COPD patient should rinse the mouth with water and spit out
requiring intensive measures, and potentially worsening the water without swallowing.
or rapidly deteriorating asthma or COPD.
Pregnancy Category: C
Dose:
Treatment of asthma, by aerosol inhalation, ADULT and ATC Code: R03AK06
CHILD ≥12 years, 1 inhalation (100/50 or 250/50) twice
daily; start dose based on asthma severity; CHILD 4–11
years, 1 inhalation (100/50) twice daily.
Maintenance treatment of COPD, by aerosol inhalation,
Rx IPRATROPIUM + FENOTEROL
ADULT, 1 inhalation (250/50) twice daily.
Inhalation:
Precautions: MDI:
Deterioration of disease and acute episodes: do not initiate 20 micrograms ipratropium (as bromide) + 50
in acutely deteriorating asthma or to treat acute micrograms fenoterol (as hydrobromide) x 10 mL doses
symptoms; Do NOT combine LABAs because of risk of
overdose; Localized infections; Immunosuppression; A combination product containing an inhaled nonselective
Pneumonia; Cardiovascular and CNS disorders; competitive antimuscarinic agent, and a direct acting
Hypercorticolism and adrenal suppression; Decreased beta2 sympathomimetic agent. They collectively cause
bone mineral density; Growth effects; Glaucoma and

560
RESPIRATORY SYSTEM

bronchodilation and bronchial smooth muscle Reduces therapeutic effect of Ipratropium + Fenoterol:
relaxation. Beta Blockers (bronchodilator effect)

Indications: For acute asthma attacks; maintenance Administration: Rinse mouth every after inhalation.
treatment of airflow obstruction, and reduction of
exacerbations in patients with COPD; intermittent and Avoid contact with eyes.
long-term treatment of asthma and COPD
Pregnancy Category: C
Contraindications: Hypersensitivity to atropine or any of its
derivatives; Hypertrophic obstructive cardiomyopathy; ATC Code: R03AL01
tachyarrhythmia;

Dose:
Acute asthma attack, by aerosol inhalation, ADULT, 1 puff Rx IPRATROPIUM + SALBUTAMOL
for prompt relief, if there is no improvement after 5
minutes, 1 additional dose may be given; if there is no Inhalation:
relief after 2 administrations, further doses may be MDI:
required. 21 micrograms ipratropium (as bromide) + 120
Asthma and COPD, intermittent and long-term treatment, by micrograms salbutamol x 200 doses x 10 mL
aerosol inhalation, ADULT, 1 to 2 puffs, up to 3 times
daily (maximum, 8 puffs daily). Respiratory solution for nebulization:
500 micrograms ipratropium (as bromide anhydrous) +
Dose Adjustment: No information found 2.5 mg salbutamol (as base) x 2.5 mL (unit dose)

Precautions: A combination of a cholinergic antagonist and a short-

Cardiovascular disease; cystic fibrosis; diabetes mellitus; acting, beta2-adrenoceptor agonist, which is used for the
narrow-angle glaucoma; pheochromocytoma; prostatic treatment of chronic obstructive pulmonary diseases; in
hyperplasia or bladder-neck obstruction; which monotherapy is deemed to be insufficient.
hyperthyroidism; seizure disorder; Children; Lactation.
Indications: Treatment of COPD in patients who are
SKILLED TASKS. May cause dizziness, tremor and visual currently on a regular bronchodilator, who continue to
disturbances. Do NOT drive or operate machinery. have evidence of bronchospasm and require a second
bronchodilator
Adverse Drug Reactions:

R
Common and Less Common: Hypokalemia, atrial fibrillation, Contraindications: Tachyarrhythmias; hypertrophic
cardiac arrhythmia, ischemic heart disease, palpitations, obstructive cardiomyopathy; Hypersensitivity to atropine
QT prolongation, supraventricular tachycardia, or any of its derivatives
tachycardia, headache, nervousness, tremor, weakness,
dizziness, hypertension, palpitation, hot flushes, Dose:
hypotension, glossitis, xerostomia, nausea, stomatitis, Bronchospasm, by aerosol inhalation, ADULT, 1 inhalation
constipation, diarrhea, vomiting, throat irritation, cough, 4 times a day, should not exceed 6 inhalations in 24
pharyngitis, hoarseness, urinary retention, hours.
hyperglycemia, muscle cramps, myalgia, visual Treatment of acute attacks, by inhalation of nebulized
accommodation disturbance, eye pain, increased solution using a suitable nebulizer or an intermittent
intraocular pressure, mydriasis, acute angle-closure positive pressure ventilator, ADULT, 1 unit-dose vial; 2
glaucoma, diaphoresis, paradoxical bronchospasm unit-dose vials may be required for severe cases, which
(potentially fatal) have not been relieved by 1 unit-dose vial; consult the
Rare: Anaphylaxis (e.g., urticaria, angioedema, rash, physician immediately.
bronchospasm) Maintenance treatment of acute attacks, by inhalation of
nebulized solution using a suitable nebulizer or an
Drug Interactions: intermittent positive pressure ventilator, ADULT, 1 unit-
Avoid concomitant use with: dose vial 3–4 times daily.
Enhances therapeutic effect of Ipratropium + Fenoterol:
Βeta Agonists, Salbutamol (bronchodilator effect) NOTE: Do NOT administer unit-dose vial orally or
MAO Inhibitors e.g. Phenelzine parenterally. The content does not need to be diluted for
Tricyclic Antidepressants e.g. Amitryptilline nebulization.
Xanthine Derivatives e.g. Theophylline (bronchodilator
effect) Dose Adjustment:
Renal and Hepatic Impairment:
Increases risk of adverse or toxic effects of Ipratropium + For mild-to-moderate impairment, use with caution.
Fenoterol: For severe impairment, refer patient to a specialist.
Corticosteroids (hypokalemia)
Diuretics (hypokalemia) Precautions:
Halogenated Hydrocarbons e.g. Halothane Some preparations contain soya lecithin (do NOT use in
(cardiovascular effects) patients allergic to soya lecithin or related food products,
Xanthine Derivatives e.g. Theophylline (hypokalemia) such as soybean and peanut); Patients with

561
 RESPIRATORY SYSTEM

cardiovascular system disorders (use with caution due to Sympathomimetic Amines e.g., Ephedrine,
beta-adrenergic stimulation); urinary retention (use with Phenylephrine (sympathetic adverse effects e.g., tremor,
caution in patients with prostatic hyperplasia or bladder tachycardia, headache)
neck obstruction); paradoxical bronchospasm
(discontinue immediately and treat with alternative Reduces therapeutic effect of Ipratropium + Salbutamol:
therapy); Ocular effects (avoid spraying into the eyes; Anticholinesterases e.g. Neostigmine (anticholinergic
contact a physician if blurred vision, halos, or other visual effect), Beta Blockers e.g. Propranolol (may precipitate
disturbances occur); Carefully monitor patients with asthma)
narrow-angle glaucoma; Hypersensitivity reactions
(discontinue treatment); hyperthyroidism; diabetes Administration: Metered-dose inhalers require good hand-
mellitus; convulsive disorders; Children; (safety and breath coordination (unsuitable for use alone in children
efficacy have not been established). <8 years or for people with poor dexterity).
Pregnancy (restricted to those where the benefits clearly
outweigh the risk). The respiratory solution for nebulization should be
administered via a mouth piece. If this is not available, a
Adverse Drug Reactions: nebulizer mask should be used, and it should fit
Common: Back pain, bronchitis, cough, dryness of mouth, perfectly. Patients who may be predisposed to glaucoma
dyspepsia, dyspnea, headache, influenza-like symptoms, should be warned specifically to protect their eyes.
musculoskeletal pain, myalgia, nasopharyngitis, nausea,
pharyngitis, sinusitis, taste disturbance, throat irritation, Pregnancy Category: C
tremor, upper respiratory inflammation and infection,
urinary tract infection ATC Code: R03AL02
Less Common: Agitation, blurred vision, diarrhea, dizziness,
fatigue, hyperactivity in children, hyperglycemia (high
doses), insomnia, vomiting ADRENERGICS IN COMBINATION WITH
Rare: Acute closed-angle glaucoma, arrhythmias, asthenia, ANTICHOLINERGICS INCL. TRIPLE COMBINATIONS
atrial fibrillation, chest discomfort, constipation, dental WITH CORTICOSTERIODS
caries, dryness of skin, eye pain, hypersensitivity
reactions (including anaphylaxis, angioedema,
bronchospasm, rash, urticaria and oropharyngeal Rx INDACATEROL+ GLYCOPYRRONIUM
edema), hypokalemia, palpitations, paradoxical
bronchospasm, tachycardia, urinary retention, wheezing
Inhalation: 110 mcg Indacaterol + 50 mcg
Drug Interactions: Glycopyrronium inhalation powder in hard
R

Monitor closely with: capsules

Enhances therapeutic effect of Salbutamol on the vascular
system: Indacaterol is a long-acting beta 2 agonist while
MAO Inhibitors e.g. Phenelzine, Tricyclic Antidepressants glycopyronium is a long-acting muscarinic antagonist.
e.g. Amitryptilline
Indication: Long-term maintenance treatment of chronic
Increases risk of adverse or toxic effects (hypokalemia) of obstructive pulmonary disease (COPD).
Ipratropium + Salbutamol:
Corticosteroids e.g. Hydrocortisone, Diuretics e.g., Contraindications: Hypersensitivity to indacaterol,
Hydrochlorothiazide, Furosemide, Drugs reducing glycopyrrolate, or any component of the formulation;
Potassium Concentration e.g., Amphotericin B, monotherapy in patients with asthma.
Theophylline
Dose:
Avoid concomitant use with: Chronic obstructive pulmonary disease (COPD), by powder
Enhances therapeutic effect of Ipratropium + Salbutamol: inhalation, ADULT, one capsule (indacaterol 110
Anticholinergic Drugs mcg/glycopyrrolate 50 mcg) inhaled once daily
Other Drugs with Anticholinergic Effects (maximum: 1 capsule/day); CHILD, safety and efficacy
not established.
Increases risk of adverse or toxic effects of Ipratropium +
Salbutamol: Dose Adjustment:
Anticholinergic Drugs (central anticholinergic delirium), Renal and Hepatic impairment:
Drugs increasing Blood Glucose Concentration e.g., No dosage adjustment necessary; use with caution.
Glucocorticoids, Antipsychotics, Calcineurin Inhibitors,
high-dose Thiazide Diuretics, Somatropin Precautions:
(hyperglycemia) Asthma-related deaths (Indacaterol/glycopyrrolate is not
Other Drugs with Anticholinergic Effects (central indicated for the treatment of asthma);
anticholinergic delirium) CNS depression (Patient must be cautioned about
performing tasks which require mental alertness);
Increases risk of adverse or toxic effects of the following Hypersensitivity (Discontinue immediately if signs and
drugs: symptoms of an allergic reaction occur);
Cardiovascular disease (Use with caution in patients with
cardiovascular disease);

562
RESPIRATORY SYSTEM

Beta-agonists may cause elevation in blood pressure and OTHER DRUGS FOR OBSTRUCTIVE
heart rate; AIRWAY DISEASES, INHALANTS
Diabetes (aggravate preexisting diabetes and ketoacidosis
and increase serum glucose);
Severe hepatic function impairment; Rx BUDESONIDE
Hyperthyroidism;
Hypokalemia (decrease serum potassium);
Narrow angle glaucoma; Inhalation:
Prostatic hyperplasia/bladder neck obstruction (may DPI:
worsen urinary retention; 100 micrograms/dose x 200 doses with appropriate
Renal function impairment (Use with caution in patients with accompanying dispenser
severe renal impairment (GFR <30 mL/minute/1.73 m2) 200 micrograms/dose x 100 doses and 200 doses with
or end-stage renal disease (ESRD) on dialysis; monitor appropriate accompanying dispenser
closely);
Seizure disorders (CNS stimulation/excitation) Respiratory solution for nebulization:
250 micrograms/mL, 2 mL (unit dose)
Adverse Drug Reactions:
Less Common: Hypertension, headache, hyperglycemia, A corticosteroid with potent glucocorticoid activity and weak
diarrhea, gastroesophageal reflux disease, back pain, mineralocorticoid activity. It controls the rate of protein
nasopharyngitis, lower and upper respiratory tract synthesis, depresses the migration of
infection, pneumonia, rhinitis, and oropharyngeal pain. polymorphonuclear leukocytes, fibroblasts, and reverses
Rare: Atrial fibrillation, bladder outflow obstruction, chest capillary permeability and lysosomal stabilization at the
pain, dizziness, dyspepsia, fatigue, gastroenteritis, cellular level to prevent or control inflammation.
hypersensitivity reaction, insomnia, palpitations,
peripheral edema, pruritus, skin rash, tachycardia, and Indications: Maintenance and prophylactic treatment of
urinary retention. asthma; includes patients who require oral
corticosteroids and those who may benefit from systemic
Drug Interactions: dose reduction or elimination
Monitor closely with:
Increases toxicity of the following drugs: Contraindications: Primary treatment of status asthmaticus
Long Acting Beta2-Agonists e.g. Salbutamol, Systemic and acute episodes of asthma
Corticosteroids, Glucagon, Loop Diuretics e.g.
Furosemide, Opioid Analgesics, Potassium Chloride, NOTE: NOT for the relief of acute bronchospasm.
Potassium Citrate, QT-Prolonging Agents,

R
Sympathomimetics, Thiazide And Thiazide-Like Diuretics, Dose:
Tiotropium, Topiramate. NOTE: A low-dose inhaled corticosteroid (in addition to an
as-needed short acting beta 2­agonist) is the initial
Administration: For oral inhalation only; do not swallow preferred long-term control medication for children,
capsules. Administer at the same time each day. Do not adolescents, and adult patients with persistent asthma
remove capsules from blister until immediately before who are candidates for treatment according to a step-
use. Discard any capsules that are exposed to air and not wise treatment approach.
used immediately. Use the new inhaler device included
with each prescription. Asthma, by inhalation, ADULT, initially 360 micrograms
twice daily, some patients may be initiated at 180
Pregnancy Category: C micrograms twice daily (maximum, 720 micrograms
twice daily), may increase dose after 1–2 weeks of
ATC Code: R03AL04 therapy in patients who are not adequately controlled;
CHILD ≥6 years, initially 180 micrograms twice daily,
some patients may be initiated at 360 micrograms twice
daily (maximum: 360 micrograms twice daily), may
increase dose after 1–2 weeks of therapy in patients
who are not adequately controlled;
by nebulization, CHILD 12 months – 8 years, initially
0.25 mg daily;
If previously on bronchodilators alone, 0.5 mg daily
administered as a single dose or divided twice daily
(maximum daily dose, 0.5 mg);
If previously on inhaled corticosteroids, 0.5 mg daily
administered as a single dose or divided twice daily
(maximum daily dose, 1 mg);
If previously on oral corticosteroids, 1 mg/day
administered as a single dose or divided twice daily
(maximum daily dose, 1 mg).

NOTE: Titrate to lowest effective dose once patient is stable.

563
 RESPIRATORY SYSTEM

Conversion from oral systemic to orally inhaled

corticosteroid. Initiation of oral inhalation therapy should Dose:
begin in patients whose asthma is reasonably stabilized Asthma prophylaxis, by aerosol inhalation, ADULT, 100–
on oral corticosteroids (OCS). A gradual dose reduction 200 micrograms 1–2 times daily in mild asthma; up to
of OCS should begin ~7 to 10 days after starting inhaled 500–1,000 micrograms twice daily in severe cases;
therapy. CHILD 4–16 years, 50–100 micrograms twice daily,
increased to 200 micrograms twice daily, if necessary.
Administration: Severe chronic asthma, by inhalation of nebulized solution,
For dry powder inhalers (DPI): ADULT, 500–2,000 micrograms twice daily CHILD 4–16
Hold inhaler in upright position (mouthpiece up) to load years, 1,000 micrograms twice daily.
dose. Do NOT shake prior to use. Unit should be primed
prior to first use only. It will not need to be primed again, Dose Adjustment: No information found
even if not used for a long time. Place mouthpiece
between lips and inhale forcefully and deeply. Do NOT Precautions:
exhale through inhaler. Do NOT use a spacer. Dose Patient with active or latent TB; Fungal, bacterial or systemic
indicator does NOT move with every dose, usually only viral infection; Cataracts and/or glaucoma; Untreated
after 5 doses. Discard when dose indicator reads “0”. localized infection of the nasal mucosa; Untreated
Rinse mouth with water after each use to reduce cutaneous infection, rosacea, acne vulgaris, perioral
incidence of candidiasis. dermatitis, perianal or genital pruritus, pruritus without
inflammation; Hepatic impairment; Avoid abrupt
For respiratory solutions for nebulization: withdrawal when switching from systemic to oral or orally
Shake well before use. Use with jet nebulizer connected inhaled corticosteroid; Children; Pregnancy and
to an air compressor. Administer with mouthpiece or lactation.
facemask. Do NOT use ultrasonic nebulizer. Do NOT mix
with other medications in the nebulizer. Rinse mouth Adverse Drug Reactions:
following treatments to decrease risk of oral candidiasis. Common and Less Common: Eosinophilic conditions,
Wash face if face mask was used. adrenal insufficiency, growth retardation, Cushing's
syndrome, decreased bone density, cataract, glaucoma,
See Budesonide under Nasal Preparations – paradoxical bronchospasm (potentially fatal)
Decongestants and other nasal preparations for topical Rare: Psychological effects
use in 12: Respiratory System for other information.
Drug Interactions:
Pregnancy Category: B Increases serum concentration of Fluticasone:
CYP3A4 Inhibitors e.g. Ritonavir
R

ATC Code: R03BA02

Administration: Administer twice daily every day by the orally
inhaled route only. After inhalation, rinse the mouth with
water and spit out the water without swallowing.
OTC FLUTICASONE
Pregnancy Category: C
Inhalation:
Nasal Aqueous Solution: ATC Code: R03BA05
0.05%/dose (as propionate) x 120 doses

DPI:
50 micrograms/dose (as propionate) with appropriate
Rx IPRATROPIUM
accompanying dispenser
250 micrograms/dose (as propionate) with appropriate Inhalation:
accompanying dispenser MDI:
20 micrograms/dose (as bromide) x 200 doses
MDI:
50 micrograms/dose (as propionate) x 60 doses and Respiratory solution for nebulization:
120 doses 250 micrograms/mL (as bromide), 2 mL (unit dose)
125 micrograms/dose (as propionate) x 60 doses and
120 doses A selective, anticholinergic bronchodilator that is a
quaternary ammonium compound chemically related to
Respiratory solution for nebulization: atropine, and provides local, site-specific effect rather
250 micrograms/mL (as propionate), 2 mL (unit dose) than a systemic effect.

A glucocorticoid with a fluorocarbothioate ester linkage at Indication: Chronic asthma

the 17-carbon position. It has potent vasoconstrictive
and anti-inflammatory activity, but weak hypothalamic- Dose:
pituitary-adrenal (HPA) inhibitory effect when applied Adjunct in acute bronchospasm, by inhalation of nebulized
topically. solution, ADULT, 500 micrograms repeated as required;
CHILD 6–12 years, 250 micrograms (maximum, 1 mg
Indication: Prophylaxis of asthma

564
RESPIRATORY SYSTEM

daily); CHILD <6 years, 125–250 micrograms

(maximum, 1 mg daily). Rx TIOTROPIUM
Chronic asthma, by aerosol inhalation, ADULT, 20–40
micrograms, 3–4 times daily; CHILD 6–12 years, 20–40 Inhalation:
micrograms 3 times daily; CHILD <6 years, 20 DPI:
micrograms 3 times daily. 18 micrograms/dose (as bromide) with appropriate
accompanying dispenser
Dose Adjustment:
Renal and Hepatic Impairment: A competitively acetylcholine inhibitor that reversibly
For mild-to-moderate impairment, use with caution. inhibits its action at type 3 muscarinic (M3) receptors in
For severe impairment, refer patient to a specialist. bronchial smooth muscle causing bronchodilation.

Precautions: Indications: Maintenance treatment of bronchospasm

Prostatic hypertrophy; glaucoma (care needed to protect the associated with chronic obstructive pulmonary disease
patient's eyes from drug powder or nebulized drug); (COPD), including chronic bronchitis and emphysema;
myasthenia gravis; paradoxical bronchospasm (should reduction of COPD exacerbations
be distinguished from inadequate response); Medical
supervision is necessary for first dose of nebulized Contraindications: Hypersensitivity to atropine or its
solution; Elderly (they may find it difficult to use the MDI; derivatives
a spacer device may be useful to monitor urinary function
in elderly men with benign prostatic hypertrophy);
Pregnancy (inhaled ipratropium may be recommended Dose:
for use as additional therapy for severe asthma COPD, by aerosol inhalation, ADULT, 18 micrograms daily
exacerbations); breastfeeding (use with caution in via inhaler device at the same time each day.
nursing women).
NOTE: Must be used in combination with an inhaled
Adverse Drug Reactions: corticosteroid and a long-acting beta2-agonist.
Common: Back pain, bronchitis, COPD exacerbation, cough,
dry mouth, dyspepsia, dyspnea, headache, influenza-like Dose Adjustment:
symptoms, nausea, sinusitis, taste disturbance, throat Renal Impairment:
irritation, urinary tract infections In patients with CrCl ≤50 mL/minute, use with caution.
Less Common: Blurred vision, dizziness Monitor patient closely.
Rare: Acute closed-angle glaucoma, allergy (urticaria, rash,
angioedema, anaphylaxis), atrial fibrillation,

R
Precautions:
constipation, dental caries, dryness of skin, palpitations, Bronchospasm; CNS effects; Hypersensitivity reactions;
tachycardia, urinary retention Glaucoma; Prostatic hyperplasia or bladder neck
obstruction; renal impairment (monitor closely for
Drug Interactions: anticholinergic events); Elderly (renal clearance is
Avoid concomitant use with: decreased, and plasma concentrations are increased
Increases risk of adverse or toxic effects of Ipratropium: due to decreased renal function; monitor urinary
Analgesics, Opioids (constipation; urinary retention), function of men with benign prostatic hyperplasia);
Anticholinergic Drugs e.g. Atropine (central Pregnancy and lactation.
anticholinergic delirium)
Other Drugs with Anticholinergic Effects (central SKILLED TASKS. May impair the ability to perform certain
anticholinergic delirium) tasks, e.g., operating machinery or driving.

Increases serum concentration of Thiazide Diuretics Adverse Drug Reactions:

e.g. Hydrochlorothiazide Common: Chest pain, edema, angina pectoris (including
exacerbation), palpitations, headache, depression,
Administration: Dilute solution for nebulization to 2–3 mL insomnia, dizziness, paresthesia, voice disorder, skin
with sodium chloride 0.9%. rash, pruritus, hypercholesterolemia, hyperglycemia,
xerostomia, abdominal pain, dyspepsia, constipation,
NOTE: Do NOT reduce or stop inhaled corticosteroids even omitting, GERD, oropharyngeal candidiasis, stomatitis,
if the patient feels better after starting this drug. UTI, hypersensitivity reaction, infection, herpes zoster,
arthralgia, myalgia, arthritis, leg pain, skeletal pain,
Do NOT let the mist from the nebulizer get into the eyes cataract, upper respiratory tract infection, pharyngitis,
(close eyes or wear eye protection). sinusitis, rhinitis, epistaxis, cough, flu-like symptoms,
laryngitis
Pregnancy Category: B Less Common: Anaphylaxis, angioedema, application site
irritation (including glossitis, oral mucosa ulcer,
ATC Code: R03BB01 pharyngolaryngeal pain), atrial fibrillation, blurred vision,
bronchospasm, dehydration, dermal ulcer, dysphagia,
dysuria, gingivitis, glaucoma, glossitis, hoarseness,
increased intraocular pressure, intestinal obstruction
(including paralytic ileus), joint swelling, paradoxical
bronchospasm, skin infection, mydriasis (contact with

565
 RESPIRATORY SYSTEM

eyes), supraventricular tachycardia, tachycardia, throat ADRENERGICS FOR SYSTEMIC USE

irritation, urinary retention, urticaria, xeroderma

Drug Interactions: Rx SALBUTAMOL

Monitor closely with:
Enhances therapeutic effect of Tiotropium:
Oral: 2 mg/5 mL syrup (as sulfate), 60 mL
Mianserin (anticholinergic effect)
A short-acting, beta2-adrenergic agonist used in the
Enhances anticholinergic effect of the following drugs:
treatment or prevention of bronchospasm.
Abobotulinumtoxin-A, Onabotulinumtoxin-A,
Rimabotulinumtoxin-B
Indications: Prophylaxis and treatment of asthma;
bronchospasm in patients with reversible obstructive
Increases risk of adverse or toxic effects of the following
airway disease; prevention of exercise-induced
drugs:
bronchospasm
Analgesics, Opioid (constipation; urinary retention)
Mirabegron
Contraindications: Severe pre-eclampsia and eclampsia;
Topiramate
intrauterine infection; intrauterine fetal death; ante-
Ramosetron (constipation)
partum hemorrhage, placenta previa; cord compression;
threatened miscarriage; cardiac disease;
Reduces therapeutic effect of Tiotropium:
Acetylcholinesterase Inhibitors e.g. Neostigmine
Dose:
Reduces therapeutic effect of the following drugs:
Chronic asthma, by mouth, ADULT, 2–4 mg 3–4 times daily
Gastrointestinal Agents, Prokinetic
(maximum, 8 mg 3–4 times daily); CHILD 6–12 years, 2
Itopride
mg 3–4 times daily; CHILD 2–6 years, 1–2 mg 3–4 times
daily; CHILD <2 years, 100 micrograms/kg 4 times daily.
Avoid concomitant use with:
Enhances anticholinergic effect of Tiotropium:
Administration: Multi-dose solution for nebulization may
Aclidinium, Ipratropium, Other Anticholinergic Agents,
need dilution with 0.9% sodium chloride to obtain final
Pramlintide, Umeclidinium
volume for the nebulizer.
Enhances anticholinergic effect of Cimetropium
See Salbutamol under Drugs for obstructive airway
diseases – Adrenergics, Inhalants in Chapter 12:
Increases risk of adverse or toxic effects of the following
Respiratory System for other information.
drugs:
R

Eluxadoline (constipation), Glucagon (GI adverse

Pregnancy Category: C
effects), Loxapine, Potassium Chloride (ulcerogenic
effect)
ATC Code: R03CC02
Reduces therapeutic effect of the following drugs:
Levosulpiride, Secretin
Rx TERBUTALINE
Administration: Use only with appropriate accompanying
dispenser.
Oral: 5 mg and 1.5 mg/5 mL syrup (as sulfate), 60 mL
Prior to first use, insert cartridge into the inhaler and
prime the unit by actuating the inhaler toward the ground A direct acting sympathomimetic drug with beta-adrenergic
until an aerosol cloud is visible. Repeat 3 more times. activity, selectively on beta2 receptors.
The unit is then primed and ready for use.
Indications: Bronchodilator in reversible airway obstruction
If not used for more than 3 days, actuate the inhaler once and bronchial asthma
to prepare the inhaler for use.
Contraindications: Acute or chronic use in the prevention,
If not used for more than 21 days, actuate the inhaler treatment, or management of preterm labor
until an aerosol cloud is visible and then repeat the
process 3 more times. Dose:
Asthma or bronchospasm, by mouth, ADULT and
Pregnancy Category: C ADOLESCENT >15 years, 5 mg per dose every 6 hours 3
times daily; if side effects occur, reduce dose to 2.5 mg
ATC Code: R03BB04 every 6 hours (maximum, 15 mg in 24 hours);
ADOLESCENT 12–15 years, 2.5 mg every 6 hours 3
times daily (maximum, 7.5 mg in 24 hours); CHILD <12
years, initially 0.05 mg/kg per dose 3 times daily,
increased gradually as required (maximum, 0.15 mg/kg
per dose 3–4 times daily or a total of 5 mg per 24 hours.

566
RESPIRATORY SYSTEM

Administration: Give drug around-the-clock to promote (nonsmokers), 0.63 mg/kg per hour (equivalent to
decrease in variation in peak and trough serum levels. theophylline 0.5 mg/kg per hour), (maximum daily dose,
1139 mg aminophylline; equivalent to 900 mg
See Terbutaline under Other Gynecologicals – theophylline) unless serum levels indicate need for larger
Sympathomimetics, Labor Repressants in Chapter 5: dose; CHILD 12–16 years, (cigarette or marijuana
Genito Urinary System and Sex Hormones for other smokers), 0.89 mg/kg per hour (equivalent to
information. theophylline 0.7 mg/kg per hour); CHILD 9–12 years:
0.89 mg/kg per hour (equivalent to theophylline 0.7
Pregnancy Category: C mg/kg per hour); CHILD 1–9 years, 1.01 mg/kg per hour
(equivalent to theophylline 0.8 mg/kg per hour); INFANT
ATC Code: R03CC03 6–52 weeks, calculate dose as follows:

Dose (mg/kg/hour) = [(0.008 x age in weeks) + 0.21]

OTHER SYSTEMIC DRUGS FOR divided by 0.79
OBSTRUCTIVE AIRWAY DISEASES
Equivalent to theophylline:
Dose (mg/kg/hour) = [(0.008 x age in weeks) + 0.21])
AMINOPHYLLINE (THEOPHYLLINE
Rx
ETHYLENEDIAMINE) NOTE: To achieve a target theophylline concentration of 10
micrograms/mL unless otherwise noted. Lower initial
Inj.: 25 mg/mL, 10 mL ampule (IV) doses may be required in patients with reduced
theophylline clearance. Dosage should be adjusted
A xanthine derivative that blocks phosphodiesterase-3 (PDE according to serum level measurements during the first
III). It is a complex of theophylline and ethylenediamine 12- to 24-hour period.
that promotes catecholamine stimulation of lipolysis,
glycogenolysis, and gluconeogenesis. It induces the Chronic conditions, by IV injection, ADULT 16–60 years
release of epinephrine from adrenal medulla cells, which without risk factors for impaired theophylline clearance,
results in bronchodilation, diuresis, CNS and cardiac 380 mg daily (equivalent to theophylline 300 mg daily) in
stimulation, and gastric acid secretion. divided doses every 6–8 hours for 3 days, increase to
507 mg daily (equivalent to theophylline 400 mg daily) in
Indications: Treatment of symptoms and reversible airway divided doses every 6–8 hours for 3 days (maintenance
obstruction due to asthma or other chronic lung diseases dose, 760 mg daily; equivalent to theophylline 600 mg
(e.g., emphysema, chronic bronchitis) daily) in divided doses every 6–8 hours.

R
Dose: NOTE: Increase dose only if tolerated. Consider lowering
NOTE: Doses should be individualized based on peak serum dose or using a slower titration if caffeine-like adverse
concentrations and should be based on ideal body events occur. Smaller doses given more frequently may
weight. Theophylline dose is 80% of aminophylline dose. be used in patients with a more rapid metabolism to
prevent breakthrough symptoms, which could occur due
The treatment of asthma exacerbations with to low trough concentration prior to the next dose.
aminophylline is not supported or recommended by
current clinical practice guidelines. In patients with risk factors for impaired theophylline
clearance and patients in whom monitoring serum
Acute symptoms, by IV injection, ADULT (not currently theophylline levels is not feasible, do NOT exceed a dose
receiving aminophylline or theophylline), 5.7 mg/kg of aminophylline 507 mg daily (equivalent to
(equivalent to theophylline 4.6 mg/kg). theophylline 400 mg daily).
Acute symptoms, by IV injection, ADULT (currently receiving
aminophylline or theophylline), a loading dose is not Dose Adjustment:
recommended without first obtaining a serum Geriatric:
theophylline concentration in patients who have received Do not exceed a dose of aminophylline 507 mg daily
aminophylline or theophylline within the past 24 hours; (equivalent to theophylline 400 mg daily).
calculate loading dose as follows:
Renal Impairment:
Dose = (desired serum theophylline concentration ­ In infants 1–3 months, consider dose reduction and
measured serum theophylline concentration) (Vd) frequent monitoring of serum theophylline
concentrations.
Acute symptoms, maintenance, by IV injection, ADULT 16–
60 years (otherwise healthy, nonsmokers), 0.51 mg/kg Hepatic Impairment:
per hour (equivalent to theophylline 0.4 mg/kg per hour), Initiate therapy at 0.25 mg/kg per hour (equivalent to
(maximum daily dose, 1139 mg aminophylline theophylline 0.2 mg/kg per hour). Maximum daily dose,
(equivalent to 900 mg theophylline) unless serum levels 507 mg aminophylline daily (equivalent to 400 mg
indicate need for larger dose; ADULT >60 years, 0.38 theophylline day) unless serum concentrations indicate
mg/kg per hour (equivalent to theophylline 0.3 mg/kg need for larger dose.
per hour), (maximum daily dose, 507 mg aminophylline Use with caution and monitor serum theophylline
(equivalent to 400 mg theophylline) unless serum levels concentrations frequently.
indicate need for larger dose; ADOLESCENT 12–16 years

567
 RESPIRATORY SYSTEM

Cardiac Decompensation, cor pulmonale, hepatic Phenytoin

dysfunction, sepsis with multiorgan failure, shock:
0.25 mg/kg per hour (equivalent to theophylline 0.2 mg/kg Decreases serum concentration of the following drugs:
per hour), (maximum daily dose, 507 mg aminophylline Carbamazepine, Fosphenytoin, Phenytoin
(equivalent to 400 mg theophylline) unless serum levels
indicate need for larger dose Enhances therapeutic effect of Aminophylline:
Linezolid (hypertensive effect)
After serum theophylline measurements:
Within normal limits, asthma: 5–15 micrograms/mL, Increases risk of adverse or toxic effects of the following
maintain dosage if tolerated. Recheck serum drugs:
theophylline concentration at 24-hour intervals. Finer Doxofylline, Pancuronium, Quinolone Antibiotics e.g.,
adjustments in dosage may be needed for some Ciprofloxacin, Enoxacin [except Gemifloxacin,
patients. If levels ≥15 micrograms/mL, consider 10% Levofloxacin, Lomefloxacin, Moxifloxacin, Nalidixic Acid,
dose reduction to improve safety margin. Sparfloxacin] (augments seizure-producing potential),
20–24.9 micrograms/mL, decrease dose by ~25%. [see Riociguat (hypotensive effect)
NOTE].
25–30 micrograms/mL, stop infusion for 12 hours Increases serum concentration of Aminophylline:
(children) or 24 hours (adults) and decrease subsequent Cimetidine, Conivaptan, CYP1A2 Inhibitors, CYP3A4
doses by ~25%. [see NOTE]. Inhibitors, Fluvoxamine, Fusidic Acid (Systemic),
>30 micrograms/mL, stop dosing and treat overdose. If Idelalisib
resumed, decrease subsequent doses by 50%. [see Macrolide Antibiotics [except Azithromycin, Fidaxomicin,
NOTE]. Spiramycin, Telithromycin]
<9.9 micrograms/mL, if tolerated, but symptoms remain, Mexiletine, Mifepristone, Quinolone Antibiotics e.g.
increase dose by ~25%. [see NOTE]. Ciprofloxacin [except Gemifloxacin, Levofloxacin,
Lomefloxacin, Moxifloxacin, Nalidixic Acid, Sparfloxacin]
NOTE: Recheck serum theophylline levels after 12 hours Stiripentol, Thiabendazole, Vemurafenib
(children) or 24 hours (adults).
Precautions: Increases serum concentration of the following drugs:
Extravasation (ensure proper catheter or needle position Tizanidine [if concomitant use cannot be avoided, initiate
prior to and during infusion; avoid extravasation); tizanidine at 2 mg and increase in 2–4 mg increments
Theophylline toxicity (if signs and symptoms develop, based on patient response]
e.g., persistent, repetitive vomiting, measure serum level
and withhold subsequent doses); Cardiovascular Reduces therapeutic effect of Aminophylline:
disease, hyperthyroidism, peptic ulcer disease, and Nonselective Beta Blockers (bronchodilator effect)
R

seizure disorder; Elderly (use lower initial doses due to

slower hepatic clearance; monitor closely for response Reduces therapeutic effect of the following drugs:
and adverse reactions greater risk for toxicity due to Adenosine
concomitant disease and drug use). Benzodiazepines e.g. Diazepam, Iobenguane I 123
Pancuronium (neuromuscular-blocking effect)
Adverse Drug Reactions: Flutter, tachycardia, behavior Regadenoson (vasodilatory effect)
alterations (children), headache, insomnia, irritability,
restlessness, seizures, allergic skin reactions, exfoliative TEST INTERACTION. May increase plasma glucose, uric acid,
dermatitis, diarrhea, nausea, vomiting, tremor, diuresis free fatty acids, total cholesterol, HDL, HDL/LDL ratio,
(transient) and urinary free cortisol excretion. May decrease
triiodothyronine.
Drug Interactions:
Monitor closely with: Administration: For IV use only. IM use is NOT
Enhances therapeutic effect of Aminophylline: recommended). Loading doses should be administered
Atomoxetine (hypertensive and tachycardic effect), over 30 minutes. Infusion rate should not exceed 21
Cannabinoid-containing Products (tachycardic effect), mg/hour (equivalent to theophylline 17 mg/hour) in
Tedizolid (hypertensive and tachycardic effect) patients with cor pulmonale, cardiac decompensation,
liver dysfunction, patients >60 years, or patients taking
Increases risk of adverse or toxic effects of the following medications which reduce theophylline clearance.
drugs:
Formoterol (hypokalemic effect), Indacaterol Vesicant. Ensure proper needle or catheter placement
(hypokalemic effect), Olodaterol (hypokalemic effect), prior to and during IV infusion. Avoid extravasation.
Other Sympathomimetics
EXTRAVASATION MANAGEMENT: If extravasation occurs,
Reduces therapeutic effect of Aminophylline: stop infusion immediately and disconnect. Leave needle
Beta Blockers e.g. Propranolol (bronchodilator effect) or cannula in place. gently aspirate extravasated
solution. Do NOT flush the line. Initiate hyaluronidase
Avoid concomitant use with: antidote. Remove needle or cannula; apply dry cold
Decreases serum concentration of Aminophylline: compresses and elevate extremity.
Carbamazepine, CYP1A2 Inducers (Strong), CYP3A4
Inducers (Strong) Pregnancy Category: C
Dabrafenib, Fosphenytoin, Mitotane

568
RESPIRATORY SYSTEM

ATC Code: R03DA05

Rx MONTELUKAST

Oral: 4 mg granules (as sodium salt), sachet

Rx EPINEPHRINE (ADRENALINE) 4 mg and 5 mg chewable tablet (as sodium salt)
10 mg tablet (as sodium salt)
Inj.: 1 mg/mL (as hydrochloride), 1 mL ampule (IM, SC)
0.3 mg auto-injector (IM-preload), 0.3 mL preloaded A selective, leukotriene-receptor inhibitor, which
injection pen. [May be used in cases of serious and antagonizes airway smooth muscle contraction and
fatal anaphylaxis] inflammation caused by leukotrienes.

A direct-acting, mixed alpha- and beta-adrenoceptor Indications: Prophylaxis and treatment of asthma (as an
agonist; a sympathomimetic catecholamine, which is a adjunctive therapy in combination with a corticosteroid);
potent cardiac stimulant vasoconstrictor and symptomatic relief of seasonal allergic rhinitis in patients
bronchodilator. with asthma

NOTE: Vasodilator at low dose (beta2 receptors); but, NOTE: There is a place for montelukast in children aged 2–
vasoconstrictor at high dose (alpha receptors). 5 years with intermittent viral-induced asthma, where
leukotrienes play a minor role.
Indications: For anaphylactic shock; may be used in cases
of serious and fatal anaphylaxis; severe angioedema Dose:
with laryngeal swelling or airway obstruction Prophylaxis of asthma, by mouth, ADULT and CHILD >15
years, 10 mg once daily in the evening; CHILD 6–15
Contraindications: Pheochromocytoma; use in local years, 5 mg chewable tablet once daily in the evening;
anesthesia of fingers, toes, ears, nose or genitalia; CHILD 2–6 years, 4 mg chewable tablet once daily in the
shock; organic heart disease or cardiac dilatation; evening; INFANT 6–23 months, 1 packet (4 mg oral
closed-angle glaucoma; labor granules).
NOTE: There are no absolute contraindications to the use of Seasonal allergic rhinitis, by mouth, ADULT and CHILD >15
epinephrine in life-threatening allergic reactions. years, 10 mg daily in the evening.

Dose: Dose Adjustment:

Anaphylaxis, by IM or SC injection of 1:1,000 epinephrine Renal and Hepatic Impairment:
injection, ADULT and ADOLESCENT, 500 micrograms For severe impairment, refer patient to a specialist.

R
(0.5 mL); CHILD 6-12 years, 250 micrograms (0.25 mL); Precautions:
CHILD 6 months-6 years, 120 micrograms (0.12 mL);
INFANT <6 months, 50 micrograms (0.05 mL); by SC WARNING: Montelukast has no role in the treatment of
injection of 1:1,000 epinephrine injection, CHILD, 10 status asthmaticus. It cannot be substituted for
micrograms/kg (0.01 mL/kg) bodyweight, repeat if inhaled or oral corticosteroids especially for
necessary at intervals of 20 minutes to 4 hours persistent asthma. It should not be used as
depending on the response of the patient and the monotherapy for exercise-induced bronchospasm
severity of the condition (maximum single dose, 500
micrograms). Eosinophilia and vasculitis; neuropsychiatric events;
phenylketonuria; Patients are instructed to have
Administration: Epinephrine is best administered as an SC appropriate rescue treatment available while on
or IM injection into the anterolateral aspect of the middle montelukast; when this is being given with systemic
third of the thigh for anaphylaxis, and by IV injection for corticosteroids, appropriate tapering of corticosteroids is
cardiac arrest or emergency situations. needed under medical supervision; Children; Pregnancy
(may be administered at normal dose in women who
NOTE: Do NOT mix with alkaline solutions. Discard after 24 have shown a significant improvement in asthma, which
hours or if solution is discolored or contains precipitate. is not achievable with other drugs before becoming
pregnant); breastfeeding (avoid use unless essential).
See Epinephrine (Adrenaline) under Cardiac Therapy –
Cardiac Stimulants, excluding Cardiac Glycosides in NOTE: Rarely, the reduction of a systemic corticosteroid
Chapter 3: Cardiovascular System for other information. while on another leukotriene receptor antagonist has
been reported to manifest with eosinophilia, vasculitic
Pregnancy Category: C rash, worsening pulmonary symptoms, cardiac
complications, or neuropathy, sometimes presenting as
ATC Code: C01CA24 Churg-Strauss syndrome.

Adverse Drug Reactions:

Common: Abdominal pain and discomfort, cough, diarrhea,
fatigue, fever, headache, hyperkinesia, otitis media,
pharyngitis, rash, sinusitis, thirst, upper respiratory
infection, weakness
Less Common: Abnormal dreams, arthralgia, bruising,
dizziness, dry mouth, dyspepsia, edema, epistaxis,

569
 RESPIRATORY SYSTEM

hypesthesia, malaise, myalgia, paresthesia, pruritus, Chronic conditions, treatment, by mouth, CHILD ≥1 year and
seizures, sleep disturbances, sleepwalking <45 kg, initially 10 – 14 mg/kg once daily (maximum,
Rare: Allergy (including urticaria, angioedema, anaphylaxis), 300 mg daily); maintenance dose, up to 20 mg/kg daily
bleeding, Churg-Strauss syndrome, disorientation, (maximum, 600 mg daily).
eosinophilia, erythema multiforme, erythema nodosum,
hallucinations, hepatic disorders, mood or behavioral NOTE: Increase dose only if tolerated. Consider lowering
changes e.g., anxiety, depression and aggression; dose or using a slower titration if caffeine-like adverse
neuropsychiatric effects e.g., nightmares and events occur. Smaller doses given more frequently may
hallucinations; palpitations, suicidal thoughts and be used in patients with a more rapid metabolism to
behavior, tremor prevent breakthrough symptoms, which could occur due
to low trough concentration prior to the next dose.
Drug Interactions:
Monitor closely with: In patients with risk factors for impaired theophylline
Reduces therapeutic effect of Montelukast by decreasing clearance and patients in whom monitoring serum
AUC: theophylline levels is not feasible, do NOT exceed a dose
CYP450 Inducers e.g., Phenobarbital, Rifampicin of theophylline 400 mg daily.

Administration: Take the drug at only one dose daily in the Dose Adjustment:
evening. Geriatric:
Use lower initial doses and monitor closely for response and
Administer the oral granules (sachet) within 15 minutes adverse reactions.
after opening the packet (with or without mixing with
food). Renal Impairment:
In infants 1–3 months, consider dose reduction and
NOTE: Do NOT use this drug to relieve symptoms of an frequent monitoring of serum theophylline
asthma attack. Use a short-acting reliever. concentrations.

Pregnancy Category: B Hepatic Impairment:

In patients with decreased hepatic function (e.g., cirrhosis,
ATC Code: R03DC03 acute hepatitis, cholestasis), dose reduction and
frequent monitoring of serum theophylline concentration
are required (maximum daily dose, 400 mg).
Rx THEOPHYLLINE (ANHYDROUS) After serum theophylline measurements:
R

Within normal limits, asthma:

Oral: 150 mg and 200 mg tablet CHILD, 5–10 micrograms/mL, maintain dose if tolerated.
200 mg MR tablet Recheck serum theophylline concentration at 6- to 12-
25 mg/5mL (26.7 mg/5 mL) syrup, 100 mL month intervals. Finer adjustments in dosage may be
needed for some patients. If levels ≥15 micrograms/mL,
A xanthine derivative that blocks phosphodiesterase-3 (PDE consider 10% dose reduction to improve safety margin.
III) promoting catecholamine stimulation of lipolysis,
glycogenolysis, and gluconeogenesis and induces NOTE: Recheck serum theophylline levels after 3 days in
release of epinephrine from adrenal medulla cells. It children.
causes bronchodilation, diuresis, CNS and cardiac
stimulation, and gastric acid secretion. Precautions:
CNS effects; Theophylline toxicity (if signs and symptoms
Indications: Treatment of symptoms and reversible airway develop, e.g., persistent, repetitive vomiting, measure
obstruction due to chronic asthma, or other chronic lung serum level and withhold subsequent doses);
diseases Cardiovascular disease, hyperthyroidism, peptic ulcer
disease, and seizure disorder; Elderly (use lower initial
Contraindications: Allergy to corn-related products doses due to slower hepatic clearance; monitor closely
for response and adverse reactions; greater risk for
Dose: toxicity due to concomitant disease and drug use).
NOTE: For every 1 mg/kg theophylline given, blood levels will
rise 2 micrograms/mL. Adverse Drug Reactions: Flutter, tachycardia, headache,
hyperactivity (children), insomnia, irritability,
Asthma exacerbation, by mouth, ADULT (no theophylline restlessness, seizures, status epilepticus (non-
received within the previous 24 hours), 5 mg/kg. convulsive), hypercalcemia (with concomitant
Asthma exacerbation, by mouth, ADULT (theophylline was hyperthyroid disease), nausea, reflux or ulcer
administered in the previous 24 hours), calculate loading aggravation, vomiting, difficulty urinating (elderly males
dose as follows: with prostatism), tremor, diuresis (transient)

Dose = (desired serum theophylline concentration ­

measured serum theophylline concentration) (Vd)

570
RESPIRATORY SYSTEM

Drug Interactions: Adenosine

Monitor closely with: Benzodiazepines, Iobenguane I 123, Regadenoson
Enhances therapeutic effect of Theophylline: (vasodilatory effect)
Atomoxetine (hypertensive and tachycardic effect), Pancuronium (neuromuscular-blocking effect)
Cannabinoid-containing Products [except Cannabidiol]
(tachycardic effect) TEST INTERACTION. May increase plasma glucose, uric acid,
Tedizolid (hypertensive and tachycardic effect) free fatty acids, total cholesterol, HDL, HDL/LDL ratio,
and urinary free cortisol excretion. May decrease
Increases risk of adverse or toxic effects of Theophylline: triiodothyronine.
Other Sympathomimetics
Administration: For IV use only. IM use is NOT
Increases risk of adverse or toxic effects of the following recommended). Loading doses should be administered
drugs: over 30 minutes. Infusion rate should not exceed 21
Formoterol (hypokalemic effect) mg/hour (equivalent to theophylline 17 mg/hour) in
Indacaterol (hypokalemic effect) patients with cor pulmonale, cardiac decompensation,
Olodaterol (hypokalemic effect) liver dysfunction, patients >60 years, or patients taking
medications which reduce theophylline clearance.
Reduces therapeutic effect of Theophylline:
Beta Blockers (bronchodilator effect) Pregnancy Category: C

Avoid concomitant use with: ATC Code: R03DA04

Decreases serum concentration of Theophylline:
Carbamazepine
CYP1A2 Inducers
CYP3A4 Inducers COUGH AND COLD PREPARATIONS
Dabrafenib, Fosphenytoin, Mitotane, Phenytoin

Decreases serum concentration of the following drugs: COUGH SUPPRESSANTS,

Carbamazepine, Fosphenytoin EXCLUDING COMBINATIONS
WITH EXPECTORANTS
Enhances therapeutic effect of Theophylline:
Linezolid (hypertensive effect)
OTC BUTAMIRATE
Increases risk of adverse or toxic effects of the following

R
drugs: Oral: 50 mg MR tablet (as citrate)
Doxofylline, Pancuronium, Quinolone Antibiotics e.g., 7.5 mg/5 mL syrup (as citrate), 120 mL
Ciprofloxacin, Enoxacin [except Gemifloxacin,
Levofloxacin, Lomefloxacin, Moxifloxacin, Nalidixic Acid, A centrally-acting antitussive, which is neither chemically
Sparfloxacin] (augments seizure-producing potential), nor pharmacologically related to the opioids, intended as
Riociguat (hypotensive effect) a cough suppressant.
Increases serum concentration of Theophylline: Indications: Chronic, non-productive, irritative cough;
Cimetidine, Conivaptan symptomatic treatment of cough of various origins
CYP1A2 Inhibitors
CYP3A4 Inhibitors Dose:
Fluvoxamine, Fusidic Acid (Systemic) Cough, by mouth, ADULT and CHILD >12 years, 10 to 20 mg
Idelalisib, Macrolide Antibiotics [except Azithromycin, every 4 hours or 30 mg every 6–8 hours; INFANT and
Fidaxomicin, Spiramycin, Telithromycin], Mexiletine, CHILD 6–12 years, 1 mg/kg daily divide every 6–8 hours;
Mifepristone Alternatively, ADULT, 1 tablet 2–3 times daily; ADULT and
Quinolone Antibiotics e.g., Ciprofloxacin, Enoxacin CHILD >9 years, 1–2 tablespoon 3 times daily; CHILD 1–
[except Gemifloxacin, Levofloxacin, Lomefloxacin, 9 years, 1–2 teaspoon syrup 2–3 times daily.
Moxifloxacin, Nalidixic Acid, Sparfloxacin], Stiripentol
Thiabendazole, Vemurafenib, Zileuton [if concomitant Precautions:
use cannot be avoided, reduce theophylline dose by 50% Pregnancy (use in the first trimester is not recommended;
upon initiation of zileuton] during the rest of pregnancy, use only if drug therapy is
essential).
Increases serum concentration of Tizanidine [if concomitant
use cannot be avoided, initiate tizanidine at 2 mg and SKILLED TASKS. May impair ability to drive or operate
increase in 2–4 mg increments based on patient machinery.
response] May cause somnolence. Take caution while driving or
performing other tasks which require alertness.
Reduces therapeutic effect of Theophylline:
Nonselective Beta-blockers e.g. Propranolol Adverse Drug Reactions:
(bronchodilator effect) Rare: Diarrhea, dizziness, GI discomfort, nausea, skin rash,
somnolence, urticaria
Reduces therapeutic effect of the following drugs:

571
 RESPIRATORY SYSTEM

Drug Interactions: Increases risk of adverse or toxic effects of

Avoid concomitant use with: Dextromethorphan:
Incompatible with the following products: Antiemetics, 5-HT3 Antagonists (serotonin syndrome)
Penicillins, Phenobarbital, Salicylates, Tetracyclines
Increases risk of adverse or toxic effects of the following
Increases risk of adverse or toxic effects of Butamirate: drugs:
Expectorants (bronchospasm; airways infection) Antipsychotic Agents (neuroleptic malignant syndrome;
serotonin syndrome)
Administration: May be taken with or without food. Memantine, Metoclopramide (neuroleptic malignant
syndrome; serotonin syndrome), Parecoxib,
Pregnancy Category: C Peginterferon Alfa-2b

ATC Code: R05DB13 Avoid concomitant use with:

Enhances therapeutic effect of Dextromethorphan:
MAO Inhibitors e.g. Phenelzine (serotonergic effect),
Selective Serotonin Reuptake Inhibitors [except
OTC DEXTROMETHORPHAN Fluvoxamine] (serotonergic effect)

Oral: 10 mg tablet (as hydrobromide) Increases risk of adverse or toxic effects of

Dextromethorphan:
An N-methyl-D-aspartate receptor antagonist that Dapoxetine, MAO Inhibitors e.g. Phenelzine (serotonin
decreases the sensitivity of cough receptors and syndrome), Other Serotonin Modulators [except
interrupts cough impulse transmission by depressing the Tedizolid] (serotonin syndrome)
medullary cough center through sigma receptor
stimulation. Increases serum concentration of Dextromethorphan:
Abiraterone Acetate, CYP2D6 Inhibitors, Panobinostat,
Indication: Symptomatic relief of coughs caused by the Quinidine, Selective Serotonin Reuptake Inhibitors
common cold or inhaled irritants [except Fluvoxamine]

Contraindications: Known hypersensitivity to TEST INTERACTIONS: False-positive phencyclidine, opioids

dextromethorphan or any component of the formulation; and heroin urine drug screen.
concurrent administration with or within 2 weeks of
discontinuing an MAO inhibitor Administration: May be taken with or without food.
R

Dose: Pregnancy Category: C

Cough suppressant, by mouth, ADULT and CHILD >12 years,
10–20 mg every 4 hours or 30 mg every 6–8 hours ATC Code: R05DA09
(maximum 120 mg daily); CHILD 6–12 years, 5–10 mg
every 4 hours or 15 mg every 6–8 hours (maximum 60
mg every 24 hours). ANTIHISTAMINES FOR
SYSTEMIC USE
NOTE: NOT for use in children <4 years of age.

