Complementary Medicine Interactions Guide

10TH EDITION
MARCH 2019
Blackmores Institute Research About this guide
Blackmores Institute is committed to This Complementary Medicine Interactions Guide is a concise and comprehensive
Blackmores Institute is the academic
supporting scientifically rigorous research reference resource designed to give healthcare professionals clinically relevant,
and professional arm of Blackmores
that improves the understanding of the evidence-based information about potential interactions between complementary
Limited, established to support and drive
role complementary medicine plays in medicines and pharmaceutical medications.
an evidence-based approach to natural
advancing public health. We work with
medicine. With a focus on research and
some of Australia’s best education and For the most part, complementary medicines can be used alongside conventional
education, our primary purpose is to
research bodies and support a wide range pharmaceutical drug treatments. However, some complementary medicines may
improve the quality use of natural medicine
of complementary medicine research. interact with certain medications to reduce, or sometimes increase, their effect, or
by contributing to the evidence base and
Global research programs are currently to cause potential adverse effects. In addition, some complementary medicines may
translating this knowledge into practical
being conducted involving Australia, South have the ability to reduce drug side effects and also some common medications may
healthcare education and clinical resources.
East Asia, China and Europe. adversely affect the nutritional status of individuals over time.
We partner with leading academic Severity, likelihood and level of evidence is provided in this guide to assist in
institutions and research bodies to Membership assessment of risk and to support appropriate recommendations.
investigate novel ingredient development,
discovery and innovation, and legacy Blackmores Institute is grateful to the University of Sydney School of Pharmacy for
Our members enjoy free world-class their role in reviewing the evidence and contribution to this updated guide.
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healthcare professionals, educators and Theoretical
communicators, working together to in vitro and/or animal Unlikely
evaluate natural health literacy through Healthcare Professional Likelihood evidence with unclear Evidence suggests this
Possible
Evidence suggests this
Likely
Evidence suggests this
implications, However, interaction can occur, but
• Research funding
Advisory Service of
interaction it cannot exclude the is not likely to occur in
interaction might occur in interaction is likely to
occur in most patients
some patients
possibility of occurring in many patients
• Education programs humans
• Healthcare professional advisory services Our Healthcare Professional Advisory
• Research symposia and conferences Service has been providing free
High
• Interactions guidelines quality support and trusted advice in Low Moderate Clinical evaluation by a
Severity Variable
complementary medicine for over 30 years, Healthcare professional Intervention by a healthcare professional is
• News and research updates of Nature of interaction
intervention unlikely to healthcare professional
to help guide the safe and appropriate use interaction may vary recommended to assess
• Systematic reviews be required may be required the degree of intervention
• Academic projects of natural medicines. Call our Naturopathic required
Advisory Service line on 1800 803 760 or
email [email protected]
Education A - At least 1 good
Level of quality randomised,
evidence placebo-controlled trial B - Lower quality C - Case reports D - in vitro or animal
Blackmores Institute offers award-winning or meta-analysis or human study studies
CPD-accredited, evidence-based education systematic review
for health professionals. We believe that
education is key to helping pharmacists,
doctors and other health professionals
translate evidence into practice, to integrate
natural medicine into patient care. NOTE: Blackmores has made every effort to ensure that the information in this guide is accurate
and up-to-date but this does not guarantee that every possible interaction is included. Blackmores
cannot be held responsible for any future changes that may occur in this constantly expanding
area of study. The information in this guide is for informational purposes only and is not intended
as a substitute for professional advice. Healthcare professionals who consult this document are
cautioned that any medical or product-related decision is the sole responsibility of the healthcare
professional. Blackmores advises that healthcare professionals should ask patients about both
complementary medicine and drug use. Should an adverse event occur, send a ‘blue card’ adverse
reaction reporting form to the TGA or go online to www.tga.gov. au/reporting-problems-0#medicine
10th Edition and inform the manufacturer of both the complementary medicine and the medication.
Printed on FSC paper

Pg.2 Pg.3
DRUG, DRUG CLASS,
DRUG/CLASS/ENZYME/ NATURE of MECHANISM of LIKELIHOOD SEVERITY
SEVERITY
INGREDIENT MECHANISM EVIDENCE LIKELIHOOD
of of
of RECOMMENDATIONS
RECOMMENDATION
ENZYME or TRANSPORTER
TRANSPORTER INTERACTION INTERACTION OUTCOME
INTERACTION OUTCOME
Acidophilus See ‘Probiotics’
Antioxidants may
Alpha-lipoic acid May increase or decrease the activity of Level D
Chemotherapeutic agents
decrease drug effect chemotherapy or make Animal study Theoretical Moderate - Avoid concomitant use
High
chemotherapy more
effective
Level A
May increase drug May have additive Clinical trials suggest ALA may Use with caution under supervision of a
Hypoglycaemic drugs Possible Moderate -
effect hypoglycaemic effect affect glucose-lowering effect of healthcare professional and monitor
High
these medications
Co-administration of
May decrease drug levothyroxine with ALA Level D Use with caution under supervision of a
Levothyroxine Theoretical Moderate
effect may decrease conversion Preliminary animal studies healthcare professional and monitor
to active T3 form
Anticoagulants and May increase drug May have additive effect Level D Moderate Use with caution under supervision of a
Andrographis to drug Animal and in vitro study Theoretical
antiplatelet agents effect - High healthcare professional and monitor
Andrographis
paniculata May increase or decrease Variable
CYP450 enzyme substrates May increase or blood levels of substrates Level D (depending Use with caution under supervision of a
(CYP1A1, CYP1A2 and decrease drug effect Animal and in vitro study Theoretical on drug
via inhibition of these healthcare professional and monitor
CYP2B) and disease
enzyme activities state)
May decrease drug May have opposing Level C Moderate