Dose Adjustment:
Hepatic Impairment: OTC CETIRIZINE
Use with caution. Metabolized in the liver.
Oral: 10 mg tablet (as dihydrochloride)
Precautions: 2.5 mg/mL syrup (oral drops) (as dihydrochloride), 10
Serotonin syndrome (symptoms of agitation, confusion, mL
hallucinations, hyper­reflexia, myoclonus, shivering, and 10 mg/mL drops (as dihydrochloride), 10 mL
tachycardia may occur with concomitant pro- 1 mg/mL solution (as dihydrochloride), 30 mL and 60
serotonergic drugs); Elderly (no specific information mL
found on use in elderly); children; debilitated patients 5 mg/5 mL syrup (as dihydrochloride), 30 mL
Adverse Drug Reactions: Confusion, excitement, irritability, A piperazine-derived, long-acting, second-generation H1
nervousness, serotonin syndrome receptor antagonist, which is often better tolerated than
sedating antihistamines due to less sedating and less
Drug Interactions: anticholinergic effects.
Monitor closely with:
Enhances therapeutic effect of Dextromethorphan: Indications: Perennial and seasonal allergic rhinitis; other
Antiemetics, 5-HT3 Antagonists (serotonergic effect) allergic symptoms such as hay fever, conjunctivitis, and
chronic idiopathic urticaria
Enhances therapeutic effect of Antipsychotic Agents
(dopamine blockade; serotonergic effect) Contraindications: Known hypersensitivity reactions to
cetirizine, levocetirizine, or hydroxyzine or any
component of the formulation; severe renal impairment

572
RESPIRATORY SYSTEM

Dose: ATC Code: R06AE07

Symptomatic relief of allergy, by mouth, ADULT, 10 mg once
daily or 5 mg twice daily, may be increased as necessary,
(maximum recommended daily dose 20 mg); CHILD >6 CHLORPHENAMINE
years, 10 mg daily or 5 mg twice daily; CHILD 2 to 6 years, OTC
(CHLORPHENIRAMINE)
5 mg once daily or 2.5 mg twice daily; CHILD 1–2 years,
0.25 mg/kg twice daily.
Oral: 4 mg tablet (as maleate)
2.5 mg/5 mL syrup (as maleate), 60 mL
Dose Adjustment:
Inj.: 10 mg/mL (as maleate), 1 mL ampule/vial (IM, IV)
Geriatric (≥77 years):
Use lower dose (5 mg daily).
An H1-receptor antagonist which competitively blocks H1-
Renal and Hepatic Impairment:
receptor sites on tissues.
For mild-to-moderate impairment, dose reduction is
warranted (5 mg daily).
Indications: For allergic conditions; an adjunct in
anaphylactic shock
Precautions:
WARNING: May cause CNS depression, which may Contraindication: Neonates
impair physical or mental abilities.
Dose:
CNS stimulation may occur with antihistamines, especially Allergic conditions, by mouth, ADULT, 4 mg every 4 to 6
in children (caution is advised in patients suffering from hours (maximum, 24 mg daily); CHILD 6–12 years, 2 mg
epilepsy); Children and elderly (risk of sedation and every 4–6 hours (maximum, 12 mg daily); CHILD 2–5
anticholinergic effects are increased; not recommended years, 1 mg every 4–6 hours (maximum, 6 mg daily);
for children <12 months); Renal impairment; hepatic CHILD 1–2 years, 1 mg twice daily (maximum, 6 mg
impairment; excess alcohol intake; avoid use of other daily).
sedative drugs; Lactation (excreted into breast milk). Adjunct in anaphylactic shock, by IV or IM injection, ADULT,
10–20 mg (maximum 40 mg daily).
SKILLED TASKS. May impair ability to perform certain tasks,
e.g., operating machinery or driving. Dose Adjustment: No information found

Adverse Drug Reactions: Precautions:

Common: Dizziness, drowsiness, dryness of mouth, fatigue, Pylori duodenal obstruction; angle-closure glaucoma;
headache, insomnia, malaise, nausea, pharyngitis, urinary retention; prostatic hyperplasia; epilepsy; renal

R
somnolence and hepatic impairment; BPH; bladder neck obstruction;
Less Common: Abdominal pain, anorexia, arthralgia, chest hypertension; Elderly.
pain, diarrhea, dyspepsia, dyspnea, epistaxis, fever,
flushing, increased appetite, myalgia, tachycardia, thirst, SKILLED TASKS. May impair ability to drive or operate
vomiting, weight gain machinery.
Rare: Dystonia, hemolytic anemia, hepatitis,
hypersensitivity (including anaphylaxis and Adverse Drug Reactions:
bronchospasm), hypotension, rash, thrombocytopenia Common and Less Common: CNS depression, sedation,
drowsiness, lassitude, dizziness, GI upsets, anorexia,
Drug Interactions: increased appetite, epigastric pain, blurring of vision,
Monitor closely with: dysuria, dryness of mouth, tightness in chest,
Enhances therapeutic effect of Cetirizine: hypotension, muscular weakness, tinnitus, euphoria,
Anticholinergics e.g., Ipratropium, Tiotropium headache, paradoxical CNS stimulation
(anticholinergic effect), CNS Depressants e.g., Alcohol, Potentially Fatal: CV collapse, respiratory failure
Sedatives (sedative effect)
Drug Interactions:
Increases risk of adverse or toxic effects of the following Monitor closely with:
drugs: Enhances therapeutic effect of Chlorphenamine:
Analgesics, Opioids (constipation; urinary retention), Psychotropic Drugs e.g., Barbiturates, Hypnotics, Opioid
CNS Depressants e.g., Alcohol, Sedatives, Warfarin Analgesics, Anxiolytics, Antipsychotics (sedative effect)
(increased INR; epistaxis)
Avoid concomitant use with:
Reduces therapeutic effect of Cetirizine: Increases risk of adverse or toxic effects of the following
Acetylcholinesterase Inhibitors (Central) drugs:
Alcohol, Ethyl (sedation or excitation), Clomipramine,
Avoid concomitant use with: Cyclobenzaprine
Increases risk of adverse or toxic effects of Cetirizine: Desipramine, Maprotiline, Melitracen
Doxylamine (CNS depression; psychomotor retardation) Nortriptyline, Opipramol, Protriptyline
Trimipramine
Administration: May be administered with or without food.
Administration: May be taken with or without food.
Pregnancy Category: B
Pregnancy Category: C

573
 RESPIRATORY SYSTEM

ATC Code: R06AB04

Rx HYDROXYZINE

Rx (Inj.) Oral: 25 mg tablet (as dihydrochloride)

OTC (Oral)
DIPHENHYDRAMINE 2 mg/mL syrup (as dihydrochloride or as
hydrochloride), 100 mL
Oral: 25 mg and 50 mg capsule (as hydrochloride)
12.5 mg/5 mL syrup (as hydrochloride), 30 and 60 A piperazine derivative, blocks histamine H1-receptors on
mL effector cells of the GI tract, blood vessels and
Inj.: 50 mg/mL (as hydrochloride), 1 mL ampule (IM, IV) respiratory tract. It is a sedating antihistamine with
antimuscarinic and significant sedative properties.
A monoethanolamine-derived, first-generation H1-receptor
antagonist that exhibits antimuscarinic and pronounced Indications: Control of anxiety or agitation; adjunct to pre- or
sedative property, with low incidence of GI side effects. post-operative sedation; short-term management of
anxiety; pruritus
Indications: Relief of allergic symptoms caused by
histamine release, including rhinitis, cough, Contraindications: Pregnancy; lactation
conjunctivitis and allergic dermatoses; moderate to
severe angioedema and anaphylaxis (adjunct to Dose:
epinephrine) Adjunct to pre- or post-operative sedation,
by mouth, ADULT, 50–100 mg; CHILD, 600
Contraindications: Acute asthma; neonates or premature micrograms/kg.
infants; breastfeeding; use of the parenteral form as a Short-term management of anxiety, by mouth, ADULT, 50–
local anesthetic 100 mg 4 times daily.
Pruritus in acute and chronic urticaria and dermatosis, by
Dose: mouth, ADULT, initially 25 mg at night, may be increased
Allergic reactions, by mouth, ADULT, 25–50 mg every 6–8 if required up to 25 mg 3–4 times daily; CHILD >6 years,
hours, CHILD >12 years, 25–50 mg every 4–6 hours initially 15–25 mg daily, may be increased up to 50–100
(maximum, 300 mg daily); CHILD 6 to <12 years, 12.5– mg daily in divided doses; CHILD 6 months–6 years,
25 mg every 4–6 hours (maximum, 10 mg daily); CHILD initially 5–15 mg daily, may be increased up to 50 mg
2 to <6 years, 6.25 mg every 4–6 hours (maximum, 37.5 daily in divided doses.
mg daily).
Allergic reactions, by IM or IV injection, ADULT, 10 to 50 mg Dose Adjustment:
R

per dose, as a single dose, for up to 100 mg if needed Renal Impairment:

(maximum, 400 mg daily); CHILD, 5 mg/kg daily or 150 For moderate-to-severe impairment, reduce dose by 50%.
mg/m2 daily in divided doses every 6–8 hours (maximum
300 mg daily). Hepatic Impairment:
For oral preparations, reduce total daily dose by 33%.
Dose Adjustment:
Geriatric: Precautions:
For emergency allergic reactions only. Advanced age is Porphyria; glaucoma; bladder outflow obstruction;
associated with reduced clearance of drug decreased GI motility; myasthenia gravis; dementia;
If used, consider lower doses. Use only smallest effective renal and hepatic impairment; Cardiovascular effects
dose, 25 mg oral or IV every 8 to 12 hours. (use with caution in patients with known predisposing
factor to cardiac arrhythmia, including electrolyte
Administration: imbalance, increased potential for convulsions, and pre-
For oral administration, may be taken with or without existing heart disease).
food.
SKILLED TASKS. May impair ability to perform certain tasks,
For parenteral administration, for IV or IM administration e.g., operating machinery or driving.
only. Visually inspect parenteral products for particulate
matter and discoloration prior to administration. Adverse Drug Reactions:
Common and Less Common: Dizziness, ataxia, fatigue,
For IV administration, do NOT exceed a rate of 25 drowsiness, hallucination, seizure, dry mouth,
mg/minute. nervousness, xerostomia, involuntary movements,
slurred speech, headache, paresthesia, tremor, blurred
IM administration must be deep. Local necrosis may vision, respiratory depression, pruritus, rash, urticaria,
result with SC or intradermal use. allergic reaction

See Diphenhydramine under Anti-Parkinson Drugs in Drug Interactions:

Chapter 10: Nervous System for other information. Enhances therapeutic effect of Hydroxyzine:
Analgesics (CNS depressant effects)
Pregnancy Category: B Anesthesia (CNS depressant effects)
Barbiturates (CNS depressant effects)
ATC Code: R06AA02 MAO Inhibitors (antimuscarinic effects)
Opiates (CNS depressant effects)

574
RESPIRATORY SYSTEM

Other Sedatives (CNS depressant effects) Rare: Abnormal hepatic function, agitation, alopecia,
Tricyclic Antidepressants (antimuscarinic effects) amnesia, angle-closure glaucoma, blood disorders,
bronchitis, chest pain, confusion, convulsions,
Administration: May be taken with or without food. depression, dermatitis, dizziness, erythema multiforme,
EPS, hemoptysis, hepatic necrosis, hepatitis,
NOTE: Do NOT administer by SC, IV, or intra-arterial hypotension, hypersensitivity reactions, including
injection. anaphylaxis; hypertension, impotence, palpitation,
peripheral edema, purpura, seizures, sleep disturbance,
Pregnancy Category: C (in 2nd and 3rd trimester); supraventricular tachyarrhythmias, syncope,
X (in first trimester) tachycardia, thrombocytopenia, urticaria, vertigo

ATC Code: Not available Drug Interactions:

NOTE: Sedative interactions apply to a lesser extent to the
non-sedating antihistamines. Interactions do not
generally apply to antihistamines used for topical action,
OTC LORATADINE as well as inhalation.

Oral: 10 mg tablet / film coated tablet Monitor closely with:

5 mg/5 mL syrup, 30 mL Enhances therapeutic effect of Loratadine:
Alcohol (CNS depressant effect)
A piperidine-derived, non-sedating, second-generation H1-
receptor antagonist, which is extensively converted into Enhances therapeutic effect of the following drugs:
a metabolite having a longer half-life. Azithromycin, Conjugated Estrogens

Indications: Relief of nasal and non-nasal symptoms of Increases risk of adverse or toxic effects of SSRIs
seasonal allergic rhinitis; hay fever; chronic idiopathic (psychomotor impairment)
urticaria, and other allergic dermatological disorder
Administration: May be taken with or without food.
Contraindications: Children <2 years of age; pregnancy;
breastfeeding Pregnancy Category: B

Dose: ATC Code: R06AX13

Chronic idiopathic urticaria and seasonal allergic rhinitis, by

R
mouth, ADULT, 10 mg once daily (not to exceed 10 mg
per day); CHILD >30 kg or >6 years, 10 mg once daily; OTHER RESPIRATORY SYSTEM
CHILD <30 kg or 2–5 years, 5 mg once daily. PRODUCTS
NOTE: Safety and efficacy is not established for allergic
rhinitis in CHILD <2 years, and for urticaria in CHILD <6 LUNG SURFACTANTS
years.
PHOSPHOLIPID FRACTION FROM
Dose Adjustment: Rx
Renal and Hepatic Impairment: BOVINE LUNG
For mild-to-moderate impairment, the dose frequency is
reduced to alternate days. Inj: 45 mg/mL (54 mg/1.2 mL) lyophilized powder for
For severe impairment, refer patient to a specialist. suspension (intratracheal admistration)

Precautions: A sterile, non-pyrogenic pulmonary surfactant intended for

Renal or hepatic impairment; prostatic hypertrophy; urinary intratracheal use only.
retention; susceptibility to angle-closure glaucoma and
pyloroduodenal obstruction; epilepsy; Elderly (may be Indication: Treatment of respiratory distress syndrome in
inappropriate in certain comorbidities, such as dementia premature neonates.
and delirium; increased risk of sedation and
anticholinergic effects); Lactation. Dose:
Respiratory distress syndrome, by intratracheal injection,
Adverse Drug Reactions: NEONATE, 4 mL per kg birth weight. Four doses can be
Common: Abdominal pain, blurred vision, conjunctivitis, administered in the first 48 hours of life. Doses should
drowsiness, dryness of mouth, dysphonia, earache, be given no more frequently than every 6 hours.
epistaxis, fatigue, GI disturbances, headache,
hyperkinesia, impaired concentration, influenza-type Dose Adjustment:
symptoms, laryngitis, malaise, nausea, nervousness, No dosage adjustments provided in the manufacturer’s
psychomotor impairment, somnolence, stomatitis, upper labeling.
respiratory tract infection, urinary retention, viral
infection, wheezing Precautions:
Less Common: Increased appetite, insomnia, weight gain May cause transient rales and moist breath sounds after
administration;

575
 RESPIRATORY SYSTEM

Increased probability of post-treatment nosocomial sepsis; compliance that may require frequent adjustments to
Use in infant less than 600 g or more than 1750 g birth oxygen delivery and ventilator settings).
weight has not been evaluated.
Adverse Drug Reactions:
Adverse Drug Reactions: Common: Transient bradycardia, oxygen desaturation
Common: Bradycardia and oxygen desaturation. Less Common: Apnea, endotracheal tube blockage,
Rare: Endotracheal tube reflux, pallor, vasoconstriction, hypercarbia, hypertension, hypocarbia, hypotension,
hypotension, endotracheal tube blockage, hypertension, pallor, pulmonary air leaks, pulmonary interstitial
hypocarbia, hypercarba, and apnea. emphysema, increased probability of post-treatment
nosocomial sepsis, vasoconstriction
Drug Interactions:
No information provided in the manufacturer’s labeling. Drug Interactions:
Monitor closely with:
Administration: For intratracheal administration only. Increases risk of adverse or toxic effects of Beractant:
Bretylium (AV blockade), Ruxolitinib (bradycardic effect)
Pregnancy Category: N/A Tofacitinib (bradycardic effect)
Other Bradycardia-causing Agents
ATC Code: R07AA02
Increases risk of adverse or toxic effects of the following
drugs:
Ivabradine (bradycardic effect), Lacosamide (AV-
Rx BERACTANT blocking effect)

Avoid concomitant use with:

Inj.: 25 mg/mL suspension, 4 mL and 8 mL vial
Increases risk of adverse or toxic effects of Ceritinib
(intrathecal)
(bradycardic effect)
NOTE: Restricted to tertiary hospitals with adequately
Administration: For endotracheal administration only.
trained neonatologist and facilities for neonatal intensive
care
Administer endotracheally by instillation through a 5-
French end-hole catheter inserted into the infant's
A respiratory surfactant that replaces deficient or ineffective
endotracheal tube.
endogenous lung surfactant in neonates with respiratory
distress syndrome (RDS) or in neonates at risk of
Administer the dose in four 1 mL/kg aliquots. Each
R

developing RDS. Surfactants prevent the alveoli from

quarter-dose is instilled over 2–3 seconds followed by at
collapsing during expiration by lowering surface tension
least 30 seconds of manual ventilation or until stable.
between air and alveolar surfaces.
Each quarter-dose is administered with the infant in a
different position. Slightly downward inclination with
Indications: Prevention and treatment of respiratory
head turned to the right, then repeat with head turned to
distress syndrome (RDS) in premature infants
the left, then slightly upward inclination with head turned
to the right, then repeat with head turned to the left.
NOTE: Beractant is only indicated for use in premature
Following administration of 1 full dose, withhold
infants.
suctioning for 1 hour unless signs of significant airway
obstruction.
Dose:
Respiratory distress, prophylactic treatment, by
Suction infant prior to administration. Inspect solution to
endotracheal injection, PREMATURE INFANT, 4 mL/kg
verify complete mixing of the suspension. Mixture may be
(100 mg phospholipids/kg) as soon as possible; as many
swirled gently. Do NOT SHAKE. Do NOT filter dose and
as 4 doses may be administered during the first 48 hours
avoid shaking.
of life, no more frequently than 6 hours apart.
Rapidly affects oxygenation and lung compliance. Use is
NOTE: The need for additional doses is determined by
restricted to highly supervised clinical setting with
evidence of continuing respiratory distress; if the infant
immediately available clinicians experienced in
is still intubated and requiring at least 30% inspired
intubation and ventilatory management of premature
oxygen to maintain a PaO2 ≤80 torr.
infants.
Respiratory distress, rescue treatment, by endotracheal
Pregnancy Category: Not classified
injection, PREMATURE INFANT, 4 mL/kg (100 mg
phospholipids/kg) as soon as the diagnosis of RDS is
ATC Code: Not available
made, may repeat if needed, no more frequently than
every 6 hours to a maximum of 4 doses.

Precautions:
Transient adverse effects such as transient episodes of
bradycardia and decreased oxygen saturation occur
Acute changes in oxygenation and lung compliance
(produces rapid improvements in lung oxygenation and

576
RESPIRATORY SYSTEM

Weight Initial dose Repeat dose

Rx PORACTANT ALFA (grams) 2.5 mL/kg 1.25 mL/kg
1951 – 2000 5.00 2.50
Inj.: 80 mg/mL sterile suspension (intratracheal /
intrabronchial), 1.5 mL and 3 mL vial Dose Adjustment: No information found

A sterile, non-pyrogenic pulmonary surfactant intended for Precautions:

intratracheal use only. It is an extract of natural porcine WARNING: Should only be administered by those
lung surfactant consisting of 99% polar lipids (mainly trained and experienced in the care, resuscitation,
phospholipids) and 1% hydrophobic low molecular and stabilization of pre-term infants.
weight proteins (surfactant associated proteins SP-B and
SP-C).
Acute changes in oxygenation and lung compliance
(produces rapid improvements in lung oxygenation and
It reduces surface tension at the air-liquid interface of the
alveoli during ventilation and stabilizes the alveoli compliance that may require frequent adjustments to
oxygen delivery and ventilator settings); Transient
against collapse at resting transpulmonary pressures.
adverse effects; (associated with transient episodes of
Indications: For the rescue treatment of respiratory distress bradycardia, hypotension, endotracheal tube blockade,
syndrome (RDS) in pre-term babies; prophylactic use in and oxygen desaturation).
premature infants at risk of RDS Children (safety and efficacy in full term infants or older
pediatric patients with respiratory failure has not been
Dose: established).
RDS, by intratracheal injection, PREMATURE INFANT,
Adverse Drug Reactions:
initially 2.5 mL/kg of birth weight [see below],
administered as 1 or 2 aliquots depending on the
Common: Acquired pneumonia, acquired septicemia,
bronchopulmonary dysplasia, intracranial hemorrhage,
instillation procedure; up to 2 repeat doses of 1.25
patent ductus arteriosus, pneumothorax, pulmonary
mL/kg birth weight each may be administered at
interstitial emphysema
approximately 12-hour intervals in infants who remain
intubated and in whom RDS is considered responsible Less Common: Pulmonary hemorrhage
for their persisting or deteriorating respiratory status
Drug Interactions:
(maximum total dose, 5 mL/kg).
Monitor closely with:
Reduces therapeutic effect of the following drugs:
Weight Initial dose Repeat dose
Paromomycin, Spectinomycin, Streptomycin

R
(grams) 2.5 mL/kg 1.25 mL/kg
Each dose (mL) Avoid concomitant use with:
600 – 650 1.60 0.80 Reduces therapeutic effect of the following drugs:
651 – 700 1.70 0.85 Amikacin, Amphotericin B, Gentamicin, Kanamycin,
701 – 750 1.80 0.90 Neomycin, Tobramycin, Vancomycin
751 – 800 2.00 1.00
801 – 850 2.10 1.05 Administration: For intratracheal administration only.
851 – 900 2.20 1.10
Slowly withdraw contents of the vial into a 3 or 5 mL
901 – 950 2.30 1.15
plastic syringe through a large-gauge needle (at least 20
951 – 1000 2.50 1.25 gauge). Each vial is single-use only. Attach the pre-cut 9-
1001 – 1050 2.60 1.30 cm 5-French end-hole catheter to the syringe. Fill the
1051 – 1100 2.70 1.35 catheter with the suspension. Discard excess
1101 – 1150 2.80 1.40 suspension through the catheter so that only the
1151 – 1200 3.00 1.50 required dose remains in the syringe. Administer in 2
1201 – 1250 3.10 1.55 divided aliquots:
1st dose: 1.25 mL/kg birth weight (BW)
1251 – 1300 3.20 1.60
Succeeding doses: 0.635 mL/kg BW
1301 – 1350 3.30 1.65
1351 – 1400 3.50 1.75 Should be administered by, or under the supervision of
1401 – 1450 3.60 1.80 clinicians experienced in intubation, ventilator
1451 – 1500 3.70 1.85 management, and general care of premature infants.
1501 – 1550 3.80 1.90
1551 – 1600 4.00 2.00 Prior to administration, ensure proper placement and
patency of the endotracheal tube. At the discretion of the
1601 – 1650 4.10 2.05
clinician, the endotracheal tube may be suctioned before
1651 – 1700 4.20 2.10 administration. Allow the infant to stabilize before
1701 – 1750 4.30 2.15 proceeding with dosing.
1751 – 1800 4.50 2.25
1801 – 1850 4.60 2.30 Administer either:
1851 – 1900 4.70 2.35 Intratracheally by instillation in 2 divided aliquots
1901 – 1950 4.80 2.40 through a 5-French end-hole catheter after briefly

577
 RESPIRATORY SYSTEM

disconnecting the endotracheal tube from the ventilator;

or
Intratracheally in a single aliquot through the secondary
lumen of a dual lumen endotracheal tube without
interrupting mechanical ventilation.

Pregnancy Category: Not classified

ATC Code: Not available

R

578
SENSORY ORGANS

Rx ERYTHROMYCIN
SENSORY ORGANS
Ophth.: 0.5% eye ointment, 3.5 g and 5 g tube

OPHTHALMOLOGICALS A macrolide antibiotic used for superficial ocular infections

caused by susceptible organisms. It inhibits protein
synthesis by irreversibly binding to the 50s ribosomal
ANTIINFECTIVES subunit resulting in inhibition of cell growth.

Indications: Treatment of superficial ocular infections

Rx ACYCLOVIR (ACICLOVIR) involving the conjunctiva or cornea caused by organisms
susceptible to erythromycin; prophylaxis of ophthalmia
Ophth.: 3% eye ointment, 4.5 g tube neonatorum from both N. gonorrhoeae and C.
trachomatis.
An acyclic purine nucleoside analogue which inhibits viral
DNA polymerase, thus preventing viral DNA synthesis. Contraindications: Minor ocular irritation

Indication: Treatment of herpes simplex keratitis Dose:

Conjunctivitis, into the eye, ADULT, apply a half-inch (1.25
Contraindication: Hypersensitivity to acyclovir, valacyclovir, cm) on the affected eye(s) every 3–4 hours, 2–6 times a
or any component of the formulation day depending on the severity of the infection.
Prophylaxis of ophthalmia neonatorum, into the eye,
Dose: NEWBORN INFANT, apply 1 cm ribbon into each lower
Herpes simplex keratitis, into the eye, ADULT, apply a small conjunctival sac immediately after birth, then gently
amount (~1 cm ribbon) into the affected eye(s) 5 times massage the closed eyelids to spread the ointment.
daily at approx. 4-hour intervals while awake, continue
treatment for at least 3 days after resolution of keratitis. NOTE: Prophylaxis should not be delayed by more than 1
hour after delivery since delayed application may reduce
Dose Adjustment: Dose adjustment is unlikely due to low efficacy. Ideally, a new tube or a single-use container of
systemic absorption ointment should be used for each neonate.

Precautions: Dose Adjustment: No information found

Ocular effects (e.g., transient stinging immediately following
application; blurred vision). Precautions:

S
Superinfection;
Adverse Drug Reactions: Pregnancy and breastfeeding.
Common: Foreign body sensation of the eye, epithelial
keratopathy, eye irritation, conjunctivitis, stinging of the Adverse Drug Reactions:
eye Common: Minor ocular reactions, redness
Less Common: Blepharitis, eyelid edema, hypersensitivity Rare: Hypersensitivity reactions
reaction
Drug Interactions:
Drug Interactions: No known significant interactions Monitor closely with:
Increases risk of adverse or toxic effects of the following
Administration: For ophthalmic application only. drugs:
Digoxin (digoxin toxicity), Vitamin K Antagonists e.g.,
Apply to the inside of the lower eyelid, then close the Warfarin (bleeding)
eye(s) for 30 seconds following application.
Administration: For ophthalmic use only.
Do NOT wear contact lenses during treatment. Avoid
touching the applicator to the eye or other surfaces. Apply ointment directly to the infected eye through the
pocket made by the lower lid and the eye. It is advisable
Pregnancy Category: B to apply the ointment at night.

ATC Code: S01AD03 Avoid contaminating the applicator tip with the material
from the eyes, fingers, or other sources.

Pregnancy Category: B

ATC Code: S01AA17

579
 SENSORY ORGANS

FUSIDATE SODIUM Rx GANCICLOVIR

Rx
(FUSIDIC ACID)
Ophth.: 1% eye drops suspension (as sulfate), 5 g tube Ophth.: 0.15% eye gel, 5 g tube

An aqueous sustained-release formulation of a narrow- An acyclic nucleoside analogue of 2’-deoxyguanosine that

spectrum antibiotic isolated from Fusidium coccineus. has antiviral effect against human cytomegalovirus and
Fusidic acid is active against staphylococci (including other human herpes viruses. It is phosphorylated to a
methicillin-resistant strains) and streptococci. substrate, which competitively inhibits the binding of
deoxyguanosine triphosphate to DNA polymerase
Indications: Bacterial infections of the eye caused by resulting in inhibition of viral DNA synthesis.
susceptible organisms in conjunctivitis, blepharitis, stye,
keratitis, dacryocystitis; prophylaxis in ophthalmic Indication: Treatment of acute herpetic keratitis (dendritic
surgery and in connection with removal of foreign bodies. ulcers)

Contraindications: Infections caused by non-susceptible Contraindication: Hypersensitivity to ganciclovir,

organisms. valganciclovir, other antivirals, or any component of the
formulation.
Dose:
Ophthalmic infections, into the eye, ADULT, 1 drop in the Dose:
conjunctival sac every 4 hours for the 1st day of Herpetic keratitis, into the eye, ADULT, instill 1 drop into the
treatment, then reduce dose to 1 drop every 12 hours; inferior conjunctival sac of the affected eye 5 times daily
continue treatment 2 days after the eye appears normal. (approximately every 3 hours while awake) until the
Surgical prophylaxis, into the eye, ADULT, 1 drop in the corneal ulcer heals, then 1 drop 3 times daily for 7 days.
conjunctival sac every 12 hours, 24–48 hours before
operation. Dose Adjustment: Dose adjustment is unlikely due to low
systemic absorption.
Dose Adjustment:
Hepatic Impairment: Precautions:
Impaired biliary excretion may possibly increase risk of WARNING: Hazardous agent. Use appropriate
hepatotoxicity. Avoid use or reduce dose. Monitor liver precautions for handling and disposal.
function.

Precautions: Ocular adverse effects (e.g., blurred vision and eye

Should not be used for more than 10 days (e.g., fungal irritation);
S

superinfection with prolonged use; discontinue Elderly (evaluate the patient’s or caregiver’s ability to safely
treatment if superinfection occurs; evaluate and treat and correctly administer the medication);
appropriately); Pregnancy and lactation (use with caution; safety has not
Avoid extended or recurrent use; been established).
Pregnancy;
Breastfeeding. Adverse Drug Reactions:
Common: Blurred vision, irritation, punctate keratitis,
Adverse Drug Reactions: conjunctival hyperemia
Common: Stinging (transient)
Drug Interactions: No known significant interactions
Drug Interactions:
Monitor closely with: Administration: For ophthalmic use only.
Reduces therapeutic effect of Penicillins
Do NOT use contact lenses during treatment. Avoid
Reduces therapeutic effect of Ciprofloxacin (antagonistic touching tip of applicator to eye or other surfaces.
effect)
Pregnancy Category: C
Avoid concomitant use with:
Increases risk of adverse or toxic effects of HMG-CoA ATC Code: S01AD09
Reductase Inhibitors (muscle toxicities, e.g.,
rhabdomyolysis)

Administration: For ophthalmic use only. Keep out of reach

of children.

Do NOT use contact lenses during treatment.

Pregnancy Category: C

ATC Code: S01AA13

580
SENSORY ORGANS

Rx LEVOFLOXACIN Rx MOXIFLOXACIN HYDROCHLORIDE

Eye Drops: 5 mg/mL (0.5% w/v) ophthalmic solution Eye Drops Solution: 5 mg/mL (0.5% w/v), 5 mL bottle

Levofloxacin inhibits DNA-gyrase and topoisomerase IV in Moxifloxacin is a DNA gyrase inhibitor, and also inhibits
susceptible organisms and thereby inhibits relaxation of topoisomerase IV. DNA gyrase is required for DNA
supercoiled DNA and promotes breakage of DNA replication and transcription, DNA repair, recombination,
strands. and transposition; inhibition is bactericidal.

Indications: Treatment of bacterial conjunctivitis secondary Indications: Pre and postoperative sterilization.
to contact lens use.
Contraindications: Hypersensitivity to moxifloxacin, other
Contraindications: Hypersensitivity to levofloxacin, other quinolones, or to any component of the formulation.
quinolones, or to any component of the formulation.
Dose:
Pre and postoperative sterilization, ADULT, instill 1 drop into
operative eye every 5-15 minutes for five doses within
Dose: the hour prior to the start of the procedure.
Bacterial conjunctivitis, ADULT and CHILD ≥6 years, days 1-
2: instill 1-2 drops into affected eye(s) every 2 hours Dose Adjustment:
while awake, up to 8 times daily; days 3-7: instill 1-2 Renal and Hepatic impairment:
drops into affected eye(s) every 4 hours while awake, up No dosage adjustments provided in the manufacturer’s
to 4 times daily. labeling.

Dose Adjustment: Precautions:

Renal and Hepatic impairment: May cause severe hypersensitivity reactions including
No dosage adjustments provided. anaphylaxis, angioedema, dermatologic reactions, and
superinfection.
Precautions:
Hypersensitivity: serious hypersensitivity reactions, Adverse Drug Reactions:
including anaphylaxis have been reported with system c Less Common: Eye irritation, conjunctivitis, decreased
quinolone therapy. Prolonged use may lead to visual acuity, eye discomfort, eye pain, eye pruritus,
overgrowth of non susceptible organisms including fungi. lacrimation, ocular hyperemia, subconjunctival
Superinfection. hemorrhage, and xerophthalmia.

S
Adverse Drug Reactions: Drg Interactions:
Less Common: Headache, burning sensation of eyes, eye None known.
pain, foreign body sensation of eye, photophobia, vision
loss, pharyngitis, and fever. Administration: For topical ophthalmic use only; not for
Rare: Dry eye syndrome, eyelid edema, eye pruritus, and injection. Avoid touching tip of applicator to eye or other
hypersensitivity reaction. surfaces.

Drug Interactions: Pregnancy Category: C

None known.
ATC Code: S01AE07
Administration: For ophthalmic use only; not for injection.
Avoid touching tip of applicator to eye or other surfaces.

Pregnancy Category: C Rx OFLOXACIN

ATC Code: S01AE05 Ophth.: 0.3% eye drops solution, 5 mL bottle

A DNA gyrase inhibitor that interferes with replication,

transcription, repair, recombination, and transposition of
bacterial DNA.

Indication: Treatment of superficial ocular infections

involving the conjunctiva or cornea due to strains of
susceptible organisms.

Contraindications: Hypersensitivity to ofloxacin or other

members of the quinolone group.

581
 SENSORY ORGANS

Dose:
Conjunctivitis, into the eye, ADULT and CHILD ≥1 year, instill Rx TOBRAMYCIN
1–2 drops into the affected eye(s) every 2–4 hours for
the first 2 days, then use 4 times daily for an additional Ophth.: 0.3% eye drops solution, 5 mL bottle
5 days. 0.3% eye ointment, 3.5 g tube
Corneal ulcer, into the eye, ADULT and CHILD ≥1 year, instill
1–2 drops every 30 minutes while awake and every 4–6 A topical ophthalmic antibiotic which binds to bacterial 30s
hours after retiring for the first 2 days; Beginning on day and 50s ribosomal subunits and interferes with bacterial
3, instill 1–2 drops every hour while awake for 4–6 protein synthesis.
additional days;
Thereafter, 1–2 drops 4 times daily until clinical cure. Indication: Treatment of external infections of the eye

Dose Adjustment: Dose adjustment is unlikely due to low Contraindication: Known hypersensitivity to tobramycin,
systemic absorption. other aminoglycosides, or any component of the
formulation
Precautions:
Hypersensitivity reactions (e.g., anaphylaxis); Dose:
Superinfection (e.g., fungal or bacterial superinfection with Ocular infection, mild-to-moderate, into the eye, ADULT and
prolonged use); CHILD ≥1 year,
Tendon inflammation or rupture; as eye drops solution, instill 1 drop into the conjunctival
Elderly (evaluate the patient’s or caregiver’s ability to safely sac twice daily (morning and evening);
and correctly administer the medication). as eye ointment, apply ½ inch of ribbon into the affected
Pregnancy and lactation. eye(s) 2–3 times daily.
Ocular infection, severe, into the eye, ADULT and CHILD ≥1
Adverse Drug Reactions: year,
Common and Less Common: Dizziness, nausea, blurred as eye drops solution, instill 4 times on the affected
vision, burning, chemical conjunctivitis or keratitis, eye(s);
ocular discomfort, eye dryness, ocular edema, eye pain, as eye ointment, apply ½ inch of ribbon into the affected
foreign body sensation in the eye, itching of the eye, eye(s) every 3–4 hours.
photophobia, redness of the eye, ocular stinging, tearing
of the eye. Dose Adjustment: Dose adjustment is unlikely due to low
Rare: Stevens-Johnson syndrome, toxic epidermal systemic absorption.
necrolysis.
Precautions:
Drug Interactions: Hypersensitivity reactions (e.g., anaphylaxis);
S

Avoid concomitant use with: Superinfection (e.g., fungal or bacterial superinfection with
Decreases serum concentration of Ofloxacin: prolonged use);
Antacids containing Magnesium, Aluminum, or Calcium Tendon inflammation or rupture;
Elderly (evaluate the patient’s or caregiver’s ability to safely
Enhances therapeutic effect of Ofloxacin: and correctly administer the medication);
Aminoglycosides, e.g., Amikacin, Tobramycin (additive Children;
antibacterial activity) Pregnancy and lactation.

Increases risk of adverse or toxic effects of the following Adverse Drug Reactions:
drugs: Common: Hypersensitivity reactions, lid itching, lid swelling,
Class IA Antiarrhythmics, e.g., Quinidine, Procainamide conjunctival erythema
(QT interval prolongation), Class III Antiarrhythmics, e.g.,
Sotalol, Amiodarone (QT interval prolongation), Drug Interactions: No information found
Corticosteroids (severe tendon disorders), Theophylline
(theophylline-related adverse effects) Administration: For ophthalmic use only. Do NOT inject into
the eye.
Increases risk of adverse or toxic effects of Ofloxacin:
NSAIDs (seizures) Do NOT use contact lenses during treatment. Avoid
touching tip of applicator to eye or other surfaces.
Increases serum concentration of Theophylline
Pregnancy Category: B
Administration: For ophthalmic use only.
ATC Code: S01AA12
Avoid touching tip of applicator to eye or other surfaces.

WARNING: Do NOT use for longer than 2 weeks at a

time.

Pregnancy Category: C

ATC Code: S01AE01

582
SENSORY ORGANS

ANTIINFLAMMATORY AGENTS
NOTE: Taper dose prior to discontinuation.

Rx DEXAMETHASONE Pregnancy Category: C

ATC Code: S01BA01

Ophth.: 0.1% eye drops suspension, 5 mL bottle

A topical ophthalmic corticosteroid that decreases

inflammation by suppressing neutrophil migration, Rx NEPAFENAC
decreasing production of inflammatory mediators, and
reversing of increased capillary permeability.
Ophth.: 1 mg/mL eye suspension, 5 mL bottle
Indications: Management of steroid-responsive
inflammatory conditions such as allergic conjunctivitis, A nonsteroidal anti-inflammatory and analgesic prodrug. It
iritis, or cyclitis; symptomatic treatment of corneal injury penetrates the cornea and is converted to amfenac by
from chemical, radiation, or thermal burns, or ocular tissue hydrolases. Amfenac inhibits the action of
penetration of foreign bodies. prostaglandin H synthase resulting to inhibited
prostaglandin production.
Contraindications: Viral disease of the cornea and
conjunctiva (including epithelial herpes simplex keratitis, Indication: Treatment of pain and inflammation associated
vaccinia, varicella) ; mycobacterial or fungal infection of with cataract surgery.
the eye.
Contraindication: Hypersensitivity to nepafenac, NSAIDs, or
Dose: any component of the formulation.
Anti-inflammatory, into the eye, ADULT, instill 1–2 drops into
the conjunctival sac up to 4–6 times daily, may use Dose:
hourly for severe inflammation. Cataract surgery, into the eye, ADULT, instill 1 drop into the
affected eye(s) 3 times daily beginning 1 day prior to
Dose Adjustment: cataract surgery, continued on the day of surgery and
Geriatric: through the first 2 weeks post-op.
Use with caution in the smallest possible dose.
Dose Adjustment: No information found
Precautions:
Immunosuppression; Precautions:
Ocular effects (e.g., ocular hypertension and/or glaucoma Cross-sensitivity;

S
with prolonged use, with damage to the optic nerve, Bleeding time;
defects in visual acuity and fields of vision, and posterior Delayed healing;
subcapsular cataract formation; perforations in diseases Complicated ocular surgeries, corneal denervation, corneal
which cause thinning of the cornea or sclera). epithelial defects, diabetes mellitus, ocular surface
Elderly (evaluate the patient’s or caregiver’s ability to safely diseases, rheumatoid arthritis, or repeat ocular surgeries
and correctly administer the medication); within a short period of time (increases risk for corneal
Lactation. adverse events, which may become sight threatening).

Adverse Drug Reactions: Adverse Drug Reactions:

Common and Less Common: Burning sensation of eyes, Common: Capsular opacity, decreased visual acuity, foreign
cataract, decreased visual acuity, eye perforation, body sensation, increased intraocular pressure, sticky
filtering blebs, glaucoma (with optic nerve damage), sensation, conjunctival edema, corneal edema, dry eye,
secondary ocular infection, stinging of eyes, visual field lid margin crusting, ocular discomfort, ocular hyperemia,
defect. ocular pain, ocular pruritus, photophobia, tearing,
vitreous detachment, headache, hypertension, nausea,
Drug Interactions: vomiting, sinusitis.
Monitor closely with:
Increases risk of adverse or toxic effects of the following Drug Interactions:
drugs: Monitor closely with:
Ceritinib (hyperglycemic effect), Amphotericin B, Loop Increases risk of adverse or toxic effects of Nepafenac:
diuretics e.g., Furosemide (hypokalemia), Steroids, Topical (healing problems)

Increases risk of adverse or toxic effects of Dexamethasone: Avoid concomitant use with:
NSAID, Ophthalmic (delayed healing of ophthalmic tissue Increases risk of adverse or toxic effects of drugs that
with concomitant administration) prolong bleeding time (hemorrhage)

Administration: Shake well prior to use. Administration: Shake well prior to use.

Do NOT touch tip of container to eye. Product may If concomitant topical ophthalmic medication is being
contain benzalkonium chloride. Do NOT use contact used, administer medications at least 5 minutes apart.
lenses during treatment.

583
 SENSORY ORGANS

Do NOT touch tip of container to eye. Do NOT use contact NSAID, Ophthalmic (delayed healing of ophthalmic tissue
lenses during treatment. with concomitant administration)

Pregnancy Category: C Reduces therapeutic effect of the following drugs:

Insulin, Oral Hypoglycemics e.g., Gliclazide
ATC Code: S01BC10
Administration: For topical ophthalmic use only. Shake well
before use.
Rx PREDNISOLONE Apply finger pressure to the lacrimal sac (inside corner of
the eye) during and for 1–2 minutes after instillation to
Ophth.: 0.5% and 1% eye drops suspension (as decrease risk of absorption and systemic effects.
acetate), 5 mL bottle
Do NOT touch dropper tip to eyelids or other surfaces
An adrenocortical steroid product prepared as sterile when placing drops in eyes to avoid contamination.
ophthalmic suspension. It reduces inflammation by
inhibiting edema, leukocyte migration, fibrin deposition, NOTE: Do NOT discontinue therapy prematurely. Withdraw
capillary proliferation and dilation, collagen deposition, therapy with gradual tapering of dose in chronic
and scar formation. conditions.

Indications: Treatment of corneal injury from chemical, Pregnancy Category: C

thermal, or radiation burns, or from penetration of
foreign bodies; treatment of steroid-responsive ATC Code: S01BA04
inflammatory conditions of the palpebral and bulbar
conjunctiva, cornea, and anterior segment of the globe
such as acne rosacea, allergic conjunctivitis, cyclitis, ANTIINFLAMMATORY AGENTS AND
herpes zoster keratitis, iritis, superficial punctate ANTIINFECTIVES IN COMBINATION
keratitis, and selected infective conjunctivitis.

Contraindications: Acute untreated purulent ocular Rx SULFACETAMIDE + PREDNISOLONE

infections; viral diseases of the cornea and conjunctiva;
mycobacterial or fungal infections of the eye; Ophth.: 10% sulfacetamide + 0.25% prednisolone (as
hypersensitivity to other corticosteroids. acetate) eye drops suspension, 5 mL bottle
Dose: A sterile topical anti-inflammatory (prednisolone) and anti-
S

Ophthalmic inflammatory conditions or corneal injury, into infective (sulfacetamide) product indicated for
the eye, ADULT, instill 1–2 drops in the affected eye(s) ophthalmic use.
2–4 times daily; during the initial 24–48 hours, dosing
frequency may be increased if necessary; if signs and Indications: For steroid-responsive inflammatory ocular
symptoms fail to improve after 2 days, re­evaluate. conditions for which a corticosteroid is indicated and
where superficial bacterial ocular infection or a risk of
Dose Adjustment: No dose adjustments provided in bacterial ocular infection exists.
manufacturer’s labeling.
Contraindications: Viral diseases of the cornea and
Precautions: conjunctiva, including epithelial herpes simplex keratitis,
Cataracts; vaccinia, and varicella; mycobacterial infection of the
Corneal thinning; eye; fungal diseases of ocular structures.
Glaucoma;
Immunosuppression; Dose:
Pregnancy; Uveitis, bacterial conjunctivitis, keratoconjuctivitis, or
Lactation. keratitis, into the eye, ADULT, instill 2 drops into the
conjunctival sac every 4 hours during the day and at
Adverse Drug Reactions: bedtime; if signs and symptoms fail to improve after 2
Common and Less Common: Conjunctival hyperemia, days, re-evaluate.
conjunctivitis, corneal ulcers, delayed wound healing,
glaucoma, increased intraocular pressure, keratitis, loss Dose Adjustment: No information found
of accommodation, optic nerve damage, mydriasis,
posterior subcapsular cataract formation, ptosis, Precautions:
secondary ocular infection. Cataracts;
Corneal thinning;
Drug Interactions: Glaucoma;
Monitor closely with: Immunosuppression;
Increases risk of adverse or toxic effects of Ceritinib Pregnancy;
(hyperglycemic effect)
Lactation.
Increases risk of adverse or toxic effects of Prednisolone:

584
SENSORY ORGANS

Adverse Drug Reactions: Dose:

Common and Less Common: Cataract, dizziness, eye Ocular inflammation with suspected or confirmed bacterial
discharge, eyelid edema, eyelid erythema, eye irritation, infection, into the eye, ADULT,
eye pain, eye pruritus, and hypersensitivity including as eye drops suspension, instill 1–2 drops into the
rash, skin pruritus, urticaria, ocular hyperemia, visual conjunctival sac(s) every 4–6 hours, may be increased to
disturbance (blurry vision), delayed wound healing, every 2 hours during the initial 24–hour to 48–hour
elevation of intraocular pressure (IOP) with possible period, decrease frequency gradually as improvement
development of glaucoma and infrequent optic nerve seen;
damage, anterior uveitis or perforation of the globe, as eye ointment, apply about ½ inch of ointment into the
mydriasis, loss of accommodation, ptosis, secondary conjunctival sac(s) up to 3–4 times daily.
bacterial ocular infection.
Rare: SJS, toxic epidermal necrolysis, fulminant hepatic Precautions:
necrosis, agranulocytosis, aplastic anemia and other Glaucoma (e.g., optic nerve damage);
blood dyscrasias, systemic hypercorticoidism. Cataracts (e.g., posterior subcapsular cataract formation
with prolonged use);
Drug Interactions: Sensitivity;
Avoid concomitant use with: Secondary infection;
Incompatible with the following products: Children;
Silver-containing Preparations Pregnancy;
Lactation.
Reduces therapeutic effect of Sulfacetamide:
Local Anesthetics related to p-aminobenzoic Acid Adverse Drug Reactions:
Common: Hypersensitivity reactions, lid itching and
Administration: Shake well before use. swelling, conjunctival erythema.
Less Common: Increased intraocular pressure, glaucoma,
The initial prescription and renewal of the medication optic nerve damage, posterior subcapsular cataract
order beyond 20 mL should be made by a physician only formation, delayed wound healing, secondary infections
after examination of the patient with the aid of (prolonged use).
magnification, such as slit lamp biomicroscopy and,
where appropriate, fluorescein staining. If signs and Administration: For external use only. NOT for injection.
symptoms fail to improve after two days, the patient
should be re-evaluated. Do NOT prescribe more than 20 mL or 8 g, initially. Do
NOT refill prescription without further evaluation.
Do NOT prescribe more than 20 mL initially. Do NOT refill
prescription without further evaluation. See individual monographs for Tobramycin and

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Dexamethasone under Ophthalmologicals in Chapter
Do NOT Inject into the eye. 13: Sensory Organs for other information.

NOTE: Do NOT discontinue therapy prematurely. Withdraw Pregnancy Category: C

therapy with gradual tapering of dose in chronic
conditions. ATC Code: S01CA01

Pregnancy Category: C
ANTIGLAUCOMA PREPARATIONS AND MIOTICS
ATC Code: S01CA02

Rx ACETAZOLAMIDE
Rx TOBRAMYCIN + DEXAMETHASONE
Oral: 250 mg tablet
Ophth.: 0.3% tobramycin + 0.1% dexamethasone eye A reversible carbonic anhydrase inhibitor that causes
drops suspension, 5 mL bottle reduced hydrogen ion secretion and increased renal
0.3% tobramycin + 0.1% dexamethasone eye
excretion of sodium, potassium, bicarbonate, and water.
ointment, 3.5 g tube
It decreases the production of aqueous humor and
inhibits carbonic anhydrase in CNS to retard abnormal
A sterile topical anti-inflammatory (dexamethasone) and and excessive discharge from CNS neurons.
anti-infective (tobramycin) product indicated for
ophthalmic use. Indications: Adjunct in open-angle glaucoma; preoperative
management of angle-closure glaucoma.
Indication: Steroid-responsive ocular inflammation with
suspected or confirmed bacterial infection Contraindications: Sodium and/or potassium depletion;
suprarenal gland failure; hyperchloremic acidosis;
Contraindications: Viral infections of cornea and conjunctiva hepatic cirrhosis; chronic non-congestive angle-closure
(e.g., epithelial herpes simplex keratitis, vaccinia, glaucoma; marked renal or hepatic impairment.
varicella); mycobacterial or fungal infection of the eye; Dose:
uncomplicated removal of a foreign body.

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 SENSORY ORGANS

Adjunct in open-angle glaucoma; preoperative management Pregnancy Category: C

of angle-closure glaucoma, by mouth, ADULT, 250–1000
mg daily, given in divided doses for amounts over 250 ATC Code: S01EC01
mg.

Precautions:
Diabetes mellitus; Rx BETAXOLOL
Respiratory acidosis;
Elderly; Ophth.: 0.25% eye drops suspension (as
Children; hydrochloride), 5 mL bottle
Pregnancy; 0.5% eye drops solution (as hydrochloride), 5
Lactation. mL and 10 mL bottle

Adverse Drug Reactions: A cardio-selective beta blocking agent in a sterile isotonic

Common and Less Common: Malaise, fatigue, depression, solution. When instilled into the eye, it reduces
excitement, headache, weight loss, GI disturbances, intraocular pressure.
drowsiness, paresthesia, diuresis, metabolic acidosis,
electrolyte imbalance, crystalluria, renal calculi, renal Indications: Treatment of ocular hypertension and chronic
colic, renal lesions, allergic skin reactions, fever, thirst, open-angle glaucoma.
dizziness, ataxia, irritability, confusion, reduced libido,
hematuria, glucosuria, renal failure, abnormal LFTs, loss Contraindications: Sinus bradycardia greater than first-
of appetite, taste alterations, transient myopia, tinnitus, degree atrioventricular block; cardiogenic shock; overt
hearing disturbance. cardiac failure.
Potentially fatal: Erythema multiforme, SJS, toxic
epidermal necrolysis, fulminant hepatic necrosis, Dose:
anaphylaxis. Ocular hypertension; open-angle glaucoma, into the eye,
Rare: Photosensitivity, cholestatic jaundice or hepatitis, ADULT, instill 2 drops into the affected eye(s) twice daily.
flaccid paralysis, convulsions, blood dyscrasias
(potentially fatal). Dose Adjustment: No information found

Drug Interactions: Precautions:

Monitor closely with: WARNING: Has been shown to have a minor effect on
Decreases excretion of the following drugs: heart rate and blood pressure. Use with caution in
Amphetamines, Quinidine patients with a history of cardiac failure or heart block.
Discontinue at the first signs of cardiac failure.
S

Enhances therapeutic effect of Folic Acid Antagonists

Diabetes mellitus (use with caution; may mask signs and
Increases risk of adverse or toxic effects of Phenytoin
(osteomalacia) symptoms of acute hypoglycemia);
Thyrotoxicosis;
Avoid concomitant use with: Muscle weakness;
Increases excretion of Lithium Major surgery;
Pulmonary effects (e.g., asthmatic attacks);
Increases risk of adverse or toxic effects of Acetazolamide: Children;
Aspirin, High-Dose (anorexia, tachypnea, lethargy, Pregnancy;
metabolic acidosis, coma, death) Lactation.

Adverse Drug Reactions:

Increases risk of adverse or toxic effects of the following
drugs:
Common: Eye discomfort (stinging and burning); occasional
tearing.
Sodium Bicarbonate (renal calculus formation)
Less Common: Blurred vision, foreign body sensation,
dryness of eyes, inflammation, discharge, ocular pain,
Increases serum concentration of Cyclosporine
decreased visual acuity, crusty lashes.
Reduces therapeutic effect of Methamine (urinary Rare: Decreased corneal sensitivity, erythema, itchy
sensation, corneal punctate staining, keratitis,
antiseptic effect)
anisocoria, edema, photophobia, bradycardia, heart
Administration: Should be taken with food. block, congestive failure, pulmonary distress, insomnia,
dizziness, vertigo, headaches, depression, lethargy,
Doses more than 1 g per 24 hours does NOT produce an increased signs and symptoms of myasthenia gravis,
increased effect. Adjust doses carefully, paying attention hives, toxic epidermal necrolysis, hair loss, glossitis.
to symptoms and ocular tension. Continuous supervision
by a physician is advisable. A complementary effect has Drug Interactions:
been noted when acetazolamide has been used in
Monitor closely with:
Enhances therapeutic effect of Betaxolol by exerting
conjunction with miotics or mydriatics as the case
potential additive effects:
demanded.

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SENSORY ORGANS

Antiarrhythmics, Beta Blockers, Calcium Channel edema, conjunctival hemorrhage, conjunctivitis, cough,
Blockers, Catecholamine-depleting Drugs, e.g., dizziness, diabetes mellitus, dyspepsia, dyspnea,
Reserpine, Guanethidine, Parasympathomimetic Agents epiphora, eye discharge, eye dryness, eye irritation, eye
pain, eyelid edema, eyelid erythema, fatigue, flu
Enhances therapeutic effect of Betaxolol: syndrome, follicular conjunctivitis, foreign body
Catecholamine-depleting Drugs, e.g., Reserpine (additive sensation, gastrointestinal disorder, headache,
effects) hypercholesterolemia, hypotension, infection, insomnia,
joint disorder, keratitis, lid disorder, osteoporosis,
Increases risk of adverse or toxic effects of Betaxolol: pharyngitis, photophobia, rash, rhinitis, sinus infection,
Catecholamine-depleting Drugs, e.g., Reserpine sinusitis, somnolence, stinging, superficial punctate
(hypotension and/or bradycardia), Digitalis keratopathy, tearing, visual field defect, vitreous
(bradycardia), Epinephrine (mydriasis) detachment, vitreous disorder, vitreous floaters,
worsened visual acuity.
Administration: For topical ophthalmic use only. Shake Less Common: Corneal erosion, nasal dryness, taste
suspension well before use. perversion.
Rare: Bradycardia, iritis, miosis, skin reactions, tachycardia,
Do NOT touch dropper tip to eyelids or other surfaces apnea, hypothermia, hypotonia.
when placing drops in eyes to avoid contamination.
Drug Interactions:
NOTE: Intraocular pressure may require a few weeks to Monitor closely with:
stabilize in some patients. If intraocular pressure is not Enhances therapeutic effect of Brimonidine:
adequately controlled on this regimen, concomitant CNS Depressants e.g., Alcohol (additive or potentiation
therapy with pilocarpine and other miotics and/or effect)
epinephrine and/or carbonic anhydrase inhibitors can be
instituted. Increases risk of adverse or toxic effects of Brimonidine:
MAO Inhibitors e.g., Sertraline (systemic side effects)
Pregnancy Category: C
Avoid concomitant use with:
ATC Code: S01ED02 Enhances therapeutic effect of Alpha2 Agonists e.g.,
Methyldopa (reduced blood pressure)

Decreases metabolism of Brimonidine:

Rx BRIMONIDINE Tricyclic Antidepressants e.g., Amitriptyline (increased
uptake of circulating amines)
Ophth.: 0.15% ophthalmic solution (as tartrate), 5 mL

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bottle Administration: For ophthalmic use only.

A relatively selective alpha2 adrenergic agonist for NOTE: May be used concomitantly with other topical
ophthalmic use. It acts by reducing aqueous humor and ophthalmic drug products to lower intraocular pressure.
increasing uveoscleral outflow. If more than one topical ophthalmic product is being
used, administer at least 5 minutes apart.
Indication: For the lowering of intraocular pressure in open-
angle glaucoma or ocular hypertension Pregnancy Category: B

Contraindication: Hypersensitivity to any component of the ATC Code: S01EA05

formulation

Dose:
For lowering of intraocular pressure, into the eye, ADULT,
Rx BRINZOLAMIDE
instill 1 drop into the affected eye(s) every 8 hours.
Ophth.: 1% ophthalmic suspension, 5 mL bottle
Dose Adjustment: No information found
A carbonic anhydrase inhibitor that inhibits the reversible
Precautions: reaction involving carbon dioxide hydration. Inhibition of
Vascular insufficiency; carbonic anhydrase in the eye decreases aqueous
Children; humor secretion, resulting in a reduction in intraocular
Pregnancy; pressure (IOP).
Lactation.
Indication: Treatment of elevated intraocular pressure in
Adverse Drug Reactions: ocular hypertension or open-angle glaucoma
Common: Allergic conjunctivitis, conjunctival hyperemia,
eye pruritus, burning sensation, conjunctival folliculosis, Contraindication: Hypersensitivity to any component of the
hypertension, ocular allergic reaction, oral dryness, formulation
visual disturbance, allergic reaction, arthralgia, arthritis,
asthenia, blepharitis, blepharoconjunctivitis, blurred
vision, bronchitis, cataract, chest pain, conjunctival

587
 SENSORY ORGANS

Dose: Dose:
Elevated intraocular pressure, into the eye, ADULT, 1 drop Miosis during surgery, reduction of postoperative rises in
into the affected eye(s) 3 times daily. intraocular pressure, by intraocular injection, ADULT,
instill up to 0.5 mL into the anterior chamber before or
Precautions: after securing sutures.
Cross-sensitivity;
Corneal endothelium; Dose Adjustment: No information found
Acute angle-closure glaucoma;
Renal impairment (not recommended in severe renal Precautions:
impairment); WARNING: The vial stopper contains natural rubber
Pregnancy; (latex), which may cause severe allergic reactions.
Lactation.
Children;
Adverse Drug Reactions: Pregnancy.
Common: Blurred vision, taste disturbance (bitter, sour, or
unusual), blepharitis, dermatitis, dry eye, foreign body Adverse Drug Reactions:
sensation, headache, hyperemia, ocular discharge, Common: Corneal clouding, persistent bullous keratopathy,
ocular discomfort, ocular keratitis, ocular pain, ocular retinal detachment, postoperative iritis following
pruritus, rhinitis. cataract extraction, eye irritation (transient), burning and
Less Common: Allergic reactions, alopecia, chest pain, stinging of the eye (transient), ciliary spasm, lacrimation,
conjunctivitis, diarrhea, diplopia, dizziness, dry mouth, difficulty in dark adaptation, increased pupillary block,
dyspnea, dyspepsia, eye fatigue, hypertonia, vitreous hemorrhage, conjunctival vascular congestion,
keratoconjunctivits, keratopathy, kidney pain, lid margin lens changes, lid sensitization, conjunctiva.
crusting, sticky sensation, nausea, pharyngitis, tearing, Less Common: Corneal edema, prolonged miosis, eye
urticarial. inflammation, eye pain, increased intraocular pressure,
ocular hyperemia, blurred vision, visual impairment,
Drug Interactions: vomiting.
Monitor closely with: Rare: Nausea, vomiting, flushing, sweating, diarrhea,
Increases risk of adverse or toxic effects of Brinzolamide: headache, brow ache, abdominal pain, bronchial asthma
Salicylates e.g., Aspirin (acid-base and electrolyte and spasm, pulmonary edema, GI distress, salivation,
alterations) urinary frequency, cardiac arrhythmia, peripheral
vasodilation, tightness in urinary bladder.
Avoid concomitant use with:
Enhances systemic therapeutic effect of Brinzolamide: Drug Interactions:
Carbonic Anhydrase Inhibitors (Oral) e.g., Acetazolamide Monitor closely with:
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Reduces therapeutic effect of Carbachol:

Administration: For topical ophthalmic use only. Cyclopentolate (Ophthalmic), NSAIDs (Ophthalmic)
Do NOT wear contact lenses during treatment. Avoid Avoid concomitant use with:
touching the applicator to the eye or other surfaces. Increases risk of adverse or toxic effects of Carbachol:
Acetylcholinesterase Inhibitors e.g., Neostigmine, Beta
NOTE: May be used concomitantly with other topical Blockers (cardiac conduction abnormalities;
ophthalmic drug products to lower intraocular pressure. bronchoconstriction)
If more than one topical ophthalmic product is being
used, administer at least 5 minutes apart. Administration: For single-dose intraocular use only.
Pregnancy Category: C Use only if container is undamaged. Discard unused
portion.
ATC Code: S01EC04
Aseptically remove the sterile vial from the blister
package by peeling the backing paper and dropping the
Rx CARBACHOL vial onto a sterile tray. Withdraw the contents into a dry
sterile syringe and replace the needle with an atraumatic
cannula. Gently instill no more than ½ milliliter into the
Ophth.: 0.01% intraocular solution, 1.5 mL vial anterior chamber to produce satisfactory miosis. It may
be instilled before or after securing sutures. Miosis is
A sterile balanced salt solution of carbachol for intraocular usually maximal within 2–5 minutes.
injection. It is a potent cholinergic
(parasympathomimetic) agent, which produces Pregnancy Category: C
constriction of the iris and ciliary body resulting in
reduced intraocular pressure. ATC Code: S01EB02

Indications: For obtaining miosis during surgery; for

reduction of the intensity of intraocular pressure
elevation in the first 24 hours following cataract surgery.

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SENSORY ORGANS

Rx DORZOLAMIDE Rx GLYCEROL (GLYCERIN)

Ophth.: 2% eye drops solution (as hydrochloride), 5 mL Oral: USP grade

vial
An osmotic dehydrating agent with hygroscopic and
A carbonic anhydrase inhibitor that inhibits the reversible lubricating properties. Glycerol increases plasma
reaction involving carbon dioxide hydration. Dorzolamide osmolality, resulting in the movement of water from
decreases aqueous humor secretion, resulting in a extravascular spaces into the plasma through osmosis.
reduction in intraocular pressure (IOP).
Indications: Management of glaucoma; reduction of
Indication: Treatment of elevated intraocular pressure in intraocular pressure prior to eye surgery
ocular hypertension or open-angle glaucoma
Dose:
Dose: Elevated intraocular pressure, by mouth, ADULT, 1–2 g/kg
Elevated intraocular pressure, into the eye, ADULT, instill 1 taken as a single dose; additional doses of 500 mg/kg
drop in the affected eye(s) 3 times daily. every 6 hours may be taken if needed; CHILD, 1–1.5
g/kg taken as a single dose, may be repeated in 4–8
Precautions: hours if needed.
Cross-sensitivity;
Allergic reactions (local ocular adverse effects, i.e., Dose Adjustment: No information found
conjunctivitis, lid reactions, have been reported with
chronic use); Administration: For use as an oral demulcent. Do NOT
Bacterial keratitis; swallow excessive amounts.
Corneal endothelium;
Acute angle-closure glaucoma; Mix it with a small amount of unsweetened lemon, lime,
Renal and hepatic impairment (use is not recommended); or orange juice, pour over cracked ice, and sip through a
Pregnancy (use with caution); straw to mask its unpleasant taste. Lie down when taking
Lactation (use with caution). this medicine and for a short time after taking it to
prevent or relieve headaches.
Adverse Drug Reactions:
Common: Ocular burning or stinging, ocular discomfort, NOTE: When used preoperatively, administer 60–90
bitter taste, superficial punctate keratitis, ocular allergic minutes prior to surgery. Precautions should be taken to
reaction, conjunctivitis, lid reactions, blurred vision, eye avoid acute urinary retention.
redness, eye tearing, eye dryness, photophobia.

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Less Common: Headache, nausea, asthenia or fatigue. See Glycerol (Glycerin) under Other Nervous System Drugs
Rare: Skin rashes, urolithiasis, iridocyclitis. in Chapter 10: Nervous System for other information.

Drug Interactions: Pregnancy Category: C

Monitor closely with:
Increases risk of adverse or toxic effects of Dorzolamide: ATC Code: Not available
Alpha / Beta Agonists, Indirect Acting e.g., Methyldopa;
Salicylates, High-dose (acid-base and electrolyte
alterations)
Rx LATANOPROST
Avoid concomitant use with:
Enhances systemic therapeutic effect of Dorzolamide: Ophth.: 50 micrograms/mL eye drops solution, 2.5 mL
Carbonic Anhydrase Inhibitors, Oral bottle

Administration: For topical ophthalmic use only. A prostaglandin F2α analogue that reduces intraocular
pressure by increasing the outflow of aqueous humor.
May be used concomitantly with other topical ophthalmic
drug products to lower intraocular pressure. If more than Indication: Reduction of elevated intraocular pressure (IOP)
one topical ophthalmic product is being used, administer in patients with open-angle glaucoma or ocular
at least 5 minutes apart. hypertension.

Pregnancy Category: C Contraindication: Known hypersensitivity to latanoprost,

benzalkonium chloride, or any other ingredients in this
ATC Code: S01EC03 product.

Dose:
Elevated intraocular pressure, into the eye, ADULT, instill 1
drop into the affected eye(s) once daily in the evening.

Dose Adjustment: No information found

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 SENSORY ORGANS

Precautions: Contraindications: Severe renal disease (anuria); severe

Pigmentation; dehydration; active intracranial bleeding except during
Macular edema (use with caution); craniotomy; progressive heart failure, pulmonary
Intraocular inflammation (use with caution); congestion, or renal dysfunction after mannitol
Eyelash changes (e.g., increased length, thickness, administration; severe pulmonary edema or congestion.
pigmentation, number of lashes or hairs, and
misdirected growth of lashes); Dose:
Bacterial keratitis and herpetic keratitis; Reduction of intraocular pressure, by IV injection, ADULT,
Pregnancy (no adequate and well-controlled studies); 0.25-2 g/kg administered over 30-60 minutes 1-1.5
Lactation (not known if excreted in breast milk). hours prior to surgery; CHILD, 1-2 g/kg or 30-60 g/m2
administered over 30-60 minutes 1-1.5 hours prior to
Adverse Drug Reactions: surgery.
Common: Iris pigmentation changes, eyelid skin darkening, Reduction of intraocular pressure (traumatic hyphema), by
eyelash changes, intraocular inflammation, macular IV injection, ADULT, 1.5 g/kg administered over 45
edema, foreign body sensation, punctate keratitis, minutes twice daily for IOP >35 mm Hg; may administer
stinging, conjunctival hyperemia, blurred vision, itching, every 8 hours; CHILD, 1.5 g/kg administered over 45
burning, excessive tearing, eyelid discomfort or pain, dry minutes twice daily for IOP >35 mm Hg; may administer
eye, eye pain, eyelid margin crusting, erythema of the every 8 hours in patients with extremely high pressure.
eyelid, photophobia, eyelid edema, upper respiratory
tract infection, nasopharyngitis, myalgia, arthralgia, back Administration: For IV administration. Determine
pain, allergic skin reaction. concentration and rate of administration based on
Less Common: Dizziness, headache, toxic epidermal indication or severity, or adjusted to urine flow.
necrolysis, asthma, dyspnea, pruritus, herpes keratitis,
angina, chest pain, trichiasis, iris cyst. Inspect for crystals prior to administration. If crystals are
present, re-dissolve by warming solution. Use filter type
Drug Interactions: administration set for infusion solutions containing
Avoid concomitant use with: ≥20% Mannitol.
Reduces therapeutic effect of Latanoprost:
Prostaglandins and Prostaglandin Analogs (paradoxical Do NOT administer until adequacy of renal function and
elevations in IOP) urine flow is established. Use 1–2 test doses to assess
renal response.
Administration: For topical ophthalmic use only. Do NOT
exceed once daily. NEVER add to whole blood for transfusion or administer
through the same set by which blood is being infused to
Contact lenses should be removed prior to prevent crenation and agglutination of red blood cells.
S

administration and may be reinserted 15 minutes after

administration. See Mannitol under Blood Substitutes and Perfusion
Solutions – IV Solutions Producing Osmotic Diuresis in
NOTE: May be used concomitantly with other topical Chapter 2: Blood and Blood Forming Organs for other
ophthalmic drug products to lower IOP. If more than one information.
topical ophthalmic drug is being used, administer drugs
at least 5 minutes apart. Pregnancy Category: C

MISSED DOSE. In case of missed dose, continue with the ATC Code: Not available
next dose as normal.

Pregnancy Category: C
Rx PILOCARPINE
ATC Code: S01EE01
Ophth.:
1% eye drops solution (as hydrochloride), 10 mL and 15 mL
bottle
Rx MANNITOL 2% eye drops solution (as hydrochloride), 10 mL and 15 mL
bottle
Inj.: 20%, 250 mL and 500 mL bottle (IV)
A direct acting cholinergic parasympathomimetic agent that
A hexahydric alcohol related to mannose that acts as an acts through direct stimulation of muscarinic receptors
osmotic agent. When given parenterally, mannitol raises and smooth muscle, such as the iris and secretory
the osmotic pressure of the plasma, thus drawing water glands. It contracts the ciliary muscle, causing increased
out of body tissues and producing osmotic diuresis. tension on the scleral spur and opening of the trabecular
meshwork spaces. This reduces outflow resistance,
Indication: Reduction of increased intraocular pressure resulting in a decrease in intraocular pressure (IOP).
Pilocarpine also causes a contraction of the iris sphincter
NOTE: NOT recommended to be used for the prevention of muscle, producing miosis.
acute renal failure and/or promotion of diuresis.

590
SENSORY ORGANS

Indications: Reduction of elevated IOP in open-angle Parasympathomimetics (additive effect)

glaucoma or ocular hypertension; management of acute
angle-closure glaucoma; prevention of post-operative Increases risk of adverse or toxic effects of the following
elevated IOP associated with laser surgery; induction of drugs:
miosis. Beta Blockers (conduction disturbances), Miotic drugs
(toxic reactions)
Contraindication: Conditions where constriction is
undesirable (e.g., acute iritis). Reduces anticholinergic effects of Pilocarpine:
Atropine, Ipratropium (Inhalation)
Dose:
Reduction of elevated IOP in open-angle glaucoma or ocular Administration: For topical ophthalmic use only. NOT for
hypertension, into the eye, ADULT, 1 drop of 2% solution injection
in the affected eye(s) up to 4 times daily; CHILD <2 years,
1 drop of 2% solution in the affected eye(s) 3 times daily Apply finger pressure to the lacrimal sac (inside corner of
[NOTE: The frequency of instillation and concentration of the eye) during and for 1–2 minutes after instillation to
pilocarpine are determined by the severity of the decrease risk of absorption and systemic effects.
elevated IOP and miotic response of the patient].
Contact lenses should be removed prior to the
Management of acute angle-closure glaucoma, into the eye, administration and may be reinserted 10 minutes after
ADULT, initially 1 drop of 2% solution in the affected administration.
eye(s) up to 3 times over a 30-minute period [NOTE:
Treatment with secretory suppressants and Do NOT touch dropper tip to eyelids or other surfaces
hyperosmotic agents may be needed to lower IOP below when placing drops in eyes to avoid contamination.
50 mmHg and relieve iris ischemia prior to
administration. If laser iridoplasty or iridotomy is used to NOTE: Pilocarpine-naïve patients should be started on 1%
break the attack, instill 1 drop of 4% solution prior to the concentration as higher concentrations are often not
procedure. Following laser iridoplasty, instill 1 drop of 2% tolerated initially.
solution 4 times daily until an iridotomy can be
performed]. May be used in combination with beta blockers, carbonic
anhydrase inhibitors, hyperosmotic agents, or
Prevention of post-operative elevated IOP associated with sympathomimetics. If more than one topical ophthalmic
laser surgery, into the eye, ADULT, instill 1 drop of 1% or product is being used, administer at least 5 minutes
2% solution in the affected eye(s) 15–60 minutes prior apart.
to surgery, or 2 drops 5 minutes apart.
Pregnancy Category: C

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Induction of miosis, into the eye, ADULT, instill 1 drop of 2%
solution in the affected eye(s) or 2 drops 5 minutes ATC Code: S01EB01
apart; CHILD <2 years, 1 drop 2% solution in the affected
eye(s) 15 to 60 minutes prior to surgery.

Dose Adjustment: No information found Rx TAFLUPROST

Precautions: Eye Drops Solution: 15 mcg/mL, 0.3 mL bottle (single dose)

Poor illumination (e.g., accommodation spasm);
Pre-existing retinal disease (e.g., rare cases of retinal Tafluprost acid is a fluorinated prostaglandin F2-alpha
detachment); analog believed to reduce intraocular pressure by
Iritis; increasing outflow of aqueous humor via the uveoscleral
Primary congenital glaucoma (e.g., cases of paradoxical pathway; exact mechanism by which it reduces
increase in IOP); intraocular pressure is unknown.
Pregnancy (administer only if clearly needed);
Lactation (not known if excreted in breast milk). Indications: Reduction of intraocular pressure in patients
with open-angle glaucoma or ocular hypertension.
SKILLED TASKS. May cause blurred vision. Avoid performing
tasks, which require mental alertness, e.g., operating Contraindications: None.
machinery or driving.
Dose:
Adverse Drug Reactions: Elevated intraocular pressure, ADULT, instill affected eye(s)
Common: Headache, brow ache, accommodative change, once daily in the evening.
blurred vision, eye irritation, visual impairment, eye pain,
ciliary spasm, conjunctival vascular congestion, induced Dose Adjustment:
myopia, reduced visual acuity in poor illumination, lens Renal and Hepatic impairment:
opacity (prolonged use). No dosage adjustments provided in the manufacturer’s
labeling.
Drug Interactions:
Avoid concomitant use with:
Enhances therapeutic effect of Pilocarpine:

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 SENSORY ORGANS

Precautions: If handled improperly, ophthalmic medications can

May cause changes to pigmented tissues and macular become contaminated by common bacteria known
edema; to cause eye infections, which may cause serious
Use in caution in patients with intraocular inflammation. damage to the eye and subsequent loss of vision

Adverse Drug Reactions: Cardiac failure;

Common: Conjunctival hyperemia. Obstructive pulmonary disease;
Less Common: Headache, urinary tract infection, common Major surgery (impairs response of heart to beta-
cold, eye irritation, stinging of eyes, conjunctivitis, adrenergically mediated reflex stimuli; may augment risk
cataract, eye pain, xerophthalmia, blurred vision, of general anesthesia in surgical procedures);
hyperpigmentation of eyelashes, increased eyelash Muscle weakness;
length, and cough. Diabetes mellitus (may mask signs and symptoms of acute
Rare: Dyspnea, exacerbation of asthma, iris hypoglycemia);
hyperpigmentation, iritis, and uveitis. Thyrotoxicosis;
Bacterial keratitis (associated with use of multiple dose
Drug Interactions: containers of topical ophthalmic products);
None known. Angle-closure glaucoma;
Children;
Administration: Instill into conjunctival sac of affected Pregnancy;
eye(s). Do not exceed once daily dosing regimen. If other Lactation (detected in human milk).
ophthalmics are prescribed, each should be
administered 5 minutes apart. Use immediately after Adverse Drug Reactions:
opening preservative-free product. Common: Eye burning and stinging
Less Common: Headache, asthenia, fatigue, chest pain,
Pregnancy Category: C bradycardia, arrhythmia, hypotension, hypertension,
syncope, heart block, cerebral vascular accident,
ATC Code: S01EE05 cerebral ischemia, cardiac failure, worsening of angina
pectoris, palpitation, cardiac arrest, pulmonary edema,
edema, claudication, Raynaud's phenomenon, cold
Rx TIMOLOL hands and feet, nausea, diarrhea, dyspepsia, anorexia,
dry mouth, systemic lupus erythematosus, dizziness,
increase in signs and symptoms of myasthenia gravis,
Ophth.: 0.5% eye drops solution (as maleate), 5 mL paresthesia, somnolence, insomnia, nightmares,
bottle behavioral changes, psychic disturbances, alopecia,
psoriasiform rash or exacerbation of psoriasis, signs and
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A non-selective beta blocking agent that reduces intraocular symptoms of systemic allergic reactions, anaphylaxis,
pressure (IOP) whether accompanied by glaucoma or bronchospasm, respiratory failure, dyspnea, nasal
not. congestion, cough, upper respiratory infections, ocular
irritation, ptosis, decreased corneal sensitivity, cystoid
Indication: Treatment of elevated IOP in ocular hypertension macular edema, visual disturbances,
or open-angle glaucoma. pseudopemphigoid, choroidal detachment following
filtration surgery, tinnitus, retinoperitoneal fibrosis,
Contraindications: Bronchial asthma; severe chronic decreased libido, impotence, Peyronie’s disease.
obstructive pulmonary disease; sinus bradycardia;
second or third-degree atrioventricular block; overt Drug Interactions:
cardiac failure. Monitor closely with:
Dose: Enhances therapeutic effect of Timolol:
Elevated IOP, into the eye, ADULT, 1 drop in the affected Catecholamine-depleting Drugs, e.g., Reserpine (additive
eye(s) twice daily. effects), Quinidine (potentiated systemic beta blockade)

NOTE: Evaluate after approximately 4 weeks of treatment to Enhances therapeutic effect of the following drugs:
determine IOP. Clonidine (exacerbates rebound hypertension following
withdrawal of clonidine), Digitalis (prolonged
If IOP is maintained at satisfactory levels, the dosage atrioventricular conduction time)
schedule may be changed to 1 drop once daily in the
affected eye(s). Measure IOP at different times during Increases risk of adverse or toxic effects of Timolol:
the day to best determine response to once-a-day dose Catecholamine-depleting Drugs, e.g., Reserpine
due to diurnal variations in intraocular pressure. (hypotension and/or marked bradycardia)

Dose Adjustment: No information found Avoid concomitant use with:

Enhances therapeutic effect of Timolol:
Precautions: Beta Blockers
WARNING: May exhibit the same adverse reactions as
with systemic beta blockers, including severe Increases risk of adverse or toxic effects of Timolol:
respiratory reactions and cardiac reactions. Calcium Antagonists (atrioventricular conduction
disturbances; left ventricular failure; hypotension)

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SENSORY ORGANS

Reduces therapeutic effect of Epinephrine Eyelash changes (e.g., increased length, thickness, and
(unresponsiveness to usual doses used in anaphylaxis) number of lashes);
Intraocular inflammation;
Administration: For topical ophthalmic use only. Macular edema;
Angle-closure, inflammatory, or neovascular glaucoma;
If using a bottle for the first time, make sure the safety seal Bacterial keratitis (associated with use of multiple-dose
is unbroken. containers)
Children (not recommended for patients <16 years due to
Drop-tainer bottle: Wash hands before each use. Shake potential safety concerns related to increased
once and remove the screw cap. Invert the bottle and pigmentation following long-term chronic use).
hold the bottle between your thumb and middle finger. (If Pregnancy;
self-administered, instruct patient that the tips of the Lactation.
fingers point towards them). Tilt head back and position
the bottle above the affected eye. With the opposite Adverse Drug Reactions:
hand, place a finger under the eye and gently pull down Common: Ocular hyperemia, conjunctival hyperemia,
until a “V” pocket is made between the eye and the lower decreased visual acuity, eye discomfort, foreign body
lid. With the hand holding the bottle, place the index sensation, eye pain, eye pruritus, abnormal vision,
finger on the bottom of the bottle and push the bottom blepharitis, blurred vision, cataract, conjunctivitis,
of the bottle to dispense 1 drop. Do NOT squeeze the corneal staining, dry eye, iris discoloration, keratitis, lid
sides of the bottle. Repeat with the other eye if needed. margin crusting, ocular inflammation, photophobia,
Replace screw cap by turning until firmly touching the subconjunctival hemorrhage, tearing, allergy, angina
bottle. pectoris, anxiety, arthritis, back pain, bradycardia,
bronchitis, chest pain, cold or flu syndrome, depression,
Do NOT touch dropper tip to eyelids or other surfaces dyspepsia, GI disorder, infection, headache,
when placing drops in eyes to avoid contamination. hypercholesterolemia, hypertension, hypotension, pain,
prostate disorder, sinusitis, urinary incontinence, urinary
The dispenser tip is designed to provide a pre-measured tract infections.
drop. Do NOT enlarge the hole of the dispenser tip. Less Common: Arrhythmia, vomiting, epistaxis, tachycardia,
insomnia.
NOTE: Doses above 1 drop twice daily have not shown to
produce further reduction in IOP. If IOP is still not at a Drug Interactions:
satisfactory level on this regimen, concomitant therapy Avoid concomitant use with:
with other agent(s) for lowering intraocular pressure can Reduces therapeutic effect of Travoprost:
be instituted. Concomitant use of 2 topical beta blockers NSAIDs
is not recommended.

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Administration: For topical ophthalmic use only.
If more than one topical ophthalmic product is being
used, administer at least 5 minutes apart. Do NOT administer more than once daily since it has
been shown to decrease IOP lowering effect.
Pregnancy Category: C
Contact lenses should be removed prior to the
ATC Code: S01ED01 administration and may be reinserted 15 minutes after
administration.

NOTE: May be used in combination with other topical

Rx TRAVOPROST ophthalmic drugs to lower IOP. If more than one topical
ophthalmic product is being used, administer at least 5
Ophth.: 0.004% ophthalmic solution, 2.5 mL bottle minutes apart.

A synthetic prostaglandin F analogue that reduces Pregnancy Category: C

intraocular pressure (IOP) by increasing uveoscleral
outflow. ATC Code: S01EE04

Indication: For the reduction of elevated IOP in patients with

open-angle glaucoma or ocular hypertension

Contraindication: Hypersensitivity to any component of the

formulation.

Dose:
Elevated IOP, into the eye, ADULT, 1 drop in the affected
eye(s) once daily in the evening.

Precautions:
Pigmentation (e.g., increased pigmentation to the iris,
eyelid, and eyelashes);

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 SENSORY ORGANS

MYDRIATICS AND CYCLOPLEGICS Drug Interactions:

Monitor closely with:
Enhances anticholinergic effects of Atropine by exhibiting
Rx ATROPINE additive effects:
Antidepressants, Antihistamines e.g., Diphenhydramine,
Quinidine
Ophth.: 1% eye drops solution (as sulfate), 5 mL and 10
mL bottle
Avoid concomitant use with:
Increases risk of adverse or toxic effects of MAO Inhibitors
An alkaloid from Atropa belladonna that acts as an
e.g., Selegeline (hypertensive crisis)
anticholinergic agent. Atropine blocks the responses of
the sphincter muscle of the iris and the accommodative
Administration: For topical ophthalmic use only. NOT for
muscle of the ciliary body of cholinergic stimulation,
injection. Keep out of reach of children.
producing pupillary dilation (mydriasis) and paralysis of
accommodation (cycloplegia).
Always wash hands before and after administration.
Indications: For mydriasis and/or cycloplegia; for cycloplegic
Drop-tainer bottle: Wash hands before each use. Shake
refraction; for pupillary dilation desired in inflammatory
once and remove the screw cap. Invert the bottle and
conditions of the iris and uveal tract.
hold the bottle between your thumb and middle finger. (If
self-administered, instruct patient that the tips of the
Contraindications: Primary glaucoma or tendency toward
fingers point towards them). Tilt head back and position
glaucoma.
the bottle above the affected eye. With the opposite
hand, place a finger under the eye and gently pull down
Dose:
until a “V” pocket is made between the eye and the lower
For eye refraction, into the eye, ADULT, instill 1 drop to the
lid. With the hand holding the bottle, place the index
eye(s) for 1–2 days before the procedure or on a single
finger on the bottom of the bottle and push the bottom
occasion 1 hour before refraction; CHILD, instill 1 drop
of the bottle to dispense 1 drop. Do NOT squeeze the
twice daily for 1–3 days before the procedure with an
sides of the bottle. Repeat with the other eye if needed.
additional dose 1 hour before the procedure.
Replace screw cap by turning until firmly touching the
For uveitis and inflammatory eye disorders, into the eye,
bottle.
ADULT, 1–2 drops of 1% solution to each eye up to 3–4
times daily; CHILD, instill 1 drop up to 3 times daily.
Apply finger pressure to the lacrimal sac (inside corner of
the eye) during and for a few minutes after instillation to
Dose Adjustment: No information found
decrease risk of absorption and systemic effects.
Precautions:
S

Contact lenses should be removed prior to the

WARNING: Excessive use in children or certain administration and may be reinserted 10 minutes after
individuals with previous history of susceptibility to administration.
belladonna alkaloids may produce systemic
symptoms of atropine poisoning. Do NOT touch dropper tip to eyelids or other surfaces
when placing drops in eyes to avoid contamination.
Photophobia and blurred vision (e.g., sensitivity to light; may Pregnancy Category: C
last up to 2 weeks);
Elevation of blood pressure; ATC Code: S01FA01
Children (use of 1% solution is not recommended in children
<3 months; limit use in children <3 years with Down
syndrome, spastic paralysis or brain damage to no more
than 1 drop per eye per day). Rx PHENYLEPHRINE
Pregnancy;
Lactation. Ophth.: 2.5% eye drops solution (as hydrochloride), 5
mL bottle
SKILLED TASKS. Causes dilation of pupils, which may impair
ability to perform tasks that require mental alertness, An alpha receptor sympathomimetic agent used in local
e.g., operating machinery or driving. ocular disorders because of its vasoconstrictor and
mydriatic action.
Adverse Drug Reactions:
Common: Photophobia, blurred vision, superficial keratitis, Indications: Vasoconstrictor, decongestant, and mydriatic in
decreased lacrimation, papillary conjunctivitis, contact a variety of ophthalmic conditions and procedures;
dermatitis, lid edema, decreased secretions from pupillary dilation in uveitis; for refraction without
mucous membranes, restlessness, irritability, delirium, cycloplegia; for funduscopy and other diagnostic
tachycardia, flushed skin of face and neck. procedures.
Less Common: Vascular congestion, exudate, eczematoid
dermatitis, hypotension with progressive respiratory Contraindications: Narrow angle glaucoma; low birth weight
depression, coma, death. infants; severe arteriosclerotic cardiovascular or
cerebrovascular disease; intraocular operative

594
SENSORY ORGANS

procedures where corneal epithelial barrier has been Apply finger pressure to the lacrimal sac (inside corner of
disturbed. the eye) during and for 2–3 minutes after instillation to
decrease risk of absorption and systemic effects.
Dose:
Vasoconstriction and pupil dilation, into the eye, ADULT, 1 Do NOT touch dropper tip to eyelids or other surfaces
drop on the upper limbus, may repeat after 1 hour if when placing drops in eyes to avoid contamination.
needed.
Uveitis, into the eye, ADULT, 1 drop to the upper surface of Pregnancy Category: C
the cornea, may be repeated as necessary, not to exceed
3 times; treatment may be continued the following day if ATC Code: S01FB01
necessary.
Mydriasis, into the eye, ADULT and CHILD ≥1 year, instill 1
drop, may repeat in 10–60 minutes as needed; CHILD
<1 year, instill 1 drop 15–30 minutes prior to procedure. Rx TROPICAMIDE
Ophthalmoscopic examination, into the eye, ADULT, 1 drop
in each eye; sufficient mydriasis to permit examination is Ophth.: 0.5% eye drops solution, 5 mL bottle
produced in 15–30 minutes; dilation lasts for 1–3 hours.
Blanching test, into the eye, ADULT, instill 1–2 drops to the An anticholinergic agent that blocks the responses of the
injected eye; examine for perilimbal blanching after 5 sphincter muscle of the iris and the ciliary muscle to
minutes [if blanching occurs, congestion is superficial]. cholinergic stimulation, producing mydriasis, with only
slight cycloplegia. It acts rapidly, and the duration of
NOTE: May instill a suitable topical anesthetic a few minutes activity is relatively short.
prior to phenylephrine to prevent stinging and
consequent dilution of the solution by lacrimation. Indication: For mydriasis and cycloplegia for diagnostic
procedures.
Dose Adjustment: No information found
Contraindications: Primary glaucoma
Precautions:
WARNING: Prolonged exposure to air or strong light Dose:
may cause oxidation and discoloration. Do NOT use Examination of fundus, into the eye, ADULT, instill 1 to 2
if solution is brown or contains a precipitate. drops 15–20 minutes prior to examination.

Cardiac disease; NOTE: Patients with heavily pigmented irides may require
Significant hypertension; larger doses.
Advanced arteriosclerosis;

S
Elderly (rebound miosis has been reported; may develop Mydriasis will reverse spontaneously with time, typically
transient pigment floaters in the aqueous humor 40–45 4–8 hours. Some cases may take up to 24 hours.
minutes following administration);
Children and infants (use with caution in children with Dose Adjustment: No information found
known cardiac anomalies).
Pregnancy (use only if clearly needed); Precautions:
Lactation (use with caution). WARNING: May cause CNS disturbances, which may
be dangerous in pediatric patients.

Adverse Drug Reactions:

Common: Marked increase in blood pressure, syncope, Reproductive effects;
myocardial infarction, tachycardia, arrhythmia, fatal CNS effects (e.g., psychotic reaction and behavioral
subarachnoid hemorrhage. disturbances);
Photophobia and blurred vision (e.g., sensitivity to light; may
Drug Interactions: last up to 2 weeks);
Monitor closely with: Elderly;
Increases risk of systemic adverse effects of Beta Blockers Children (psychotic reactions, behavioral disturbances, and
e.g., Propranolol vasomotor or cardiorespiratory collapse have been
reported);
Enhances therapeutic effect of MAO inhibitors e.g., Pregnancy;
Selegeline (adrenergic effects) Lactation.

SKILLED TASKS. Causes dilation of pupils, which may impair

Avoid concomitant use with:
Enhances systemic pressor effects of Phenylephrine, ability to perform tasks that require mental alertness,
including tachycardia: e.g., operating machinery or driving.
Atropine, Tricyclic antidepressants e.g., Amitriptyline
Adverse Drug Reactions:
Administration: For topical ophthalmic use only. NOT for
Common: Increased intraocular pressure, psychotic
reactions, behavioral disturbances, transient stinging,
intraocular use.
cardiorespiratory collapse (children), dryness of mouth,
blurred vision, photophobia with or without corneal

595
 SENSORY ORGANS

staining, tachycardia, headache, parasympathetic Adverse Drug Reactions:

stimulation, allergic reaction. Clinically Significant: Shock, anaphylactoid reaction such as
erythema, rash, dyspnea, decreased blood pressure, and
Drug Interactions: eyelid edema, etc.
Monitor closely with: Incidence Unknown: Blepharitis, eyelid dermatitis, itching,
Reduces antihypertensive effect of the following drugs: conjunctivitis, corneal epithelium disorder, increased
Carbachol, Cholinesterase Inhibitors (Ophthalmic), intraocular pressure, dry mouth, facial flushing,
Pilocarpine tachycardia, and hypertension.

Administration: For topical ophthalmic use only. NOT for Drug Interactions:
injection. MAO inhibitors- rapid increase in blood pressure may occur.
Tricyclic/tetracyclic antidepressants e.g. Amitriptyline- rapid
Apply finger pressure to the lacrimal sac (inside corner of increase in blood pressure may occur.
the eye) during and for 2–3 minutes after instillation to
decrease risk of absorption and systemic effects. Administration: For ophthalmic use only. Apply into the
conjunctival sac after eyelid retraction, while the patient
Always wash hands before and after administration. is in a supine position. After application, the treated eye
should be closed for 1-5 minutes, while the lacrimal sac
Contact lenses should be removed prior to is compressed appropriately.
administration.
Pregnancy Category: C
Do NOT touch dropper tip to eyelids or other surfaces
when placing drops in eyes to avoid contamination. ATC Code: S01FA56

Pregnancy Category: C
DIAGNOSTIC AGENTS
ATC Code: S01FA06

Rx FLUORESCEIN
TROPICAMIDE + PHENYLEPHRINE
Rx
HYDROCHLORIDE) Inj.: 10% (100 mg/mL) (as sodium salt), 5 mL ampule (IV)

Eye Drops Solution: 5mg/5 mg per mL (fixed dose Ophth.: 1 mg and 9 mg strips (as sodium salt)
combination), 10 mL bottle
A precursor of eosins that temporarily stains any cell it
S

A clear colorless to pale yellow aqueous ophthalmic enters, marking damaged areas.
solution.
Indications: Angiography of the retina and iris vasculature;
Indications: Mydriasis and cyclopegia for the purpose of aid in the fitting of hard contact lenses; detection of
diagnosis or treatment. corneal lesions and foreign bodies; diagnostic
ophthalmic procedures; applanation tonometry.
Contraindications: Patients with glaucoma or predisposed
to ocular hypertension Dose:
Angiography of the retinal and iris vasculature, by
antecubital vein, ADULT, 500 mg over 5–10 seconds;
Dose: CHILD, 7.5 mg/kg.
Mydriasis, ADULT and CHILD, instill 1-2 drops once or 1 drop Aid in the fitting of hard contact lenses, detection of corneal
twice every 3-5 minutes. lesions and foreign bodies, and diagnostic ophthalmic
procedures, into the eye, ADULT, instill into the desired
Cyclopegia, ADULT and CHILD, 1 drop 2-3 times every 3-5 eye(s), may be given in combination with a local
minutes. anesthetic as 0.25% solution with oxybuprocaine HCl or
proxymetacaine HCl.
Dose Adjustment:
Use in Elderly: Dose Adjustment: No information found
Caution should be exercised when used in elderly.
Precautions:
Precautions: WARNING: An emergency tray should be available
Use in caution in children, hypertensive patients, patients prior to the injection of fluorescein.
with arteriosclerosis, heart disease, diabetes, and
hyperthyroidism;
May cause bradycardia, apnea when administered to Respiratory reaction;
premature infants; Severe local tissue damage (e.g., severe pain in the arm,
Activities requiring clear vision must be avoided; sloughing of the skin, superficial phlebitis, subcutaneous
Protection from direct sunlight or other powerful light should granuloma, and toxic neuritis along the median curve in
be exercised. the antecubital area);

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SENSORY ORGANS

GI effects (e.g., nausea, vomiting, and GI distress commonly OTHER OPHTHALMOLOGICALS

occur within the first few minutes following injection);
Pregnancy (use only if clearly needed); FOR DRY EYES
Lactation (excreted in breast milk for up to 4 days; following
fluorescein angiography, discontinue breastfeeding for
at least 4 days and the milk should be pumped off and OTC CARBOXYMETHYLCELLULOSE
discarded during this period).

Adverse Drug Reactions: Ophth.: 0.5% eye drops solution (as sodium),
Common: Nausea, vomiting, GI distress, strong taste, 0.4 mL and 15 mL bottle
extravasation, hypersensitivity reactions, transient
coloration of skin and urine, staining of the skin or A cellulose derivative prepared by the treatment of cellulose
clothing, staining of soft contact lenses, headache, with alkali and monochloroacetic acid or its sodium salt.
thrombophlebitis.
Rare: Cardiac arrest, basilar artery ischemia, severe shock, Indications: For the temporary relief of burning, irritation,
convulsions, syncope. and discomfort due to dryness of the eye or from
irritation from wind or sun; for protection against further
Drug Interactions: No information found irritation. It is commonly used in its salt form as a
viscosity enhancer and emulsifier in food products or as
Administration: a lubricant in eye drops.
For IV administration, inspect visually for particulate
matter and discoloration prior to administration. Do NOT Dose:
mix or dilute with other solutions or drugs. Attach a Eye irritation, into the eye, ADULT and CHILD, 1–2 drops in
syringe into a transparent tubing and a 23-gauge the affected eye(s) as needed.
butterfly needle for injection. Insert the needle and draw
the patient’s blood to the hub of the syringe so that a Dose Adjustment: No information found
small air bubble separates the patient’s blood in the
tubing from the fluorescein. With the room lights on, Precautions:
slowly inject the blood back into the vein while watching Stop use and consult a doctor if eye pain, changes in vision,
the skin over the needle tip. If the needle has or continued redness or irritation of the eye occurs and
extravasated, blood will be seen to bulge the skin over persists for more than 72 hours.
the needle tip. If this occurs, stop before any fluorescein
is injected. When assured that extravasation has not Adverse Drug Reactions:
occurred, the room light may be turned off and the Rare: Allergic reaction, hives, itching, red, swollen, blistered,
fluorescein injected rapidly (1 mL/second) into the or peeling skin with or without fever, wheezing, tightness

S
antecubital vein. Luminescence usually appears in the in the chest or throat, trouble breathing, swallowing, or
retina and choroidal vessels in 7–14 seconds and can talking, unusual hoarseness, swelling of the mouth, face,
be observed by standard viewing equipment. Flush IV lips, tongue, or throat, change in eyesight, eye pain, or
cannulas before and after drugs are injected to avoid very bad eye irritation.
physical incompatibility reactions.
Drug Interactions: No information found
For sterile ophthalmic strips, hold the package in the
middle and tear down toward the sterile strip. Turn the Administration: For external use only. Always replace cap
package over and tear down from the other side, taking after use.
care not to tear the sterile strip. Grasp each end of the
package firmly and pull apart. Do NOT touch the sterile Keep out of reach of children. If swallowed, get medical
strip. Moisten the strip with 1–2 drops of sterile irrigating help or contact a poison control center immediately.
or saline solution prior to application to ensure full
fluorescence and patient comfort. Touch the conjunctiva Tilt head back and drop the product directly into the eye.
or fornix as required with the moistened tip. Instruct Apply finger pressure to the lacrimal sac (inside corner of
patient to blink several times after application. Contents the eye) during and for 1–2 minutes after instillation to
may not be sterile if individual strips have been damaged decrease risk of absorption and systemic effects.
or previously opened.
Do NOT use if solution is cloudy, leaking, has particles,
Pregnancy Category: C or changes color. Do NOT use if neck band is broken or
missing.
ATC Code: S01JA01
Do NOT wear contact lenses during treatment. Do NOT
touch dropper tip to eyelids or other surfaces when
placing drops in eyes to avoid contamination.

Pregnancy Category: Not classified

ATC Code: S01XA20

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 SENSORY ORGANS

Rx CYCLOSPORINE (CICLOSPORIN) OTC HYPROMELLOSE

Ophth.: 0.05% ophthalmic emulsion, 0.4 mL vial Ophth.: 5 mg/mL eye drop solution, and 10 mg/mL eye
drops solution,10 mL and 15 mL bottle
An immunosuppressant prepared as a sterile ophthalmic 0.3% ophthalmic solution, 10 mL bottle
preparation. Cyclosporine increases tear production that
has been reduced due to inflammation in the eye(s). A methyl and hydroxypropyl mixed ether of cellulose that is
used as artificial tears to prevent conjunctival and
Indication: To increase tear production when suppressed corneal damage due to impaired lacrimal secretions.
tear production is presumed to be due to ocular
inflammation. Indications: Protectant against further irritation or to relieve
dryness of the eye.
Dose:
Dry eyes, into the eye, ADULT, instill 1 drop once (0.1%) or Dose:
twice (0.05%) daily in each eye, approximately 12 hours Dry eyes, into the eye, ADULT, instill 1–2 drops into the
apart. affected eye(s) as needed.

Dose Adjustment: NOTE: Consult your doctor if symptoms worsen or persist for
Renal and Hepatic Impairment: more than 72 hours.
Dose adjustment unlikely due to low systemic absorption.
Dose Adjustment: No information found
Precautions:
Eye effects (e.g., burning sensation; vision changes, eye Precautions:
pain, or severe eye irritation may occur); Ocular effects (e.g., transient blurring of vision on
Pregnancy (not recommended in women of childbearing instillation);
potential not using effective contraception); Glaucoma;
Lactation (not known if excreted in breastmilk). Elderly and children (use with caution);
Pregnancy and lactation (use with caution).
Adverse Drug Reactions:
Common: Burning sensation of eyes, foreign body sensation SKILLED TASKS. May impair ability to perform tasks, which
in the eye, blurred vision, conjunctival hyperemia, require mental alertness, e.g., operating machinery or
epiphora, eye discharge, eye pain, eye pruritus, stinging driving.
of eyes, visual disturbance.
Less Common: Eye injury, hypersensitivity reaction (e.g., Adverse Drug Reactions:
S

angioedema, dyspnea, facial swelling, pharyngeal Common: Eye pain, changes in vision, blurred vision, mild
edema, swelling of eye, swollen tongue, urticaria). stinging of the eye, foreign body sensation, continued
redness, eye irritation, ocular hyperemia.
Drug Interactions: No known significant interactions
Drug Interactions: No information found
Administration: For topical application to the eye only.
Invert bottle or vial several times to obtain a uniform Administration: For external use only. Keep container tightly
emulsion. closed if not in use.

If using a multi-dose bottle for the first time, prime bottle Wash hands. Tilt the head back and pull the lower lid
by squeezing 2 drops onto a tissue. Do NOT let bottle tip away from the eye to form a pouch. Drop the medicine
touch tissue. into the pouch and gently close the eyes. Do not blink.
Keep the eyes closed for 1–2 minutes to allow
If using a single-dose bottle, administer immediately absorption of medicine.
after opening vial. Discard remaining contents after use.
If using a single-dose bottle, discard remaining contents
Contact lenses should be removed prior to the after use.
administration and may be reinserted 15 minutes after
administration. Do NOT use if solution is cloudy, leaking, has particles,
or changes color. Do NOT use if neck band is broken or
Do NOT touch dropper tip to eyelids or other surfaces missing.
when placing drops in eyes to avoid contamination.
Do NOT touch dropper tip to eyelids or other surfaces
NOTE: May be used with lubricant eye drops. If more than when placing drops in eyes to avoid contamination.
one topical ophthalmic product is being used, administer
at least 15 minutes apart. Pregnancy Category: C

Pregnancy Category: Not classified ATC Code: S01KA02

ATC Code: S01XA18

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SENSORY ORGANS

LOCAL ANESTHETICS
Rx SODIUM HYALURONATE

Ophth.: 0.1% (1 mg/mL) ophthalmic solution, 5 mL Rx BUPIVACAINE

bottle
Inj.: 0.5% (as hydrochloride), 5 mL, 10 mL, and 20 mL vial
A polysaccharide which functions as a tissue lubricant in 0.5% (as hydrochloride), 5 mL, 10 mL, 20 mL and 50
ophthalmic surgery because it forms a viscoelastic mL ampul/vial (local infiltration)
solution in water. It is a suitable substitute for aqueous 0.5% (as hydrochloride) 4 mL ampul (spinal) with 8%
and vitreous humor. dextrose
0.5% (as hydrochloride) (isobaric), 5 mL ampul
Indication: Surgical aid in the anterior segment during (spinal)
cataract extraction and intraocular lens implantation.
A local anesthetic that blocks the generation and
Contraindications: Bleeding disorders; skin infection or skin conduction of nerve impulses by increasing the threshold
problem. for electrical excitation, by slowing the propagation of
nerve impulse, and by reducing the rate of rise of the
Dose: action potential.
Surgical aid in the anterior segment during cataract
extraction and intraocular lens implantation, into the Indication: To produce local or regional anesthesia in
eye, ADULT, slowly administer a sufficient quantity into ophthalmic surgery.
the eye.
Contraindications: Obstetrical paracervical block
Dose Adjustment: No information found anesthesia.
Precautions: Dose:
Intraocular pressure (may cause a transient increase); NOTE: Dose should be individualized and varies with
Pregnancy and lactation (use with caution). anesthetic procedure, area to be anesthetized, tissue
vasculature, number of neuronal segments to be
Adverse Drug Reactions: blocked, depth of anesthesia, degree of muscle
Common: Increased intraocular pressure (transient), relaxation required, duration of anesthesia required,
hypotensive crisis, change in eyesight, eye pain, very bad individual tolerance, and the physical condition of the
eye irritation. patient.
Rare: Allergic reaction, hives, itching, red, swollen, blistered,
or peeling skin with or without fever, wheezing, tightness Administer the smallest dose and concentration required

S
in the chest or throat, trouble breathing, swallowing, or to produce the desired result.
talking, unusual hoarseness, swelling of the mouth, face,
lips, tongue, or throat, post-operative inflammation, Moderate to complete motor block of peripheral nerves, by
corneal edema, corneal decompensation. IV injection, ADULT, 5 mL (12.5 mg).
Drug Interactions: No known significant interactions Dose Adjustment:
Geriatric, Acutely ill Patients, and Debilitated Patients:
Administration: For external use only. Keep container tightly Use with caution. Dose reduction may be required.
closed if not in use.
Hepatic Impairment and/or Cardiac Disease:
Do NOT use if solution is cloudy, leaking, has particles, Reduce doses.
or changes color. Do NOT use if neck band is broken or
missing. Administration: Do NOT use solutions containing
preservatives for epidural or caudal blocks. Avoid rapid
Pregnancy Category: Not classified injection of large volume. Use fractional (incremental)
doses when feasible.
ATC Code: Not available
Use an infusion pump to slowly administer local
anesthetics to or around surgical wound sites and/or
near peripheral nerves for postoperative analgesia.

Avoid IV injections. Perform aspiration prior to

administration. Re-position the needle until no return of
blood can be elicited by aspiration. However, absence of
blood in the syringe does NOT guarantee that IV injection
has been avoided. Intravenous regional anesthesia (Bier
block) is not recommended;

Mixing or the prior or intercurrent use with other local

anesthetic is not recommended due to insufficient data
on the clinical use of such mixtures.

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 SENSORY ORGANS

NOTE: Duration of anesthetic effect may be prolonged by the

addition of epinephrine. Rx PROXYMETACAINE (PROPARACAINE)

See Bupivacaine under Anesthetics – Anesthetics, Local Ophth.: 0.5% eye drops solution (as hydrochloride), 5
(Amides) in Chapter 10: Nervous System for other mL and 15 mL bottle
information.
A rapid acting topical anesthetic which induces anesthesia
Pregnancy Category: C that lasts approximately 10–20 minutes.

ATC Code: Not available Indication: Surface anesthesia; for procedures where
corneal anesthesia of short duration is indicated, (e.g.
tonometry, gonioscopy, removal of corneal foreign
bodies, short corneal and conjunctival procedures).
Rx LIDOCAINE
Contraindication: Preterm neonates
Inj.: 1% (as hydrochloride), 20 mL ampule
2% (as hydrochloride), 2 mL, 5 mL, 20 mL, and 50 mL Dose:
ampule/vial Removal of foreign bodies and sutures, and tonometry, into
2% (as hydrochloride), 5 mL and 50 mL vial (epidural, the eye, ADULT, 1–2 drops as single instillation in each
local infiltration) eye before operation.
Tonometry, into the eye, ADULT and CHILD, 1–2 drops
A moderately long-acting, local anesthetic, which blocks immediately before measurement.
initiation and transmission of nerve impulses at the site Short corneal and conjunctival procedures, into the eye,
of application by stabilizing neuronal membrane. ADULT, 1 drop in the eye every 5–10 minutes for 5–7
doses.
Indication: Surface anesthesia
Dose Adjustment: No information found
Contraindications: Adjacent skin infection or inflamed skin
to the proposed site of injection; concomitant therapy Precautions:
with anticoagulants or an abnormal bleeding tendency; WARNING: Permanent corneal opacification with
severe anemia or heart disease; spinal or epidural accompanying visual loss has been reported with
anesthesia in dehydrated or hypovolemic patients. prolonged use.
Dose:
Surface anesthesia, into the eye, ADULT, apply 2 drops to
S

the ocular area where procedure will take place; may re- Hyperallergic corneal reaction (a rare, severe, immediate-
apply to maintain effect. type, apparently hyperallergic corneal reaction
characterized by acute, intense and diffuse epithelial
Dose Adjustment: keratitis, a gray, ground glass appearance, sloughing of
Geriatric and/or Debilitated Patients: large areas of necrotic epithelium, corneal filaments
Administer reduced doses commensurate with their age and, sometimes, iritis with descemetitis has been
and physical status. reported).
Prolonged use;
Renal and Hepatic Impairment: Known allergies;
Reduce dose during prolonged infusion (>24 hours) or Cardiac disease;
repeated IV doses. Hyperthyroidism;
Inflamed eye;
Administration: For parenteral administration, use an Pregnancy (not known if it causes fetal harm; administer
infusion pump to slowly administer lidocaine to or around only if clearly needed);
surgical wound sites and/or near nerves for pre- or Lactation (not known if excreted in breastmilk).
postoperative regional anesthesia.
SKILLED TASKS. May cause transient blurring of vision.
Visually inspect for particulate matter and discoloration Avoid performing tasks which require mental alertness,
prior to administration whenever the solution and e.g., operating machinery or driving.
container permit. Solutions that are discolored and/or
contain particulate matter should NOT be used. Unused Adverse Drug Reactions:
portion should be discarded. Common: Occasional temporary stinging, burning, and
conjunctival redness, allergic contact dermatitis
See Lidocaine under Anesthetics – Anesthetics, Local Rare: Hyperallergic corneal reaction
(Amides) in Chapter 10: Nervous System for other
information. Drug Interactions: No information found

Pregnancy Category: B Administration: For topical ophthalmic use only. NOT for
injection.
ATC Code: S01HA07

600
SENSORY ORGANS

Proxymetacaine should be clear to straw-colored. If the Remove the outer overwrap. Clean and disinfect the
solution becomes darker, discard the solution. rubber stopper using a sterile alcohol wipe. Insert the
spike aseptically into the bag through the target area of
Pregnancy Category: C the rubber stopper. Allow the fluid to flow and remove air
from the tubing before irrigating.
ATC Code: S01HA04
For SINGLE patient use only. Unused content should be
discarded.
ADJUVANT TO SURGERY
Do NOT use unless outer overwrap and seal are intact,
product is clear, and bag is undamaged. Do NOT use if
INTRAOCULAR IRRIGATING product is discolored or contains a precipitate.
Rx SOLUTION (BALANCED SALT
SOLUTION) Pregnancy Category: C

Ophth.: 15 mL, 250 mL, and 500 mL bottle ATC Code: S01XA20

Composition:

Sodium chloride 0.64 % OTOLOGICALS

Potassium chloride 0.075 %
Calcium chloride 0.048 %
Magnesium chloride hexahydrate 0.03 % ANTIINFECTIVES
Sodium acetate 0.39 %

Sodium citrate 0.17 % Rx CLOTRIMAZOLE

Water for injection to make 100.00 %
Otic: 1% otic solution
A solution used as an intraocular irrigant during ocular
surgeries. The solution typically contains a combination A broad-spectrum imidazole that acts against fungi (both
of sodium chloride, potassium chloride, calcium chloride, dermatophytes and yeasts) and gram-positive cocci
and magnesium chloride. This solution mimics the (Staphylococcus and Streptococcus spp.).
aqueous humor as closely as possible.
Indication: Treatment of acute bacterial otitis externa
Indications: Irrigant during ocular surgery involving caused by organisms susceptible to the action of

S
perfusion of the eye with an expected maximum duration ciprofloxacin, such as Pseudomonas aeruginosa,
of less than 60 minutes. Staphylococcus aureus, and Enterobacteriaceae.

Dose: NOTE: NOT indicated for the treatment of otitis media

NOTE: Enhanced BSS solutions may be desirable for longer
ocular surgical procedures but are considerably costlier. Contraindications: Known or suspected perforated
tympanic membrane.
Irrigant during ocular surgery, into the eye, ADULT and
CHILD, consult specialized references for proper Dose:
administration technique during various ocular surgery Otitis externa, into the ear, CHILD ≥2 years, instill 3 drops
types. into the affected ear twice daily for 7 days or as directed
by the physician.
Dose Adjustment: No information found
Precautions:
Precautions: Hypersensitivity;
WARNING: Open under aseptic conditions only. Superinfection;
Pregnancy and lactation (use with caution; safety has not
been established in this population).
Diabetes mellitus (use with caution in diabetic patients
undergoing vitrectomy; intraoperative lens changes have Adverse Drug Reactions:
been observed). Less Common: Hypesthesia, paresthesia, pruritis, rash,
urticaria.
Adverse Drug Reactions: Corneal swelling, bullous Rare: Ear discomfort, hearing disorders, ear pain.
keratopathy, corneal edema, corneal decompensation.
Drug Interactions:
Drug Interactions: No known significant interactions Monitor closely with:
Reduces therapeutic effect of Clotrimazole:
Administration: For topical ophthalmic use only. NOT for Polyene Antibiotics e.g., Nystatin
injection or IV infusion.
Administration: Prior to first administration, remove the
closure and put the dropper assembly in place on the

601
 SENSORY ORGANS

bottle. Avoid contaminating the dropper with material Less Common: Diarrhea, fever, headache, hearing loss
from the ear, fingers or other sources. Warm to room (transient), hypertension, nausea, otorrhagia, tinnitus,
temperature prior to administration. tremor, vomiting, xerostomia.

Lie down with the affected ear upward. Instill the Drug Interactions: No known significant interactions
medication. Remain in this position for at least 30
seconds to facilitate penetration of the drops into the Administration: NOT for injection or for ophthalmic use.
external ear canal. Repeat, if necessary, for the opposite
ear. Prior to use, warm solution by holding container in hands
for 1–2 minutes.
Discard unused portion after treatment is completed.
Lie down with the affected ear upward. Instill the
Pregnancy Category: C medication. Pump the tragus (cartilage flap over the
opening of the ear canal) 4 times to ensure penetration
ATC Code: S02AA15 of medication. Remain in this position for 5 minutes.

Pregnancy Category: C
Rx OFLOXACIN ATC Code: S02AA16

Otic: 0.3% ear drops solution, 5 mL bottle

CORTICOSTEROIDS AND ANTIINFECTIVES IN
A DNA gyrase inhibitor that interferes with replication, COMBINATION
transcription, repair, recombination, and transposition of
bacterial DNA.
NEOMYCIN + POLYMYXIN B +
Rx
Indications: Otitis externa; chronic suppurative otitis media; FLUOCINOLONE ACETONIDE
acute otitis media.
Otic: 3.5 mg neomycin (as sulfate) + 10,000 units
Contraindications: Hypersensitivity to ofloxacin or other polymyxin B (as sulfate) + 0.025% fluocinolone
members of the quinolone group, such as oxolinic acid, acetonide per mL ear drops solution, 5 mL bottle
cinoxacin, norfloxacin, and ciprofloxacin.
A combination of a corticosteroid and anti-infectives
Dose: (aminoglycoside and basic peptides), which is used in
Otitis media or chronic suppurative with perforated treating ear diseases.
S

tympanic membranes, into the ear, ADULT and CHILD,

instill 10 drops into affected ear twice daily for 14 days. Indications: Otitis externa, with or without associated otitis
Otitis externa, into the ear, ADULT, instill 10 drops into media; adjunct therapy to acute or chronic dermatoses
affected ear(s) once daily for 7 days; CHILD 6 months – of the external ear; chronic suppurative otitis media;
13 years, instill 5 drops into affected ear(s) once daily for draining mastoidectomy cavities; otorrhea from
7 days. ventilation tubes.
Acute otitis media with tympanotomy tubes, into the ear,
CHILD 1–12 years, instill 5 drops into affected ear twice Contraindications: Primary infection of the skin caused by
daily for 10 days. bacteria, fungi, acne rosacea, perioral dermatitis;
patients with herpes simplex, vaccinia, and varicella;
Dose Adjustment: Dose adjustment unlikely due to low untreated fungal or viral infections; pregnancy (first
systemic absorption. trimester).

Precautions: Dose:
Hypersensitivity reactions (e.g., severe hypersensitivity Ear infections, into the ear, ADULT and CHILD, instill 3–4
reactions, including anaphylaxis, have occurred; itching, drops 2–4 times daily. [NOTE: Limit treatment to 5–7
urticaria, rash, or edema may occur after a single dose; days. Refer to ENT specialist if discharge continues].
Stevens-Johnson, toxic epidermal necrolysis, vasculitis,
pneumonitis, nephritis, hepatic failure or necrosis, Precautions:
anemia, or cytopenias may occur after multiple doses); Patients with perforated eardrum or long-standing chronic
Superinfection; otitis media; prolonged use.

Tendon inflammation or rupture; Adverse Drug Reactions:

Elderly (evaluate the patient's or caregiver's ability to safely Common: Allergic dermatitis
and correctly administer the medication); Less Common: Acneiform eruptions, burning, decreased
Pregnancy and lactation (use with caution; safety has not hearing, dryness, ear pain, folliculitis, fungal overgrowth
been established). inside ear canal, hypertrichosis, hypopigmentation,
irritation, itching, miliaria, perioral dermatitis, secondary
Adverse Drug Reactions: infections, tinnitus.
Common: Application site reaction, dizziness, vertigo, Rare: Inner ear damage
pruritus, taste perversion, paresthesia.

602
SENSORY ORGANS

Drug Interactions: No information found Administration: For external use only.

Administration: Warm container in cup of warm water to Clean the affected area prior to application. May be
reduce viscosity. The ears should be clean and dry. Lie covered with a sterile bandage. Not intended for use on
down with the affected ear upward. existing scars. Do NOT use for longer than 1 week unless
prescribed by a physician.
Gentle massage or pressure on the tragus (cartilage flap
over the opening of the ear canal) to aid penetration of Do NOT use in or near the eyes. Do NOT use over large
the drops. areas of the body. Keep out of reach of children. If
Method of drug application based on degree of swelling swallowed, get medical help or contact a Poison Control
in ear canal: Center right away.

For minimal swelling, instill drops directly into the ear Pregnancy Category: Not classified
canal then remain in position for a few minutes.
ATC Code: Not available
For swelling that narrows the ear canal, saturate a
sponge wick or ribbon gauze with drops and insert into
the ear canal; review daily until swelling settles.
OTC FLUTICASONE
Pregnancy Category: C
Topical: 0.05% nasal aqueous solution (as propionate)
ATC Code: Not available per dose x 120 doses

A glucocorticoid with a fluorocarbothioate ester linkage at

the 17-carbon position. It has potent vasoconstrictive
EAR, NOSE, AND THROAT PREPARATIONS and anti-inflammatory activities, but weak hypothalamic-
pituitary-adrenal (HPA) inhibitory effect when applied
topically.
BACITRACIN + NEOMYCIN +
OTC Indication: For the temporary relief of symptoms of upper
POLYMYXIN B
respiratory allergies, including nasal congestion, runny
Topical: 200 units bacitracin + 3 mg neomycin (as nose, sneezing, and itchy nose.
sulfate) + 4,000 units polymyxin B (as sulfate)
per gram ointment, 10 g tube NOTE: NOT for the treatment of asthma

S
A combination of a corticosteroid and anti-infectives Contraindications: Injury or surgery to the nose that is not
(aminoglycoside and basic peptides). fully healed.

Indications: First aid for the prevention and treatment of Dose:

infection in minor cuts, scrapes, burns, abrasions, insect Symptomatic relief, by nasal administration,
bites, pimples, pustules and other skin breaks. ADULT and CHILD ≥12 years,
Week 1: 2 sprays in each nostril once daily;
Contraindication: Week 2–6 months: use 1–2 sprays in each nostril once
daily, as needed to treat symptoms;
Dose: CHILD 4–11 years, 1 spray in each nostril once daily.
Treatment or prevention of infection, by topical
administration, ADULT and CHILD, apply 1 FTU on the Dose Adjustment: No information found
area 1–3 times daily.
Precautions:
See General Information on Corticosteroids under WARNING: Do NOT use in children under 4 years of
Corticosteroids, Dermatological Preparations in Chapter age.
4: Dermatologicals for information on fingertip units
(FTU). Glaucoma;
Cataracts;
Dose Adjustment: No information found Growth effects;
Local site application reactions (e.g., stinging or sneezing
Precautions: may occur a few seconds right after use);
In case of deep puncture wounds, animal bites or serious Pregnancy and lactation (use with caution; consult a health
burns, consult a physician. professional before use).
Stop use and consult a physician if the condition persists or
gets worse, or if rash or other allergic reactions develop. Adverse Drug Reactions:
Common: Stinging, sneezing.
Adverse Drug Reactions: No information found Rare: Severe facial pain, thick nasal discharge, whistling
sound from the nose, visual changes, frequent
Drug Interactions: No information found nosebleeds.

603
 SENSORY ORGANS

Drug Interactions: * Reduce dose during controlled ventilation

Avoid concomitant use with:
Increases serum concentration of Fluticasone: Local anesthetic for oral mucous membrane, by topical
CYP3A4 Inhibitors, e.g. Ritonavir, Ketoconazole administration, ADULT, apply to the affected area ≤4
times daily as needed (maximum dose, 3 mg/kg, not to
Administration: For nasal use only. Do NOT spray into the exceed 300 mg); CHILD and ADOLESCENT, dose varies
eyes or mouth. with age and weight (maximum dose, 3 mg/kg).

Keep out of reach of children. If swallowed, get medical Dose Adjustment:

help or contact a Poison Control Center right away. Geriatric:
Administer reduced doses commensurate with their age
Pregnancy Category: C and physical status.

ATC Code: Not available Administration: For external use only.

Apply a moderately thick layer to affected area (~1/8
inch thick), and allow time for numbness to develop,
approximately 20–60 minutes. Reapply if needed. It is
OTC LIDOCAINE unnecessary to dry the site prior to application.

Topical: 10% spray (as hydrochloride), 50 mL Do NOT use in large quantities, particularly over raw
surfaces or blistered areas. Avoid contact with eyes, in
A moderately long-acting, local anesthetic, which blocks case of accidental contact with eyes, rinse immediately
initiation and transmission of nerve impulses at the site with copious amounts of eyewash and seek treatment by
of application by stabilizing neuronal membrane. an eye care specialist.

Indication: Short duration local anesthesia (10 to 15 Keep out of reach of children. If swallowed, get medical
minutes) of the oral mucous membrane. help or contact a Poison Control Center right away.

Contraindications: Seizures; liver disease; pregnancy; See Lidocaine under Anesthetics – Anesthetics, Local
lactation. (Amides) in Chapter 10: Nervous System for other
information.
Dose:
Procedure-specific dose recommendations for adults: Pregnancy Category: B

ATC Code: S02DA01

Maximum Dose

Maximum Dose
Recommended
S

(mg) for Short

Procedures
Dose (mg)

Prolonged
(mg) for
Area

P d

Nasal procedures
(e.g., puncture of
20–60 500 600
the maxillary
sinus)
Oral and dental
20–
procedures (e.g., 500 600
200
prior to injection)
Procedures in the
oropharynx (e.g., 20–
500 600
gastrointestinal 200
endoscopy)
Procedures in the
50–
larynx, trachea, 200* 400
200
and bronchi
Procedures in the
respiratory tract
50–
(e.g., insertion of 400 600
400
instruments and
tubes)

NOTE: For short procedures, give drug for less than 1

minute.
For prolonged procedures, the duration of application is
>5 minutes.

604
VARIOUS

Caution during multiple doses due to danger of intestinal

VARIOUS impaction (reduce initial dose to half to prevent
impaction;
Lavage should be followed by sodium sulfate cathartic).
ALL OTHER THERAPEUTIC PRODUCTS Adverse Drug Reactions:
Common: Black stools, blackening of teeth and mouth,
colicky abdominal pain (discomfort, swelling),
GENERAL ANTIDOTES constipation, nausea, vomiting
Less Common: Diarrhea, hypotension
Rare: Bowel obstruction, charcoal embolism, hypoglycemia,
Rx ACTIVATED CHARCOAL hypothermia, pneumonitis (due to aspiration)

Oral: USP grade powder, given as slurry Drug Interactions:

Monitor closely with:
A fine, smooth, odorless, tasteless, black powder, prepared Increases risk of adverse or toxic effects of Laxatives, e.g.,
from the carbonization of organic matter. Activated Mannitol, Sorbitol (volume depletion; electrolyte
charcoal reduces drug or poison absorption either by abnormalities)
binding to the drug in the GI tract or by interrupting its
entry into the enterohepatic recirculation. Avoid concomitant use with:
Reduces therapeutic effect of Activated Charcoal:
Indications: Gastrointestinal decontamination for specific Food, e.g., Milk, Ice Cream, Sherbet (decreased
drug or poison ingestion associated with significant risk adsorptive capacity)
of toxicity; acute, oral poisoning
Reduces therapeutic effect of the following drugs due to
Contraindications: Bowel obstruction; poisoning by decreased absorption, reducing systemic circulation:
hydrocarbons (e.g., petroleum distillates) with high Anti-epileptics, Oral Contraceptives, Other Charcoal
potential for harm if aspirated; poisoning by corrosive Interactants, e.g., Digoxin, Paracetamol, Furosemide,
substances; GI tract not anatomically intact; unprotected Salicylates, Sulfonylureas, Sulfones, Tetracyclines,
airway Theophylline, Tricyclic Antidepressants

Dose: Administration: In preparing lavage, ensure that the patient

Reduction of absorption, by mouth, ADULT and CHILD >12 is in trendelenburg (supine with feet higher than the
years, 50–100 g in 100–150 mL distilled water as a head) and left lateral decubitus position (lying on the
slurry given as a single dose, as soon as possible after left).
ingestion of poison; CHILD 1–12 years, 25 g as a single
dose (50 g in severe poisoning) in 50–100 mL distilled Administer as a slurry (thick suspension) to increase
water; INFANT, 1 g/kg as a single dose (maximum, 50 g) adsorptive capacity. Do NOT administer with food due to
[NOTE: May repeat lavage every 6 hours for 48–72 decreased efficacy. Administer the smallest dose slowly

V
hours. To produce effective adsorption, a ratio of about to avoid vomiting.
10-parts activated charcoal to 1-part poison is needed].
Adsorptive effectiveness is time-dependent. It is best
Active elimination, by mouth, ADULT, 50 g every 4 hours (in administered within 1 hour after poison ingestion.
case of intolerance, 25 g every 2 hours); CHILD >1 year,
25–50 g every 4–6 hours; INFANT, 1 g/kg every 4–6 NOT for use in poisoning with the following substances:
hours. alcohols (e.g., ethanol, methanol), clofenotane (e.g.,
dicophane, DDT), corrosive substances, cyanides,
Dose Adjustment: malathion, and metal salts, (e.g., iron, lithium).
Uremic Adult Patients:
Administer orally 20–50 g once daily. NOTE: If the patient is conscious and cooperative, a slurry
form of the activated charcoal may be orally
Precautions: administered. But in cases where NGT may be
WARNING: Electrolyte abnormalities (hypernatremia, obstructed, further dilution is allowed.
hypokalemia, hypermagnesemia) have been
reported to occur with the concomitant use of Pregnancy Category: B
cathartics, namely sorbitol.
ATC Code: A07BA01
NOT generally recommended in children <1 year.

Monitor for active bowel sounds before administering;

Drowsy, unconscious or comatose patient (ensure that
airway is protected);
Decreased peristalsis (administer within 1 hour of
ingestion);

605
 VARIOUS

Rx SODIUM SULFATE Pregnancy Category: C

Oral: USP grade powder ATC Code: A06AD13; A12CA02

A moderately water– and acid–soluble sodium source for

uses compatible with sulfates. It is a gastrointestinal SPECIFIC ANTIDOTES
drug administered as a 0.5% solution as an osmotic
laxative to prompt bowel evacuation.
Indications: Gastrointestinal decontamination for specific Rx ACETYLCYSTEINE
drug or poison ingestion
Oral: 600 mg effervescent tablet
Dose: 100 mg and 200 mg sachet
Bowel cleansing, by mouth, ADULT, dilute with water to 100 mg/5 mL granules for suspension, 150 mL
approximately 450 mL and ingest as instructed. Inj.: 200 mg/mL, 10 mL ampule and 25 mL bottle (IV
infusion)
Precautions:
WARNING: Direct ingestion of dry powder may A cysteine derivative with a free thiol (-SH) nucleophilic
increase the risk of nausea, vomiting, dehydration, group able to interact directly with electrophilic group of
and electrolyte disturbances. oxidant radicals. It acts as a hepatoprotective agent that
restores hepatic glutathione. It serves as a glutathione
substitute and enhances the nontoxic sulfate
Gout; conjugation of acetaminophen.
Elderly (use with caution);
Children; Indications: Management of paracetamol, white or yellow
Lactation (use with caution). phosphorus "watusi," zinc phosphide, and carbon
tetrachloride (CCl4) poisoning; for cyclophosphamide-
Adverse Drug Reactions: induced hemorrhagic cystitis
Common: Overall discomfort, increased anion gap,
decreased bicarbonate, increased osmolality, Dose:
hyperkalemia increase potassium and hypernatremia Poisoning, by mouth, ADULT, 72-hour regimen consisting of
increased sodium, hyperuricemia, abdominal distension, 18 doses (total dose, 1330 mg/kg), initially administer
abdominal pain, nausea, vomiting, headache 140 mg/kg loading dose; then administer 70 mg/kg
Less Common: GI upset, bloating, stomach cramps every 4 hours as maintenance dose;
Rare: Allergic reactions, electrolyte abnormalities, irregular by IV infusion, ADULT, 21-hour regimen consisting of 3
heartbeat, dizziness, headache, rectal pain, rectal doses (total dose, 300 mg/kg), initially administer 150
bleeding, black, tarry, or bloody stools mg/kg in 200 mL D5W over 60 minutes as loading dose
(maximum, 15 g); followed by a second dose of 50 mg/kg
Drug Interactions: in 500 mL D5W over 4 hours; then administer a third
V

Monitor closely with: dose of 100 mg/kg in 1000 mL D5W over 16 hours
Increases risk of adverse or toxic effects of Sodium Sulfate, (maximum, 10 g).
particularly, affects renal function:
ACE Inhibitors, Angiotensin Receptor Blockers, Diuretics,
NSAIDs

Increases risk of adverse or toxic effects of the following

drugs:
QT-prolonging Drugs, e.g., Amiodarone, Clozapine,
Quinidine (ventricular arrhythmia, particularly torsade de
pointes)

Avoid concomitant use with:

Increases risk of adverse or toxic effects Sodium Sulfate:
Alcohol (seizures; arrhythmia; kidney problems),
Laxatives, Stool Softeners (electrolyte imbalance;
dehydration)

Administration: Mix with water and shake well prior to

ingestion. To be taken with additional water to improve
patient tolerance. Do NOT swallow the dry powder. Do
NOT take food or other drugs within 1 hour of
administration.

Drink lots of clear liquids before, during, and after

administration to prevent dehydration. Avoid purple or
red fluids.

606
VARIOUS

Dose Adjustment:
Patients weighing <40 kg: In patients who continue to experience symptoms of
Administer as follows: hepatotoxicity or elevated liver function tests after a 72-
hour oral or 21-hour IV regimen, extending the treatment

over 4 hours
course may be appropriate, specifically in patients with a
over 1 hour
150 mg/kg

100 mg/kg
Third Dose
50 mg/kg
Loading

over 16
Second
suspected massive overdose, concomitant ingestion of

hours
Dose

Dose
Body Weight (kg)

other substances, or patients with preexisting liver

disease.

NOTE: Consultation with a poison control center or clinical

toxicologist is highly recommended to determine optimal
IV drug

IV drug

IV drug
D5W

D5W

D5W
(mL)

(mL)

(mL)

(mL)

(mL)

(mL)
patient care.

Pregnancy Category: B
40 30 100 10 250 20 500
30 22.5 100 7.5 250 15 500 ATC Code: V03AB23
21 15.75 100 5.25 250 10.5 500
20 15 60 5 140 10 280
15 11.25 45 3.75 105 7.5 210 Rx ALCOHOL, ETHYL
10 7.5 30 2.5 70 5 140
5 3.75 15 1.25 35 2.5 70 Oral: 95%, USP grade
Inj.: absolute, 1 mL ampule (IV)
NOTE: Decreased volume of diluent may cause solution to Topical: 70% solution
remain hyperosmolar. Adjust osmolarity to
physiologically safe level prior to administration. A clear, aqueous solution of ethyl alcohol that is used in the
treatment of methanol toxicity due to its higher affinity to
Obesity: alcohol dehydrogenase, thus inhibiting the formation of
In patients >100 kg, administer a total dose of 30 g by IV toxic metabolites of methanol
infusion:
Loading dose: 15 g over 60 minutes Indication: Antidote for methyl alcohol (methanol) poisoning
Second dose: 5 g over 4 hours NOTE: Preferred antidote for methanol poisoning is
Third dose: 10 g over 16 hours fomepizole. Use only if fomepizole is unavailable.

Precautions: Dose:
Anaphylactoid reactions; NOTE: IV administration is the preferred route. Continue
Acute acetaminophen poisoning (treatment should begin therapy until methanol is no longer detected or at <20
within 8 hours of ingestion or as soon as possible after mg/dL AND the patient is asymptomatic and metabolic
ingestion); acidosis has been corrected.

V
Repeated supratherapeutic ingestion (RSTI) of
acetaminophen; Methanol poisoning, by IV injection, ADULT and CHILD,
Lactation (use with caution). initially 600–700 mg/kg (equivalent to 7.6 to 8.9 mL/kg
using a 10% solution);
Adverse Drug Reactions: maintenance dose for nondrinkers, 66 mg/kg per hour
Common: Anaphylactoid reaction, flushing, tachycardia, maintenance dose (equivalent to 0.83 mL/kg per hour
edema, tachycardia, urticaria, rash, pruritus, nausea, using a 10% solution);
vomiting, pharyngitis, rhinorrhea, rhonchi, throat maintenance dose for chronic drinkers, 154 mg/kg per
tightness hour maintenance dose (equivalent to 1.96 mL/kg per
Less Common: Anaphylaxis, angioedema, bronchospasm, hour using a 10% solution).
chest tightness, cough, dizziness, dyspnea, headache,
hypotension, respiratory distress, stridor, wheezing NOTE: Goal of therapy is to maintain serum alcohol levels
>100 mg/dL.
Drug Interactions: No known significant interactions
Methanol poisoning, by mouth, ADULT and CHILD, initially
Administration: 600–700 mg/kg (equivalent to 0.09 mL/kg per hour
For oral administration, administer as 5% solution within using a 98% solution); maintenance dose for
1 hour of preparation. May be diluted with cola, orange nondrinkers, 66 mg/kg per hour maintenance dose
juice, or other soft drink. If patient vomits within 1 hour (equivalent to 0.78 mL/kg per hour using a 98%
of administration, re-administer dose. solution);
maintenance dose for chronic drinkers, 154 mg/kg per
For IV administration, use a slow infusion rate to avoid hour maintenance dose (equivalent to 0.20 mL/kg per
hypersensitivity reactions. Dilute with D5W or physiologic hour using a 98% solution).
solution.
Dose Adjustment:
Undiluted acetylcysteine solution (IV) is hyperosmolar. Hemodialysis:
Adjust as instructed prior to administration. Maintenance dose via IV administration:

607
 VARIOUS

For nondrinkers, 169 mg/kg per hour (equivalent to 0.22

mL/kg per hour using a 10% solution). Rx ASCORBIC ACID
For chronic drinkers, 257 mg/kg per hour (equivalent to
3.26 mL/kg per hour using a 10% solution). Inj.: 250 mg/mL, 2 mL ampule (IV)

Maintenance dose via oral administration: A water-soluble vitamin that acts as a free radical, an
For nondrinkers, 169 mg/kg per hour (equivalent to 0.22 antioxidant scavenger, and plays a major role in
mL/kg per hour using a 98% solution). oxidation-reduction reactions; Ascorbic acid is a cofactor
For chronic drinkers, 257 mg/kg per hour (equivalent to for enzymes involved in the biosynthesis of collagen,
0.33 mL/kg per hour using a 98% solution). carnitine, and neurotransmitters.

Precautions: Indications: Treatment of methemoglobinemia; urinary

Diabetes; acidification
Hepatic impairment or shock (use with caution);
Children; Contraindications: Anemia, breastfeeding, diabetes
Pregnancy (crosses the placenta, enters fetal circulation, mellitus, G6PD deficiency, hemochromatosis,
and has teratogenic effects); nephrolithiasis, pregnancy, sideroblastic anemia,
Lactation. sodium restriction, thalassemia

Adverse Drug Reactions: Dose:

Common: Flushing, hypotension, agitation, CNS depression, Idiopathic methemoglobinemia, by mouth, ADULT, 300–
coma, disorientation, drowsiness, encephalopathy, 600 mg daily in divided doses.
headache, sedation, vertigo, hypoglycemia, gastric Urinary acidification, by mouth, ADULT, 4–12 mg daily in 3-
irritation, nausea, vomiting, urinary retention, nerve and 4 divided doses; CHILD, 500 mg every 6–8 hours.
tissue destruction, phlebitis, polyuria, intoxication
Rare: Seizure Administration: Avoid rapid IV injection as this may cause
temporary faintness or dizziness.
Drug Interactions: No information found
See Ascorbic Acid (Vitamin C) under Vitamins in Chapter 1:
NOTE: Ethanol may interact with other medications. See Alimentary Tract and Metabolism for other information.
specific drug monographs for details on interactions with
ethanol. Pregnancy Category: C

Administration: ATC Code: A11GA01

For IV administration, administer via a central vein as a
10% solution in D5W. Administer the initial dose over 1
hour.
Rx ATROPINE
For oral administration, dilute solutions to ≤20%
V

concentration with water or juice and administer every Oral: 600 micrograms (as sulfate) (equivalent to 500 mcg
hour. May also be administered via nasogastric tube. atropine) tablet
Alcoholic beverages may be substituted, but may contain Inj.: 500 micrograms/mL, 600 micrograms/mL and 1
different percentages of ethanol: mg/mL (as sulfate), 1 mL ampule (IM, IV, SC)
Vodka ~40%
Wine ~12% A naturally occurring tertiary amine anti-muscarinic alkaloid
Beer ~5% from Atropa belladonna that competitively blocks
Out-of-hospital management is not recommended. acetylcholine action in central and peripheral muscarinic
autonomic receptors.
NOTE: Absolute ethyl alcohol [98% (196 proof) = 77.4 g
ethanol/dL] Indications: For organophosphate and carbamate
poisoning; for anticholinesterase and muscarinic
Pregnancy Category: C symptoms
ATC Code: V03AB16 Contraindications: Angle-closure glaucoma; severe
inflammatory GI disease or GI obstruction; prostatic
hypertrophy; prostatism and urinary obstruction;
myasthenia gravis; thyrotoxicosis; organochlorine
poisoning; pyloric stenosis; poisoning caused by CNS
adrenergic stimulants; phenothiazines; tricyclic
antidepressants and other anticholinergics

Dose:
NOTE: Dose required varies considerably with the severity of
poisoning. Total amount of atropine used for carbamate
poisoning is usually less than with organophosphate
insecticide or nerve agent poisoning.

608
VARIOUS

Severely poisoned patients may exhibit significant

tolerance to atropine requiring ≥2 times the suggested Rx BROMOCRIPTINE
dose. Titrate to pulmonary status (decreased bronchial
secretions). Oral: 2.5 mg (as mesilate) tablet
Consider administration of atropine via continuous IV
infusion in patients requiring large doses of atropine. A semisynthetic ergot alkaloid derivative and a dopamine
Once patient is stable, decrease the dose or dosing receptor agonist, which activates postsynaptic dopamine
frequency. receptors in the tuberoinfundibular and nigrostriatal
pathways, inhibiting prolactin secretion and enhancing
Organophosphate or carbamate insecticide or nerve agent coordinated motor control.
poisoning, by IV or IM injection, ADULT, initially 1–6 mg,
repeat every 3–5 minutes as needed; CHILD, initially Indication: Treatment of neuroleptic malignant syndrome
0.05–0.1 mg/kg, repeat every 5–10 minutes as needed
[NOTE: Double the dose if previous dose did not induce Contraindications: Syncopal migraine; uncontrolled
atropinization. Maintain atropinization by administering hypertension; postpartum women with a history of
repeat doses as needed for ≥2 to 12 hours based on coronary artery disease or other severe cardiovascular
recurrence of symptoms.] conditions
by IV infusion, ADULT and CHILD, following Dose:
atropinization, administer 10–20% of the total loading Neuroleptic malignant syndrome, by mouth, ADULT, 2.5 mg
dose required to induce atropinization every hour, adjust every 8–12 hours, increased if needed (maximum 45 mg
as needed to maintain adequate atropinization. daily).
Mild symptoms of poisoning, by IM injection, ADULT, 2 mg
as soon as exposure is known or strongly suspected; Dose Adjustment:
CHILD, administer weight-based dose [see below] as Hepatic Impairment:
soon as exposure is known or strongly suspected [NOTE: May require dose adjustment. Undergoes extensive hepatic
If severe symptoms develop after the first dose, metabolism. Use with caution.
administer 2 additional doses in rapid succession 10
minutes after the first dose. Do NOT administer more Administration: Administer with food to decrease GI
than 3 doses]. distress.
Severe symptoms of poisoning, by IM injection, ADULT,
immediately administer three 2–mg doses in rapid Do NOT discontinue abruptly to prevent acute
succession; CHILD, immediately administer three weight- exacerbation. Discontinue gradually over a period of 1
based doses in rapid succession. week.

WEIGHT-BASED DOSING: See Bromocriptine under Anti-Parkinson Drugs –

>41 kg (90 lbs) 2 mg per dose Dopaminergic Agents in Chapter 10: Nervous System for
18–41 kg (40–90 lbs) 1 mg per dose other information.
6.8–18 kg (15–40 lbs) 0.5 mg per dose
<6.8 kg (15 lbs) 0.25 mg per dose Pregnancy Category: B

V
Administration: ATC Code: N04BC01
For oral administration, may be taken with or without
food.

For IV administration, administer undiluted by rapid IV

CALCIUM FOLINATE
Rx
injection. (LEUCOVORIN CALCIUM)

See Atropine under Drugs for Functional Gastrointestinal Inj.: 10 mg/mL, 5 mL ampule/vial (IM, IV)
Disorders in Chapter 1: Alimentary Tract and Metabolism 50 mg vial (IM, IV infusion)
for other information.
A reduced form of folic acid that supplies the necessary
Pregnancy Category: C cofactor blocked by methotrexate. It actively competes
with methotrexate for transport sites, displaces
ATC Code: A03BA01 methotrexate from intracellular binding sites, and
restores active folate stores required for DNA/RNA
synthesis. It aids in the elimination of formic acid by
serving as a source of tetrahydrofolate.

Indications: Rescue agent after high-dose methotrexate

treatment; to diminish toxicity and counteract the effects
of impaired methotrexate elimination and of inadvertent
overdosage of folic acid antagonists; adjunct cofactor
therapy in methanol toxicity; antidote for formaldehyde
and methyl alcohol poisoning

609
 VARIOUS

Contraindication: Pernicious anemia and other 100 to 1000

megaloblastic anemias secondary to vitamin B12 ≥10
mg/m2 every 3 to
deficiency micromolar
6 hours
At 72 ~1 to 10 10 to 100 mg/m2
Dose: hours micromolar every 3 hours
High-dose methotrexate rescue, by IM or IV injection, ADULT
~0.1 to 1 10 mg/m2 every
and CHILD, 15 mg (~10 mg/m2) 24 hours after beginning
micromolar 3 to 6 hours
methotrexate infusion, continue every 6 hours for 10
doses until methotrexate level is <0.05 micromolar.
Adjust dose as follows:
NOTE: If serum creatinine is increased more than 50%
Methotrexate Serum
Dose above baseline, increase the standard leucovorin
elimination methotrexate
adjustment dose to 100 mg/m2 every 3 hours, then adjust
type level
according to methotrexate levels above.
~10 15 mg every Follow methotrexate levels daily, leucovorin may be
micromolar at 6 hours for discontinued when methotrexate level is <0.1
24 hours; 1 60 hours (10 micromolar.
micromolar at doses)
Normal
48 hours; beginning 24 Methotrexate overdose, inadvertent (begin as soon as
<0.2 hours after possible after overdose), by IM or IV injection, ADULT, 10
micromolar at the start of mg/m2 every 6 hours until the methotrexate level is <
72 hours infusion 0.01 micromolar [NOTE: If serum creatinine is increased
>0.2 15 mg every more than 50% above baseline 24 hours after
micromolar at 6 hours until methotrexate administration, if 24 hour methotrexate
72 hours; methotrexate level is >5 micromolar, or if 48 hour methotrexate level
Delayed late
>0.05 level is is >0.9 micromolar, increase leucovorin dose to 100
micromolar at <0.05 mg/m2 (IV) every 3 hours until the methotrexate level is
96 hours micromolar <0.01 micromolar].
150 mg Cofactor therapy in methanol toxicity, by IV injection, ADULT
every 3 and CHILD, 1 mg/kg over 30–60 minutes every 4–6
Delayed ≥50
hours until hours (maximum dose 50 mg); continue until methanol
early micromolar at
methotrexate and formic acid have been completely eliminated.
24 hours; ≥5
level is <1
micromolar at
micromolar, Administration: Administer by IV or IM route as a rescue
48 hours;
then 15 mg after folate antagonists. Administer by IM injection, IV
doubling of
every 3 push, or by IV infusion for 15 minutes to 2 hours. Do NOT
serum
Acute renal hours until administer at a rate >160 mg/minute due to calcium
creatinine
injury methotrexate content.
level at 24
level is
hours
<0.05
V

Do NOT administer intrathecally.

micromolar
Do NOT administer IV solutions at a rate >160
High-dose methotrexate overexposure, by IM or IV injection, mg/minute due to calcium content.
ADULT,
Serum NOTE: Do NOT administer concurrently with methotrexate. It
Duration methotrexate Dose adjustment is commonly initiated 24 hours after the start of
level methotrexate. Toxicity to normal tissues may be
Initially 1000 irreversible if leucovorin is not initiated by ~40 hours
≥100
mg/m2 every 6 after the start of methotrexate.
micromolar
hours
Initially 100 Fluorouracil is usually given after, or at the midpoint, of
At 24 ≥10 to <100
mg/m2 every 3 or leucovorin infusion by IV bolus injection or short IV
hours micromolar
6 hours infusion over 10–120 minutes. Other administration
Initially 10 schedules have been used; refer to individual protocols.
~1 to 10
mg/m2 every 3 or
micromolar See Calcium Folinate (Leucovorin Calcium) under
6 hours
≥100 1000 mg/m2 Antineoplastic Agents – Adjuncts to Antineoplastic
micromolar every 6 hours Chemotherapy in Chapter 8: Antineoplastic and
Immunomodulating Agents for other information.
≥10 to <100 100 mg/m2 every
micromolar 3 hours
At 48 Pregnancy Category: C
hours 100 mg/m2 every
6 hours ATC Code: V03AF03
~1 to 10
micromolar 10 to 100
mg/m2 every 3
hours

610
VARIOUS

Rx CALCIUM SALT Rx COBRA ANTIVENIN

Oral: powder (as chloride), USP grade Inj.: 800 IU/mL, 5 mL ampule (IV infusion)
Inj.: 10% solution (as gluconate), 10 mL ampule (IV) 800 MU/4.8 mL, 1 mL ampule (IV infusion)

The most abundant cation and is essential for the The purified and concentrated serum of horses
maintenance of the nervous, muscular, and skeletal hyperimmunized with the venom of the Philippine cobra
systems, as well as for cell membrane and capillary [TAG: Ulupong] (Naja-Naja philippinensis) and preserved
permeability. with 1:10,000 merthiolate.
Indications: Antidote for poisoning with white or yellow
phosphorus "watusi," organochlorines, and severe Indications: Antidote for cobra bites
jellyfish bites; verapamil toxicity; calcium antagonist
toxicity Dose: See Administration for dosing details

Contraindications: Breastfeeding; cardiac arrhythmias; Dose Adjustment: No information found

dehydration; diarrhea; digitalis toxicity; extravasation;
hypercalcemia; hypercalciuria; hyperphosphatemia; Precautions:
hypoparathyroidism; necrotizing enterocolitis; WARNING: Usual preparation necessary for treatment
pregnancy; sarcoidosis; ventricular fibrillation; vitamin D of anaphylactic reaction must be immediately
toxicity available prior to administration.

Dose: Adverse Drug Reactions:

Verapamil toxicity or calcium antagonist toxicity, by Common and Less Common:
intravenous injection, ADULT, 500-800 mg (maximum [Early (within a few hours)]: Urticaria, itching, dry cough,
dose, 3 g); CHILD and INFANT, 100 mg/kg (maximum fever, nausea, vomiting, abdominal colic, diarrhea,
dose, 3 g). tachycardia, chills, vasodilation
Calcium channel blocking agent overdose, by IV infusion, [Late (5 days or more)]: Nausea, vomiting, diarrhea,
CHILD, as 10% calcium chloride, 0.272 mEq/kg (0.2 itching, urticarial rash, pain in joints and muscles,
mL/kg) over 5–10 minutes. recurrent urticaria, fever, enlargement of lymph glands,
proteinuria
Administration: Rare:
Acetate, carbonate, citrate, gluconate, lactate, and [Late (5 days or more)]: Encephalitis
phosphate salts are administered orally. Administer 1–
1.5 hours after meals or with a demulcent (e.g., milk). Drug Interactions: No information found
Except calcium carbonate powder, which should be
mixed with food for administration. Administration: SC or IM administration is preferred.
Administer by IV only when symptoms of poisoning are
Calcium chloride or gluconate may be administered

V
evident.
intravenously . Calcium gluconate usually is administered
as a 10% solution and calcium chloride as a 2–10% Most effective when injected immediately after the bite.
solution. Administer calcium salts slowly through a small When possible, test for sensitivity to horse serum prior to
needle into a large vein to avoid too rapid increase in administration.
serum calcium and extravasation of calcium solution into
the surrounding tissue with resultant necrosis. Following Kill and keep the snake responsible for the bite,
IV injections, the patient should remain recumbent for a whenever possible, to identify the specific venom.
short time.
Apply a tourniquet immediately above the bite. It should
Closely monitor serum calcium concentrations during IV be tight enough to impede venous and lymph flow to and
administration of calcium. Replace IV calcium therapy from the bitten part but allows a finger to be inserted
with oral calcium supplements or calcium-rich foods as under it. Loosen tourniquet every 15 minutes for 15–30
soon as possible. seconds to allow blood flow.
NOTE: In patients with end-stage renal disease, administer If done immediately or shortly after the bite, make short
with meals (e.g., 10–15 minutes before or during). deep incisions (¼ to ½ inch long and ½ inch deep) over
the site of the bite through the fang marks under aseptic
See individual monographs under Mineral Supplements conditions. Avoid principal blood vessels.
– Calcium in Chapter 1: Alimentary Tract and
Metabolism for other information. Suction the blood with the mouth or with a mechanical
device to draw out the poison. If done using the mouth,
Pregnancy Category: C make sure there are no open lesions on the mucous
membrane. Rinse mouth with a mild solution of
ATC Code: Not available potassium permanganate or water.

611
 VARIOUS

Inject part of the antivenin into the site of the bite and prior to surgery; by IV injection, ADULT, 2.5 mg/kg ~1¼
around it if done soon after. Inject most of the antivenin hours prior to anesthesia and infused over at least 1
above the tourniquet, then slowly release the tourniquet. minute (Ryanodex) or 1 hour (Dantrium, Revonto) with
additional doses as needed and individualized.
Administer saline, plasma, or blood to combat shock. Malignant hyperthermia, crisis, by IV injection, ADULT, 2.5
Antibiotics and antitoxins may be needed for infections mg/kg; continuously repeat dose until symptoms
commonly associated with snakebites. Antihistamines subside or a cumulative dose of 10 mg/kg is reached;
may be necessary to control manifestations of allergy. rarely, some patients may require up to 30 mg/kg for
initial treatment.
Patient should remain lying down. Do NOT allow to
patient to walk or run around, become overheated, or NOTE: Manufacturer's labeling suggests an initial minimum
take alcohol stimulants as thes hasten blood flow. dose of 1 mg/kg.

Black coffee or strong tea may be given to combat Malignant hyperthermia, post-crisis follow up, by continuous
weakness or giddiness. IV infusion, ADULT, 0.25 mg/kg per hour for at least 24
hours; by mouth, ADULT, 4 to 8 mg/kg per day in 4
Do NOT cauterize the wound with strong acid, potassium divided doses for 1–3 days
permanganate or heat. NOTE: IV dantrolene may be used to prevent or attenuate
recurrence of MH signs when oral therapy is not
Pregnancy Category: Not classified practical.

ATC Code: Not available Administration: For IV preparation, reconstitute with 60 mL

sterile water for injection.

Therapeutic or emergency dose can be administered by

Rx DANTROLENE rapid continuous IV push. Follow-up doses should be
administered over at least 1 minute (Ryanodex) or 1 hour
Oral: 25 mg and 50 mg (as sodium salt) capsule (Dantrium, Revonto).
Inj.: 20 mg (as sodium salt) with 3 g mannitol per vial (for
reconstitution with 60 mL sterile water for injection) EXTRAVASATION MANAGEMENT: Ensure proper needle or
(IV) catheter placement prior to and during infusion to avoid
extravasation. If extravasation occurs, stop infusion
A skeletal muscle relaxant that acts directly on skeletal immediately and disconnect (leave cannula or needle in
muscle by interfering with release of calcium ion from the place), then gently aspirate extravasated solution (do
sarcoplasmic reticulum. This prevents or reduces the NOT flush the line). Remove needle or cannula and
increase in myoplasmic calcium ion concentration that elevate extremity.
activates the acute catabolic processes associated with
malignant hyperthermia. See Dantrolene under Muscle Relaxants – Directly Acting
Agents in Chapter 9: Musculo-Skeletal System for other
V

Indications: Management of malignant hyperthermia (MH); information.

prevention of MH in susceptible individuals (preoperative
or postoperative administration); for neuroleptic Pregnancy Category: C
malignant syndrome
ATC Code: M03CA01
NOTE: Dantrolene prophylaxis is NOT recommended for
most MH-susceptible patients, provided non-triggering
anesthetics are used and an adequate supply of
dantrolene is available.
Rx DIMERCAPROL

Contraindications: Active liver disease; should not be used Inj.: 50 mg/mL in oil, 2 mL ampule (IM)
when spasticity is used to maintain posture/balance
during locomotion or to obtain or maintain increased A specific antidote with a sulfhydryl group that combines
function with ions of various heavy metals to form relatively
stable, nontoxic, soluble chelates excreted in the urine.
Dose:
NOTE: Dose should be titrated and individualized for Indications: Antidote to gold, arsenic, or acute mercury
maximum effect. Use the lowest dose compatible with poisoning (excluding arsine and non-alkyl mercury) ;
optimal response. Some patients may not respond until adjunct to edetate calcium disodium in acute lead
a higher daily dosage is achieved. Each dose level should poisoning
be maintained for 7 days to determine patient response.
If no further benefit observed with the higher dose level, NOTE: NOT indicated for the treatment of iron, cadmium, or
then decrease dosage to previous dose level. selenium poisoning. May result in toxic dimercaprol-
metal complexes.
Malignant hyperthermia, preoperative prophylaxis, by
mouth, ADULT, 4–8 mg/kg per day in 3–4 divided doses, Contraindication: Hepatic insufficiency (unless due to
begin 1–2 days prior to surgery with last dose 3–4 hours arsenic poisoning)

612
VARIOUS

Dose: DIMERCAPTOPROPANE SULFONATE

Arsenic or gold poisoning (acute, mild), by deep IM injection, Rx
(DMPS)
ADULT and CHILD, 2.5 mg/kg every 6 hours for 2 days,
then every 12 hours for 1 day, followed by once daily for
Inj.: 100 mg/mL, 1 mL ampule and 10 mL vial (IM)
10 days.
Arsenic or gold poisoning (acute, severe), by deep IM
A sulfonic acid salt with free SH-groups that form complexes
injection, ADULT and CHILD, 3 mg/kg every 4 hours for 2
with heavy metals, such as mercury, cadmium, arsenic,
days, then every 6 hours for 1 day, followed every 12
lead, copper, silver, tin, etc.
hours for 10 days.
Mercury poisoning (acute), by deep IM injection, ADULT and
Indication: Antidote to arsenic and methyl mercury
CHILD, initially 5 mg/kg, followed by 2.5 mg/kg 1–2
poisoning
times daily for 10 days.
Lead poisoning (blood lead levels ≥70 micrograms/dL,
Contraindications: Pregnancy; lactation
symptomatic lead poisoning, or lead encephalopathy, in
conjunction with edetate calcium disodium), by deep IM
Dose:
injection, ADULT and CHILD, 4 mg/kg every 4 hours for
Heavy metal poisoning, by slow IV injection, ADULT, 3 mg/kg
2–7 days for at least 3 days. [NOTE: Begin treatment with
over 5 minutes.
edetate calcium disodium with the second dimercaprol
dose. Administer drugs at separate sites.]
Dose Adjustment: No information found

Precautions:
Precautions:
Nephrotoxicity (discontinue if acute renal insufficiency WARNING: Do NOT use in patients with silver
develops during therapy; dimercaprol-metal chelate is amalgam fillings as this may lead to acute toxicity
removed by hemodialysis); from heavy metal injury to the mucosa of the gut.
Glucose 6­phosphate dehydrogenase deficiency;
Children; Patients will feel better within 3–4 weeks following
Lactation. administration, then worsen due to manifestations of
heavy metals still present in the system.
Adverse Drug Reactions:
Common: Chest pain, hypertension (dose related), Adverse Drug Reactions:
tachycardia (dose related), anxiety, fever (children), NOTE: May exhibit adverse effects associated with toxicity
headache, nervousness, abscess, abdominal pain, of a specific heavy metal several days after
burning sensation (lips, mouth, throat), nausea, administration.
salivation, throat irritation or pain, vomiting, burning
sensation (penis), leukopenia (polymorphonuclear), Common: Pain, burning, GI problems, injection site
injection site pain, paresthesia (hand), weakness, reactions, feeling of emptiness in the head, difficulty
blepharospasm, conjunctivitis, lacrimation, acute renal concentrating
insufficiency, rhinorrhea, throat constriction, diaphoresis Less Common: Temporary lowering of blood pressure,

V
allergic reactions, skin rash
Drug Interactions:
Avoid concomitant use with: Drug Interactions: No information found
Increases risk of adverse or toxic effects of the following
drugs: Administration: Draw up drug into a 5 mL syringe and slowly
Iron Salts (nephrotoxic effect) injected into the patient with a 25-gauge butterfly over 5
Multivitamins / Minerals with Vitamins ADEK, Folate, Iron minutes (1 mL per minute).
(nephrotoxic effect)
Administer additional doses if any of the toxic metals are
TEST INTERACTION. May decrease iodine I131 thyroidal elevated above normal or mercury excretion is more than
uptake values. 1 microgram in 24 hours. Six to eight treatments may be
needed to get the heavy metal burden down to normal.
Administration: Administer by deep IM injection. Rotate
injection sites. NOT for IV administration Collect all urine for 24 hours and test for special mercury
and elements. Add nitric acid into the container as soon
Keep urine alkaline to protect renal function. as the first urine is collected. Do NOT administer mineral
supplements 24 hours before and 48 hours after the
NOTE: Premedication with a histamine H1 antagonist (e.g., test.
diphenhydramine) is recommended.
Pregnancy Category: Not classified
Pregnancy Category: C
ATC Code: Not available
ATC Code: V03AB09

613
 VARIOUS

Dose:
Rx DIPHENHYDRAMINE Beta blocker or calcium channel blocker toxicity, by IV
injection, ADULT, 3–10 mg (0.05–0.15 mg/kg) bolus,
Inj.: 50 mg/mL (as hydrochloride), 1 mL ampule (IM, IV) followed by an infusion of 3–5 mg/hour (0.05–0.1
mg/kg per hour); titrate infusion rate to achieve
A monoethanolamine-derived, first-generation H1-receptor adequate clinical response.
antagonist that exhibits antimuscarinic and pronounced
sedative property, with low incidence of GI side effects. Administration: Administer parenterally because glucagon is
destroyed in the GI tract.
Indication: For phenothiazine extrapyramidal side effects
Reconstitute as per manufacturer’s instructions. Use
Contraindications: Acute asthma; neonates or premature reconstituted glucagon immediately. Discard any unused
infants; breastfeeding; use of the parenteral form as a portion.
local anesthetic
Do NOT use at concentrations greater than 1 mg/mL (1
Dose: unit/mL).
NOTE: Dose should be individualized according to the needs
and response of the patient. NOTE: Patients with Type 1 diabetes may have less of an
increase in blood glucose levels compared with a stable
Drug-induced extrapyramidal effects, by IV infusion, ADULT, Type 2 patient. Administer supplementary carbohydrate
10–50 mg at a rate not exceeding 25 mg/min (maximum as soon as possible, especially to pediatric patients.
daily dose, 400 mg); CHILD, 5 mg/kg every 24 hours or
150 mg/m2 every 24 hours in 4 divided doses at a rate See Glucagon under Other Alimentary Tract and
not exceeding 25 mg/min (maximum daily dose, 300 Metabolism Products – Anti-Hypoglycemics in Chapter 1:
mg); Alimentary Tract and Metabolism for other information.
by deep IM injection, ADULT, 100 mg (maximum daily
dose, 400 mg); CHILD, 5 mg/kg every 24 hours or 150 Pregnancy Category: B
mg/m2 every 24 hours in 4 divided doses at a rate not
exceeding 25 mg/min (maximum daily dose, 300 mg). ATC Code: Not available

Administration:
For IV administration, do NOT exceed a rate of 25
mg/minute.
Rx FLUMAZENIL

IM administration must be deep. Local necrosis may Inj.: 100 micrograms/mL, 5 mL ampule (slow IV, IV
result with SC or ID use. infusion)

Inspect visually for particulate matter and discoloration Competitive inhibitor of the benzodiazepine receptor on the
prior to administration. GABA / benzodiazepine receptor complex. It does not
V

antagonize the CNS effect of drugs affecting GABA–ergic

See Diphenhydramine under Anti-Parkinson Drugs in neurons by means other than the benzodiazepine
Chapter 10: Nervous System for other information. receptor (ethanol, barbiturates, general anesthetics) and
does not reverse the effects of opioids.
Pregnancy Category: B
Indication: For benzodiazepine, zolpidem, and zopiclone
ATC Code: Not available poisoning

Contraindications: Patients given benzodiazepines for

control of potentially life-threatening conditions, e.g.,
Rx GLUCAGON control of intracranial pressure or status epilepticus;
patients who are showing signs of serious cyclic-
Inj.: 1 mg lyophilized powder (as hydrochloride) + solvent antidepressant overdose
(IM, IV, SC)
Dose:
A polypeptide that is produced by α cells of islets of NOTE: Individualize doses and be prepared to manage
Langerhans in the pancreas. It promotes hepatic seizures.
glycogenolysis and gluconeogenesis, thus causing an
increase in blood glucose levels. Glucagon is synthesized Suspected benzodiazepine overdose, non-benzodiazepine
in a special non-pathogenic laboratory strain of hypnotic overdose, by IV injection, ADULT, initially 0.2 mg
genetically altered Escherichia coli bacteria over 30 seconds; if the desired level of consciousness is
not obtained 30 seconds after the dose, administer 0.3
Indications: Beta blocker-induced or calcium channel mg over 30 seconds; repeat doses, of 0.5 mg over 30
blocker-induced myocardial depression (with or without seconds may be repeated at 1–minute intervals
hypotension) unresponsive to standard measures (maximum total cumulative dose, 3 mg; usual total dose,
1–3 mg);
Contraindications: Pheochromocytoma

614
VARIOUS

CHILD, initially 0.01 mg/kg (maximum dose, 0.2 mg) with Administration: Administer in freely-running IV into a large
repeated doses of 0.01 mg/kg (maximum dose, 0.2 mg) vein over 30 seconds.
every minute to maximum cumulative dose of 1 mg; or
by continuous infusion, 0.005–0.01 mg/kg per hour; Pregnancy Category: C
RE-SEDATION, repeat doses at 20-minute intervals
(maximum, 1 mg per dose) at 0.05 mg/minute and 3 ATC Code: V03AB25
mg/hour.

NOTE: If a patient has not responded 5 minutes after FOMEPIZOLE

cumulative dose of 5 mg, the major cause of sedation is Rx
(4-METHYLPRAZOLE)
not likely due to benzodiazepines.
Inj.: 1 mg/mL, 1.5 mL vial (IV)
For re-sedation, repeat doses of 0.5 mg/minute may be
given at 20–minute intervals to a maximum of 1 mg total
A competitive inhibitor of alcohol dehydrogenase. It
dose and 3 mg in 1 hour.
prevents the metabolism of ethylene glycol and
methanol to their toxic metabolites.
Dose Adjustment:
Hepatic Impairment:
Indication: Antidote for methanol and ethylene glycol
Reduce dose or frequency for repeat doses.
poisoning
Precautions:
Dose:
WARNING: Benzodiazepine reversal may result in Methanol or ethylene glycol poisoning, by slow IV infusion,
seizures. May occur more frequently in patients on ADULT, 15 mg/kg loading dose, followed by 4 doses of
long-term benzodiazepine or following tricyclic 10 mg/kg every 12 hours, then 15 mg/kg every 12
antidepressant overdose. hours.

Amnesia; Dose Adjustment:

CNS effects; Renal Impairment:
Re-sedation; In patients undergoing hemodialysis:
Seizures; If at the beginning of hemodialysis and ≥6 hours since
Respiratory depression; last fomepizole dose, administer next scheduled dose.
Head injury; During hemodialysis, administer dose every 4 hours.
Hepatic impairment; At completion of hemodialysis, administer next
Panic disorder; scheduled dose after 3 hours. If between 1–3 hours
Elderly; since end of hemodialysis, administer ½ of the next
Lactation. scheduled dose. If <1 hour since end of hemodialysis, do
NOT administer dose.
SKILLED TASKS. May impair ability to perform tasks which
Off hemodialysis, administer next scheduled dose 12

V
require mental alertness, such as operating machinery
or driving. hours from last dose as maintenance.

Precautions:
Adverse Drug Reactions: Local site irritation;
Common: Palpitation, flushing, vasodilation, ataxia, Allergic reactions;
dizziness, vertigo, agitation, anxiety, insomnia, Elderly and children;
nervousness, abnormal crying, depersonalization, Lactation.
depression, dysphoria, emotional lability, euphoria,
fatigue, headache, malaise, paranoia, hot flashes, Adverse Drug Reactions:
vomiting, xerostomia, nausea, pain at injection site, Common: Headache, nausea, dizziness, increased
injection site reaction, rash, skin abnormality, drowsiness, bad or metallic taste
thrombophlebitis, hypoesthesia, paresthesia, weakness, Less Common: Abdominal pain, fever, multi-organ system
tremor, blurred vision, abnormal vision, lacrimation, failure, pain or inflammation at injection site, lumbalgia
dyspnea, hyperventilation, diaphoresis or backache, hangover, bradycardia, phlebosclerosis,
Less Common: Abnormal hearing, altered blood pressure, tachycardia, phlebitis, shock, hypotension, vomiting,
arrhythmia, bradycardia, chest pain, confusion, coldness diarrhea, dyspepsia, heartburn, decreased appetite,
sensation, delirium, difficulty concentrating, dysphonia, transient transaminitis, hypereosinophilia or
generalized seizure, hiccups, hyperacusis, hypertension, eosinophilia, lymphangitis, disseminated intravascular
junctional tachycardia, rigors, seizure, shivering, coagulation, anemia, lightheadedness, seizure,
somnolence, stupor, tachycardia, thick tongue, tinnitus, agitation, feeling drunk, facial flush, vertigo, nystagmus,
transient hearing impairment anxiety, feeling of strangeness, decreased
environmental awareness, hiccups, pharyngitis,
Drug Interactions: application site reaction, rash, abnormal smell, speech
Monitor closely with: or visual disturbances, transient blurred vision, roar in
Reduces sedative effect of the following drugs: ear
Hypnotics, Non-Benzodiazepine [except Ramelteon,
Suvorexant,]

615
 VARIOUS

Drug Interactions: Dose:

Monitor closely with: Methemoglobinemia, by IV injection, ADULT and CHILD, 1–
Decreases rate of elimination of Ethanol 2 mg/kg or 25–50 mg/m2 over 5–10 minutes, may be
repeated in 1 hour if necessary.
Administration: Administer each dose as a slow IV infusion
over 30 minutes. Do NOT administer undiluted or by Precautions:
bolus injection. WARNING: Vesicant. Ensure proper needle or
catheter placement prior to and during infusion to
Using sterile technique, draw the appropriate dose from avoid extravasation.
the vial with a syringe and inject into at least 100 mL of
sterile 0.9% sodium chloride injection or dextrose 5% Methemoglobinemia; renal impairment; G6PD deficiency
injection. Mix well. Infuse the resulting solution over 30 (use with caution); Pregnancy (hemolytic anemia,
minutes. methemoglobinemia, and phototoxicity in neonates
following in utero exposure).
Visually inspect parenteral products for particulate
matter and discoloration prior to administration. Do NOT Adverse Drug Reactions:
use solutions showing haziness, particulate matter, Common: Angina, arrhythmia, hypertension, precordial
precipitate, discoloration, or leakage. pain, dizziness, headache, fever, mental confusion,
staining of skin, abdominal pain, diarrhea, discoloration
NOTE: Begin fomepizole treatment immediately upon of urine and feces (blue-green), nausea, vomiting,
suspicion of ethylene glycol or methanol ingestion, or a bladder irritation, anemia, paradoxical
documented serum ethylene glycol or methanol methemoglobinemia (high doses), transient reduction in
concentration greater than 20 mg/dL. oxygen saturation, dyspnea, diaphoresis
Less Common: Serotonin syndrome
Discontinue treatment when ethylene glycol or methanol
concentrations are undetectable or have been reduced Drug Interactions:
below 20 mg/dL, and the patient is asymptomatic with Monitor closely with:
normal pH. Enhances therapeutic effect of the following drugs:
Abobotulinumtoxin-A, Onabotulinumtoxin-A,
Consider hemodialysis to remove ethylene glycol or Rimabotulinumtoxin-B, Clemastine, Doxylamine
methanol and the respective toxic metabolites of these (anticholinergic effect), Antihypertensives (hypotensive
alcohols in patients with high ethylene glycol or methanol effect), Blood Glucose Lowering Agents e.g., Insulin
concentrations (≥50 mg/dL), significant metabolic (hypoglycemic effect), Doxapram, Epinephrine,
acidosis, or renal failure. Dialyze to correct metabolic Norepinephrine (hypertensive effect)
abnormalities and to lower the ethylene glycol
concentrations below 50 mg/dL. Increases risk of adverse or toxic effects of Methylene Blue:
Antiemetics / 5HT3 Antagonists (serotonin syndrome),
Fomepizole solidifies at temperatures <25°C (77°F). If Antipsychotic Agents (neuroleptic malignant syndrome),
this occurs, liquefy the solution by running the vial under Buprenorphine
V

warm water or by holding in the hand. Solidification does

not affect the efficacy, safety, or stability of fomepizole. Increases risk of adverse or toxic effects of the following
Fomepizole diluted as stated above remains stable and drugs:
sterile for at least 24 hours when stored in a refrigerator Analgesics, Opioid e.g Morphine (constipation, urinary
or at room temperature. Do NOT use beyond 24 hours. retention), Anticholinergic Agents [except, Nasal],
Fomepizole does NOT contain preservatives. Antihypertensives (orthostatic hypotension),
Antipsychotic Agents e.g., Risperidone (dopamine
Pregnancy Category: C blockade), Beta2 Agonists, e.g. Salbutamol Brimonidine,
Ophthalmic, Domperidone, Metoclopramide (serotonin
ATC Code: V03AB34 syndrome; neuroleptic malignant syndrome), Orthostatic
Hypotension Producing Agents, Ramosetron
(constipation), Topiramate
Rx METHYLENE BLUE
Reduces therapeutic effect of Methylene Blue:
Domperidone
Oral: 1% solution
Inj.: 10 mg/mL, 1 mL and 10 mL ampule / vial Reduces therapeutic effect of the following drugs:
Acetylcholinesterase Inhibitors e.g., Neostigmine,
A thiazine dye that hastens the conversion of Domperidone, Gastrointestinal Agents, Prokinetic e.g.
methemoglobin to hemoglobin. Metoclopramide, Itopride

Indication: Treatment of drug-induced methemoglobinemia Avoid concomitant use with:

Enhances therapeutic effect of the following drugs:
Contraindications: Pregnancy or intention to become Cimetropium, Cyproheptadine, Aclidinium, Ipratropium,
pregnant Pizotifen, Pramlintide (anticholinergic GI effects),
Tiotropium, Umeclidinium, Alpha / Beta Agonists,
Indirect-Acting, Alpha1 Agonists, Amphetamines,

616
VARIOUS

Atropine (Ophthalmic), Bupropion, Diethylpropion,

Mequitazine, Methylphenidate, Tetrahydrozoline, (Nasal) Rx N-ACETYL PENICILLAMINE
(hypertensive effect)
Oral: crystals, 25 g/bottle
Increases risk of adverse or toxic effects (e.g. serotonin
syndrome, hypertensive effect) Methylene Blue: A chelating agent that chelates with lead, copper, mercury
Anilidopiperidine Opioids e.g. Fentanyl [avoid and other heavy metals to form stable, soluble
concomitant use within 14 days of either drug], complexes that are excreted in urine.
Buspirone, Carbamazepine [avoid concomitant use
within 14 days of either drug], COMT Inhibitors, Ethyl Indications: For copper, lead, and mercury poisoning
Alcohol, Levodopa, MAO Inhibitors e.g. Mirtazapine,
Oxymorphone, Selective Serotonin Reuptake Inhibitors Contraindications: Patients with previous penicillamine-
e.g. Fluoxetine, Serotonin / Norepinephrine Reuptake related aplastic anemia or agranulocytosis;
Inhibitors e.g. Venlafaxine, Tapentadol, Tramadol breastfeeding
(neuroexcitatory and/or seizure-potentiating effect),
Tricyclic Antidepressants, Tryptophan Dose:
NOTE: Consider dose reduction to 250 mg daily prior to
Increases risk of adverse or toxic effects of the following surgical procedures. May resume normal recommended
drugs: dosing post-operatively once healing is complete.
Atomoxetine (neurotoxic / central effect), Dapoxetine,
Dextromethorphan (serotonin syndrome), Lead poisoning, by mouth, ADULT, 900–1,500 mg daily in 3
(constipation), Glucagon (GI adverse effects), , Linezolid, divided doses for 1–2 weeks, then 750 mg daily in
Lithium, Meperidine (serotonin syndrome), Methadone, divided doses until blood lead concentration is <60
Methyldopa, (neurotoxic effect), Moclobemide, micrograms/dL or urinary lead excretion is <500
Morphine, Oxycodone [avoid concomitant use within 14 micrograms/L for 2 consecutive months; CHILD, 30–40
days of either drug], Potassium Chloride (ulcerogenic mg/kg daily or 600–750 mg/m2 daily in 1–2 divided
effect), Reserpine (paradoxical effects of reserpine, e.g., doses (maximum dose, 750 mg daily). Treat until blood
excitation, hypertension), Serotonin Modulators [except lead concentration is <40 micrograms/dL for 2
Tedizolid] (serotonin syndrome) consecutive months AND decrease in erythrocyte
protoporphyrin level to <3–5 times the average normal
Increases serum concentration of Serotonin 5-HT1D level OR the excretion of coproporphyrin or delta–
Receptor Agonists e.g Sumatriptan aminolevulinic acid decrease to the upper limit of
normal.
Reduces serotonergic effect of Methylene Blue: Wilson’s disease, by mouth, ADULT, 750–1,500 mg daily in
Cyproheptadine divided doses (maximum dose, 2,000 mg daily); CHILD,
20 mg/kg daily in 2–3 divided doses, round off to the
Reduces therapeutic effect of the following drugs: nearest 250 mg dose [NOTE: Dose that results in an
Levosulpiride, Secretin initial 24–hour urinary copper excretion of >2 mg daily
should be continued for approximately 3 months.

V
Administration: Administer undiluted by direct IV injection Establish maintenance dose where serum copper levels
over 5–10 minutes. If administered by continuous IV are controlled at <10 micrograms/dL].
infusion, administer via central line to minimize the risk
of extravasation injury. Dose Adjustment:
Geriatric:
Do NOT administer by intraspinal or subcutaneous Initiate at low end of dosing range and “go slow” with dose
injection. increase intervals. Do NOT exceed 750 mg daily.

Consider concomitant dextrose administration, Renal Impairment:

especially in patients who are hypoglycemic, to ensure Avoid use in patients with CrCl<50 mL/minute.
efficacy of methylene blue. In patients undergoing hemodialysis, administer 33% of
usual dose. Drug is dialyzable.
EXTRAVASATION MANAGEMENT. If extravasation occurs,
immediately stop infusion and disconnect, leaving the Pregnancy:
cannula or needle in place. Gently aspirate extravasated Limit daily dose to 750 mg daily.
solution. Do NOT flush the line. Remove the cannula or If planned caesarian, limit dose to 250 mg daily during last
needle. Elevate extremity. Dry warm compresses may be 6 weeks of pregnancy and postoperatively until wound
applied proximal to the injection site. healing is complete.

Pregnancy Category: X Precautions:

WARNING: Must be administered by physicians
ATC Code: Not available familiar with its toxicity, special dosage
considerations, and therapeutic benefits. Closely
supervise patient during therapy.

617
 VARIOUS

Patients should be warned to report promptly any Antacids, Iron Salts, Oral [except Ferric Carboxymaltose,
symptoms suggesting toxicity (fever, sore throat, Ferric Gluconate, Ferric Pyrophosphate Citrate,
chills, bruising, or bleeding). Ferumoxytol, Iron Dextran Complex, Iron Sucrose]
(decreased absorption)
Allergic reactions;
Increases serum concentration of Penicillamine:
Dermatologic effects;
Multivitamins / Minerals with Vit ADEK, Folate, Iron [if
Bronchiolitis obliterans;
concomitant use cannot be avoided, separate doses by
Drug fever;
2 or more hours]
Goodpasture's syndrome;
Pemphigus;
Administration: Administer on an empty stomach, 1 hour
Myasthenia gravis;
before or 2 hours after meals, and at least 1 hour apart
Gastrointestinal effects (eg. taste alteration, oral
from other drugs, milk, antacids, and zinc or iron-
ulceration);
containing products. Penicillamine serum levels may be
Lupus erythematosus-like syndrome;
decreased if taken with food. Certain disease states
Hematologic toxicities (fatalities due to agranulocytosis,
require further diet adjustment.
aplastic anemia, and thrombocytopenia);
Hepatotoxicity (eg. intrahepatic cholestasis, toxic hepatitis);
Administer doses ≤500 mg as a single dose.
Proteinuria or hematuria;
Administer doses >500 mg in divided doses.
Renal impairment;
Cystinuria;
For patients who cannot swallow, contents of capsules
Elderly;
may be administered in 15–30 mL of chilled puréed fruit
Children (use only if asymptomatic with blood lead
or fruit juice.
concentrations of 50–80 micrograms/dL, erythrocyte
protoporphyrin level >400–500 micrograms/dL
Pyridoxine supplementation is recommended.
erythrocytes, excessive excretion of delta–aminolevulinic
acid and/or coproporphyrin);
NOTE: Patients with Wilson's disease should receive 25–50
Pregnancy (birth defects, including congenital cutix laxa and
mg daily of pyridoxine. A multivitamin (without copper)
associated defects, have been reported; discontinuation
may also be considered. Decrease copper in diet to <1–
has detrimental maternal and fetal effects);
2 mg daily and omit chocolate, nuts, shellfish,
Lactation.
mushrooms, liver, raisins, broccoli, copper-enriched
cereal, multivitamins with copper, and molasses. May
Adverse Drug Reactions:
consider short courses of iron supplementation if dietary
Common: Vasculitis, anxiety, agitation, fever, Guillain-Barré
modifications result in iron deficiency.
syndrome, hyperpyrexia, psychiatric disturbances,
worsening neurologic symptoms, alopecia, cheilosis,
For lead poisoning, decrease calcium in diet.
dermatomyositis, drug eruptions, exfoliative dermatitis,
lichen planus, pemphigus, pruritus, rash, increased skin
Pediatric patients and menstruating women may be
friability, toxic epidermal necrolysis, urticaria, excessive
particularly susceptible to iron deficiency. Allow 2 hours
wrinkling, yellow nail syndrome, hypoglycemia,
V

between administration of iron supplementation and

thyroiditis, diarrhea, taste alteration, anorexia, epigastric
penicillamine as iron may decrease drug absorption.
pain, gingivostomatitis, glossitis, nausea, oral
ulcerations, pancreatitis, peptic ulcer reactivation,
Pregnancy Category: D
vomiting, thrombocytopenia, leukopenia,
agranulocytosis, aplastic anemia, eosinophilia,
ATC Code: Not available
hemolytic anemia, leukocytosis, monocytosis, red cell
aplasia, sideroblastic anemia, thrombotic
thrombocytopenia purpura, thrombocytosis, increased
alkaline phosphatase, hepatic failure, intrahepatic Rx NALOXONE
cholestasis, toxic hepatitis, thrombophlebitis, white
papules at venipuncture and surgical sites, arthralgia,
dystonia, myasthenia gravis, muscle weakness, Inj.: 400 micrograms/mL (as hydrochloride), 1 mL ampule
neuropathies, polyarthralgia (migratory, often with (IM, IV, SC)
objective synovitis), polymyositis, diplopia, extraocular
muscle weakness, optic neuritis, ptosis, visual A pure opioid antagonist that competes and displaces
disturbances, tinnitus, proteinuria, Goodpasture's opioids at opioid receptor sites.
syndrome, hematuria, nephrotic syndrome, renal failure,
renal vasculitis, asthma, interstitial pneumonitis, Indication: For the complete or partial reversal of opioid
pulmonary fibrosis, obliterative bronchiolitis, allergic depression (including respiratory depression) induced by
alveolitis, anetoderma, elastosis perforans serpiginosa, natural and synthetic opioids (e.g., propoxyphene,
lupus-like syndrome, l, lymphadenopathy, mammary methadone, nalbuphine, butorphanol, pentazocine)
hyperplasia, positive ANA test
Dose:
Drug Interactions: Opioid overdose (with standard ACLS protocols), by IV, IM,
Avoid concomitant use with: or SQ injection, ADULT, initially 0.4–2 mg, may need to
Decreases serum concentration of Penicillamine: repeat doses every 2–3 minutes; ADOLESCENT, INFANT,
and CHILD ≥5 years or >20 kg, 2 mg; if no response,

618
VARIOUS

repeat every 2 to 3 minutes; ADOLESCENT, CHILD <5 Administration:

years or ≤20 kg, and INFANT, 0.1 mg/kg per dose IV administration is the preferred route. Administer via IV
(maximum dose, 2 mg), repeat every 2–3 minutes if push over 30 seconds as undiluted preparation or via
needed. [NOTE: After reversal, re-administration of slow IV push as diluted preparation by diluting 0.4 mg (1
dose(s) may be needed at a later interval (i.e., 20–60 mL) ampule with 9 mL of normal saline for a total volume
minutes) depending on type or duration of opioid. If no of 10 mL to achieve a concentration of 0.04 mg/mL. May
response is observed after 10 mg total, consider other also be administered via continuous IV infusion a diluted
causes of respiratory depression]. preparation by diluting 2 mg in 500 mL of D5W or normal
Reversal of respiratory depression with therapeutic opioid saline to make 4 micrograms/mL.
doses, by IV, IM, or SQ injection, ADULT, initially 0.04–
0.4 mg, may repeat until desired response achieved; May administer by IM or SQ route if unable to obtain IV
ADOLESCENT, CHILD, and INFANT, 0.001–0.015 mg/kg access.
per dose; may be repeated as needed. [NOTE: If desired
response is not observed after 0.8 mg total, consider Pregnancy Category: B / C (product-specific)
other causes of respiratory depression].
Reversal of respiratory depression in opioid-dependent ATC Code: V03AB15
patients being treated for cancer pain, by slow IV push,
ADULT, 40–80 micrograms every 30 to 60 seconds until
improvement in symptoms. [NOTE: If no response is
observed after total naloxone dose 1 mg, consider other Rx NEOSTIGMINE
causes of respiratory depression.]
Postoperative reversal, by IV injection, ADULT, 0.1–0.2 mg Inj.: 500 micrograms/mL, 10 mL vial
every 2–3 minutes until desired response (adequate 500 mcg/mL solution for injection (IM/IV/SC), 1 mL
ventilation and alertness without significant pain); repeat ampule
doses may be needed within 1– to 2-hour intervals
depending on type, dose, and timing of the last dose of A cholinesterase inhibitor competitively binds to
opioid administered; ADOLESCENT, CHILD, and INFANT, acetylcholinesterase binding sites, inhibiting the
0.005–0.01 mg/kg, may repeat every 2–3 minutes as hydrolysis of acetylcholine.
needed based on response (adequate ventilation
without significant pain). Indication: Reversal of neuromuscular blockade
Precautions:
Acute opioid withdrawal (e.g. precipitate acute withdrawal, Contraindications: Peritonitis; mechanical GI; urinary
unmask pain); obstruction
Cardiovascular disease (e.g. pulmonary edema,
cardiovascular instability, including ventricular Dose:
fibrillation); NOTE: individualize doses based on weight. Determine time
Seizures (use with caution); of initiation of neostigmine and need for additional doses
Pregnancy (use with caution in mild-to-moderate using a peripheral nerve stimulator.
hypertension during labor; severe hypertension may

V
occur); Reversal of neuromuscular blockade, by IV injection, ADULT
Lactation (consider opioid concentrations in the milk of a and CHILD, 0.05–0.07 mg/kg over 60 seconds, as
breast­feeding mother and potential transfer of the required.
opioid to the infant).
Dose Adjustment:
Adverse Drug Reactions: Renal Impairment:
NOTE: Adverse reactions are related to reversing Dose adjustment may be required.
dependency and precipitating withdrawal. Withdrawal
symptoms are the result of sympathetic excess. Precautions:
WARNING: Should be administered by trained healthcare
Common: Cardiac arrest, fever, flushing, hypotension,
providers familiar with the use, actions, characteristics,
hypertension, tachycardia, ventricular fibrillation
and complications of neuromuscular blocking agents
ventricular tachycardia, agitation, hallucination, crying
(NMBA) and neuromuscular block reversal agents.
(excessive; neonates), encephalopathy, irritability,
nervousness, restlessness, seizure (neonates),
tremulousness, abdominal cramps, coma, diarrhea, Bradycardia;
nausea, vomiting, injection site reaction, ache, Cardiovascular disorders;
hyperreflexia (neonates), paresthesia, piloerection, Bronchial asthma;
tremor, weakness, dyspnea, hypoxia, pulmonary edema, Neuromuscular dysfunction;
respiratory depression, rhinorrhea, sneezing, Peptic ulcer disease;
diaphoresis, hot flashes, shivering, yawning Vagotonia;
Epilepsy;
Drug Interactions: Parkinsonism;
Avoid concomitant use with: Hyperthyroidism;
Increases risk of adverse or toxic effects of Naloxone: Recent intestinal or bladder surgery;
Methylnaltrexone (opioid withdrawal) Renal impairment;
Elderly (use with caution);

619
 VARIOUS

Children; PENICILLIN G CRYSTALLINE

Pregnancy; Rx
(BENZYLPENICILLIN)
Lactation.
Inj.: 1 MU and 5 MU (as sodium salt) (IM, IV)
Adverse Drug Reactions:
Common: Bradycardia, hypotension, tachycardia, dry
A beta lactamase-sensitive penicillin that protects against
mouth, nausea, vomiting, incision site complication,
lethal doses of amanitin by displacing amanitin from
pharyngolaryngeal pain, procedural complication,
plasma proteins, thus increasing renal excretion. It
procedural pain, dizziness, headache, postoperative
inhibits amanitin from entering hepatocytes by binding to
shivering, prolonged neuromuscular blockade, insomnia,
acid amanitin.
dyspnea, oxygen desaturation <90%, pruritus
Less Common: Hypersensitivity reactions, allergic reactions,
NOTE: Peak plasma concentrations are reached within 15–
convulsions, drowsiness, dysarthria, fasciculation, loss
30 minutes.
of consciousness, miosis, visual changes, cardiac arrest,
cardiac arrhythmias, non-specific EKG changes,
Indication: For amanita mushroom poisoning
syncope, bronchospasm, increased salivation,
Dose:
respiratory arrest, rash, urticaria, abdominal cramps,
Amanita mushroom poisoning, by IV injection, ADULT and
diarrhea, flatulence, increased peristalsis, urinary
CHILD, 250 mg/kg daily.
frequency, arthralgia, muscle cramps, spasms,
weakness, diaphoresis, flushing, neuromuscular
Dose Adjustment:
dysfunction (high doses), respiratory failure (potentially
Renal Impairment:
fatal)
For mild-to-moderate renal impairment, reduce dose.
For severe impairment, refer patient to a specialist.
Drug Interactions:
Do not exceed 6 g daily in renal failure.
Monitor closely with:
Reduces therapeutic effect of Neostigmine:
Precautions:
Chloroquine, Hydroxychloroquine, Lithium,
Penicillin allergy;
Procainamide, Propafenone, Quinidine, Quinine
Renal failure;
Neurotoxicity (eg. cerebral irritation, convulsions, or coma);
Avoid concomitant use with:
Sodium restriction, heart failure;
Increases risk of adverse or toxic effects of the following
Syphilis (eg. Jarisch-Herxheimer reaction);
drugs:
Lactation (safe in usual dosage; monitor infant).
Beta Blockers (prolonged bradycardia), Depolarizing
Muscle Relaxants, e.g., Suxamethonium (prolonged
Adverse Drug Reactions:
apnea due to potentiation of neuromuscular blockade)
Common: Pain and sterile inflammation at injection site,
phlebitis
Administration: For IV use only. Inject slowly over a period of
Less Common: Antibiotic-associated colitis, diarrhea,
at least 1 minute.
glossitis, nausea, stomatitis, vomiting
Rare: CNS toxicity, electrolyte disturbances, hemolytic
V

Prior to administration and until complete recovery of

anemia, hypersensitivity reactions including anaphylaxis;
normal ventilation, keep patient well-ventilated, and
interstitial nephritis, Jarisch-Herxheimer reaction,
maintain a patent airway.
neutropenia, non-allergic (embolic-toxic) reaction,
thrombocytopenia
Administer an anticholinergic agent, e.g., atropine
sulfate or glycopyrrolate prior to or concomitantly with
Drug Interactions:
neostigmine. Administer intravenously using a separate
Monitor closely with:
syringe. In the presence of bradycardia, administer the
Enhances therapeutic effect of Anticoagulants, e.g.,
anticholinergic agent prior to neostigmine.
Warfarin
NOTE: Judge satisfactory recovery based on adequacy of
Reduces therapeutic effect of Oral Contraceptives
skeletal muscle tone and respiratory measurements in
addition to response to peripheral nerve stimulation.
Avoid concomitant use with:
Increases serum concentration of Benzylpenicillin:
Pregnancy Category: C
Probenecid
ATC Code: N07AA01
Reduces therapeutic effect of Benzylpenicillin:
Tetracycline (antagonistic effect)

TEST INTERACTION. Produces a false positive urinary

glucose if tested for reducing substances.

Administration: Inspect reconstituted solutions visually. Use

only clear solutions, free of visible particles. Freshly-
prepared solutions for injection or infusion should be
used immediately.

620
VARIOUS

Avoid intrathecal route.

Drug Interactions:
NOTE: IV route is preferred for neonates and infants. Doses Monitor closely with:
over 1.2 g should be given by the IV route only. Enhances therapeutic effect of the following drugs:
Beta Blockers [except Levobunolol, Metipranolol]
See Penicillin G Crystalline (Benzylpenicillin) under (bradycardic effect)
Antibacterials for Systemic Use – Beta-Lactam
Antibacterials, Penicillins in Chapter 7: Antiinfectives for Increases risk of adverse or toxic effects of Physostigmine:
Systemic Use for other information. Corticosteroids, Systemic (increased muscular
weakness)
Pregnancy Category: B
Increases risk of adverse or toxic effects of Cholinergic
ATC Code: Not available Agonists

Reduces therapeutic effect of Physostigmine:

Dipyridamole
Rx PHYSOSTIGMINE
Reduces therapeutic effect of the following drugs:
Inj.: 1 mg/mL (as salicylate), 2 mL ampule (IM, IV) Anticholinergic Agents, Neuromuscular-blocking Agents,
Nondepolarizing
A carbamate that inhibits acetylcholinesterase and prolongs
the central and peripheral effects of acetylcholine. Avoid concomitant use with:
Increases serum concentration Succinylcholine
Indications: Reversal of central nervous system
anticholinergic syndrome (i.e., atropine poisoning); Administration: If administered by IV injection, administer
adjunct to cobra bite no faster than 1 mg/minute in adults or 0.5 mg/minute
in children to prevent bradycardia, respiratory distress,
NOTE: Consult with a clinical toxicologist or poison control and seizures from too rapid administration.
center.
May also be administered via IM route.
Contraindications: Gastrointestinal or genitourinary
obstruction; asthma; gangrene; diabetes; cardiovascular Pregnancy Category: C
disease; vagotonic state; co-administration of choline
esters and depolarizing neuromuscular-blocking agents ATC Code: V03AB19
(e.g. succinylcholine)

Dose: PHYTOMENADIONE
Reversal of toxic anticholinergic effects, by IM or IV injection, Rx
(PHYTONADIONE, VITAMIN K1)
ADULT, 0.5–2 mg, may repeat every 10–30 minutes until

V
response occurs; CHILD, initially 0.02 mg/kg, may repeat Oral: 2 mg/0.2 mL (as mixed micelle) pediatric ampule
every 5–10 minutes until response occurs (maximum Inj.: 2 mg/0.2 mL (as mixed micelle) pediatric ampule (IM,
total dose, 2 mg). IV)
10 mg/mL (as mixed micelle), 1 mL ampule (IM, IV)
Precautions: 10 mg/mL (as aqueous colloidal solution with benzyl
WARNING: Should only be used to reverse toxic, life- alcohol), 1 mL ampule (IM, IV)
threatening delirium caused by pure
anticholinergic agents (i.e., atropine, A fat-soluble vitamin that is an essential cofactor in the
diphenhydramine, dimenhydrinate, deadly synthesis of blood coagulation factors: prothrombin (II),
nightshade [Atropa belladonna], or jimson weed VII, IX, X, and proteins C and S.
[Datura spp]).
Hazardous agent. Use appropriate precautions for Indications: For warfarin and white or yellow phosphorus
handling and disposal. “watusi” poisoning
Arrhythmia (use with caution);
Contraindications: Avoid IM if bleeding; pregnancy (3rd
Cholinergic effects (eg. excessive cholinergic activity);
trimester); it is not effective in hereditary
Hypersensitivity or overdose reactions;
hypoprothrombinemia and that caused by liver disease
Lactation.
Dose:
Adverse Drug Reactions:
Warfarin-induced hypoprothrombinemia, minor bleeding or
Common: Asystole, bradycardia, palpitation, hallucinations,
not bleeding, by slow IV injection, ADULT, 500
nervousness, restlessness, seizure, defecation,
micrograms.
diarrhea, nausea, salivation, stomach pain, vomiting,
Warfarin-induced hypoprothrombinemia, moderate
urinary frequency, twitching, lacrimation, miosis,
hemorrhage, by IM injection, ADULT, 10–20 mg.
bronchospasm, dyspnea, pulmonary edema, respiratory
Warfarin-induced hypoprothrombinemia, severe
distress, respiratory paralysis, diaphoresis,
hemorrhage, by slow IV injection, ADULT, 5–10 mg.
hypersensitivity

621
 VARIOUS

Administration: administer by slow IV injection over 30

seconds. Rapid infusion can cause dyspnea, chest and Drug Interactions: No known significant interactions
back pain.
See Phytomenadione (Phytonadione, Vitamin K1) under Administration: Administer via IV infusion as 10–20 mg/mL
Vitamins in Chapter 1: Alimentary Tract and Metabolism solution over 15–30 minutes. In the presence of
for other information. pulmonary edema and/or fluid restriction, administer as
a 50 mg/mL solution by slow IV injection over ≥5
Pregnancy Category: C; X in 3rd trimester or near term minutes.

ATC Code: Not available Administer continuous or intermittent IV infusion at a

rate not exceeding 200 mg/minute.

PRALIDOXIME CHLORIDE Discard any unused portions.

Rx
(2-PAM)
Consider IM or SQ administration when IV administration
is not feasible.
Inj.: 50 mg/mL, 20 mL vial (IV)
DILUTION. Dilute 1,000 mg with 20 mL SWFI to make 50
An antidote that reactivates cholinesterase that had been
mg/mL for fluid-restricted patients or where a more rapid
inactivated by phosphorylation due to exposure to
administration is required. For all other patients, further
organophosphate pesticides and cholinesterase-
dilute with NS to a final concentration of 10–20 mg/mL.
inhibiting nerve agents.
Pregnancy Category: C
Indication: Treatment of muscle weakness and/or
respiratory depression secondary to poisoning due to
ATC Code: V03AB04
organophosphate anticholinesterase pesticides and
chemicals (e.g., nerve agents)

Dose: Rx PROTAMINE SULFATE

NOTE: Used in conjunction with atropine. Establish a
response to atropine before administering pralidoxime.
Inj.: 10 mg/mL, 5 mL and 25 mL ampule (IV)
Organophosphate poisoning, by IV injection, ADULT and
ADOLESCENT >16 years, 1,000–2,000 mg loading dose, Simple proteins of low molecular weight that are rich in
followed by maintenance repeat bolus of 1,000–2,000 arginine and strongly basic. Forms a stable salt with
mg after 1 hour and repeated every 10–12 hours heparin (strongly acidic) to inhibit the anticoagulant
thereafter, as needed; or 30 mg/kg loading dose activity of both drugs.
followed by a maintenance infusion of 8 mg/kg per hour;
ADOLESCENT ≤16 years and CHILD, 20–50 mg/kg Indication: Treatment of heparin overdose
loading dose (maximum, 2,000 mg/dose), then
V

administer maintenance infusion of 10–20 mg/kg per Contraindication: Known drug intolerance
hour; or a repeat bolus of 20–50 mg/kg (maximum,
2000, mg/dose) may be administered after 1 hour and Dose:
repeated every 10–12 hours thereafter, as needed. NOTE: Individualize doses based on administered heparin,
its route of administration, time elapsed since heparin
NOTE: For persistent symptoms, repeat the entire series administration, and blood coagulation studies. Each mg
(severe symptoms) approximately 1 hour after of protamine, calculated on the dried basis, neutralizes
administration of the last injection. not less than 100 USP heparin units.

Dose Adjustment: Dosing should be guided by blood coagulation studies.

Renal Impairment: Since heparin disappears rapidly from circulation,
Dose reduction is recommended. protamine dose should also decrease with time elapsed
following heparin administration.
Heparin overdose (heparin administered via IV injection), by
Precautions: IV injection, ADULT, administer at ≤5 mg/minute
Myasthenia gravis; (maximum, 50 mg/dose);
Renal impairment; a few minutes after heparin administration, 1 mg for
Hepatic impairment; every 100 U of heparin;
Lactation. 30–60 minutes after heparin administration, 0.5–0.75
mg for every 100 U of heparin;
Adverse Drug Reactions: ≥2 hours after heparin administration, 0.25 to 0.375 mg
Common: Cardiac arrest, hypertension, tachycardia, for every 100 U of heparin.
dizziness, drowsiness, headache, paralysis, seizure, skin Heparin overdose (heparin administered via IV infusion), by
rash, nausea, fasciculations, laryngospasm, muscle IV injection, ADULT, 25–50 mg after stopping heparin
rigidity, weakness, accommodation disturbance, blurred administration.
vision, diplopia, renal insufficiency, apnea, Heparin overdose (heparin administered via SQ injection),
hyperventilation by IV injection, ADULT, 1–1.5 mg for every 100 U of

622
VARIOUS

heparin; or 25–50 mg loading dose via slow IV injection,

and the remaining dose via continuous IV infusion over OTC PYRIDOXINE (VITAMIN B6)
8–16 hours, or the expected duration of heparin
absorption. Oral: 100 mg tablet
Enoxaparin overdose, by IV infusion, ADULT, if ≤8 hours
since administration, 1 mg for every 1 mg of enoxaparin; A naturally occurring, water-soluble vitamin. It is converted
if >8 hours since administration, 0.5 mg for every 1 mg in erythrocytes to its active moiety, pyridoxal phosphate,
of enoxaparin. which acts as coenzymes in metabolic processes,
Dalteparin overdose, by IV infusion, ADULT, 1 mg for every including metabolism of fat, protein, and carbohydrate.
100 anti-Xa U of dalteparin; if aPTT remains prolonged
2–4 hours after first infusion, administer a second Indications: Management of isoniazid, hydralazine,
infusion. hydrogen sulfide, gynomethrin mushroom, and
theophylline poisoning; to prevent development of
Precautions: peripheral neuritis in patients receiving isoniazid or
WARNING: Can cause severe hypotension, hydralazine
cardiovascular collapse, noncardiogenic
pulmonary edema, catastrophic pulmonary Contraindications: Breastfeeding, pregnancy, premature
vasoconstriction, and pulmonary hypertension. neonates, renal impairment
Vasopressors and resuscitation equipment should
be immediately available in case of a severe Dose:
reaction to protamine. NOTE: Dose is individualized and determined by the
Should NOT be given when bleeding occurs without physician.
prior heparin use.
Hyperheparinemia or bleeding has been reported For hydralazine toxicity related to pyridoxine deficiency, by
30 minutes – 18 hours after cardiac surgery. Keep mouth, ADULT and ADOLESCENT, 100–300 mg daily;
patient under close observation after cardiac CHILD, 10 to 50 mg daily.
surgery. Hydralazine toxicity prophylaxis, by mouth, ADULT, 100 mg
once daily; ADOLESCENT, 25–100 mg daily; CHILD, 1–2
Do NOT administer more than 50 mg over a short mg/kg daily.
period unless a larger dose is clearly needed. For isoniazid toxicity related to pyridoxine deficiency,
excluding seizures, by mouth, ADULT and ADOLESCENT,
Hypersensitivity; 25–100 mg daily; CHILD, 1–2 mg/kg daily.
Children; Isoniazid toxicity prophylaxis, by mouth, ADULT, 10 to 75 mg
Lactation. daily; or 25 mg daily; ADOLESCENT, 25–100 mg daily; or
25 mg daily; CHILD, 1–2 mg/kg daily. [NOTE: Guidelines
Adverse Drug Reactions: recommend prophylaxis only in patients at risk for
Common: Bradycardia, hypotension, flushing (transient), peripheral neuropathy, including those with nutritional
feeling of warmth, dyspnea, nausea, vomiting, lassitude, deficiency, diabetes, symptomatic HIV infection, renal
back pain, anaphylaxis or anaphylactoid reactions failure, or in patients who are breastfed.]

V
For the treatment of drug-induced seizures secondary to
Drug Interactions: acute isoniazid overdose, by mouth, ADOLESCENT,
Avoid concomitant use with: CHILD, and INFANT,
Incompatible with the following products: Acute ingestion of known amount, pyridoxine dose equal
Antibiotics, e.g., Cephalosporins, Penicillins to amount of isoniazid ingested (maximum, 70 mg/kg
per dose, up to 5 g);
Administration: For IV use only. Acute ingestion of unknown amount, 70 mg/kg per dose
(maximum, 5 g per dose); administer until seizure stops
Administer undiluted via very slow IV injection over a 10- or maximum initial dose has been administered; if the
minute period in doses not exceeding 50 mg. If further entire initial dose is not administered, give remaining
dilution is desired, dilute using D5W or NS. Do NOT store initial dose over the next 4–6 hours; may repeat dose
diluted solutions. every 5–30 minutes as needed if seizures do not resolve
or consciousness is not regained;
Inspect visually for particulate matter and discoloration Asymptomatic patients present within 2 hours of acute
prior to administration. ingestion, treat prophylactically with the initial ingestion
dose (e.g., 70 mg/kg per dose or 5 g) and monitor for 6
Pregnancy Category: C hours.
ATC Code: V03AB14 Seizures due to acute mushroom poisoning, by IV injection,
ADULT, 25 mg/kg over 15–30 minutes, may be repeated
as necessary to a total dose of 15–20 g daily;
ADOLESCENT, CHILD, and INFANT, 25 mg/kg over 15–
30 minutes (maximum initial dose, 5 g), repeat dose as
necessary up to 300 mg/kg daily (maximum daily dose,
15–20 g).

623
 VARIOUS

Administration: Administration: Administer whole. Do NOT glycosuria, proteinuria, microscopic hematuria, large
crush, break, or chew. epithelial cells in urinary sediment, tremors, headache,
numbness, tingling, cheilosis, nausea, vomiting,
See Pyridoxine (Vitamin B6) under Vitamins in Chapter 1: anorexia, excessive thirst, milk increases in SGOT and
Alimentary Tract and Metabolism for other information. SGPT, histamine-like reactions, rash, bone marrow
depression (transient), anemia, zinc deficiency,
Pregnancy Category: A hypercalcemia
Less Common: Nephrotoxicity (potentially fatal)
ATC Code: A11HA02
Drug Interactions:
Monitor closely with:
Incompatible with the following products:
Rx SODIUM CALCIUM EDETATE Zinc Insulin Preparations (chelates with zinc)

Inj.: 200 mg/mL, 5 mL ampule (IM) Administration: For IM use only.

The calcium chelate of edetate disodium. It chelates Administer IV fluid if possible prior to first dose to ensure
divalent and trivalent metals, forming stable chelates adequate diuresis and reduce incidence of treatment-
that displace calcium from the molecule, forming a induced nephrotoxicity.
water-soluble complex excreted by the kidneys.
Indication: For the reduction of blood levels and depot NOTE: Add lidocaine or procaine to minimize pain at
stores of lead in lead poisoning (acute and chronic) and injection site. Final lidocaine or procaine concentration
lead encephalopathy should be 5 mg/mL (0.5%).

Contraindications: Anuria; active renal disease; hepatitis Pregnancy Category: B

Dose: ATC Code: V03AB03

Lead poisoning, asymptomatic with blood lead levels >70
micrograms/dL or symptomatic without encephalopathy,
by deep IM injection, ADULT, 167 mg/m2 every 4 hours
for 3–5 days, may treat with dimercaprol until blood lead
Rx SODIUM NITRITE
level is <50 micrograms/dL.
Lead poisoning, blood lead levels >70 micrograms/dL Inj.: USP grade powder (IV)
and/or symptoms of encephalopathy, by deep IM
injection, ADULT, 250 mg/m2 every 4 hours for 5 days A cyanide antidote that exerts its therapeutic effect by
with dimercaprol, administer first dose at least 4 hours reacting with hemoglobin to form methemoglobin, an
after first dose of dimercaprol, may be repeated after at oxidized form of hemoglobin with high affinity to cyanide,
least 2 treatment-free days if needed [NOTE: Both drugs inhibiting the activity of cyanide on cytochrome oxidase.
may be given simultaneously at separate sites].
V

Indication: For sequential use with sodium thiosulfate for

NOTE: Total daily dose (1000 mg/m2) should be divided into the treatment of cyanide poisoning that is judged to be
equal doses spaced 8–12 hours apart. serious or life-threatening

Dose Adjustment: Contraindications: None

Renal Impairment:
May require dose reduction. Dose:
Cyanide poisoning, by slow IV injection, ADULT, 10 mL at
Precautions: 2.5–5 mL per minute; immediately followed by 50 mL
WARNING: Do NOT confuse with sodium edetate. sodium thiosulfate;
CHILD, 0.2 mL/kg (6 mg/kg or 6–8 mL/m2 BSA) at 2.5–
Capable of producing toxic effects, which can be fatal. 5 mL per minute, not to exceed 10 mL; immediately
followed by 1 mL/kg (250 mg/kg or approximately 30–
Inform physician immediately if urine output stops for 40 mL/m2 BSA) sodium thiosulfate, not to exceed 50 mL
a period of 12 hours. Stop therapy if anuria or total dose.
severe oliguria develops.
NOTE: If signs of poisoning reappear, repeat treatment
using half of original dose of both sodium nitrite and
Renal damage (eg. proteinuria and microscopic hematuria; sodium thiosulfate.
dose-dependent);
Lactation. Dose Adjustment:
Anemic patients:
Adverse Drug Reactions: Reduce dose in proportion to oxygen carrying capacity.
Common: Pain at injection site, fever, chills, malaise,
fatigue, myalgia, arthralgia, hypotension, cardiac rhythm
irregularities, acute necrosis of proximal tubules,
infrequent changes in distal tubules and glomeruli,

624
VARIOUS

Precautions: Dose:
WARNING: Causes life threatening hypotension and Cyanide poisoning, by slow IV injection, ADULT, 50 mL
methemoglobin formation, which diminishes sodium thiosulfate administered immediately after 10
oxygen carrying capacity. Monitor patient closely to mL of sodium nitrite at 2.5–5 mL per minute;
ensure adequate perfusion and oxygenation. CHILD, 1 mL/kg (250 mg/kg or approximately 30–40
mL/m2 BSA), not to exceed 50 mL total dose
Use with caution in patients where the diagnosis of administered immediately after 0.2 mL/kg (6 mg/kg or
cyanide poisoning is uncertain. 6–8 mL/m2 BSA) of sodium nitrite at 2.5–5 mL per
minute, not to exceed 10 mL.
Anemia (use with caution);
Smoke inhalation injury or carbon monoxide poisoning; NOTE: If signs of poisoning reappear, repeat treatment
Renal impairment; using ½ original dose of both sodium nitrite and sodium
G6PD deficiency; thiosulfate.
Elderly (select doses with care);
Children, neonates, and infants; Precautions:
Pregnancy; Nausea and vomiting;
Lactation. Renal impairment;
Elderly (select doses with care);
Adverse Drug Reactions: Children;
Common and Less Common: Hypotension, syncope, Lactation.
tachycardia, methemoglobinemia, palpitations,
dysrhythmia, headache, dizziness, blurred vision, Adverse Drug Reactions:
seizures, confusion, coma, nausea, vomiting, abdominal Common and Less Common: Osmotic disturbances,
pain, tachypnea, dyspnea, anxiety, diaphoresis, hypotension, headache, disorientation, nausea,
lightheadedness, injection site tingling, cyanosis, vomiting, prolonged bleeding time, salty taste in mouth,
acidosis, fatigue, weakness, urticaria, generalized warm sensation over body
numbness and tingling Drug Interactions: No information found

Drug Interactions: Administration: May be used alone or in combination with

Monitor closely with: sodium nitrite.
Increases risk of adverse or toxic effects of the following
drugs, specifically volume depletion: If to be used with other cyanide antidotes, do NOT
Diuretics, PDE5 Inhibitors administer concurrently in the same IV line.

Administration: For slow IV injection only. Pregnancy Category: C

Administer as early as possible after a diagnosis of acute ATC Code: V03AB06

life-threatening cyanide poisoning has been established.
Administer sodium thiosulfate immediately after sodium

V
nitrite.
Rx SUGAMMADEX
If to be used with other cyanide antidotes, do NOT
administer concurrently in the same IV line. Inj.: 100 mg/mL solution for injection, 2 mL vial (IV)

Pregnancy Category: C A modified gamma cyclodextrin that reverses

neuromuscular blockade induced by rocuronium and
ATC Code: V03AB08 vecuronium by complex formation, reducing the amount
of neuromuscular blocking agent available to bind to
nicotinic receptors in the neuromuscular junction.
Rx SODIUM THIOSULFATE Indication: For the reversal of neuromuscular blockade
induced by rocuronium and vecuronium in adults
Inj.: 250 mg/mL, 50 mL ampule (IV) undergoing surgery

An antidote in the treatment of cyanide poisoning. It acts as Dose:

a sulfur-donating substrate for rhodanese, speeding up NOTE: Doses and timing of administration should be based
the conversion of cyanide to thiocyanide, a non-toxic on monitoring for twitch responses and the extent of
metabolite. It is also used as an antidote in the treatment spontaneous recovery that has occurred.
of cisplatin poisoning by rapid chemical inactivation of its
platinum component. Neuromuscular blockade reversal, rocuronium and/or
vecuronium, by IV bolus injection, ADULT, 4 mg/kg if
Indications: For sequential use with sodium nitrite in the spontaneous recovery of the twitch response has
treatment of cyanide poisoning that is serious or life- reached 1 to 2 post-tetanic counts (PTC) and there are
threatening; for cisplatin poisoning no twitch responses to train-of-four (TOF) stimulation;

Contraindication: None known

625
 VARIOUS

2 mg/kg if spontaneous recovery has reached the Administration: For IV use only.
reappearance of the second twitch (T2) in response to
TOF stimulation. Administer as a single bolus injection over 10 seconds,
Neuromuscular blockade reversal, rocuronium only, by IV into an existing intravenous line of a running infusion
bolus injection, ADULT, 16 mg/kg if there is a clinical with either of the following:
need to reverse neuromuscular blockade soon 0.9% sodium chloride
(approximately 3 minutes) after administration of a 5% dextrose
single dose of 1.2 mg/kg of rocuronium. 0.45% sodium chloride and 2.5% dextrose
Isolyte P with 5% dextrose
Dose Adjustment: No information found Ringer’s lactate solution
Ringer’s solution
Precautions:
WARNING: Should be administered by trained health care Ensure the infusion line is adequately flushed between
providers familiar with the characteristics, actions, use, administration of sugammadex and other drugs.
and complications of neuromuscular blocking agents
and neuromuscular block reversal agents. Visually inspect for particulate matter and discoloration
prior to administration.
NOT for use in the reversal of neuromuscular blockade
for agents other than rocuronium or vecuronium. NOTE: Ventilatory support is mandatory until adequate
spontaneous respiration is restored and the ability to
Anaphylaxis and hypersensitivity (eg. anaphylaxis); maintain patent airway is assured.
Marked bradycardia;
Severe renal impairment (not recommended); Pregnancy Category: Not classified
Elderly;
Pregnancy; ATC Code: V03AB35
Lactation.

RE-ADMINISTRATION. A minimum waiting time is necessary SUCCIMER

before administration of steroidal neuromuscular Rx (DIMERCAPTO SUCCINIC ACID,
blocking agent after sugammadex administration. DMSA)
Minimum Waiting Time Dose to be administered
5 minutes 1.2 mg/kg rocuronium Oral: 100 mg and 200 mg capsule
0.6 mg/kg rocuronium,
4 hours or An orally active, heavy metal chelating agent that forms
0.1 mg/kg vecuronium water-soluble chelates, and consequently, increases the
urinary excretion of heavy metals.
Adverse Drug Reactions:
Common: Incision site pain, procedural complication, airway Indication: For the treatment of lead, mercury, arsenic, and
V

complication of anesthesia, anesthetic complication, other heavy metal poisoning

wound hemorrhage, nausea, vomiting, abdominal pain,
flatulence, dry mouth, pain at administration site, NOTE: NOT to be used for prophylaxis of lead-poisoning in a
pyrexia, chills, headache, dizziness, hypoesthesia, lead-containing environment.
oropharyngeal pain, cough, pain in extremity, Dose:
musculoskeletal pain, myalgia, insomnia, anxiety, Heavy metal poisoning, by mouth, ADULT, 10 mg/kg (350
decreased RBC count, abnormal ECG QT-interval, mg/m2) every 8 hours for 5 days, then 10 mg/kg (350
hypertension, hypotension, pruritus, erythema, mg/m2) every 12 hours for an additional 2 weeks of
hypocalcemia, tachycardia, bradycardia therapy; CHILD, administer as follows every 8 hours for 5
Less Common: Recurrence of neuromuscular blockade, days, followed by dosing every 12 hours for 14 days:
restlessness, depression
Rare: Hysterectomy Pediatric weight
Dose (mg)
lbs kg
Drug Interactions:
18–35 8–15 100
Monitor closely with:
Enhances therapeutic effect of the following drugs, 36–55 16–23 200
specifically increased aPTT and prothrombin time: 56–75 24–34 300
Dabigatran, Rivaroxaban, Unfractionated Heparin 76–100 35–44 400
>100 >45 500
Reduces therapeutic effect of the following drugs due to
decreased serum concentration: NOTE: A course of treatment lasts 19 days. Repeated
Hormonal Contraceptives courses may be necessary if indicated by weekly
monitoring of blood lead concentration. A minimum of 2
Avoid concomitant use with: weeks between courses is recommended unless blood
Reduces therapeutic effect of Sugammadex: lead levels indicate the need for more prompt treatment.
Fusidic Acid (delayed reversal time), Toremifene (delayed Precautions:
recovery; high binding affinity for sugammadex)

626
VARIOUS

WARNING: Mild-to-moderate neutropenia has been Dose:

observed in some patients. Withhold or Alcohol intoxication, by IV or IM injection, ADULT, initially
discontinue therapy if absolute neutrophil count 100 mg by IV injection, followed by 50 to 100 mg daily
(ANC) is below 1,200 per microliter. by IM or IV injection until a regular, balanced diet is
maintained.
Do NOT use for longer than 3 weeks. Safety of
uninterrupted dosing longer than 3 weeks has not
Administration: Parenteral administration is reserved for
been established.
patients where oral thiamine is not feasible.
Rebound blood lead levels; Inspect visually for particulate matter and discoloration
Children; prior to administration.
Pregnancy;
Lactation. For slow IV push, no dilution is necessary.
Adverse Drug Reactions: For continuous IV infusion, dilute thiamine in a
Common: Nausea, vomiting, diarrhea, appetite loss, compatible infusion solution. Administer at a rate
hemorrhoidal symptoms, loose stools, metallic taste in prescribed by the physician.
mouth, back pain, abdominal cramps, stomach pains,
head pain, rib pain, chills, flank pain, fever, flu-like For IM administration, inject deeply into a large muscle.
symptoms, heavy head/tired, head cold, headache, Aspirate prior to injection to avoid injection into a blood
moniliasis, elevated SGPT and SGOT (transient), vessel.
elevated alkaline phosphatase, elevated serum
cholesterol, drowsiness, dizziness, sleepiness, See Thiamine (Vitamin B1) under Vitamins in Chapter 1:
sensorimotor neuropathy, paresthesia, popular rash, Alimentary Tract and Metabolism for other information.
herpetic rash, rash, mucocutaneous eruptions, pruritus,
cloudy film in eye, ears plugged, otitis media, watery Pregnancy Category: A
eyes, sore throat, rhinorrhea, nasal congestion, cough,
decreased urination, voiding difficulty, increased ATC Code: A11DA01
proteinuria, kneecap pain, leg pain
Less Common: Arrhythmia, mild-to-moderate neutropenia, IRON CHELATING AGENTS
intermittent eosinophilia

Drug Interactions: No known significant interactions DEFEROXAMINE

Rx
(DESFERRIOXAMINE)
TEST INTERACTIONS. False-positive results for ketones in
urine using nitroprusside reagents; false decrease in Inj.: 500 mg powder (as mesylate), vial (IM, IV infusion,
measurements of serum uric acid and CPK. SC)

Administration: Keep out of reach of children. A chelating agent that complexes with ferric trivalent ions to

V
form ferrioxamine, which is removed by the kidneys. This
NOTE: The treatment of lead poisoning should always be slows accumulation of hepatic iron and retards or
accompanied by identification and removal of the source eliminated progression of hepatic fibrosis.
of lead exposure.
Indications: Adjunct in the treatment of acute iron
Pregnancy Category: C intoxication; treatment of chronic iron overload
secondary to multiple transfusions
ATC Code: Not available
Contraindications: Severe renal disease; anuria

THIAMINE Dose:
Rx Acute iron toxicity, by IM injection, ADULT, initially 1,000 mg,
(VITAMIN B1)
may be followed by 500 mg every 4 hours for 2 doses,
subsequent doses of 500 mg have been administered
Inj.: 100 mg/mL, 1 mL ampule/vial (IV)
every 4–12 hours based on clinical response (maximum
100 mg/mL (as hydrochloride), 10 mL vial (IM, IV)
recommended dose, 6,000 mg daily); ADOLESCENT and
CHILD, 90 mg/kg per dose every 8 hours (maximum,
A wat A water-soluble vitamin found in yeast, cereal grains,
6,000 mg in 24 hours);
legumes, peas, nuts, pork, and beef. It is used to prevent
by IV infusion, ADULT, initially 1,000 mg at 15 mg/kg per
peripheral neuritis associated with pellagra and
hour, subsequent doses may be given over 4–12 hours
pregnancy. It combines with adenosine triphosphate
at a rate not to exceed 125 mg/hour; ADOLESCENT and
(ATP) to form thiamine pyrophosphate, an essential
CHILD, 15 mg/kg per hour (maximum, 6,000 mg in 24
coenzyme in carbohydrate metabolism.
hours).
Indication: For alcohol intoxication Chronic iron overload, by IM injection, ADULT, 500 to 1,000
mg daily (maximum, 1,000 mg daily);
Contraindications: Breast-feeding; encephalopathy; by IV infusion, ADULT, 40–50 mg/kg daily (maximum, 60
mg/kg daily) over 8–12 hours for 5–7 days per week;
pregnancy

627
 VARIOUS

ADOLESCENT and CHILD ≥3 years, 20–40 mg/kg daily Increases risk of adverse or toxic effects of Prochlorperazine
over 8–12 hours for 5–7 days per week, not to exceed (prolonged loss of consciousness)
40 mg/kg daily until growth has ceased;
by SQ injection, ADULT, 1,000–2,000 mg daily or 20–40 TEST INTERATIONS. TIBC may be falsely elevated with high
mg/kg daily over 8–24 hours; ADOLESCENT and CHILD serum iron concentrations or deferoxamine therapy.
≥3 years, 20–40 mg/kg daily over 8–12 hours
(maximum daily dose, 1,000–2,000 mg). Administration: Administer by IV injection when severe
toxicity is evidenced by cardiovascular collapse or
Dose Adjustment: systemic symptoms (coma, shock, metabolic acidosis, or
Geriatric: GI bleeding) or potentially severe intoxications (peak
Initiate at the lower end of the dosing range. serum iron level >500 micrograms/dL).

Renal Impairment: IM injection may be used for patients with acute iron
Deferoxamine is readily dialyzable. toxicity that do not exhibit severe symptoms, and in the
In CrCl 10–50 mL/minute and CRRT, administer 25 to 50% treatment of chronic iron toxicity.
of normal dose.
In CrCl <10 mL/minute, hemodialysis, and peritoneal NOTE: Limit vitamin C supplements in adults at 200 mg daily
dialysis, avoid use. in divided doses, in children ≥10 years at 100 mg daily,
and in children <10 years at 50 mg daily.
Precautions:
Acute respiratory distress syndrome, ARDS; Pregnancy Category: C
Auditory effects (eg. tinnitus, high frequency hearing loss);
Ocular effects (eg. blurred vision, cataracts, corneal ATC Code: V03AC01
opacities, decreased visual acuity, impaired peripheral,
color, and night vision, optic neuritis, retinal pigment
abnormalities, scotoma, visual loss or defect);
Growth retardation; Rx DEFERIPRONE
Infection (increased susceptibility to infection with Yersinia
enterocolitica and Yersinia pseudotuberculosis); Oral: 500 mg tablet
Mucormycosis;
Renal effects (e.g., increases in serum creatinine, acute An iron- chelating agent which binds to ferric iron and
renal failure and renal tubular disorders; monitor for removes it from the blood stream.
changes in renal function);
Urine discoloration; Indication: Management of transfusional iron overload if
Elderly (eg. hearing loss and ocular disorders); current chelation therapy in patients with thalassemia is
Pregnancy; not insufficient.
Lactation.
Contraindications: Neutropenia; agranulocytosis; pregnan-
Adverse Drug Reactions: cy; lactation
V

Common and Less Common: Flushing, hypotension, shock,

tachycardia, brain disease, dizziness, headache, Dose:
neuropathy, paresthesia, seizure, skin rash, urticaria, Iron overload, by mouth, ADULT, 25 mg/kg 3 times daily for
growth suppression (children), hyperparathyroidism a total of 75 mg/kg daily (maximum dose, 33 mg/kg 3
(aggravated), hypocalcemia, abdominal distress, times daily for a total of 99 mg/kg daily).
abdominal pain, diarrhea, nausea, vomiting, dysuria,
urine discoloration (reddish), dysplasia (metaphyseal; Tablet requirement to achieve 25 mg/kg (rounded to
children <3 years; dose related), leukopenia, the nearest half-tablet) for administration 3 times
thrombocytopenia, anaphylaxis, hepatic insufficiency, daily:
muscle spasm, angioedema, hypersensitivity, infection
Body weight (kg) Dose (mg) No. of tablets
(Yersinia, mucormycosis), injection site reaction,
arthralgia, myalgia, blurred vision, cataract, 20 500 1
chromatopsia, corneal opacity, decreased peripheral 30 750 1.5
vision, decreased visual acuity, nocturnal amblyopia, 40 1,000 2
optic neuritis, retinal pigment changes, scotoma, vision 50 1,250 2.5
loss, visual field defect, hearing loss, tinnitus, acute renal 60 1,500 3
failure, renal tubular disease, acute respiratory distress
70 1,750 3.5
(dyspnea, cyanosis, and/or interstitial infiltrates),
asthma, fever 80 2,000 4

Drug Interactions: Tablet requirement to achieve 33 mg/kg (rounded to

Avoid concomitant use with: the nearest half-tablet) for administration 3 times
Increases risk of adverse or toxic effects Deferoxamine: daily:
Ascorbic Acid (left ventricular dysfunction), Multivitamins Body weight (kg) Dose (mg) No. of tablets
/ Fluoride with ADE, Multivitamins / Minerals with ADEK, 20 660 1.5
Folate, Iron (left ventricular dysfunction), Multivitamins / 30 990 2
Minerals with AE, no Iron

628
VARIOUS

40 1,320 2.5 Pregnancy Category: D

50 1,650 3.5
60 1,980 4 ATC Code: V03AC02
70 2,310 4.5
80 2,640 5.5
Rx DEFERASIROX
Iron overload in patients with thalassemia, by mouth,
ADULT, 25 mg/kg 3 times daily, may be adjusted Oral: 125 mg and 250 mg dispersible tablet
according to response and therapeutic goals (maximum,
100 mg/kg daily). An orally active iron chelating agent that binds with ferric ion
and removes it from the blood stream
Precautions:
WARNING: Can cause agranulocytosis that can lead Indications: Management of chronic iron overload due to
to serious infections and death. repetitive blood transfusions in patients > 2 years.

Agranulocytosis or neutropenia (eg. fatal agranulocytosis); Contraindications: High-risk myelodysplastic syndromes;

Hepatic impairment; advanced malignancies; platelet counts <50,000
Elderly and children; cells/mm3; renal impairment (CrCl <60 mL/min); severe
Pregnancy (can cause fetal harm); hepatic impairment
Lactation.
Dose:
Adverse Drug Reactions: Chronic iron overload, transfusion-related, by mouth, ADULT
Common: Neutropenia, agranulocytosis, nausea, and CHILD >5 to 17 years, initially 20 mg/kg once daily,
abdominal pain or discomfort, vomiting, diarrhea, adjust dose in increments or decrements of 5–10 mg/kg
dyspepsia, decreased neutrophil, increased weight, every 3–6 months when needed (maximum, 40 mg/kg
altered appetite, arthralgia, back pain, pain in extremity, daily); CHILD 2–5 years, initially 20 mg/kg once daily,
arthropathy, headache, chromaturia, decreased plasma may require higher titration doses.
zinc concentration, urine discoloration (reddish-brown) Dose Adjustment:
Less Common: Thrombocytosis, pancytopenia, atrial Renal Impairment:
fibrillation, cardiac failure, hypospadias, diplopia, In patients with CrCl of 40–60 mL/minute, reduce starting
papilledema, retinal toxicity, enterocolitis, rectal dose by 50%.
hemorrhage, gastric ulcer, pancreatitis, parotid gland Do not administer if CrCl <60 mL/minute.
enlargement, chills, pyrexia, edema peripheral, multi-
organ failure, jaundice, hepatomegaly, anaphylactic Hepatic Impairment:
shock, hypersensitivity, cryptococcal cutaneous In patients with moderate impairment, considerably reduce
infection, enteroviral encephalitis, pharyngitis, dose followed by progressive increase up to a limit of
pneumonia, sepsis, furuncle, infectious hepatitis, rash 50%.
pustular, subcutaneous abscess, metabolic acidosis, Do not administer in patients with severe hepatic

V
dehydration, myositis, chondropathy, trismus, cerebellar impairment.
syndrome, cerebral hemorrhage, convulsion, gait
disturbance, increased intracranial pressure, impaired Precautions:
psychomotor skills, pyramidal tract syndrome, WARNING: May cause acute renal failure, hepatic
somnolence, bruxism, depression, OCD, glycosuria, failure, and death. GI hemorrhages may be fatal,
hemoglobinuria, acute respiratory distress syndrome, especially in the elderly.
epistaxis, hemoptysis, pulmonary embolism,
hyperhidrosis, periorbital edema, photosensitivity Bone marrow suppression (e.g. neutropenia,
reaction, pruritus, urticaria, rash, Henoch–Schönlein agranulocytosis, worsening anemia, and
purpura, hypotension, hypertension thrombocytopenia, including fatal events);
Hypersensitivity (e.g. anaphylaxis and angioedema within
Drug Interactions: the first month of treatment);
Monitor closely with: Skin reactions (e.g. severe cutaneous adverse reactions;
Incompatible with the following products: erythema multiforme);
Products containing Polyvalent Cations (may form Auditory abnormalities (e.g. high frequency hearing loss,
chelates) and decreased hearing);
Ocular abnormalities (e.g. lens opacities, cataracts,
Avoid concomitant use with: elevations in intraocular pressure, and retinal disorders);
Increases serum concentration of Deferiprone: Elderly;
UGT1A6 Inhibitors, e.g., Phenylbutazone Children;
Lactation.
Administration: May be taken with or without food.
Adverse Drug Reactions:
Foods, medications and supplements with polyvalent Common: Gastrointestinal disturbance, headache, fatigue,
cations (e.g., iron, zinc and aluminium) should be taken dizziness, rashes, skin pigmentation, erythema
within at least a 4- hour interval. multiforme, pyrexia, pruritus, anxiety, sleep disorders,

629
 VARIOUS

infections, pharyngolaryngeal pain, edema, Dose:

leucocytoclastic vasculitis, urticaria, alopecia, renal NOTE: Given as IV bolus injection in a dose equal to 20% of
tubulopathy, proteinuria, hearing loss, visual disorders the ifosfamide dose weight by weight (w/w) at the time
Less Common: Stevens-Johnson syndrome, hypersensitivity of ifosfamide administration, then at 4 and 8 hours after
reactions, urticaria, alopecia, toxic epidermal necrolysis, each dose of ifosfamide. The total daily dose of mesna
acute renal failure, tubulointerstitial nephritis, hepatic injection is 60% of the ifosfamide dose.
failure, GI perforation, worsening anemia
Potentially Fatal: Hepatitis, agranulocytosis, Prophylaxis against ifosfamide-induced hemorrhagic
neutropenia, thrombocytopenia, upper GI ulceration and cystitis, by IV bolus injection, ADULT, recommended
haemorrhage. dosing schedule:
0 hours 4 hours 8 hours
Drug Interactions: Ifosfamid 1.2
Avoid concomitant use with: e g/m2
Decreases serum concentration of Deferasirox: 240 240 240
Bile Acid Sequestrants, e.g., Cholestyramine, CYP3A4 Mesna
mg/m2 mg/m2 mg/m2
Substrates, e.g., Cyclosporine, Hormonal Contraceptives, Repeat on each day of ifosfamide administration.
Simvastatin, UGT Inducers, e.g., Rifampicin, Phenytoin,
Phenobarbital, Ritonavir Dose Adjustment:
Geriatric:
Incompatible with the following products: Select doses with caution, reflecting greater frequency of
Aluminum-containing Antacids (chelates with aluminum) decreased hepatic, renal, or cardiac function, and of
concomitant disease or other drugs. The ratio of
Increases serum concentration of Deferasirox: ifosfamide to mesna should remain unchanged.
CYP1A2 Substrates, e.g., Duloxetine, Theophylline,
CYP2C8 Substrates, e.g., Carbamazepine, Rifampicin, Precautions:
Phenytoin
WARNING: Hazardous agent. Use appropriate
precautions for handling and disposal.
Reduces therapeutic effect of Deferasirox:
UGT Inducers, e.g., Rifampicin, Phenytoin,
Phenobarbital, Ritonavir Hypersensitivity reactions (eg. anaphylaxis; may cause
fever, hypotension, tachycardia, acute renal impairment,
Administration: Should be taken on an empty stomach, at hypoxia, respiratory distress, urticaria, angioedema,
least 30 minutes before meals, preferably at the same laboratory signs of disseminated intravascular
time daily. Do NOT swallow the tablet whole. coagulation, hematological abnormalities, nausea,
vomiting, arthralgia, myalgia);
Disperse tablet completely by stirring in 100–200 mL of Dermatologic toxicity (eg. urticaria, rash, erythema, pruritus,
water, apple juice, or orange juice until a fine suspension burning sensation, angioedema, periorbital edema,
is obtained. Disperse <1 g in 105 mL and ≥1 g in 210 mL flushing, and stomatitis reactions consistent with SJS or
of liquid. Consume contents completely. Rinse the glass TENhave);
V

with a little water or juice to resuspend any residue and Hematuria (monitor urine for hematuria; severe hematuria
drink the resulting suspension. despite utilization of mesna may require ifosfamide dose
reduction or discontinuation; examine morning urine
Do NOT disperse in fizzy drinks or milk. Do NOT chew, specimen for hematuria prior to ifosfamide or
break, or crush the tablet. cyclophosphamide treatment);
Ifosfamide or cyclophosphamide toxicities;
Pregnancy Category: C Elderly;
Children (avoid use in neonates, premature, and low-birth
ATC Code: V03AC03 weight infants);
Lactation.

DETOXIFYING AGENTS FOR Adverse Drug Reactions:

ANTINEOPLASTIC TREATMENT Common: Anorexia, arthralgia, conjunctivitis, back pain,
constipation, cough, diarrhea, dizziness, fever,
flatulence, flu-like syndrome, flushing, headache,
MESNA (SODIUM-2-MERCAPTO- hyperesthesia, rash, injection site reactions, nausea,
Rx
ETHANESULPHONATE) pharyngitis, rhinitis, rigors, somnolence, vomiting,
leukopenia, fatigue, thrombocytopenia, anemia,
Inj.: 100 mg/mL, 4 mL ampule (IV) granulocytopenia, asthenia, abdominal pain, alopecia,
dyspnea, chest pain, hypokalemia, pain, increased
A detoxifying agent that inhibits the hemorrhagic cystitis sweating, hematuria, edema, anxiety, confusion,
induced by ifosfamide by binding to the 4-hydroxy insomnia, dyspepsia, hypotension, pallor, dehydration,
ifosfamide forming a non-urotoxic 4- pneumonia
sulfoethylthioifosfamide. Less Common: Anaphylactic reaction, hypertension,
injection site erythema, injection site pain, limb pain,
Indication: Prophylactic agent in reducing incidence of malaise, myalgia, tachycardia, tachypnea
ifosfamide-induced hemorrhagic cystitis Rare: Dysgeusia, hepatitis, convulsion, hemoptysis

630
VARIOUS

Drug Interactions: No information found Adverse Drug Reactions:

Common: Elevated blood pressure, increased ear pressure,
TEST INTERACTIONS. False-positive results for urinary headache, numbness of fingers, temporary changes in
ketones with nitroprusside-based urine tests, including the eye lens, seizures
dipstick tests
Falsely low creatinine kinase levels by interfering with Drug Interactions: No information found
enzymatic creatinine kinase activity tests, which use thiol
compounds Administration: Do NOT handle until all safety precautions
False-positive results for ascorbic acid with Tillman’s have been read and understood.
reagent-based urine screening tests for ascorbic acid
Use and store in a well-ventilated place. Protect from
Administration: May be given on a fractionated dosing sunlight when ambient temperature exceeds 52°C
schedule of 3 bolus IV injections. (125°F). Keep and store away from clothing and other
combustible materials. Keep valves and fittings free from
Maintain adequate hydration and urinary output during grease and oil.
ifosfamide treatment.
Use a back-flow preventive device in the piping. Use only
See Mesna (sodium-2-mercaptoethanesulphonate) under with equipment cleaned for oxygen service. Open valve
Antineoplastic Agents – Adjuncts to Antineoplastic slowly. Close valve after each use and when empty.
Chemotherapy in Chapter 8: Antineoplastic and
Immunomodulating Agents for other information. Pregnancy Category: Not classified

Pregnancy Category: B ATC Code: V03AN01

ATC Code: V03AF01

DIAGNOSTIC AGENTS
MEDICAL GASES
3% HYPERTONIC SALINE
Rx
Rx OXYGEN SOLUTION
Neb.: 3% solution
Inhalational: Medicinal gas
A sterile nonpyrogenic hypertonic solution diagnostic agent
A medicinal gas usually used for hyperbaric oxygen
that stimulates cough reflex to help facilitate sputum
treatment.
induction.
Indication: Anesthetic adjuvant
Indications: For diagnosis of pulmonary tuberculosis

V
Contraindication: Untreated pneumothorax; chest surgery;
Contraindications: Hyper-reactive airway disease; wheezing,
emphysema; middle ear surgery; uncontrolled high
such as with asthma and COPD.
fevers; upper respiratory infections; seizures; RBC
disorders
Dose:
Sputum induction, by nebulization, ADULT and CHILD, 20
Dose: Individualize doses
mL.
Precautions:
EVALUATION. Evaluate sputum collected as follows:
WARNING: Oxidizer. May cause or intensify fire.
Sputum samples from the tracheobronchial tree (VS
WARNING: For emergency use only. saliva) are typically more viscous, purulent and
malodorous, color tinged, and may have presence of
To be administered by personnel properly trained blood.
for oxygen deficiency and resuscitation.
Administration at concentrations less than 19.5% Samples that are from a patient with retained secretions
oxygen may cause rapid suffocation. and allergic or infectious process are typically stringy,
Uninterrupted use of high concentrations over a mucoid, color tinged, and yellow or green in color.
long duration, without monitoring its effect on
oxygen content of arterial blood, may be harmful.
Do NOT attempt to use on patients who have
stopped breathing unless used in conjunction with
resuscitative equipment.

631
 VARIOUS

Certain infections or disease states may produce sputum TST interpretation: Criteria for positive TST read at 48–72
characteristics: hours:
Characteristic Infectious Agent Induratio
Interpretation
n
Thick, green, musky Pseudomonas
HIV infection (or risk factors for HIV
odor aeruginosa
infection, but unknown status);
Three-layered Recent close contact to person with
sputum, foul Bronchiectasis ≥5 mm known active TB;
smelling Persons with chest x-ray consistent
Mucus plugs or with healed TB;
Asthma
casts Immunosuppressed individuals
Thick, sticky Cystic fibrosis Clinical conditions, which increase the
risk of TB infection;
Dose Adjustment: No information found Recent immigrants;
≥10 mm IV drug users;
Precautions: Residents and employees of high-risk
WARNING: Staff performing sputum collection must settings;
wear proper recommended TB respiratory Children <4 years of age
protection and disposable gloves Persons who do not meet any of the
≥15 mm above criteria (no risk factors for
Adverse Drug Reactions: No information found TB)

Drug Interactions: No information found NOTE: A two-step test is recommended if testing will be
performed at regular intervals (e.g., for healthcare
Administration: Instill 15 mL 3% saline into a small volume workers). If the first test is negative, a second TST
nebulizer medication cup. Instruct the patient to breathe should be administered 1–3 weeks after the first test
deeply, inhaling the aerosol. Instruct the patient to cough was read.
as needed and at 5-minute intervals. Collect expectorant
into the specimen cup. TST interpretation in a healthcare setting:
Interpretatio
Test Parameter Induration
NOTE: If bronchospasm occurs, administer a bronchodilator n
via small volume nebulizer. If adverse effects occur, Baseline ≥10 mm Positive
discontinue therapy and notify the physician. Serial testing
without known ≥10 mm Positive
If there are no results after 30 minutes of nebulizer exposure
treatment, discontinue therapy and notify the physician. Positive if
≥5 mm baseline is 0
Pregnancy Category: Not classified mm
V

Positive if
ATC Code: Not available negative
Known exposure
baseline or
≥10 mm previous
TUBERCULIN, PURIFIED screening
Rx result of ≥0
PROTEIN DERIVATIVE (PPD)
mm
Inj.: 2 TU/0.1 mL solution, 1 mL and 5 mL vial (ID) Read test at 48– 0 mm or Absence of
5 TU/0.1 mL, freeze-dried powder, vial + 2 mL diluent 72 hours less than infection
ampule (ID) following the defined with M.
placement cutoff point tuberculosis
Diagnostic agent containing culture extracts called
tuberculins which can indicate infection with a variety of NOTE: Test results should be documented in millimeters
non-tuberculosis mycobacteria or vaccination with the even if classified as negative. Erythema and redness
live attenuated mycobacterial strain of M. bovis vaccine, of skin are not indicative of a positive test result.
BCG, in addition to previous natural infection with M.
tuberculosis. Dose Adjustment:
Geriatric:
Indication: Skin test in diagnosis of tuberculosis Use a two-step procedure. Repeat test 2–4 weeks after
reading first test dose to elicit a “booster effect.”
Contraindications: Previous severe reaction to tuberculin
PPD skin test (TST) Precautions:
WARNING: Epinephrine (1:1000) should be available
Dose: to treat possible allergic reactions.
Diagnosis of tuberculosis, cell-mediated immuno-
deficiencies, by ID injection, ADULT and CHILD, 0.1 mL. Burns, eczema, tuberculosis (do not administer);
Viral infections (skin testing may be deferred);

632
VARIOUS

Vaccinations (skin testing may be deferred within 1 month);

Elderly (skin test response may be delayed or reduced in GENERAL NUTRIENTS
magnitude);
Children (infants <6 weeks may have an absent or delayed
FAT / CARBOHYDRATES / PROTEINS / MINERALS /
response);
VITAMINS, COMBINATIONS
Pregnancy (use with caution).
ENTERAL FEEDING
Adverse Drug Reactions: Rash, injection site reactions and
General Information
anaphylaxis
Enteral nutrition (EN) is the provision of nutrient via the GI
Drug Interactions:
tract through a feeding tube, catheter, or stoma. It is the
Avoid concomitant use with:
preferred route for the provision of nutrient for patients
Reduces diagnostic effect of Tuberculin:
who cannot meet their nutrition needs through voluntary
Vaccines, Live [do not administer TST within 4–6 weeks
oral intake and if GIT function is compromised.
of vaccination]
Every effort should be made to feed via the GIT Parenteral
nutrition is to be used only when the gut is non-
TEST INTERACTIONS.
functioning, inaccessible, or when complete bowel rest is
May produce false positive reactions may occur with BCG
required.
vaccination
May produce false positive reactions with previous
Indications: Prolonged anorexia, severe protein-energy
mycobacteria infection (non- TB)
undernutrition, coma or depressed sensorium, liver
May produce false negative reactions in patients with
failure, inability to take oral feedings due to head or neck
impaired cell- mediated immunity
trauma, critical illnesses causing metabolic stress (e.g.,
NOTE: BCG vaccination is not contraindicated in tuberculin
burns)
PPD
Contraindications: GI perforation; GI ischemia; complete
Administration: For ID administration only. Do NOT
mechanical or non-mechanical bowel obstruction; high
administer by IV, IM, or SQ.
output enterocutaneous fistula; inability to access GIT;
patient refusal of enteral feeding; severe pancreatitis
Administer to upper third of forearm (palm up) ≥2 inches
from elbow, wrist, or other injection site. If neither arm
Dose:
can be used, administer to back of shoulder. Administer
Enteral nutrition, by continuous infusion, ADULT, initiate full-
using ¼ to ½ inch 27-gauge needle or finer tuberculin
strength formula at 25–50 mL/hour, increase infusion
syringe. Should form wheal (6–10 mm in diameter) as
rate by 10–25 mL every 4–12 hours as tolerated until
liquid is injected which will remain for approximately 10
goal rate is reached; flush a minimum of 20 mL free
minutes. Avoid placing pressure or bandage at injection
water every 4–6 hours to maintain tube patency. [NOTE:
site.
If a patient has been tolerating continuous tube feeding
for several days and is felt to be stable, intermittent
NOTE: Document the date and time of injection, person

V
feeding may be initiated].
placing TST, location of injection site, and lot number of
Enteral nutrition, by intermittent infusion, ADULT, start with
solution.
125 mL full strength formula for the first 2 feedings,
increase each subsequent feeding by 125 mL as
Pregnancy Category: C
tolerated until goal rate is reached; flush the feeding
tube with minimum 20 mL of water before and after
ATC Code: V04CE01
administration to maintain patency. [NOTE: Determine
volume per feeding by dividing the total quantity of
formula needed for a 24-hour period by the desired
number of feedings (usually 3–6 feedings during the day,
each over 30–90 minutes)].

Dose Adjustment:
Fluid Restriction:
Concentrate formula to provide 1.5–2 kcal/mL.

Diabetes mellitus, hyperglycemia:

May require adjustment of antidiabetic therapy or addition
of insulin or other antidiabetic medications.

Precautions:
WARNING: Consult dietician for initial nutritional
assessment, recommendations regarding
appropriate enteral formula, administration, goal
rate, and ongoing monitoring of nutritional status.

633
 VARIOUS

Pressure necrosis; digestive or absorptive capabilities. Review actual

Aspiration pneumonitis; product label whenever exact nutrient content is
Cardiac insufficiency and respiratory difficulty; required.
Electrolyte abnormalities;
Dehydration; Select route of administration based on condition of GIT
Delayed gastric emptying (eg. retention, diarrhea and and anticipated duration of feeding.
vomiting);
Severe malnutrition (eg. severe cardiopulmonary and Duration
neurologic complications); Route GIT Condition of
Hepatic impairment; Feeding
Hyperlipidemia; Nasoenteric tube route
Phenylketonuria; Normal gastric
Renal impairment; function;
Elderly (at greater risk of developing nasogastric tube Nasogastric
Intact gag reflex; May
problems, eg. aspiration pneumonia; more likely to (pre-pyloric) <4 – 6
increase risk of
remove nasogastric tube); aspiration weeks
Children (may have milk sensitivity and metabolic disorders; Cannot tolerate gastric
children ≤1 year are known to have immature Nasoduodenal
feeding; High risk for
gastrointestinal, hepatic, and renal systems). or nasojejunal
gastroesophageal
(post-pyloric)
reflux and aspiration
Adverse Drug Reactions:
Enterostomy tube route
Common: Aspiration, constipation, dehydration, diarrhea,
hypermagnesemia, hyperglycemia, hyperkalemia, Normal gastric
hypernatremia, hypokalemia, hypophosphatemia, emptying;
Gastrostomy
hypomagnesemia, fluid overload, hyponatremia, Little risk of
tubes
hypercapnia, GI disturbances, low serum zinc, nausea, esophageal reflux and
vomiting, electrolyte retention problems (polymeric), aspiration
essential fatty acid (EFA) deficiency Upper GI disease with >4 – 6
Less Common: Hyperphosphatemia normal small bowel weeks
function; High risk of
Drug Interactions: esophageal reflux and
Jejunostomy
NOTE: Enteral formula that are administered continuously aspiration; Long-term
tubes
may reduce the rate and/or extent of absorption of enteral nutrition
medications that must be given on an empty stomach. support where gastric
Do NOT mix medications directly with the enteral feeding is
formula. contraindicated

Monitor closely with: If using nasal or oral feeding tubes, inspect the mouth,
Reduces absorption of the following drugs: nares, and pharynx daily for ulceration, skin irritation,
V

Phenytoin, Oral [withhold enteral feeding and flush pressure necrosis, and lesions. Clean nares daily with warm
nasogastric tube 2 hours before and 2 hours after water. Check the tape on the nose or mouth or the fixator
phenytoin administration] device and change every 3–5 days, or as needed.

Reduces therapeutic effect of Warfarin (causes warfarin If using gastrostomy or jejunostomy , for the first 48–72
resistance) hours, place dressings over the feeding tube or stoma and
clean the skin with sterile normal saline and dry thoroughly.
Avoid concomitant use with: After 48–72 hours, leave healed stoma open to air without
Increases risk of adverse or toxic effects of Sucralfate dressing, clean skin with soap and warm water, and dry
(bezoar formation due to protein-binding of sucralfate) thoroughly. Clean under the discs, bumpers, or bolsters to
keep them dry. Do not place dressings under external
Reduces absorption of Ciprofloxacin bolster to prevent application of pressure to the stomach
wall, which may force the tube out of the stomach and into
WARNING: Concomintant use with other medications; if the peritoneum.
the medication is available as sold (especially EC
tablets, SR preparations and sorbitol-containing
medications only), reconsider crushing, as this may
alter the absorption characteristics of the medication
or plug the tube.

Administration: Patients should sit upright at 30–45

degrees during tube feeding and for 1–2 hours afterward
to minimize incidence of nosocomial aspiration
pneumonia and to allow gravity to help propel the food.

Select appropriate formula based on the individual

patient’s medical condition, nutritional status, and

634
VARIOUS

Determine the method of administration based on GI ADULT POLYMERIC ENTERAL

function, feeding site, patient tolerance. Rx
NUTRITION

Feeding Patient Oral:

GI function
site tolerance Composition:
Continuous Infusion Calories 100 – 475 kcal
Critically ill, Dilution 1:1 – 2:1
Small
Impaired GI function debilitated Carbohydrates 13.8 – 59 g
bowel
patients Protein 3.8 – 19.9 g
Intermittent Infusion Fat 3.4 – 21.5 g
Sodium 75 – 402 mg
Increased risk of Not for critically Potassium 370 – 580 mg
distention, Gastric ill patients; Calcium 80 – 500 mg
aspiration, and feeding Dependent on Magnesium 25 – 500 mg
other GI only functional ability Fiber 0 – 1.5 g
complications of the gut Phosphorus 47 – 307 mg
Bolus Infusion mOsm/ kg 270 – 730
GI intolerance and Into the Volume 100 mL – 1 L
Non-critical
increased risk for stomac
patients Contains intact protein from soy or casein, carbohydrate as
aspiration h only
disaccharides and polysaccharides, and variable
amounts of fat, fiber, and water. Requires normal or near
Continuous infusion is performed at 25–125 mL/hour
normal digestive and absorptive capacity and are
over 12–24 hours, usually by an enteral feeding pump.
nutritionally complete with all vitamin, minerals, and
trace elements at a specified volume.
Intermittent infusion is performed at 250–500 mL over
30 to 90 minutes several times a day, usually by gravity
Indications: Prolonged anorexia, severe protein-energy
flow or enteral feeding pump. Usually used for stable
undernutrition, coma or depressed sensorium, liver
patients requiring long-term feeding or when greater
failure, inability to take oral feedings due to head or neck
patient freedom and mobility are desired, like in a home
trauma, critical illnesses causing metabolic stress (e.g.,
setting.
burns)
Bolus infusion is performed at 200–500 mL over a short
See General Information on Enteral Feeding listed above
period of time (usually less than 15 minutes), several
for other information.
times a day by syringe. Usually used for home tube-
feeding patients or patients in rehabilitation, when
Pregnancy Category: Not classified
greater freedom and mobility are desired.
ATC Code: V06DB

V
NOTE: Use of enteral feeding pump is desirable to ensure a
constant infusion rate.

Water requirement should be based on patient’s fluid DISEASE SPECIFIC ENTERAL

Rx
status. Water requirement in a normal healthy adult is 1 NUTRITION
mL/kcal. Volume of water from all sources should be
calculated and measured against requirements, Oral:
including enteral feeding, flushes, intravenous, and oral. Composition:
Calories 100 – 1,000 kcal
Pregnancy Category: Not classified Dilution 1:1 – 2:1
Carbohydrates 10.4 – 156 g
ATC Code: V06DB Protein 5.5 – 88 g
Fat 3.3 – 108 g
Sodium 80 – 2,400 mg
Potassium 172 – 5,600 mg
Calcium 80 – 500 mg
Magnesium 25 – 500 mg
Phosphorus 50 – 1,789 mg
mOsm/kg 230 – 635
Volume 50 mL – 500 mL
50 g – 500 g

Specifically designed for patients with specific diseases or

medical conditions that may respond to nutrient
manipulation.

635
 VARIOUS

Indications: For correcting water electrolyte acid-base, and and are complete with respect to vitamin, minerals, and
caloric disturbances in major elective surgery, trauma, trace elements at a specified volume.
burns, head and neck cancer, ICU on mechanical
ventilation, and wound healing. Helps in improving Indications: Nutritional support in children to provide energy
immune cell function, modulates inflammation and and nutrients to support optimal growth, and neuromotor
reduces infection. development; inability to take enough food; maldigestion
and malabsorption; increased nutritional requirements
See General Information on Enteral Feeding listed above for (e.g., burns, trauma, cystic fibrosis, congenital heart
other information. disease); altered metabolism; primary disease
management (e.g., chronic diarrhea, Crohn’s disease)
Pregnancy Category: Not classified
NOTE: To be used on pediatric populations with growth
ATC Code: V06DB impairment but sufficiently preserved GI function:
Child <2 years with growth failure >1 month
Child >2 years with growth failure >3 months
FIBER CONTAINING ENTERAL Change on centile charts >2 growth channels
Rx Triceps skinfolds <5th percentile per age
NUTRITION
Dose:
Oral:
NOTE: Individualize dose based on age, clinical picture, and
Composition:
possibility of oral intake, absorptive and digestive
Calories 100 – 1,048 kcal
capacity, and dietary habits.
Dilution 1:1 – 2:1
Chosen approach should increase stepwise in respect to
Carbohydrates 13.8 – 148 g
underlying condition and impairment of nutritional status
Protein 3.8 – 40 g
Fat 3.4 – 34.7 g
See General Information on Enteral Feeding listed above for
mOsm/kg 270 – 375
other information.
Sodium 46.5 – 930 mg
Potassium 78.5 – 1,570 mg
Pregnancy Category: Not applicable
Phosphorus 63 – 720 mg
Fiber 2 – 10.6 g
ATC Code: V06DB
Volume 100 g – 400 g
500 mL

Serves as a source of fiber; beneficial for prevention or SEMI-ELEMENTAL ENTERAL

Rx
treatment of altered bowel function in enterally fed NUTRITION
patients.
Indications: Dietary management of diarrhea and Oral:
constipation Composition:
Calories 100 – 1,300 kcal
V

See General Information on Enteral Feeding listed above for Dilution 1:1 – 1.5:1
other information. Carbohydrates 13.8 – 177.2 g
Pregnancy Category: Not classified Protein 3 – 66.6 g
Fat 3.9 – 37.4 g
ATC Code: V06DB Sodium 66 – 1,040 mg
Potassium 135 – 1,730 mg
Phosphorus 22 – 867 mg
PEDIATRIC POLYMERIC ENTERAL mOsm/kg 375 – 575
Rx Volume 100 mL – 1 L
NUTRITION
76 g – 450 g
Oral:
Contains short chain carbohydrate or simple sugar and
Composition:
peptides or amino acid. The use of peptide-based
Calories 445 – 511 kcal
formula has been shown to be superior to free amino
Dilution 1:1
acids in promoting greater nitrogen absorption in both
Carbohydrates 14.9 – 62.2 g
healthy and disease gut.
Protein 13.4 – 54.3 g
Fat 16.2 – 26 g
Indications: Nutritional supplementation in conditions of
mOsm/kg 308 – 345
maldigestion or malabsorption
Sodium 120 – 250 mg
Potassium 400 – 750 mg
See General Information on Enteral Feeding listed above for
Phosphorus 150 – 760 mg
other information.
Volume 100 g
Pregnancy Category: Not classified
Contains protein, fat, and carbohydrates, which require
normal or near normal digestive and absorptive capacity
ATC Code: V06DB

636
VARIOUS

See Glucose (Dextrose) under Antihypoglycemics in Chapter

Rx MODULAR ENTERAL NUTRITION 01: Alimentary Tract and Metabolism for other
information.
Oral: Pregnancy Category: C
Composition:
Calories 9.5 – 380 kcal ATC Code: V06DC01
Dilution 0
Carbohydrates 0.67 – 94 g
Protein 5 – 23 g AMINO ACIDS / CARBOHYDRATES / MINERALS /
Fat 0.6 g VITAMINS, COMBINATIONS
Sodium 15 – 110 mg
Potassium 10 – 66 mg AMINO ACID SOLUTIONS
Phosphorus 5 – 30 mg
mOsm/kg 900
Volume 280 g – 400 g General Information

Provides protein, fat, or carbohydrate as single nutrients or Solution of amino acids intended to provide nutrition into
modular mixtures to allow adjustment of macronutrient the body.
mix. They are not nutritionally complete; however, they
can be added to commercial formulas to alter the Indications: Parenteral nutrition
nutrient content or caloric density.
Contraindications Severe blood acid or electrolyte
See General Information on Enteral Feeding listed above for problems; high blood ammonia levels; low blood volume;
other information. amino acid metabolism problems

Pregnancy Category: Not classified Precautions:

Sulfite allergy; Elderly, children, and newborns (increased
ATC Code: V06DB sensitivity to side effects); Pregnancy and lactation (use
with caution).

CARBOHYDRATES Adverse Drug Reactions:

Common and Less Common: Severe allergic reactions
(rash, hives, tightness in the chest, swelling of the mouth,
Rx GLUCOSE / DEXTROSE face, lips, or tongue), shortness of breath, unexplained
weight gain, swelling of the hands, ankles, legs, or feet,
symptoms of fluid or electrolyte problems (e.g.,
Inj.: 50%, 10 mL and 20 mL ampule (IV) confusion, fainting, fast or irregular heartbeat, loss of
50%, 10 mL, 20 mL, and 50 mL (85 Kcal) vial (IV) appetite, mood changes, muscle pain, twitching, or
weakness, seizures, severe or persistent dizziness,

V
A sterile, hypertonic solution of glucose, which provides a unusual tiredness or weakness
source of calories in a minimal volume of water and is
used in restoring blood glucose concentrations in the Drug Interactions:
treatment of hypoglycemia.
WARNING: Should NOT be mixed with other drugs due
to increased risk of microbial contaminations and
Indication: For parenteral nutrition during carbohydrate
incompatibilities. Mixing with other drugs may alter
depletion
the chemical and physical properties of the
solution, giving rise to toxic reactions.
Contraindications: Hyperglycemia; use of hyperosmotic
solutions in patients with anuria; diabetic coma; glucose-
galactose malabsorption syndrome; dehydrated patients Administration: Administer by IV infusion. Keep out of reach
with delirium; intracranial or intraspinal hemorrhage; of children and pets, including syringes and needles.
should not be used after ischemic attacks.
Do NOT reuse needles, syringes, or other materials.
Dose: Dispose of properly after use.
NOTE: Individualize dose based on patient requirements.
Pregnancy Category: Not classified
Carbohydrate depletion, by IV injection, ADULT, administer
as >5% solution via a peripheral vein. ATC Code: V06DE

Administration: Administer via a large vein (e.g., into a

secure IV cannula in an antecubital vein).

Visually inspect parenteral products for particulate

matter and discoloration prior to administration.

637
 VARIOUS

AMINO ACID SOLUTIONS FOR AMINO ACID SOLUTIONS FOR

Rx
HEPATIC FAILURE Rx IMMUNONUTRITION /
IMMUNOENHANCEMENT
Inj.:
Composition: Inj.:
Volume 500 mL Composition:
Concentration 5–8% Volume 50 mL and 100 mL
5–10% Protein 20 g; L-alanyl-L-glutamate
Protein 35–50 g; rich in Calories 70–90
branched-chain amino acids Electrolytes none
Calories 50–200
Electrolytes variable Solution of amino acids intended to provide nutrition into
the body.
Management of hepatic failure in patients with acute and
chronic liver diseases. Helpful in patients under Indications: Parenteral nutrition
hypercatabolic state with negative nitrogen balance due
to increased skeletal muscle breakdown. Dose: Determine dose based on individual patient’s needs.

Indication: Management See General Information on Amino Acid Solutions listed

of hepatic encephalopathy in patients with acute and above for other information.
chronic liver diseases
Contraindications: Severe renal disorder; abnormal amino Pregnancy Category: Not classified
acid metabolism other than hepatic disorders
ATC Code: V06DE
Dose:
NOTE: Individualize dose based on patient’s needs. Adjust
dose based on a patient’s age, symptoms, and body AMINO ACID SOLUTIONS FOR
weight. Rx
INFANTS
Hepatic encephalopathy, by drip IV infusion, ADULT, 500 to
1,000 mL per dose at a rate of 500 mL over 180–300 Inj.:
minutes (about 25–40 drops/minute). Composition:
Volume 100 mL
Dose Adjustment: Concentration 5–10%
Pregnancy: Protein 5–10 g; including taurine
Adjust dose to achieve a reduction to less than 5,000 IU of Calories 20-40 kcal
vitamin A daily in pregnant women of gestational month Electrolytes none
of 3 months or earlier or women who have an intention
to become pregnant. A mixture of amino acids, carbohydrates, and fat emulsions
V

that may serve as total parenteral nutrition.

Precautions:
Severe acidosis; Congestive heart failure; Elderly and Indication: For partial parenteral nutrition in premature
children; Pregnancy (may cause cranial neural crest and infants, babies, and small children
other malformations in newborns).
Contraindications: Disturbances in amino acid metabolism,
Adverse Drug Reactions: acidosis, hyperhydration, hypokalemia
Common: Acidosis, nausea, vomiting, chest discomfort,
palpitation, chills, fever, headache, vascular pain Dose:
Rare: Skin eruptions NOTE: Individualize dose based on patient’s needs.

Administration: Administer by slow IV infusion. 500–1,000 For parenteral nutrition, by IV infusion, INFANT, administer
mL is reconstitue with a dextrose solution and as required, not exceeding maximum dose, as follows:
administered over 24 hours via a central vein. Maximum daily dosage
1st year of living 1.5 – 2.5 g/kg
See General Information on Amino Acid Solutions listed 2nd–5th year of living 1.5 g/kg
above for other information. 6th–14th year of living 1 g/kg

Pregnancy Category: Not classified Dose Adjustment:

Renal and Hepatic Impairment:
ATC Code: V06DE Individualize doses.

Precautions:
Hyponatremia.

Administration: For IV infusion. Keep out of reach of

children.

638
VARIOUS

NOTE: Too rapid infusion may result in renal losses causing See General Information on Amino Acid Solutions listed
amino acid imbalance. above for other information.

See General Information on Amino Acid Solutions listed Pregnancy Category: Not classified
above for other information.
ATC Code: V06DE
Pregnancy Category: Not applicable

ATC Code: V06DE OTHER NUTRIENTS

AMINO ACID SOLUTIONS FOR Rx IODIZED OIL FLUID

Rx
RENAL CONDITIONS
Oral: 500 mg (equivalent to 200 mg elemental iodine) soft
Inj.: gel capsule
Composition:
Volume 250-500 mL NOTE: For DOH Program only.
Concentration 3.5–7%
Protein 17.5–35 g; rich in essential A salt form of iodized oil intended to meet RDI for iodine for
amino acids pregnant and lactating women (200 micrograms daily) in
Calories 50–200 kcal areas of moderate and severe iodine deficiency.

Contains essential, semi- essential and non- essential Indications: Prophylaxis of iodine-deficiency-related fetal
amino acids in optimum concentration for protein disorders, including endemic cretinism and neonatal
synthesis. hypothyroidism for administration to pregnant women
and women of childbearing age
Indications: Serves as a parenteral nutrition supplement for
renal failure following polytrauma, acute and chronic Dose:
renal insufficiency, and compensation of amino acid NOTE: Select lowest dose and frequency that will ensure
losses in patients undergoing dialysis hemofiltration, protection throughout pregnancy, and during lactation
extensive surgery and sepsis. for at least first year postpartum.

Contraindications: Metabolic acidosis, renal and amino acid Prophylaxis of iodine-deficiency-related fetal disorders, by
disturbances, hypernatremia, hyperkalemia, mouth, ADULT (pregnant women), 300–480 mg every 12
hyperhydration and congestive heart failure months; or 100–300 mg every 6 months; ADULT (non-
pregnant fertile women), 400–960 mg every 12 months;
Dose: or 200–480 mg every 6 months.
NOTE: Individualize dose based on patient’s needs. Adjust
doses according to amino acid requirements based on Dose Adjustment: No information found

V
age, body weight, and condition of patient
Precautions:
Acute and chronic renal insufficiency not treated by dialysis, Use only in pregnant women and women of childbearing age
by IV infusion, ADULT, maximum dose, 0.5 g/kg daily. where the prevalence of iodine deficiency disorder is
Acute and chronic renal insufficiency treated by classified as moderate or severe, cretinism and neonatal
hemofiltration, peritoneal dialysis, and hemodialysis, by hypothyroidism are present, or universal salt iodization
IV infusion, ADULT, maximum dose, 1 g/kg daily. programs will not reach women at reproductive age
within 1–2 years.
Precautions: Identify optimal biological and process indicators to prevent
Intolerance and increased renal losses (may be fetal brain damage as follows:
accompanied by amino acid imbalance if the solution is
infused too rapidly). Biological indicators [NOTE: At least one should be
neonatal thyroid stimulating hormone (TSH) or maternal
Adverse Drug Reactions: urinary iodine]:
Common: Nausea, vomiting, chill, fever Infants
Less Common: Chest discomfort and palpitation • Birth weight
• Perinatal mortality rate
Administration: Administer through peripheral veins or by • Neonatal serum TSH
central venous route using non-pyrogenic IV Mothers
administration set with aseptic technique. • Urinary iodine concentration
• Breastmilk iodine concentration
Unsuitable for long-term parenteral use as it does not
contain adequate non-essential amino acids. Include fat Adverse Drug Reactions: No information found
in the dietary regimen during long-term therapy to avoid
essential fatty acid deficiency. Drug Interactions: No information found

639
 VARIOUS

Administration: May be administered at any stage of the 300 mg/mL 350 mg/mL
pregnancy. Procedure
Preparation Preparation
(maximum
Pregnancy Category: Not classified
dose, 250 mL)
ATC Code: Not available

CHILD, 1–1.5
CONTRAST MEDIA CHILD, 1.5–2 mL/kg, usually
mL/kg, usually 1.25 mL/kg, of
1.75 mL/kg the 350
X-RAY CONTRAST MEDIA, IODINATED (maximum mg/mL
dose, 6 mL/kg (maximum
Rx IOHEXOL or 291 mL) dose, 5 mL/kg
or 250 mL)
CHILD, 1
Inj.: 300 mg iodine/mL, 50 mL and 100 mL vial Pulmonary
mL/kg as a
350 mg iodine/mL, 50 mL and 100 mL vial angiography
single injection
ADULT, 50–80 ADULT, 50–80
NOTE: For IV and other parenteral routes as appropriate. mL into the mL into the
aorta, may be aorta, may be
A nonionic, water-soluble radiographic contrast medium. It repeated if repeated if
will opacify blood vessels in the path of flow of the indicated indicated
contrast medium permitting radiographic visualization of (maximum (maximum
the internal structures until significant hemodilution total dose, 291 total dose, 250
occurs. mL) mL)
ADULT, 30–60 ADULT, 30–60
Indications: Angiocardiography (ventriculography, selective mL into major mL into major
coronary arteriography), aortography, including studies branches, branches,
of the aortic root, aortic arch, ascending aorta, including including
abdominal aorta and its branches; contrast celiac and celiac and
enhancement for computed tomographic head and body mesenteric mesenteric
imaging; intravenous digital subtraction angiography of arteries, may arteries, may
the head, neck, abdominal, renal and peripheral vessels; Aortography and be repeated if be repeated if
peripheral arteriography; excretory urography selective indicated indicated
visceral (maximum (maximum
Contraindications: Systemic or local infection arteriography total dose, 291 total dose, 250
mL) mL)
V

Dose: ADULT, 5–15 ADULT, 5–15

NOTE: Individualize dose based on size of the structure to mL into renal mL into renal
be visualized, anticipated degree of hemodilution, and arteries, may arteries, may
valvular competence, as well as the size, flow rate, and be repeated if be repeated if
disease state of the injected vessel. Consider weight in indicated indicated
infants and young children. (maximum (maximum
total dose, 291 total dose, 250
The volume to be administered is a more important mL) mL)
consideration than the total dose. CHILD, 1
mL/kg
By IV injection, (maximum
300 mg/mL 350 mg/mL total dose, 5
Procedure
Preparation Preparation mL/kg or 250
ADULT, 3–14 mL)
Selective
mL per ADULT, 6–12
coronary
injection, mL into the
arteriography
usually 5 mL carotid artery
ADULT, 20–75 ADULT, 8–10
Aortic root and
mL, usually 5 Cerebral mL into the
arch study,
mL as a single arteriography internal carotid
alone
injection artery
ADULT, 6–9
ADULT, 30–60 mL into the
mL, usually 40 vertebral artery
Ventriculography
mL, repeat as
necessary

640
VARIOUS

300 mg/mL 350 mg/mL By intrathecal injection,

Procedure
Preparation Preparation 300 mg/mL
Procedure
ADULT, 70– Preparation
ADULT, 80 mL
Contrast 150 mL (21– Thoracic myelography (via
(28 g)
enhanced 45 g) cervical or lumbar 6–10 mL (1.8–3 g)
computed CHILD, 1–2 injection)
tomography, mL/kg Cervical myelography (via
head imaging (maximum 6–10 mL (1.8–3 g)
lumbar injection)
dose, 35 g)
Cervical myelography (via
4–10 mL (1.2–3 g)
C1–2 injection)
Total columnar
300 mg/mL 350 mg/mL myelography (via lumbar 6–10 mL (1.8–3 g)
Procedure injection)
Preparation Preparation
Contrast
Dose Adjustment:
enhanced ADULT, 50– ADULT, 60– Pheochromocytoma:
computed 200 mL (15– 100 mL (21– Administer absolute minimum amount required.
tomography, 60 g) 35 g)
body imaging
Precautions:
ADULT, 30 –
WARNING: Procedures involving radiopaque
50 mL as a
diagnostic agents should only be done by
bolus at 7.5 –
qualified personnel with in- depth knowledge of
30 mL/second
using a the procedure to be done. Emergency treatment
Digital for severe reactions and appropriate facilities
pressure
subtraction needs to be readily available should there be
injector, may
angiography any complication in the procedure. Severe
require up to 3
delayed reactions may occur after
or more
injections, not administration; well- trained personnel and
emergency facilities should be readily available
to exceed 250
mL (87.5 g) within 30- 60 minutes after administration.
Peripheral
angiography, ADULT, 20–90 ADULT, 20–70 WARNING: Reports of serious and rarely fatal
aortofemoral mL mL thromboembolic events leading to myocardial
runoffs infarction and stroke have been documented.
Peripheral Exercise extra caution in intravascular
angiography, administration especially in angiographic
selective ADULT, 10–60 ADULT, 10–30 procedures (caution in guidewire and catheter

V
arteriograms mL mL manipulation, use of manifold systems and/or
(femoral or three-way stopcocks, frequent catheter flushing
iliac) with heparinized saline solutions and minimizing
Peripheral the length of the procedure should be
angiography, ADULT, 40– considered). Plastic syringes have decreased
venography 100 mL the possibility of in- vitro clotting.
(per leg) Potentially hazardous in patients with multiple
Excretory ADULT, 200– ADULT, 200– myeloma or other paraproteinemia, particularly
urography 350 mg/kg 350 mg/kg therapeutically resistant anuria.
CHILD, 0.5–3 May promote sickling in individuals who are
mL/kg, usually homozygous for sickle cell disease
1–1.5 mL/kg, Development of severe cutaneous adverse
not to exceed 3 reactions (SCAR) may develop after 1 hour to
mL/kg several weeks following IV administration,
including Stevens-Johnson syndrome and toxic
NOTE: When administered for multiple procedures, do NOT epidermal necrolysis (SJS/TEN), acute
exceed maximum dosage as follows: generalized exanthematous pustulosis (AGEP)
ADULT 250 mL of 350 mg/mL solution and drug reaction with eosinophilia and
CHILD 250 mL (5 mL/kg) of 350 mg/mL solution systemic symptoms (DRESS).
CHILD 291 mL (6 mL/kg) of 300 mg/mL solution
Severe liver and kidney functional disturbances, severe
thyrotoxicosis, or myelomatosis (use with extreme care);
Pheochromocytoma (measures for the treatment of
hypertensive crisis should be readily available);
Thyroid storm;
Renal impairment;

641
 VARIOUS

Hypotension; Maintaining the patient post-myelography in an upright

Slowed aortic circulation (increased likelihood for muscle position (via wheelchair or ambulation) may help
spasm); minimize adverse effects.
Epilepsy, severe cardiovascular disease, chronic
alcoholism, or multiple sclerosis (use with caution); Pregnancy Category: B
Elderly;
Children; ATC Code: V08AB02
Lactation.

Adverse Drug Reactions:

Common: Arrhythmias, angina, nausea, vomiting, Rx IOPAMIDOL
hypotension, photomas, headache, pain, dizziness
(transient), backache Inj.: 612 mg/mL equivalent to 300 mg iodine, 50 mL and
Less Common: Asystole, cardiac failure, bradycardia, 100 mL vial
tachycardia, vasovagal reaction, dyspnea, rhinitis, 755 mg/mL equivalent to 370 mg iodine, 50 mL and
coughing, laryngitis, urticaria, warm sensation 100 mL vial or bottle
Rare: Diarrhea, dyspepsia, cramp, dry mouth, purpura,
abscess, pruritus, fever, hives, stomachache, visual A non-ionic radiopaque contrast that permits radiographic
hallucination, neurological changes visualization of the internal structures of the human body
by opacifying vessels in the path of flow of the contrast
Drug Interactions: medium.
NOTE: Do NOT admix with other pharmaceuticals. Many
radiopaque contrast agents are incompatible in vitro with Indications: For angiography throughout the cardiovascular
many other drugs. system, including cerebral and peripheral arteriography,
coronary arteriography and ventriculography, selective
Avoid concomitant use with: visceral arteriography, and aortography; for peripheral
Increases risk of adverse or toxic effects Iohexol, specifically venography (phlebography); for angiocardiography; for
seizures computed tomographic (CT) imaging of the head and
[NOTE: Discontinue the following drugs at least 48 hours body.
prior to myelography]:
CNS Stimulants, MAO Inhibitors e.g., Phenothiazine Dose:
Derivatives NOTE: Individualize dose and concentration based on age,
Tricyclic Antidepressants e.g. Amitriptyline body size, size of the vessel and its blood flow rate,
Major tranquilizers, Anti- psychotics anticipated pathology and degree and extent of
opacification required, structure(s) or area to be
Administration: Always administer the lowest dose examined, disease processes affecting the patient, and
necessary to obtain adequate visualization. Apply sterile equipment and technique to be employed. Use the
technique in the withdrawal from container and lowest dose necessary to obtain adequate visualization
administration of the product. to reduce the possibility of an adverse reaction.
V

Visually inspect for particulate matter and discoloration By rapid IV injection,

prior to administration. Slightly warm to body Procedure 300 mg Iodine
temperature immediately prior to injection.
Cerebral ADULT, 8–12 mL with total multiple
Patients should be well hydrated prior to and following Arteriography doses ranging to 90 mL
administration of any contrast medium. ADULT, 5–40 mL into the femoral or
Peripheral
subclavian artery; 25–50 mL into the
Arteriography
For intrathecal administration, always keep the head aorta
elevated above the highest level of the spine. Do not Cerebral ADULT, 8–12 mL with total multiple
lower head of table more than 15o in moving contrast Arteriography doses ranging to 90 mL
medium cranially. Inject slowly (over 1–2 minutes) to ADULT, 5–40 mL into the femoral or
Peripheral
avoid excessive mixing. To maintain as a bolus, move subclavian artery; 25–50 mL into the
Arteriography
medium to distal area very slowly. Use fluoroscopic aorta
monitoring.
By rapid IV injection,
Avoid intracranial entry of bolus. Avoid early and high Procedure 370 mg Iodine
cephalad dispersion of the medium. Avoid abrupt or
active patient movement to minimize excessive mixing of Selective ADULT, 50 mL into the aorta or
medium with CSF. Instruct patient to remain passive. Visceral celiac artery; 10 mL into the renal
Move patient slowly and only as necessary. Arteriography and arteries (maximum total dose,
Aortography 225 mL)
NOTE: In patients with excessive lordosis, consider lateral Pediatric CHILD 10–18 years, 20–50 mL
position for injection and movement of the medium Angiocardiography CHILD 2–9 years, 15–30 mL
cephalad. (single injection) CHILD <2 years, 10–15 mL

By rapid IV injection,

642
VARIOUS

Procedure 370 mg Iodine WARNING: Potentially hazardous in patients with

CHILD 10–18 years, 125 mL multiple myeloma or other paraproteinemia,
Pediatric particularly therapeutically resistant anuria.
Angiocardiography CHILD 5–9 years, 100 mL
(cumulative Development of severe cutaneous adverse
CHILD 2–4 years, 50 mL
injection) reactions (SCAR) may develop after 1 hour to
CHILD <2 years, 40 mL several weeks following IV administration,
ADULT, 2–10 mL for selective including Stevens-Johnson syndrome and toxic
coronary artery injections; 25–50 epidermal necrolysis (SJS/TEN), acute
Coronary
mL following injection at the generalized exanthematous pustulosis (AGEP)
Arteriography and
aortic root (maximum total dose and drug reaction with eosinophilia and
Ventriculography
for combined procedures, 200 systemic symptoms (DRESS).
mL)
Blood coagulation;
By rapid IV injection
Thrombosis, phlebitis, severe ischemic disease, local
370 mg infection, or total obstructed venous system (use with
Procedure 300 mg Iodine
Iodine special care when venography is performed);
ADULT, Renal and hepatic impairment;
ADULT, 50 mL Thyroid storm;
40 mL
Excretory Diabetes;
Urography CHILD, 1.2 to 3.6 mL/kg,
Children (at higher risk of experiencing adverse events, eg.,
not to exceed a total dose
asthma, cyanotic heart disease, and congestive heart
of 30 g Iodine
failure);
Lactation.
Dose Adjustment:
Pheochromocytoma: Adverse Drug Reactions:
Administer absolute minimum amount required. Common: Hot flashes, angina pectoris, flushing,
bradycardia, hypotension, hives, pain, burning
Precautions: sensation, nausea, warmth
WARNING: NOT for intrathecal use. Inadvertent Less Common: Tachycardia, hypertension, myocardial
intrathecal administration has resulted in death, ischemia, circulatory collapse, bigeminy, extrasystoles,
convulsions, cerebral hemorrhage, coma, ventricular fibrillation, angina pectoris, transient
paralysis, arachnoiditis, acute renal failure, ischemic attack, thrombophlebitis, vasovagal reaction,
cardiac arrest, seizures, rhabdomyolysis, tingling in arms, grimace, faintness, vomiting, anorexia,
hyperthermia, and brain edema. throat constriction, dyspnea, pulmonary edema, rash,
urticaria, pruritus, headache, fever, chills, excessive
WARNING: Procedures involving radiopaque sweating, back spasm, taste alterations, nasal
diagnostic agents should only be done by congestion, visual disturbances, urinary retention
qualified personnel with in- depth knowledge of

V
the procedure to be done. Emergency treatment Drug Interactions:
for severe reactions and appropriate facilities Monitor closely with:
needs to be readily available should there be Increases risk of adverse or toxic effects of
any complication in the procedure. Severe Cholecystographic Agents (renal toxicity)
delayed reactions may occur after
administration; well- trained personnel and TEST INTERACTION. May interfere with iodine uptake
emergency facilities should be readily available studies, which depend on iodine estimations for up to 16
within 30- 60 minutes after administration. days following administration.
Serious, rarely fatal, thromboembolic events
Administration: For IV and other parenteral routes as
causing myocardial infarction and stroke have
appropriate.
been reported during angiographic procedures.
To minimize thromboembolic events, meticulous
Perform all preparation and administration processes in
IV administration techniques are recommended,
a suitable work area, such as laminar flow hood, utilizing
including close attention to guidewire and
catheter manipulation, use of manifold systems aseptic technique. Warm solution to body temperature
and/or three-way stopcocks, frequent catheter shortly before administration to improve tolerability and
flushing with heparinized saline solutions, and ease of injection. Do NOT admix with other drugs,
solutions, or total parenteral nutrition mixtures.
minimizing the length of the procedure. Use of
plastic syringes in place of glass syringes has
Draw product into the syringe and administer using
been reported to decrease but not eliminate the
sterile technique. The container-closure system may be
likelihood of in vitro clotting.
penetrated only one time. Once punctured, do NOT
May promote sickling in individuals who are remove from aseptic work area during the entire period
homozygous for sickle cell disease if injected of use. Fluid transfer should be completed no longer than
intravenously or intra-arterially. 10 hours from withdrawal of contents.

643
 VARIOUS

Visually inspect parenteral products for particulate ADULT, 300 mg

matter and discoloration prior to administration. Discard Iodine per kg
products that show signs of crystallization or damage to (maximum total
the container-closure system, including the glass dose, 100 mL,
container, stopper and/or crimp. Excretory equivalent to 30 g
Urography Iodine)
Discard 10 hours after initial puncture. Discard unused CHILD, 1–2
portions. mL/kg, not to
exceed 3 mL/kg as
NOTE: Patients should be well hydrated prior to and total dose
following administration. ADULT, 50–200 ADULT, 41–162
mL mL
Pregnancy Category: B Contrast CHILD, 1–2
CT, head mL/kg, not to
ATC Code: V08AB04
exceed 3 mL/kg as
total dose
ADULT, 50–200 ADULT, 41–162
Rx IOPROMIDE mL by bolus mL by bolus
injection injection
(maximum total (maximum total
Inj.: 300 mg/mL equivalent to 623 mg iodine, 50 mL and dose, 200 mL, dose, 162 mL,
100 mL vial equivalent to 60 g equivalent to 60 g
370 mg/mL equivalent to 769 mg iodine, 50 mL and Iodine) Iodine)
100 mL vial ADULT, 100–200 ADULT, 81–162
Contrast mL by rapid mL by rapid
A non-ionic, water soluble x-ray contrast agent that permits CT, body infusion infusion
radiographic visualization of the internal structures of (maximum total (maximum total
the human body by opacifying vessels in the path of flow dose, 200 mL, dose, 162 mL,
of the contrast medium via intravascular administration. equivalent to 60 g equivalent to 60 g
Iodine) Iodine)
Indications: Radiocontrast media; for cerebral and
CHILD, 1–2
peripheral arteriography; for coronary arteriography and
mL/kg, not to
left ventriculography, visceral angiography, and
exceed 3 mL/kg as
aortography; for IV excretory urography; for contrast CT
total dose
imaging of head and body

Dose:
Dose Adjustment:
By intra-arterial injection,
Renal Impairment and Pheochromocytoma:
V

Procedure 300 mg/mL Administer absolute minimum amount required.

ADULT, 3–12 mL into the carotid
arteries; Precautions:
Cerebral
4–12 mL into the vertebral arteries; WARNING: NOT for intrathecal use. Inadvertent
Arteriography
20–50 mL into the aortic arch; intrathecal administration may cause death,
(maximum total dose, 150 mL) convulsions, cerebral hemorrhage, coma,
ADULT, 5–40 mL into the subclavian or paralysis, arachnoiditis, acute renal failure,
femoral artery; cardiac arrest, seizures, rhabdomyolysis,
Peripheral
25–50 mL into the aortic bifurcation hyperthermia, and brain edema.
Arteriography
(distal runoff)
(maximum total dose, 250 mL) WARNING: Procedures involving radiopaque
diagnostic agents should only be done by
By intra-arterial injection, qualified personnel with in- depth knowledge of
Procedure 370 mg/mL the procedure to be done. Emergency treatment
Coronary ADULT, 3–14 mL into the right or for severe reactions and appropriate facilities
Arteriography left coronary artery; needs to be readily available should there be
And Left 30–60 mL into the left ventricle any complication in the procedure. Severe
Ventriculography (maximum total dose, 225 mL) delayed reactions may occur after
Cardiac administration; well- trained personnel and
CHILD >2 years, 1–2 mL/kg; not to emergency facilities should be readily available
Chambers and
exceed 4 mL/kg as total dose within 30- 60 minutes after administration.
related arteries
Life-threatening or fatal, anaphylactoid
By IV injection, reactions, may occur during or after
administration.
Procedure 300 mg/mL 370 mg/mL

644
VARIOUS

Development of severe cutaneous adverse

reactions (SCAR) may develop after 1 hour to Do NOT admix with other drugs, solutions, or total
several weeks following IV administration, parenteral nutrition mixtures.
including Stevens-Johnson syndrome and toxic
epidermal necrolysis (SJS/TEN), acute For intra-arterial administration, administer at a flow rate
generalized exanthematous pustulosis (AGEP) approximately equal to the flow rate in the vessel being
and drug reaction with eosinophilia and injected
systemic symptoms (DRESS).
NOTE: Patients should be well hydrated prior to and
Cardiovascular reactions; following administration.
Heart failure;
Thromboembolic complications (eg. local and distal organ Pregnancy Category: B
damage, ischemia, thromboembolism, and organ
failure, including stroke, brachial plexus palsy, chest ATC Code: V08AB05
pain, myocardial infarction, sinus arrest, hepato-renal
function abnormalities);
Pheochromocytoma; Rx IOVERSOL
Thyroid storm;
Renal impairment;
Nervous system effects (may disrupt blood-brain barrier; Inj.: 636 mg/mL equivalent to 300 mg/mL iodine, 50 mL
may accumulate in the brain); and 100 mL vial
Lactation. 741 mg/mL equivalent to 350 mg/mL iodine, 50 mL
and 100 mL vial
Adverse Drug Reactions:
Common: Headache, dysgeusia, abnormal vision, chest A non ionic radiographic contrast agent that opacifies
pain, vasodilation, nausea, vomiting, back pain, urinary vessels in the path of the flow of ioversol resulting in
urgency, injection site and infusion site reactions, pain adiographic visualization of the internal structures.
Less Common: Atrioventricular block, bradycardia,
ventricular extrasystole, abdominal discomfort, Indications: Radiocontrast media for cerebral and
abdominal pain, abdominal pain upper, constipation, peripheral arteriography, coronary arteriography, and left
diarrhea, dry mouth, dyspepsia, gastrointestinal ventriculography; for angiocardiography; for CT imaging
disorder, gastrointestinal pain, increased salivation, of the head and body, venography, and IV excretory
stomach discomfort, rectal tenesmus, asthenia, chest urography; for IV digital subtraction angiography (IV-DSA)
discomfort, chills, excessive thirst, extravasation, feeling
hot, hyperhidrosis, malaise, edema peripheral, pyrexia, Contraindications: Symptomatic hyperthyroidism
asthma, face edema, arthralgia, musculoskeletal pain,
myasthenia, neck pain, pain in extremity, agitation, Dose:
confusion, convulsion, dizziness, hypertonia, NOTE: Use the lowest dose necessary to obtain adequate
hypesthesia, incoordination, neuropathy, somnolence, visualization to reduce the possibility of an adverse

V
speech disorder, tremor, paresthesia, visual field defect, reaction. Individualize dose and concentration to be
anxiety, dysuria, renal pain, urinary retention, apnea, used, considering age, body size, size of the vessel and
increased cough, dyspnea, hypoxia, pharyngeal edema, its blood flow rate, anticipated pathology and degree and
pharyngitis, pleural effusion, pulmonary hypertension, extent of opacification required, structure(s) or area to
respiratory disorder, sore throat, coronary artery be examined, disease processes affecting the patient,
thrombosis, flushing, hypertension, hypotension, and equipment and technique to be employed.
peripheral vascular disorder, syncope, vascular anomaly
By intra-arterial injection
Drug Interactions: Procedure 300 mg/mL 350 mg/mL
Monitor closely with:
Cerebral
Increases risk of adverse or toxic effects of the following
Arteriography ADULT, 2–12
drugs:
(carotid or mL
Biguanides (lactic acidosis)
vertebral arteries)
Cholecystographic Agents (renal toxicity)
Cerebral
Beta- blockers
Arteriography ADULT, 20–50
(aortic arc, four mL
TEST INTERACTION. May interfere with iodine uptake vessel study)
studies, which depend on iodine estimations for up to 16
CHILD, 1.25
days following administration
mL/kg (1 – 1.5
May obscure lesions seen on non-contrast CT scans.
mL/kg), up to
a maximum
Administration: Warm solution to body temperature shortly Angiocardiography
total volume of
before administration to improve tolerability and ease of
250 mL
injection.
(maximum
cumulative
Visually inspect for particulate matter and discoloration
prior to administration.

645
 VARIOUS

dose, 5 ADULT, 30–50 mL at

mL/kg) 12–20 mL/second,
IV-DSA
may repeat as
(peripheral
necessary
injection)
(maximum dose,
250 mL)

Dose Adjustment:
Peripheral ADULT, 60 mL (20–90 mL);
Geriatric:
Arteriography maximum cumulative dose, 250
Start at the low end of dosing range, reflecting the greater
(aortic-iliac runoff) mL
frequency of decreased hepatic, renal or cardiac
Peripheral function, and of concomitant disease or other drug
ADULT, 40 mL (10–50 mL);
Arteriography therapy.
maximum cumulative dose, 250
(common iliac or
mL
femoral artery) Pheochromocytoma:
Peripheral Administer absolute minimum amount required.
ADULT, 20 mL (15–30 mL);
Arteriography
maximum cumulative dose, 250
(subclavian or
mL
brachial artery) Precautions:
Coronary ADULT, 8 mL WARNING: NOT for intrathecal use. Inadvertent
Arteriography (2–10 mL); intrathecal administration may cause death,
And Left maximum convulsions, cerebral hemorrhage, coma,
Ventriculography cumulative paralysis, arachnoiditis, acute renal failure, cardiac
(left coronary) dose, 250 mL arrest, seizures, rhabdomyolysis, hyperthermia,
Coronary ADULT, 6 mL and brain edema.
Arteriography (1–10 mL);
And Left maximum
Ventriculography cumulative WARNING: Procedures involving radiopaque
(right coronary) dose, 250 mL diagnostic agents should only be done by qualified
Coronary ADULT, 40 mL personnel with in- depth knowledge of the
Arteriography (30–50 mL); procedure to be done. Emergency treatment for
And Left maximum severe reactions and appropriate facilities needs
Ventriculography cumulative to be readily available should there be any
(left ventricle) dose, 250 mL complication in the procedure. Severe delayed
reactions may occur after administration; well-
trained personnel and emergency facilities should
By IV infusion
be readily available within 30- 60 minutes after
Procedure 300 mg/mL 350 mg/mL administration.
CT, head ADULT, 50–150 mL Procedures involving radiopaque diagnostic
V

agents should only be done by qualified personnel

CT, body ADULT, 50–150 mL with in- depth knowledge of the procedure to be
done. Emergency treatment for severe reactions
By IV bolus injection and appropriate facilities needs to be readily
Procedure 300 mg/mL 350 mg/mL available should there be any complication in the
procedure. Severe delayed reactions may occur
CT, body ADULT, 25–75 mL ADULT, 25–75 mL after administration; well- trained personnel and
emergency facilities should be readily available
By IV injection within 30- 60 minutes after administration.
Procedure 300 mg/mL 350 mg/mL Life-threatening or fatal cardiovascular reactions
have occurred, including cardiac arrest,
ADULT, 50–100 mL per extremity hypotensive collapse, and shock.
Venography
(maximum cumulative dose, 250 mL) Can cause life-threatening or fatal hypersensitivity
ADULT, 50– reactions, including anaphylaxis and anaphylactic
ADULT, 50–75 mL
IV 75 mL shock.
(maximum dose,
Urography (maximum May promote sickling in individuals who are
140 mL)
dose, 150 mL) homozygous for sickle cell disease
ADULT, 1.6
ADULT, 1.4 mL/kg Severe cutaneous adverse reactions (SCAR) may
High Dose mL/kg develop from 1 hour to several weeks following IV
(maximum dose,
Urography (maximum administration, including Stevens-Johnson
140 mL)
dose, 150 mL) syndrome and toxic epidermal necrolysis
ADULT, 30–50 mL at (SJS/TEN), acute generalized exanthematous
10–30 mL/second, pustulosis (AGEP) and drug reaction with
IV-DSA
may repeat as eosinophilia and systemic symptoms (DRESS).
(central
necessary
catheter) Renal impairment;
(maximum dose,
250 mL) Extravasation;

646
VARIOUS

Pheochromocytoma; X-RAY CONTRAST MEDIA, NON-IODINATED

Thyroid storm;
Children;
Pregnancy; Rx BARIUM SULFATE
Lactation.
Oral: USP grade powder suspended in water, 340 and 454
Adverse Drug Reactions:
g pouch, LDPE bag
Common: Nausea
Less Common: Cardiac arrest, myocardial infarction,
Powder for suspension that acts as a positive radio contrast
arrhythmia, atrioventricular block, nodal rhythm,
agent for radiographic studies. Barium sulfate is not
bradycardia, angina pectoris, palpitations, vertigo,
absorbed or metabolized and is eliminate from the GIT
tinnitus, blurred vision, periorbital edema, conjunctivitis,
unchanged
vomiting, abdominal pain, dysphagia, dry mouth, chest
pain, pain, injection site pain, injection site hematoma,
Indications: Radiographical contrast media for upper and
extravasation, pyrexia, swelling, asthenia, malaise,
lower gastrointestinal procedures by conventional x-ray
fatigue, chills, rhinitis, heat injury, vascular
or computed tomography
pseudoaneurysm, ST-segment depression, decreased
blood pressure, acidosis, muscular weakness, muscle
Contraindications: Proximal to a known obstruction of the
spasms, back pain, cerebral infarction, aphasia, tremor,
colon; known or suspected GI perforation.
dizziness, presyncope, headache, paresthesia,
dysgeusia, hallucination, disorientation, anxiety, urinary
Dose:
retention, renal pain, polyuria, laryngeal edema, hypoxia,
NOTE: Determine volume to be administered based on
pulmonary edema, dyspnea, hyperventilation, cough,
degree and extent of contrast required in the area(s)
sneezing, nasal congestion, urticaria, rash, pruritus,
under examination and on the technique employed.
swelling face, hyperhidrosis, erythema, hypertension,
hypotension, arterial spasm, vasospasm, vasodilation,
GI tract marking, by mouth, ADULT, 900–1,350 mL of
flushing
prepared suspension, 20–30 minutes prior to scheduled
procedure; for improved gastric marking, consume the
Drug Interactions:
final 200 mL immediately prior to the scan.
Monitor closely with:
Increases risk of adverse or toxic effects of the following
Dose Adjustment:
drugs:
Patients with history of food aspiration:
Cholecystographic Agents (renal toxicity), Metformin
Administer initially small amounts such as ½ teaspoon and
(lactic acidosis)
carefully observe swallowing under fluoroscopic control.
Avoid concomitant use with:
Obesity and patients with delayed transit:
Reduces therapeutic effect of Radioactive Iodine (interferes
Increase total volume up to 1,800 mL.
with thyroid uptake)
Precautions:

V
TEST INTERACTION. May interfere with iodine uptake
studies, which depend on iodine estimations for up to 16 WARNING: MRI Studies. Diagnostic procedures
days following administration. involving the use of radiopaque contrast agents
should be carried out under the direction of
Administration: For IV use only. personnel with the requisite training and a
thorough knowledge of the particular procedure to
Use sterile technique for all handling and administration. be performed.
Warm and administer at body or room temperature. Allergic Reactions. A history of bronchial asthma,
atopy, or a previous reaction to a contrast agent,
Visually inspect for particulate matter or discoloration warrant special attention. Use with caution in
before administration. Inspect glass and plastic severely debilitated patients and in those with
containers prior to use for breakage or other damage and marked hypertension or advanced cardiac disease.
do not use damaged containers. Do NOT admix with
other drugs, solutions, or total parenteral nutrition History of food aspiration (barium swallow studies required);
mixtures. Pregnancy (use radiographic procedures only if deemed
essential).
Avoid extravasation when injecting, especially in patients
with severe arterial or venous disease. Discard unused Adverse Drug Reactions:
portion after use. Less Common: weakness, pallor, tinnitus, diaphoresis,
bradycardia
NOTE: Patients should be well hydrated prior to and Rare: Aspiration pneumonitis, barium impaction, granuloma
following administration. formation, intravasation, embolization, peritonitis,
vasovagal episodes, syncopal episodes, fatalities,
Pregnancy Category: B generalized pruritus, erythema, urticaria, laryngeal
edema, bronchospasm, hypotension, peripheral
ATC Code: V08AB07 vasodilation, hypotension, reflex tachycardia, dyspnea,

647
 VARIOUS

agitation, confusion, cyanosis, unconsciousness, severe Dosing chart

stomach cramps (transient), diarrhea (transient) Body weight Total volume
Drug Interactions: No information found kg lb (mL)
TEST INTERACTION. May appear as a negative GI marker 10 22 2
with certain pulse sequences in MR studies. 20 44 4
30 66 6
Administration: Prepare solution to a concentration of 0.1%
40 88 8
w/v or 0.1% w/w. To be administered on an empty
50 110 10
stomach, free of fluids as much as possible. Patients
should be instructed to neither eat nor drink after the 60 132 12
evening meal on the night preceding the examination. 70 154 14
80 176 16
Rehydrate patient as quickly as possible following 90 198 18
barium study of the GI tract to prevent impaction of 100 220 20
barium. Cathartics may also be required. 110 242 22
120 264 24
NOTE: Saline cathartics are recommended on a routine 130 286 26
basis, especially in patients with a history of constipation,
unless clinically contraindicated. NOTE: Dosing in patients >286 lbs has not been studied
systematically.
If enema tips are used, use caution during insertion. Too
forceful or deep insertion may cause tearing or Precautions:
perforation of the rectum. WARNING: NOT for use in nephrogenic system fibrosis
(NSF). May result in fatal or debilitating fibrosis
If balloon retention tips are used, inflate under affecting the skin, muscle, and internal organs. Do
fluoroscopic control by qualified personnel. NOT administer in patients with chronic, severe
kidney disease (GFR <30 mL/min per 1.73 m2) or
NOTE: Use caution to avoid over-inflation. Overfilling or acute kidney injury. Do NOT exceed the
asymmetrical filling with tip displacement may occur, recommended dose and allow a sufficient period
which can lead to rectal perforation or barium for elimination prior to any re-administration.
granulomas.
Hypersensitivity reactions (eg. anaphylactoid and
Pregnancy Category: Not classified
anaphylactic reactions, with cardiovascular, respiratory
and/or cutaneous manifestations, resulting in death);
ATC Code: V08BA01; V08BA02
Injection site reactions (eg. skin and soft tissue necrosis,
thrombosis, fasciitis, and compartment syndrome
requiring surgical intervention);
MAGNETIC RESONANCE IMAGING CONTRAST
V

Renal failure (risk of renal failure may increase with

MEDIA increasing dose);
Children;
Lactation.
Rx DIMEGLUMINE GADOPENTETATE
Adverse Drug Reactions:
Inj.: 469 mg/mL aqueous solution, 5 mL, 10 mL, and 20 Common: Headache, nausea, injection site coldness or
mL vial localized coldness, dizziness
Less Common: Injection site reactions, substernal chest
The N-methylglucamine salt of the gadolinium complex of pain, back pain, pyrexia, asthenia, feeling cold,
diethylenetriamine penta-acetic acid. It is an injectable generalized warmth, fatigue, chest tightness,
contrast medium for magnetic resonance imaging (MRI). anaphylactoid reactions, hypotension, hypertension,
It is a paramagnetic agent that develops a magnetic tachycardia, migraine, syncope, vasodilatation, pallor,
moment when placed in a magnetic field. abdominal discomfort, teeth pain, increased salivation,
abdominal pain, vomiting, diarrhea, agitation, anxiety,
Indications: For use with MRI to visualize lesions with thirst, somnolence, diplopia, loss of consciousness,
abnormal vascularity in the brain (intracranial lesions), convulsions, paresthesia, throat irritation, rhinitis,
spine and associated tissues, head and neck; for sneezing, rash, sweating, pruritus, urticaria, facial
visualization of intracranial lesions,; to edema, conjunctivitis, taste abnormality, dry mouth,
lacrimation, eye irritation, eye pain, ear pain
Contraindications: Chronic, severe kidney disease; acute
kidney injury. Drug Interactions: No known significant interactions

Dose: TEST INTERACTION. May impair visualization of lesions seen

MRI visualization, by IV injection, ADULT, 0.2 mL/kg (0.1 on non-contrast MRI.
mmol/kg) at a rate not exceeding 10 mL per 15 seconds.
Administration: For IV administration. Administer at a rate
not to exceed 10 mL per 15 seconds. Follow with a 5-mL

648
VARIOUS

normal saline flush to ensure complete injection. Prior to initiating, determine blood pressure and weight
Complete imaging procedure within 1 hour of to evaluate patient's volume status and signs and
administration. symptoms of pulmonary congestion or respiratory
distress.
Visually inspect parenteral products for particulate
matter and discoloration prior to administration. NOTE: Obtain a basic metabolic panel of serum chemistries
Discard any unused portion. Discard IV tubing and on the morning of the procedure and on post-procedure
syringes used. days 1 and 2 or until any increase of serum creatinine
Preparation from bulk package: resolves. Obtain urinary pH measurement after initial
Transfer from bulk package in an aseptic work area, such bolus.
as a laminar flow hood, using aseptic technique. Once
punctured, do NOT remove from aseptic work area Make sure urine flow is at 150 mL/hour after procedure
during the entire 24-hour period of use. Use contents to ensure adequate hydration.
within 24 hours of initial puncture. Discard all unused
portions 24 hours after initial puncture. Pregnancy Category: Category

Pregnancy Category: C ATC Code: Not available

ATC Code: Not available

MAGNETIC RESONANCE IMAGING CONTRAST
MEDIA
Rx GAS FORMING AGENT
PARAMAGNETIC CONTRAST MEDIA
Oral:
Components per tablet: Rx GADOBUTROL
Sodium bicarbonate 470 mg
Glutamic acid 70 mg
Tartaric acid 420 mg Inj: 1.0 mmol/mL solution for injection, 15 mL vial
Silicon resin 25 mg 1.0 mmol/mL solution for injection, 5 mL pre-filled
syringe
Indications: Radiocontrast media
Gadobutrol is a gadolinium-containing, nonionic
Contraindications: Volume overload. paramagnetic agent. Exposure to an external magnetic
field induces a large local magnetic field in exposed
Dose: tissues. The local magnetism disrupts water protons in
Condition, route, ADULT/CHILD, Dose. the vicinity, resulting in a change in proton density and
spin characteristics which can be detected by imaging
Dose Adjustment: device.

V
Renal Impairment:
If CrCl <15 mL/minute, refer patient to a specialist. Indications: Use in diagnostic magnetic resonance imaging
(MRI) in adults and children.
Precautions:
Electrolyte abnormalities (e.g., hypokalemia); Contraindications: Severe hypersensitivity reactions to
Volume overload, CHF, hypertension, and oliguric renal gadobutrol or any component of the formulation.
failure (use with caution due to high sodium content).
Dose:
Adverse Drug Reactions: None known Magnetic resonance imaging, by IV injection, ADULT and
CHILD, 0.1 mmol/kg (0.1 mL/kg).
Drug Interactions:
Avoid concomitant use with: Dose Adjustment:
Increases risk of adverse or toxic effects of Gas Forming
Renal impairment:
Dose adjustment is not recommended. However, risk for
Agent, specifically nephrotoxicity [withhold drug the day
NSF development increases as renal function decreases.
before and the day of the procedure]:
Acyclovir, Amphotericin B, Aminoglycosides, Gadobutrol is removed by hemodialysis.
Cyclosporine, Foscarnet, Loop Diuretics e.g. Furosemide,
NSAIDs Precautions:
May cause extravasation, gadolinium retention,
Increases risk of adverse or toxic effects of the following hypersensitivity reactions, nephrogenic systemic fibrosis;
Use in caution in patients with renal impairment and seizure
drugs:
disorder.
Metformin (lactic acidosis) [withhold drug prior to and for
48 hours after injection of gas forming agent]
Adverse Drug Reactions:
Administration: Do NOT administer using the same IV line as Less Common: Headache and nausea.
other IV medications.

649
 VARIOUS

Rare: Injection site reactions, dysgeusia, feeling hot, ATC Code: V08CA02
dizziness, vomiting, rash, pruritus, erythema, dyspnea,
paresthesia, cardiac arrest, nephrogenic systemic
fibrosis (NSF), and hypersensitivity/anaphylactoid DIAGNOSTIC RADIOPHARMACEUTICALS
reactions.

Drug Interactions: IOTHALAMATE

Rx
None known. (SODIUM IOTHALAMATE, 125I)
Administration: Do not administer other medications in the Inj.: 600 mg/mL, 30 mL, 50 mL, and 100 mL vial (usually
same IV line simultaneously. IV)

Pregnancy Category: C A sterile, nonpyrogenic aqueous injection containing

approximately 1 mg sodium iothalamate per mL. The
ATC Code: V08CA09 radioactive concentration of the material is
approximately 250–300 microCi/mL.

Indications: Contrast medium used orally in esophagograms

Rx GADOTERIC ACID and upper GI series

Inj: 0.5mmol/mL, 10 mL, 15 mL, and 20 mL vials Dose:

Condition, route, ADULT/CHILD, Dose.
Gadolinium-based contrast agent for use in MRI of the brain,
spine, and associated tissues to detect and visualize Dose Adjustment: No information found
areas with disruption of the blood brain barrier and/or
vascularity. Precautions:
WARNING: Take care to minimize radiation exposure
Indications: Contrast medium for magnetic resonance to patients and occupational workers.
imaging (MRI) in central nervous system (CNS) and whole Should be used by healthcare practitioners
body indications including angiography. qualified by training and experience in the safe use
and handling of radionuclides.
Contraindications: Hypersensitivity to gadoteric acid or any
component of the formulation.
Children;
Dose: Pregnancy (administer only if clearly needed);
MRI imaging, by IV injection, ADULT and CHILD, 0.2 mL/kg Lactation.
(0.1 mmol/kg).
Adverse Drug Reactions: None reported
Dose Adjustment:
V

Renal impairment: Drug Interactions: No information found

Dose adjustment is not recommended. However, risk for
NSF development increases as renal function decreases. Administration: For intravenous administration. Do NOT
Gadoteric acid is removed by hemodialysis. administer by rapid or bolus-like injections.

Precautions: Do NOT administer via a central venous line.

May cause extravasation, gadolinium-retention,
hypersensitivity reactions, and nephrogenic systemic Inspect visually for particulate matter and discoloration
fibrosis; prior to administration.
Use in caution in patients with renal impairment.
Measure patient dose by suitable radioactivity
Adverse Drug Reactions: calibration system immediately prior to administration.
Less Common: Headache.
Rare: Nausea, injection site reactions, burning sensation, For continuous IV infusion, establish an adequate
feeling cold, rash, somnolence, fatigue, dizziness, diuresis by an oral water load of 1,500 mL 2 hours prior
vomiting, pruritus, asthenia, paraesthesia, dysgeusia, to the beginning of the clearance study. Insert a no. 14
pain in extremity, anxiety, hypertension, palpitations, and or 16 French Foley catheter aseptically into the bladder.
oropharyngeal discomfort. Start IV infusion lines of lactated Ringer’s solution in
each arm with two-way stopcocks (1 as injection site, 1
Drug Interactions: as blood withdrawal site). Divide dose equally into two (a
None known. priming dose to be injected as is and a sustaining dose
to be diluted in 30–60 mL of isotonic sodium chloride).
Administration: Infuse IV bolus at a rate of 1-2 mL per Inject priming dose into 1 arm, followed immediately by
second. To ensure complete injection, follow with saline the sustaining solution through the same site by IV
flush. infusion at 0.5 mL/minute. Discontinue the Lactated
Ringer’s solution during infusion. Wait 40–45 minutes to
Pregnancy Category: C achieve constant plasma concentration. Begin collecting

650
VARIOUS

urine samples every 15 minutes, 3 consecutive Dose equation corrected for 24-hour radioactive iodine
collection samples are sufficient for most clinical uptake:
studies. From the opposite arm, collect 5 mL blood Activity (mCi)
1
samples drawn 6 minutes prior to the midpoint of each ��gland wt in g × desired dose in mCi�g� �
24 hour uptake on %dose��
collection period, placed in heparinized tubes, mixed, =
1000
and centrifuged.
Thyroid cancer, by mouth, ADULT, 100–150 mCi (3,700 –
For single IV injection, administer Lugol’s solution, 3 5,550 megabecquerels).
drops orally, 3 times daily for 1–2 days prior to the test. Thyroid cancer, post-operative ablation of residual tissue, by
Begin oral water load 1 hour before the test. Start with mouth, ADULT, 50 mCi (1,850 megabecquerels).
20 mL/kg and force any clear liquid until the test is
complete. Empty the bladder and label sample as Urine Precautions:
control. Inject 10–30 mL and wait 30 to 60 minutes. WARNING: Adhere to radiation safety precautions
Collect the entire urine and label Urine discard. Draw 4– regarding radioactive iodine treatment. Use
5 mL of blood into a heparinized syringe and label appropriate precautions for handling and disposal.
Plasma #1. After another 30–60 minutes, collect the Wear waterproof gloves during preparation, handling,
entire urine and label Urine #1. Immediately draw and administration.
another blood specimen and label Plasma #2. After
another 30–60 minutes, collect the urine and label Urine
Hypersensitivity (eg. rash and hives);
#2. Immediately draw the last blood specimen and label Renal impairment;
Plasma #3. Infertility (eg. transient, dose-related testicular function
impairment);
Pregnancy Category: C
Radiation-induced thyroiditis (may occur with gland
enlargement and thyroid release);
ATC Code: V09CX03
Radiation toxicities (dose-dependent fatalities);
Thyroid enlargement (may occur with discontinuation; may
cause thyroid enlargement and obstructive
THERAPEUTIC RADIOPHARMACEUTICALS complications of the trachea, esophagus, or blood
vessels in the neck);
Elderly;
Patients <30 years (use is not recommended);
Rx SODIUM IODIDE 131 Children;
Pregnancy (may cause severe and irreversible
Oral: 0.8–100 mCi radioactivity range per capsule hypothyroidism in neonates);
1.0 to 250 mCi radioactivity range per capsule Lactation (excreted in breastmilk; discontinue
3.5–150 mCi radioactivity range solution per vial breastfeeding at least 4 weeks prior to therapy).

A radiopharmaceutical that is rapidly absorbed and Adverse Drug Reactions:

Common: Chest pain, tachycardia, metallic taste, alopecia,

V
distributed within the extracellular fluid of the body.
Iodide is concentrated in the thyroid via the pruritus, skin lesion (iododerma), skin rash, urticaria,
sodium/iodide symporter, and subsequently oxidized to hypoparathyroidism, thyroid storm, hypothyroidism,
iodine. Beta emission of sodium iodide I131 destroys thyroiditis, gastritis, hyperthyroidism, nausea (high
thyroid tissue. dose), salivary gland disease, odynophagia, sialadenitis,
sore throat, unpleasant taste, vomiting, infertility
Indication: Treatment of hyperthyroidism and thyroid (transient; permanent in repeated or high dose), acute
carcinomas (if the lesions take up iodide) ; palliative leukemia, bone marrow depression (high dose),
effects may be observed in patients with advanced hematologic abnormality, leukopenia, solid tumor,
thyroid malignancy if the metastatic lesions take up thrombocytopenia, anaphylaxis, hypersensitivity
iodide reaction, immunosuppression, neck discomfort
(tenderness or swelling), lacrimation, bronchospasm,
Contraindications: Preexisting vomiting and diarrhea anemia, cough, chromosomal abnormality, local
(treatment); concurrent antithyroid medication swelling, radiation injury
(discontinue 3–4 days prior to administration) ; women Less Common: Conjunctivitis, epiphora, radiation
who are or may become pregnant; breastfeeding; pneumonitis, xerophthalmia, xerostomia
treatment of thyroid malignancies shown to have no Rare: Neoplasm
iodide uptake (including majority of medullary and
anaplastic carcinomas) Drug Interactions:
Avoid concomitant use with:
Dose: Reduces therapeutic effect of Sodium Iodide I131:
NOTE: If dose or dose within range exceeds 1,000 Amiodarone
microcuries, express dose as millicuries (mCi). Antithyroid Agents [discontinue therapy 3 to 4 days prior
to sodium iodide I131 administration]
Hyperthyroidism, by mouth, ADULT, 4–10 mCi (148 to 370 Thyroid Products
megabecquerels).
Administration: Ensure adequate hydration before and after
treatment.

651
 VARIOUS

Pregnancy Category: X

ATC Code: V10XA01

V

652
HERBAL PREPARATIONS

HERBAL PREPARATIONS SAMBONG

OTC [Blumea balsamifera (L.) DC (Fam.
Compositae)]
Oral: 500 mg tablet
LAGUNDI
OTC [Vitex negundo L. (Fam. A natural medicinal preparation from the leaves of Blumea
Verbenaceae)] balsamifera Linn. DC (Fam. Asteraceae), which is utilized
in the treatment of urological disorders.
Oral: 300 mg and 600 mg tablet
300 mg/5 mL syrup, 60 mL and 120 mL bottle Indications: To increase urinary output in conditions
characterized by fluid retention or edema; for treatment
A natural medicinal preparation from the leaves of Vitex and prevention of kidney stones.
negundo Linn. (Fam. Verbenaceae), which is used for the
relief of cough. Contraindications: Patients with severe allergy to sambong
or any of its components.
Indication: For the relief of mild to moderate cough due to
common colds and flu Dose:
Anti-urolithiasis, by mouth, ADULT, for the 1st 2 weeks, give
Contraindications: Patients with severe allergy to Vitex 40 mg/kg/day in 3 divided doses, then decrease to
negundo or any of its components 20/mg/kg/day in 2-3 divided doses; CHILD 7–12 years,
1st 2 weeks give 40 mg/kg/day in 3 divided doses, then
Dose: decrease to 20/mg/kg/day in 2-3 divided doses.
Cough, by mouth, ADULT, as 600 mg tablet, 1 tablet 3–4
times daily; as 300 mg/5 mL, 2 tsp 3-4 times per day; Dose Adjustment: Clinical trials were performed in patients
CHILD 7–12 years, 1 tablet 3–4 times daily; as 300 with normal renal and liver function tests; no reports of
mg/5 mL syrup, 10 mL (2 tsp) 3–4 times daily,; CHILD, adverse effects in patients with renal and liver
15 mg/kg per dose (0.25 mL/kg per dose for 300 mg/5 dysfunction.
mL) administered 3 times daily; CHILD >40 kg body
weight, 2 tsp 3 times per day of 300 mg/5 mL; CHILD 6– Precautions:
12 years (20–40 kg), 1½ to 2 tsp of 300 mg/5 mL 3 Patients with excretory urogram showing signs of renal
times per day; CHILD 4–6 years (15.5–20 kg), 1 tsp of obstruction.
300 mg/5 mL 3 times daily; CHILD 2–4 years (10–15.5 Pregnancy and lactation.
kg), ½ to 1 tsp of 300mg/5mL syrup 3 times per day.
Adverse Drug Reactions: Epigastric pain, constipation.
Dose Adjustment: All clinical trials were performed in
patients with normal renal and liver function tests; no Drug Interactions: None known
reports of adverse events in patients with renal and liver
dysfunction. Administration: May be taken with or without food.

Precautions: Pregnancy Category: In vitro and animal studies have shown

Sambong to be non-mutagenic and non clastogenic.

X
Patients with known allergy to lagundi plants.

Adverse Drug Reactions: Mild adverse effects have been ATC Code: Not Available
observed, such as itchiness, nausea, vomiting, and
diarrhea.
TSAANG GUBAT
Drug Interactions: Possible interaction with ibuprofen, OTC [Carmona retusa (Vahl) Masam (Fam.
potentiates anti-inflammatory activity Boraginaceae)]
Administration: For syrup preparation, shake well before Oral: 250 mg tablet
use. May be taken with or without food.
A natural medicinal preparation from the leaves of Carmona
Pregnancy Category: In vitro and animal studies have shown retusa (Vahl) Masam (Fam. Boraginaceae) used for the
Lagundi to be non-mutagenic and non clastogenic. treatment of biliary colic.

ATC Code: Not Available Indications: For the management of acute diarrhea, colic
from acute gastroenteritis and biliary colic; anti-motility;
antispasmodic.

Contraindications: Severe allergy to tsaang gubat or any of

its components.

Dose:
Acute diarrhea, colic from acute gastroenteritis, biliary colic,
by mouth, ADULT, 15 mg/kg/dose, may repeat after 6

653
 HERBAL PREPARATIONS

hrs up to 3times a day; CHILD 7–12 years, 15

mg/kg/dose, may repeat after 6 hrs up to 3 times per
day.

Dose Adjustment: Clinical trials were performed in patients

with normal renal and liver function tests; no reports of
adverse effects in patients with renal and liver
dysfunction.

Precautions:
When symptoms persist, or irritation occurs, stop and
consult your doctor.

Adverse Drug Reactions: Nausea

Drug Interactions: None known

Administration: May be taken with or without food.

Pregnancy Category: In vitro and animal studies have shown

Tsaang Gubat to be non-mutagenic and non clastogenic.

ATC Code: Not available

V

654
APPENDICES
 SUMMARY STATISTICS
No. of Sections of Therapeutics Categories = 15

No. of active ingredients = 631

No. of active ingredients added = 92 (see Appendix B)

No. of active ingredients deleted = 88 (see Appendix C)

No. of pharmaceutical products not registered with

the FDA but considered essential = 35 (see Appendix D)

No. of Dangerous Drug Preparations (A1) = 16 (see Appendix E)

No. of Controlled Chemicals (A2) = 2 (see Appendix F)

No. of essential medicines with narrow therapeutic

index/range = 10 (see Appendix G)

No. of reserve antimicrobials = 11 (see Appendix H)

No. of medicinal plant products registered with the

FDA and included in the PNF = 3 (see Appendix I)

A1
 LIST OF DRUG MOLECULES ADDED TO THE PHILIPPINE
NATIONAL FORMULARY (PNF) 8TH EDITION
(as of SEPTEMBER 2019)
1. Abacavir 34. 3% Hypertonic Saline Solution
2. Amino acid + carbohydrate + 35. Imiglucerase
multivitamins + electrolytes 36. Imiquimod
3. Amino acid + glucose + electrolytes + 37. Inactivated Poliomyelitis Vaccine (Type
vitamin B1 1, 2 and 3)
4. Anastrozole 38. Indacaterol + glycopyrronium
5. Aripiprazole 39. Iodixanol
6. Artesunate 40. Iron sucrose
7. Atorvastatin calcium 41. Isotonic electrolyte solution
8. Aztreonam 42. Lamivudine + Efavirenz + Tenofovir
9. Bedaquiline fumarate 43. Lamivudine + Tenofovir
10. Bicalutamide 44. Lamivudine + Zidovudine
11. Capreomycin 45. Lamivudine + Zidovudine + Nevirapine
12. Carbetocin 46. Lamotrigine
13. Carboprost 47. Latanoprost + timolol maleate
14. Clotrimazole 48. Levetiracetam
15. Colistin 49. Letrozole
16. Cycloserine 50. Linezolid
17. Daclatasvir 51. Lopinavir + Ritonavir
18. Deferasirox 52. Measles and Rubella vaccine (Live
19. Delamanid attenuated)
20. Diphtheria, Tetanus, Pertussis, 53. Memantine
Hepatitis B Recombinant and 54. Micafungin
Haemophilus Influenza Type B (Hib) 55. Micronutrient Powder
Combined Vaccine 56. Moxifloxacin
21. Donepezil 57. Nicotine
22. Efavirenz 58. Olodaterol
23. Entecavir 59. Oxcarbazepine
24. Eperisone hydrochloride 60. Oxycodone + naloxone
25. Etonogestrel 61. Paliperidone palmitate
26. Formoterol 62. Para-aminosalicylic acid
27. Fosfomycin 63. Phospholipid fraction from bovine lung
28. Fluticasone + Formoterol 64. Polymixin B sulfate
29. Gadobutrol 65. Poractant alfa
30. Gadoteric acid 66. Prothionamide
31. Human Papillomavirus vaccine types 67. Rabeprazole sodium
16 and 18 (Recombinant, AS04 68. Remifentanil
Adjuvanted) 69. Ribavirin
32. Human Recombinant Tissue Type 70. Rifaximin
Plasminogen Activator (Alteplase) 71. Rifapentine
33. Hypertonic Lactate Solution 72. Rilpivirine

A2
 73. Sacubitril + valsartan 83. Tenofovir disoproxil fumarate
74. Sevelamer carbonate 84. Terazosin hydrochloride
75. Sofosbuvir 85. Tolvaptan
76. Sofosbuvir + ledipasvir 86. Triclabendazole
77. Sofosbuvir + velpatasvir 87. Tropicamide + phenylephrine
78. Soya bean oil + Medium chain 88. Valganciclovir
triglycerides + Olive oil + Purified fish oil 89. Varenicline
79. Sugammadex 90. Voriconazole
80. Sumatriptan 91. 13-valent Pneumococcal Conjugate
81. Tafluprost Vaccine
82. Tenofovir alafenamide fumarate

NOTE: Please refer to the Philippine National Formulary (PNF) 8th Edition Essential Medicines List (EML) for the
updated summary list of medicines approved for inclusion. The medicines which were approved from October
2018 onwards are listed in the EML booklet, which may be downloaded from the website of the Pharmaceutical
Division, https://pharmadiv.doh.gov.ph.

A3
 LIST OF DRUG MOLECULES DELETED FROM THE
PNF 7TH EDITION

1. Acarbose 42. Interferon Alfa 2a (human)

2. Akapulko 43. Iodamide
3. Alpha-Tocopherol (vitamin E) 44. Ioxithalamic Acid
4. Aluminum Acetate 45. Iron Dextran
5. Amidotrizoate (Diatrizoate) 46. Isoniazid + Ethambutol
6. Beclomethasone 47. Isoniazid + Thiacetazone
7. Benzoic Acid + Salicylic Acid 48. Live Attenuated Trivalent Oral Polio
8. Calcium Dialysate, Low Vaccine
9. Candesartan 49. Lomustine
10. Carbimazole 50. Lorazepam
11. Carmustine 51. Meclozine (meclizine)
12. Cefadroxil 52. Minocycline
13. Chloral Hydrate 53. Molgramostim (Gm-CSF)
14. Coal Tar 54. Nadroparin
15. Colestyramine 55. Nelfinavir
16. Conjugated Equine Estrogen + 56. Netilmicin
Medroxyprogesterone Acetate 57. Nicotinamide (vitamin B3)
17. Daunorubicin 58. Norfloxacin
18. Dextran, Low Molecular Weight 59. Oxantel + Pyrantel
(Dextran 40) 60. Pirebedil
19. Didanosine 61. Polygeline
20. Dithranol 62. Potassium Free Dialysate Acetate-
21. Edrophonium Based Containing
22. Eprosartan 63. Potassium Free Dialysate Bicarbonate-
23. Ergocalciferol (calciferol, vitamin D2) Based Containing
24. Famciclovir 64. Potassium Permanganate
25. Fluoride 65. Procarbazine
26. Flurazepam 66. Raloxifene
27. Fosphenytoin 67. Riboflavin (vitamin B2)
28. Gadodiamide 68. Ritonavir
29. Galantamine 69. Rose Bengal
30. Glibenclamide 70. Rosiglitazone
31. Glipizide 71. Saquinavir
32. Glutaraldehyde (glutaral) 72. Silver Nitrate
33. Griseofulvin 73. Stavudine
34. Human Chorionic Gonadotrophin (HCG) 74. Sulfacetamide
35. Human Growth Hormone (biosynthetic) 75. Sulfadoxine + Pyrimethamine
36. Human Menopausal Gonadotrophin 76. Terizodone
(HMG, menotropin) 77. Tetracosactide (cosyntropin)
37. Hydroxocobalamin (vitamin B12) 78. Thiacetazone
38. Imipramine 79. Triamcinolone
39. Indinavir 80. Trichloracetic Acid
40. Indomethacin 81. Vasopressin
41. Insulin Zinc Suspension, Human 82. Vitamin B12 (see Hydroxocobalamin)

A4
83. Vitamin B2 (see Riboflavin) 87. Yerba Buena
84. Vitamin B3 (see Nicotinamide) 88. Zalcitabine
85. Vitamin D2 (see Ergocalciferol)
86. Vitamin E (see Alpha-Tocopherol)

A5
 LIST OF PHARMACEUTICAL PRODUCTS NOT REGISTERED
WITH THE FDA BUT CONSIDERED ESSENTIAL

1. Acetylcysteine
Inj.: 200 mg/mL, 10 mL ampul (IV infusion)

2. Activated charcoal x
Oral: powder, USP grade

3. Alcohol, ethyl
Inj.: absolute, 1 mL ampul (IV)

4. Antilymphocyte immunoglobulin (ALG) (equine)

Inj.: 100 mg/5mL vial (IV)

5. Antithymocyte immunoglobulin (ATG) (rabbit)

Inj.: 25 mg/5 mL vial (IV)

6. Clofazimine
Oral: 50 mg and 100 mg capsule (available under DOH program)

7. Codeine
Oral: 30 mg MR capsule (as phosphate)

8. Dantrolene
Oral: 25 mg and 50 mg capsule (as sodium salt)
Inj.: 20 mg (with 3 mg mannitol/vial)
For reconstitution with 60 mL sterile water for injection (IV) (as sodium salt)

9. Deferoxamine
Inj.: powder, 500 mg vial (IM, IV infusion, SC)

10. Desmopressin
Inj.: 15 micrograms/mL, 1 mL ampul (IM, SC) (as acetate)

11. Dimercaprol
Inj.: (in oil) 50 mg/mL, 2 mL ampul (IV)

12. Dimercaptopropane sulphonate (DMPS)

Inj.: 100 mg/mL, 1 mL ampul, 10 mL vial (IM)

13. Diphtheria antitoxin

Inj.: 10,000 IU and 20,000 IU, 5 mL and 10 mL (IV)

14. Factor IX Complex Concentrate (Coagulation Factors; II, VII, IX, X)

Inj.: 100 IU/mL, 5 mL and 10 mL vial (IV)

15. Fluorescein
Strips: 1 mg and 9 mg (as sodium salt)

16. Fomepizole
Inj.: 1 g/mL, 1.5 mL vial (IV)

A6
17. Gas forming agent
Oral: Components per tablet: Sodium bicarbonate
Glutamic acid
Tartaric acid
Silicon resin

18. Iodine
Oral: Aqueous iodine solution (Lugol's solution)
5% iodine, 10 % potassium iodide (total iodine ‐ 130 mg/mL), 30 mL

19. Methylene blue

Oral: 1% solution
Inj.: 10 mg/mL, 1 mL and 10 mL ampul/vial

20. Naltrexone
Oral: 50 mg tablet (as hydrochloride)
21. Physostigmine
Inj.: 1 mg/mL, 2 mL ampul (IM, IV)

22. Potassium chloride

Oral: 1 mmol/mL syrup, 30 mL and 60 mL

23. Potassium phosphate

Inj.: 224 mg monobasic potassium phosphate equiv. to 3 mmol phosphorus and
4.4 mEq K/236 mg dibasic‐potassium phosphate anhydrous per mL in 5 mL vial
(IV)

24. Protamine sulfate

Inj.: 10 mg/mL, 5 mL and 25 mL ampul (IV)

25. Prothionamide
Oral: 250 mg film coated tablet

26. Pyrimethamine
Oral: 25 mg and 75 mg tablet

27. Rifabutin
Oral: 150 mg capsule

28. Sodium calcium edetate

Inj.: 200 mg/mL, 5 mL ampul (IM)

29. Sodium iodide

Oral: capsule with radioactivity range of 0.8 to 100 mCi per capsule
capsule with radioactivity range of 1.0 to 250 mCi per capsule
solution with radioactivity range of 3.5 to 150 mCi per vial

30. Sodium nitrite

Inj.: powder, USP grade

31. Sodium thiosulfate

Inj.: 250 mg/mL, 50 mL ampul (IV)

A7
 32. Spectinomycin
Inj.: 2 g vial (IM)

33. Succimer (dimercapto succinic acid, DMSA)

Oral: 100 mg and 200 mg capsule

34. Thiamine
Inj.: 100 mg/mL, 1 mL ampul/vial (IV)

35. Varicella zoster immunoglobulin (VZIG)

Inj.: 125 units/1.25 mL vial (IM)

A8
 LIST OF DANGEROUS DRUG PREPARATIONS INCLUDED IN
THE PNF
Drugs requiring S-2 License using DDB Prescription Form:

1. Alprazolam
2. Bromazepam
3. Clonazepam
4. Codeine (as phosphate)
5. Diazepam
6. Fentanyl (as citrate)
7. Ketamine
8. Methylphenidate
9. Midazolam
10. Morphine (as sulfate)
11. Nalbuphine
12. Oxycodone
13. Phenobarbital
14. Pethidine (meperidine)
15. Remifentanil
16. Zolpidem

A9
 LIST OF CONTROLLED CHEMICALS INCLUDED IN THE PNF
Controlled precursors and essential chemicals listed in Table I of the 1988 UN Convention Against Illicit Traffic
in Narcotic Drugs and Psychotropic Substances 16th Edition, January 2018:

1. Ephedrine (as sulfate)

2. Ergotamine (as tartrate)

A10
 LIST OF ESSENTIAL MEDICINES WITH
NARROW THERAPEUTIC RANGE

1. Carbamazepine Tablets, Oral Suspension

2. Clindamycin Hydrochloride Capsules
3. Clonidine Hydrochloride Tablets
4. Ethinyl Estradiol/Progestin Oral Contraceptive Tablets
5. Lithium Carbonate Capsules, Tablets, ER Tablets
6. Phenytoin, Sodium Capsules (Prompt or Extended), Oral Suspension
7. Theophylline Capsules, ER Capsules, Tablets, ER Tablets
8. Valproic Acid Capsules, Syrup
9. Divalproex, Sodium DR Capsules, DR Tablets
10. Warfarin, Sodium Tablets

A11
 LIST OF RESERVE ANTIMICROBIALS
Medicines in the PNF which are to be used only in hospitals with DOH accredited Antimicrobial Resistance
Surveillance Program (ARSP):

MEDICINE DOSAGE FORMS / STRENGTHS

50 mg and 100 mg colloidal suspension (as cholesteryl
Amphotericin B
complex, lipid complex), vial (IV infusion)
50 mg lyophilized powder (as deoxycholate, non-lipid
complex), vial (IV infusion)

Aztreonam 1 g powder for injection

Cefepime 500 mg, 1 g, and 2 g (as hydrochloride), vial

Colistin 2,000,000 IU lyophilized powder for injection (IV infusion)

Ertapenem 1 g powder (as sodium), vial

600 mg tablet/film-coated tablet

Linezolid
2 mg/mL (600 mg/300 mL), solution for infusion (IV)

Meropenem 500 mg and 1 g powder (as trihydrate), vial

Micafungin 50 mg lyophilized powder for infusion (IV)

500,000 units powder for solutions for injection (as sulfate),

Polymixin B
5 mL vial (Intrathecal/IM/IV)

Vancomycin 500 mg and 1 g (as hydrochloride), vial

200 mg lyophilized powder for solution for IV infusion, 30 mL

Voriconazole
vial

A12
LIST OF MEDICINAL PLANT PRODUCTS REGISTERED WITH
THE FDA AND INCLUDED IN THE PNF

1. Lagundi [Vitex negundo L. (Fam. Verbenaceae)]

2. Sambong [Blumea balsamifera (L) DC (Fam. Compositae)]
3. Tsaang Gubat [Carmona retusa (Vahl) Masam (Fam. Boraginaceae]

A13
 DEFINITION OF DOSAGE FORMS
Ampule – A final container that is all glass in which the open end is sealed by heat (a.k.a. carpule)

Capsule – Solid dosage form in which the drug is enclosed within either a hard or soft soluble shell, usually
made of gelatin

Cream – Semisolid preparation containing one or more drug substance, dissolved or dispersed in a suitable
base

Drops – Solution, emulsion, or suspension that is administered in small volumes, by means of a suitable
device

Effervescent – Dosage form containing ingredients that rapidly release carbon dioxide when in contact with
water

Elixir – Clear, sweetened hydroalcoholic solution, intended for oral use, usually flavored to enhance
palatability

Emulsion – Two-phase system prepared by dispersing one liquid in another immiscible liquid in the form of
small droplets

Enema – Rectal injection or solution

Gargle – Aqueous solution used for treating the pharynx and nasopharynx by forcing air from the lungs
through the solution held in the throat

Gel – Semisolid system composed of either a suspension of small inorganic particles or large organic
molecules, interpenetrated by a liquid and rendered jelly-like by the addition of a gelling agent

Granule – Prepared dry agglomerates of powders that may contain one or more active ingredients with or
without other ingredients

Implant – Controlled drug delivery systems in which the active pharmaceutical ingredient is impregnated into
the material and is released slowly into the body tissue for local or systemic action

Inhalation – Solution or suspension of one or more drug substances administered by the nasal or oral
respiratory route for local or systemic effect

Injection – Preparation intended for parenteral administration or for constituting or diluting a parenteral
article prior to administration

Irrigation – Sterile solution intended to bathe or flush open wounds or body cavities

Jelly – Class of gel in which the structural coherent matrix contains a high portion of water

Lotion – Liquid suspension or emulsion for external application to the body

Mixture – Oral liquid containing one or more active pharmaceutical ingredients, which are dissolved,
suspended, or dispersed in a suitable liquid vehicle

A14
Mouthwash – Aqueous solutions used by swishing the liquid in the oral cavity, to cleanse the mouth or treat
diseases of the oral mucous membranes

Ointment – Semisolid dosage form applied externally on the skin or mucous membrane

Ophthalmic ointment – A sterile ointment intended for application to the eye

Ophthalmic solution – A sterile solution, essentially free from foreign particles, suitably prepared and
packaged for instillation into the eye

Ophthalmic suspension – A sterile liquid preparation containing solid particles dispersed in a liquid vehicle
intended for application to the eye

Ophthalmic strip – A sterile single-use container or sterile impregnated paper strip containing the drug to be
applied to the eye

Orally disintegrating – A solid oral dosage form that disintegrates rapidly in the mouth to facilitate release of
the active ingredient

Otic solution – A solution intended for instillation in the outer ear

Patch – A transdermal system containing a drug reservoir entrapped between backing and adhesive layers
and a drug diffusion-controlling membrane, which allow the passage of drugs from the skin (stratum
corneum) into systemic circulation

Powder – Intimate mixtures of dry, finely divided drugs and/or chemicals, which may be used internally or
externally

Rinse – A solution used to cleanse by flushing

Shampoo – A solution, emulsion, or suspension used to clean the hair and scalp

Solution – Liquid preparation containing one or more substances dissolved in a suitable solvent or a mixture
of mutually miscible solvents

Suppository – Solid mass intended to be inserted into a body cavity / orifice in which they will melt at body
temperature or dissolve in the aqueous secretions of the body cavity to release the active pharmaceutical
ingredient and produce local or systemic actions

Suspension – Liquid preparations that consist of solid particles (suspensoid) dispersed throughout a liquid
vehicle in which the particles are not soluble

Syrup – Concentrated or nearly saturated solutions of sucrose or other sugars in water or aqueous liquid

Tablet – Solid dosage forms that contains medicinal substance(s) with or without diluents and are prepared
by molding or compression

Tablet, Chewable – A tablet formulated so that it may be chewed, producing a pleasant-tasting residue that
is easily swallowed and does not leave a bitter or unpleasant aftertaste

A15
Tincture – Alcoholic or hydroalcoholic solutions prepared from soluble constituents of vegetable drugs or from
chemical substances

Vaginal tablet – Ovoid tablet formed by compression, which are inserted into the vagina using a plastic
inserter (a.k.a. vaginal insert)

MODIFIED RELEASE FORMS

Delayed-release – Drug release is other than the time of prompt administration

Extended-release – Provides a prompt desired effect followed by gradual release of the remaining amount

Targeted-release – Drug release is concentrated or isolated in a specific body region or tissue for absorption
and metabolism

A16
FDA ADVERSE DRUG REACTION (ADR) REPORTING FORM

A19
 DIRECTORY
DEPARTMENT OF HEALTH
Website: http://www.doh.gov.ph/
Phone Number: (02) 651 7800

DOH – Antimicrobial Resistance Surveillance Program (ARSP)

Antimicrobial Resistance Surveillance Reference Laboratory
DOH Compound, Filinvest Corporate City, Alabang, Muntinlupa
Website: www.ritm.gov.ph
Telefax: (02) 809 9763
E-mail Address: [email protected]

DOH – Pharmaceutical Division

Website: https://pharmadiv.doh.gov.ph
Phone Number: (02) 875 7734 local 253 or (02) 937 5314

PHILIPPINE FOOD AND DRUG ADMINISTRATION

Website: http://www.fda.gov.ph/
E-mail Address: [email protected]

Center for Food Regulation and Research

Phone Number: (02) 857 1992; (02) 857 1993

Center for Cosmetic Regulation and Research

Phone Number: (02) 857 1940; (02) 857 1984

Center for Drugs Regulation and Research

Phone Number: (02) 857 1990

Center for Device Regulation, Radiation Health, and Research

Phone Number: (02) 749 9443; (02) 711 6824

NATIONAL DRUG INFORMATION CENTER

Website: http://www.druginfo.ph
Telefax: (02) 526 4384
E-mail Address: [email protected]

NATIONAL POISON MANAGEMENT AND CONTROL CENTER

LUZON
Philippine General Hospital
Phone Number: (02) 524 1078; (02) 554 8400 loc. 2311; (02) 404 0257; (02) 526 0062 (F)
Website: http://www.uppoisoncenter.org/network.html

East Avenue Medical Center

Phone Number: (02) 434 2511

Rizal Medical Center

Phone Number: (02) 570 6273; (02) 671 9615; (02) 6719740

Batangas Regional Hospital

A20
Phone Number: (043) 723 3578

VISAYAS
Eastern Visayas Regional Medical Center
Phone Number: (053) 321 3131; (053) 321 3129 (F)

Western Visayas Medical Center / Iloilo Doctors Hospital

Phone Number: (033) 337 7702

MINDANAO
Zamboanga Medical Center
Phone Number: (062) 991 2934; (062) 991 0537

PHILIPPINE HEALTH INSURANCE CORPORATION

Website: http://www.philhealth.gov.ph
Trunkline: (02) 441 7444
Call Center: (02) 441 7442
E-mail Address: [email protected]

PHILIPPINE INSTITUTE OF TRADITIONAL AND ALTERNATIVE HEALTH CARE (PITAHC)

Phone Number: (02) 376 3068
Website: http://www.pitahc.piaem.org
E-mail Address: [email protected]

A21
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Bravo, LC, Gatchalian, SR, Gonzales, MLM, et. al., 2011, Handbook of Pediatric Infectious Disease, 5th
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Carlos, C., et. al. Antimicrobial Resistance Surveillance Program 2015 Data Summary Report. Antimicrobial
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 INDEX
A
Artesunate, 542-43
Abacavir, 269 Ascorbic Acid (Vitamin C), 30-31, 608
Acetated Ringer’s Solution, 75-76 Asparaginase, 360-62
Acetazolamide, 585-86 Aspirin, 50, 397
Acetylcysteine, 606-07 Atenolol, 128
Acyclovir / Aciclovir, 266, 579 Atorvastatin, 148
Activated Charcoal, 605 Atracurium, 406-07
Adenosine, 103-04 Atropine, 8-9, 104, 516-17, 594, 608-09
Adrenaline (Epinephrine), 107, 569 Azathioprine, 395-96, 420-22
Albendazole, 549-50 Azithromycin, 229-30
Albumin, Human, 66-67 Aztreonam, 226
Alcohol, Ethyl, 164, 607-08
Alendronate, 417-18 B
Alendronate + Cholecalciferol Bacitracin + Neomycin + Polymyxin B, 603
(Vitamin D3), 419-20 Baclofen, 412
Alfuzosin, 184-85 Balanced Multiple Maintenance Solution, 76-77
All-in-one Admixtures (“3 in 1 Solution” or “Dual Balanced Multiple Replacement Solution, 77
Energy Solution”), 69-70 Balanced Multiple Replacement Solution
Allopurinol, 415-16 with pH 7.4, 77-78
Alprazolam, 505-06 Barium Sulfate, 647-48
Alteplase (Human Recombinant Tissue Type Basiliximab, 389-90
Plasminogen Activator), 54 BCG Vaccine, 287
Aluminum Hydroxide + Magnesium Hydroxide, 1 Benzoyl Peroxide, 165-66
Amikacin, 233-35, 260 Benzyl Benzoate, 551
Amino Acid + carbohydrate + multivitamins Beractant, 576
+ electrolytes, 70 Betahistine, 533
Amino Acid + glucose + electrolytes Betamethasone, 160-61
+ vitamin B1, 70-71 Betaxolol, 586-87
Amino Acid Solutions for Hepatic Failure, 638 Bicalutamide, 371
Amino Acid Solutions for Biperiden, 481-82
Immunonutrition/Immunoenhancement, 638 Biphasic Isophane Human Insulin 70/30
Amino Acid Solutions for Infants, 638-39 (Recombinant DNA), 24
Amino Acid Solutions for Bisacodyl, 14
Renal Conditions, 639 Bisoprolol, 128-29
Amino Acids, Crystalline Standard, 71 Bleomycin, 347-48
Aminophylline (Theophylline Brimonidine, 587
Ethylenediamine), 567-69 Brinzolamide, 587-88
Amiodarone, 98-101 Bromazepam, 507
Amlodipine, 129-30 Bromocriptine, 482-83, 609
Amoxicillin, 7, 206-07 Budesonide, 553-54, 563-64
Amoxicillin + Potassium clavulanate Budesonide + Formoterol, 558-59
(Co-amoxiclav), 213-15 Bumetanide, 143-44
Amphotericin B (Lipid Complex), 250 Bupivacaine, 432-34
Amphotericin B (Non-Lipid Complex), 250 Butamirate, 571-72
Ampicillin, 207-08 Butorphanol, 447-48
Ampicillin + Sulbactam, 212-13
Antilymphocyte Immunoglobulin C
(ALG)(Equine), 381 Calamine, Plain, 156
Anti-Rabies Serum (Equine), 280-81 Calcipotriol, 156-57
Anti-Tetanus Serum (Equine), 281 Calcipotriol + Betamethasone, 157
Antithymocyte Immunoglobulin Calcitriol, 27-28
(ATG) (Rabbit), 382 Calcium Carbonate, 34-35
Aripiprazole, 487-89 Calcium Carbonate + Cholecalciferol
Artemether + Lumefantrin, 541-42 (Vitamin D3), 36-37

A93
Calcium Folinate Conjugated Equine Estrogen, 176-78, 420
(Leucovorin Calcium), 364-65, 609-10 Conjugated Estrogens, 420
Calcium Gluconate, 35, 84-85 Cotrimoxazole
Calcium Lactate, 35-36 (Sulfamethoxazole + Trimethoprim), 228-29
Calcium Salt, 611 Crotamiton, 551-52
Calcium Sennosides (Standardized Senna Cyclophosphamide, 313-15
Concentrate), 16-17 Cycloserine, 261
Capecitabine, 323-24 Cyproterone, 182-83, 371-73
Capreomycin, 260-61 Cytarabine, 325-27
Captopril, 115-16
Carbachol, 588 D
Carbamazepine, 459-60 Dacarbazine, 318-19
Carbetocin, 188 Daclatasvir, 276-77
Carboplatin, 349-50 Dactinomycin (Actinomycin D), 339-40
Carboprost, 168-69 Danazol, 183-84
Carboxymethylcellulose, 597 Dantrolene, 413-15, 612
Carvedilol, 124-26 Dapsone, 265
Castor Oil, 14-15 Deferasirox, 629-30
Cefalexin, 216-17 Deferiprone, 628-29
Cefazolin, 217-18 Deferoxamine (Desferrioxamine), 627-28
Cefepime, 225-26 Desflurane, 424-25
Cefixime, 220 Desmopressin, 187
Cefotaxime, 220-21 Dexamethasone, 189-91, 537, 583,
Cefoxitin, 218 Dextran, High Molecular Weight (Dextran 70), 67
Ceftazidime, 222-23 Dextromethorphan, 572
Ceftriaxone, 223-25 5% Dextrose in 0.3% Sodium Chloride, 73
Cefuroxime, 219 5% Dextrose in 0.45% Sodium Chloride, 73-74
Celecoxib, 405-06 5% Dextrose in 0.9% Sodium Chloride, 74
Cetirizine, 572-73 5% Dextrose in Lactated Ringer’s, 74-75
Chlorambucil, 312-13 5% Dextrose in Water, 82
Chloramphenicol, 205-06 10% Dextrose in Water, 83
Chlorhexidine, 162-63 Diazepam, 412-13, 474-75, 509-11
Chloroquine, 540, 543 Diclofenac, 398-99, 452
Chlorphenamine (Chlorpheniramine), 573 Dicycloverine (Dicyclomine), 9
Chlorpromazine, 489-91 Diethylcarbamazine, 550
Ciclosporin, 390-92, 598 Digoxin, 94-95
Cilostazol, 51-52 Diloxanide, 540-41
Cinnarizine, 533-34 Diltiazem, 137
Ciprofloxacin, 237-38 Dimeglumine Gadopentetate, 648-49
Cisplatin, 350-52 Dimercaprol, 612-13
Clarithromycin, 7, 230-31 Dimercaptopropanesulphonate (DMPS) 613
Clindamycin, 232-33 Diphenhydramine, 486-87, 574, 614
Clobetasol, 161 Diphtheria Antitoxin, 282
Clofazimine, 264-65 Diphtheria, Tetanus, Pertussis, Hepatitis B
Clomifene, 181 (Recombinant) and Hemophilus Influenza Type
Clonazepam, 470-71, 507-09 B (Hib) Combined Vaccine, 311
Clonidine, 139-40 Diphtheria-Tetanus Toxoid (Td), 288-89
Clopidogrel, 52-53 Diphtheria-Tetanus Toxoids (DT), 287-88
Clotrimazole, 152, 601-02 Diphtheria-Tetanus Toxoids and Acellular
Cloxacillin, 211 Pertussis Vaccines (DTaP), 300-01
Clozapine, 491-93 Diphtheria-Tetanus Toxoids and Pertussis Vaccine
Co-Amoxiclav (Amoxicillin + Potassium (DTP), 289-90
Clavulanate), 213-15 Dipyridamole, 53
Cobra Antivenin, 281-82, 611-12 Divalproex Sodium, 473-74, 518-19
Codeine, 440-41 Dobutamine, 105
Colchicine, 416-17 Docetaxel, 335-37
Colistin, 245-46 Domperidone, 10-11
Combined Glucose-Amino Acid Solutions, 71-72 Donepezil, 526-28

A94
Dopamine, 106 Finasteride, 186
Dorzolamide, 589 Fluconazole, 250-52
Doxorubicin, 341-42 Flucytosine (5-fluorocytosine), 254-55
Doxycycline, 203-04, 547-48 Flumazenil, 614-15
DTaP + Hemophilus Influenza Type B (Hib), 309 Flunarizine, 464-65
DTP + Hemophilus Influenza Type B (Hib), 309 Fluocinonide, 161-62
DTP + Hepatitis B Vaccine (Recombinant), 309-10 Fluorescein, 596-97
DTP + Inactivated Polio Vaccine (IPV), 310 Fluorouracil, 327-28
DTP + IPV + Hib, 310-11 Fluoxetine, 521-23
Dydrogesterone, 179-80 Flupentixol, 493-94
Fluphenazine, 494-96
E Flutamide, 373
Efavirenz, 271-72 Fluticasone, 564, 603-04
Enalapril, 116-17 Fluticasone + Formoterol, 559-60
Enalapril + Hydrochlorothiazide, 117-18 Fluticasone + Salmeterol, 560
Enoxaparin, 45-47 Folic Acid, 31, 62-63
Entecavir, 269-70 Fomepizole (4-methylprazole), 615-16
Enteral Nutrition Fondaparinux, 56-57
Adult Polymeric, 635 Formoterol, 556-57
Disease Specific, 635-36 Fosfomycin, 259-60
Fiber Containing, 636 Furosemide, 144-45
Modular, 637 Fusidate Sodium (Fusidic Acid), 158, 580
Pediatric Polymeric, 636
Semi-Elemental, 636 G
Eperisone Hydrochloride, 413 Gabapentin, 460-61, 475-76
Ephedrine, 534-35 Gadobutrol, 649-650
Epinephrine (Adrenaline), 107, 569 Gadoteric acid, 650-51
Epirubicin, 343-44 Ganciclovir, 267-68, 570
Epoetin Alfa Gas Forming Agent, 649
(Recombinant Human Erythropoietin), 63-64 Gemcitabine, 328-29
Epoetin Beta Gentamicin, 246-47
(Recombinant Erythropoietin), 64-66 Gliclazide, 25-26
Ergotamine, 461-62 Glucagon, 42, 614
Ertapenem, 226-27 Glucose (Dextrose), 41-42, 85, 637
Erythromycin, 231-33, 579 Glycerol (Glycerin), 15, 537-38, 589
Escitalopram, 520-21 Glyceryl Trinitrate (Nitroglycerin), 110-11, 113
Esmolol, 95-96, 535-36 Goserelin, 367-68
Ethambutol, 255-56
Ethinylestradiol + Desogestrel, 172 H
Ethinylestradiol + Levonorgestrel, 172-73 Haloperidol, 496-98
Ethinylestradiol + Norethisterone, 173 Halothane, 425
Ethinylestradiol + Norgestrel, 173 Hemodialysis Liquid Acid, 93
Etonogestrel, 173-75 Hemophilus Influenzae Type B Conjugate Vaccine
Etoposide, 333-35 (Hib), 291
Everolimus, 382-85 Heparin Sodium (Unfractionated), 47-48
Hepatitis A Vaccine (Inactivated), 297
F Hepatitis B Immunoglobulin (Human), 284-85
Factor IX Complex Concentrate (Coagulation Hepatits B Vaccine (Recombinant DNA), 297
Factors II, VII, IX, X), 58-60 Human Papillomavirus Quadrivalent Vaccine
Factor VIII Concentrate, 58 (Type 6, 11, 16, 18) (Recombinant), 299
Famotidine, 2-3 Human Papillomavirus Vaccine (Type 16, 18)
Felodipine, 130-31 (Recombinant, AS04 Adjuvanted), 299-300
Fenofibrate, 151 Human Recombinant Tissue Type Plasminogen
Fentanyl, 444-46 Activator (Alteplase), 54
Ferrous Salt, 38-39, 61 Hydralazine, 112-13
Ferrous Salt + Folic Acid, 39-40, 63 Hydrochlorothiazide, 140-41
Fiber Containing Enteral Nutrition, 636 Hydrocortisone, 162, 191-92
Filgrastim (G-CSF), 374-76 Hydrogen Peroxide, 164-65

A95
Hydroxychloroquine, 422 Ketoprofen, 402-03, 453-55
Hydroxyethyl Starch, 67-68 Ketorolac, 455-57
Hydroxyurea, 362
Hydroxyzine, 574-75 L
Hyoscine (Hyoscyamine), 9-10 Lactated Ringer’s Solution (Ringer’s Lactate), 650
3% Hypertonic Saline Solution, 631-32 Lactulose, 15-16
Hypromellose, 598 Lagundi, 653
Lamivudine, 270
I Lamivudine + Tenofovir, 273-74
Ibuprofen, 399-400, 452-53 Lamivudine + Tenofovir + Efavirenz, 274
Idarubicin, 344-45 Lamivudine + Zidovudine, 274-75
Ifosfamide, 315-16 Lamivudine + Zidovudine + Nevirapine, 275
Imatinib, 358-60 Lamotrigine, 476
Imiglucerase, 41 Lansoprazole, 4-5
Imiquimod, 159 Latanoprost, 589-90
Immunoglobulin Normal, Human (IGIM), 282-83 Letrozole, 373-74
Immunoglobulin Normal, Human (IGIV), 283-84 Leucovorin calcium (Calcium folinate), 364-65,
Indacaterol + glycopyrronium, 562-63 609-10
Indapamide, 141-43 Leuproreline, 368-69
Influenza Polyvalent Vaccine, 300-01 Levodopa + Carbidopa, 483-84
Influenza Polyvalent Vaccine (Split Virion, Levofloxacin, 239-41, 262, 581
Inactivated), 301 Levothyroxine, 197-99
Interferon Alfa-2b (Human), 376-79 Lidocaine, 95, 434-36, 600-01, 604
Intraocular Irrigating Solution (Balanced Salt Linezolid, 249-48
Solution), 80, 601 Lipids, 86
Iodine, 163, 200-01 Lithium Carbonate, 498-99
Iodized Oil Fluid, 639-40 Loperamide, 18-19
Iohexol, 640-42 Lopinavir + Ritonavir, 275-76
Iopamidol, 642-44 Loratadine, 575
Iopromide, 644-45 Losartan, 119-20
Iothalamate, 650-51 Losartan + Hydrochlorothiazide, 122
Ioversol, 645-47 Lynestrenol, 180-81
Ipratropium, 564-65
Ipratropium + Fenoterol, 560-61 M
Ipratropium + Salbutamol, 561-62 Magnesium Sulfate, 86-87, 104-05, 169-70, 479
Irbesartan, 119 Mannitol, 79-80, 147, 538-39, 590
Irbesartan + Hydrochlorothiazide, 121 Measles Vaccine (Live Attenuated), 302
Irinotecan, 363-64 Measles, Mumps, and Rubella (MMR) Vaccine
Iron Sucrose, 61-62 (Live Attenuated), 302-03
Isoflurane, 425-26 Measles and Rubella (MR) Vaccine (Live
Isoniazid, 256 Attenuated), 303
Isoniazid + Rifampicin, 259 Mebendazole, 550-51
Isoniazid + Rifampicin + Ethambutol, 259 Mebeverine, 10
Isoniazid + Rifampicin + Pyrazinamide, 259 Mecobalamin, 31-32, 62
Isoniazid + Rifampicin + Pyrazinamide + Medroxyprogesterone, 175, 179
Ethambutol, 259-60 Mefenamic Acid, 403-04
Isophane Insulin Human (Recombinant DNA), 24 Mefloquine, 543-44
Isosorbide Dinitrate, 109 Megestrol, 366-67
Isosorbide Mononitrate Melphalan, 317-18
(Isosorbide-5-Mononitrate), 110 Meningococcal Polysaccharide (Neisseria
Isotonic electrolyte solution for IV infusion, 78-79 meningitides) Vaccine, 291-92
Isoxsuprine, 169 Mercaptopurine, 322-23
Itraconazole, 252-53 Meropenem, 227-28
Mesalazine, 19-20
K Mesna (Sodium-2-Mercaptoethanesulphonate),
Kanamycin, 261-262 365-66, 630-31
Ketamine, 428-429 Metformin, 24-25
Ketoconazole, 152-53 Methimazole (Thiamazole), 199-200

A96
Methotrexate, 319-22 Oseltamivir, 276
Methyldopa, 140 Oxacillin, 211
Methylene Blue, 616-17 Oxcarbazepine, 472-73
Methylergometrine (Methylergonovine), 167-68 Oxiplatin (Oxaliplatin), 352-54
Methylphenidate, 525-26 Oxycodone, 443-44
Methylprednisolone, 193-94 Oxygen, 631
Metoclopramide, 12-13 Oxymetazoline, 554
Metoprolol, 96, 129 Oxytocin, 188-89
Metronidazole, 7, 246-47, 541
Micafungin, 254-55 P
Miconazole, 153 Paclitaxel, 337-39
Micronutrient Powder, 40-41 Paliperidone, 500-02
Midazolam, 477-78 Pancuronium, 407-08
Mitoxantrone, 346-47 Para-Aminosalicylic Acid, 262-63
Modified Fluid Gelatin, 68-69 Paracetamol, 457-59
Monobasic / Dibasic Sodium Phosphate, 16, 17 Peginterferon Alfa-2a, 379-81
Montelukast, 569-70 Penicillin G Benzathine (Benzathine
Morphine, 441-42 Benzylpenicillin), 208-09
Moxifloxacin, 241-43, 581 Penicillin G Crystalline (Benzylpenicillin), 209-10
Multivitamins, 26-27 Penicillin V (Phenoxymethylpenicillin), 210-11
Mumps Vaccine (Live Attenuated), 303-04 Peritoneal Dialysis Solution, 80-81
Mupirocin, 158 Permethrin, 552
Mycophenolate Mofetil, 385-87 Pethidine (Meperidine), 446-47
Mycophenolic Acid Petrolatum (Petroleum), 156
(as Mycophenolate Sodium), 387 Phenobarbital, 465-67
Phenylephrine, 594-95
N Phenytoin, 467-70
n-Acetyl Penicillamine, 617-18 Phospholipid fraction from bovine lung, 575-76
Nalbuphine, 448-49 Physostigmine, 621
Nalidixic Acid, 236-37 Phytomenadione
Naloxone, 618-19 (Phytonadione, Vitamin K1), 621-22
Naltrexone, 531-33 Pilocarpine, 590-91
Naproxen, 400-01 Piperacillin + Tazobactam, 215-16
Neomycin + Polymyxin B + Pneumococcal Conjugate
Fluocinolone Acetonide, 602-03 Vaccine (13-valent), 293-94
Neostigmine, 529-30, 619-20 Pneumococcal Polyvalent Vaccine, 294
Nepafenac, 583-84 Poliomyelitis Vaccine, Trivalent (Type 1, 2, 3)
Nevirapine, 272-73 (Inactivated), 304-05
Nicardipine, 131-33 Poractant Alfa, 577-78
Nifedipine, 133-35 Potassium Chloride, 37, 87-88
Nimodipine, 135-36 Potassium Citrate, 37
Nitrofurantoin, 247-48 Potassium Phosphate, 88-89
Nitroglycerin (Glyceryl Trinitrate), 110-11, 113 Povidone-Iodine, 163-64
Nitrous Oxide, 429-30 Pralidoxime Chloride, 622
Norepinephrine, 108-09 Praziquantel, 548-49
Norethisterone, 180-81 Prednisolone, 194-96, 584
Nystatin, 255 Prednisone, 196-97
Primaquine, 544-45
O Propofol, 430-31
Octreotide, 20-21 Propranolol, 97-98, 126, 201, 465
Ofloxacin, 238-39, 262, 581-82, 602 Propylthiouracil, 199
Olanzapine, 499-500 Protamine Sulfate, 622-23
Olodaterol, 557 Prothionamide, 263
Omeprazole, 5-6 Proxymetacaine (Proparacaine), 600-01
Ondansetron, 11-12 Pyrazinamide, 257
Oral Polio Vaccine, Bivalent (Type 1&3) (Live Pyridostigmine, 530-31
Attenuated), 304-05 Pyridoxine (Vitamin B6), 32-33, 623-24
Oral Rehydration Salts (ORS 75-replacement), 18 Pyrimethamine, 545-46

A97
 Sofosbuvir + Velpatasvir, 280
Q Somatostatin, 21-22
Quetiapine, 502-03 Soya bean oil + Medium chain triglycerides +
Quinine, 546-47 Olive oil + Purified fish oil, 72
Spectinomycin, 249
R Spironolactone, 146-47
Rabeprazole, 6-7 Standard Senna Concentrate, 16-17
Rabies Immunoglobulin (Human), 285 Sterile Water for Injection, 90-91
Rabies Vaccines – Chick Embryo Cell (Purified, Streptokinase, 54-55
Inactivated), 305-06 Streptomycin, 258
Rabies Vaccines – Vero Cell (Purified), 306 Succimer
Ranitidine, 3-4 (Dimercapto Succinic Acid, DMSA), 626-27
Regular, Insulin (Recombinant DNA, Human), 23- Sucralfate, 7
24 Sugammadex, 625-26
Retinol (Vitamin A), 28 Sulfacetamide + Prednisolone, 584-85
Ribavirin, 277-78 Sulfamethoxazole + trimethoprim (Cotrimoxazole),
Rifabutin, 263-64 228-229
Rifampicin, 257-58, 265 Sulfur, 552
Rifaximin, 17-18 Sumatriptan, 462-63
Rilpivirine, 273 Suxamethonium (Succinylcholine), 409-10
Risperidone, 503-05
Rituximab, 354-56 T
Rivastigmine, 528-29 Tacrolimus, 392-94
Rocuronium, 408-09 Tafluprost, 591-92
Ropivacaine, 436-38 Tamoxifen, 369-70
Rosuvastatin, 148-49 Tamsulosin, 185
Rubella vaccine (Live Attenuated), 306-07 Tegafur + Uracil, 329-30
Telmisartan, 120
S Telmisartan + Hydrochlorothiazide, 123
Sacubitril + Valsartan, 122-23 Tenofovir Alafenamide Fumarate, 270
Salbutamol, 555-56, 566 Tenofovir Disoproxil Fumarate, 271
Salicylic Acid, 153-54, 157 Terazosin, 185-86
Sambong, 653 Terbinafine, 154-55
Selegiline, 485-86 Terbutaline, 556-57, 566-67
Selenium Sulfide, 154 Testosterone, 175-76
Semi-Elemental Enteral Nutrition, 636 Tetanus Immunoglobulin (Human), 285-86
Sertraline, 523-25 Tetanus Toxoid, 295
Sevoflurane, 426-27 Tetracaine, 432
Silver Sulfadiazine, 159 Tetracycline, 204-05, 548
Simvastatin, 149-50 Theophylline (Anhydrous), 570-71
Sirolimus, 387-89 Thiamazole (Methimazole), 199-200
Sodium Bicarbonate, 1-2, 89-90 Thiamine (Vitamin B1), 29, 627
Sodium Bicarbonate for Hemodialysis, 89-90 Thiopental Sodium, 427-28, 479
Sodium Calcium Edetate, 624 Timolol, 592-93
Sodium Chloride, 90 Tinzaparin, 48-50
0.9% Sodium Chloride, 81-82 Tiotropium, 565-66
Sodium Dichloroisocyanurate, 165 Tobramycin, 582
Sodium Hyaluronate, 599 Tobramycin + Dexamethasone, 585
Sodium Hypochlorite, 165 Topiramate, 479-481
Sodium Iodide 1311, 651-52 Trace Elements, 91
Sodium Nitroprusside, 113-15 Tramadol, 450-51
Sodium Sulfate, 606 Tranexamic Acid, 57-58
Sodium Thiosulfate, 155, 625 Trastuzumab, 356-58
Sodium valproate, 473-74, 518-19 Travoprost, 593
Sodium valproate + valproic acid, 473-74, 518- Triclabendazole, 549
19 Trimetazidine, 111-12
Sofosbuvir, 278-79 Tropicamide, 595-96
Sofosbuvir + Ledipasvir, 279-80 Tropicamide + phenylephrine hydrochloride, 596

A98
Tsaang Gubat, 653-54 Vitamin B6 (Pyridoxine), 32-33, 623
Tuberculin, Purified Protein Derivative Vitamin C (Ascorbic Acid), 30-31, 608
(PPD), 632-33 Vitamins Intravenous (IV), Fat-Soluble, 91-92
Typhoid Vaccine, 295-96 Vitamins Intravenous (IV), Water-Soluble, 92
Vitamin K1 (Phytomenadione), 32, 621-22
U Voriconazole, 253
Ursodeoxycholic Acid, 13-14
W
V Warfarin, 42-44
Valaciclovir, 267
Valganciclovir, 268 Y
Valproic acid, 473-74, 518-19 Yellow Fever Vaccine, 308-09
Valsartan, 120-21
Valsartan + Hydrochlorothiazide, 123-24
Vancomycin, 243-45 Z
Varicella Vaccine (Live Attenuated), 307-08 Zidovudine, 271
Varicella Zoster Immunoglobulin (VZIG), 286 Zinc Gluconate, 38
Vecuronium, 410 Zinc Sulfate, 38
Verapamil, 101-03, 137-39 Zolmitriptan, 463-64
Vinblastine, 331-32 Zolpidem, 515-16
Vincristine, 332-33
Vitamin A (Retinol), 28
Vitamin B1 B6 B12 29-30

A99
Notes