Immunosuppressants Possible Avoid concomitant use
effect effect to drug Case report - High
Level D
Ashwagandha May have additive effect Animal study (Co-administration of Moderate
Benzodiazepines May increase drug Use with caution under supervision of a
Withania to drug due to GABAergic extract of withania somnifera (50 Theoretical - High
(Diazepam) effect healthcare professional and monitor
somnifera activity mg/kg) and diazepam (0.5 mg/kg)
increased the seizure threshold)
Level B
Chemotherapeutic agents Herb effect on drug
Human study (Withania somnifera Use with caution under supervision of a
(Doxorubicin, cyclophospha- (May improve che- Unknown mechanism of Possible Variable
Low
6 g/d throughout 6 months healthcare professional and monitor
mide, epirubicin, fluorouracil) motherapy-induced the interaction
chemotherapy in breast cancer
fatigue)
patients) Moderate
Level A
Clinical trials (Adjunctive treat-
ment with extract of Withania
Moderate Use with caution under supervision of a
Psychotropic drugs (Olan- Herb effect on drug May improve neurotrans- somnifera 1000 mg/d improved
zapine, typical antipsychot- (May improve nega- mitter dysfunctions due negative symptoms and stress in healthcare professional and monitor. Mild
ics, antidepressants, mood tive, general and total to GABAergic and NMDA patients with recent exacerbation Possible Low to moderate and transient side effects
stabilisers, antianxiety, symptoms and stress) potentiating activity of of schizophrenia. Another clinical were reported such as somnolence,
hypnotic) withania trial showed extract of Witha- epigastric discomfort or loose stools
nia somnifera 500 mg/d improved Moderate
cognitive abilities without serious
adverse effects.)
Astragalus No significant adverse effect or reduction

Astragalus Chemotherapeutic agents Herb effect on drug Level A
No direct interaction Low in the effectiveness of chemotherapy
(Cisplatin and vinorelbine) (May decrease drug Clinical trials Possible
membranaceus identified in studies. Supplementation
side effect)
may reduce side effects
Pg.4 Pg.5
DRUG, DRUG CLASS,
SEVERITY
of of
of RECOMMENDATIONS
RECOMMENDATION
INTERACTION OUTCOME
Astragalus
Astragalus May decrease drug Astragalus may have Level D Moderate Avoid concomitant use
Immunosuppressants Theoretical
membranaceus effect immunostimulant activity Animal and in vitro study - High
Bacopa See “Brahmi”
Drug effect on Interaction may be minimised by

Betacarotene Betacarotene absorption Level A
nutrient (May separating dose of medication and
Orlistat, plant sterols may be decreased by Clinical trials Likely Low
decrease nutrient betacarotene by at least 2 hours.
these drugs
effect) Supplementation recommended
Herb effect on drug

Bilberry (The combination May improve the viability Level D
Antibiotics (Doxycycline Use with caution under supervision of a
Vaccinium may have an of thymocytes in vitro study Theoretical Moderate
and cephalosporins) healthcare professional and monitor
myrtillus immunostimulatory
effect)
Level D
Bilberry anthocyanins in vitro study (Drug-herb
Anticancer agent (Erlotinib) May decrease drug may modulate the interaction was not directly Theoretical Moderate Avoid concomitant use
effect growth-inhibitory effect of studied. Bilberry extract in- - High
erlotinib creased IC50 values of erlotinib)
Level C
Anticoagulants and May increase risk of May have additive effect Moderate - Use with caution under supervision of a
Case report (Rectal bleeding after Possible
antiplatelet agents bleeding to drug High healthcare professional and monitor
taking warfarin with bilberry)
Level D
in vitro study (Drug-herb
interaction was not directly Moderate
Antihypertensive drugs Use with caution under supervision of a
May increase drug May have additive effect studied. A significant dose-de- Theoretical - High
(ACE inhibitors) healthcare professional and monitor
effect to drug pendent inhibition of ACE activity
was seen after incubation with
bilberry extract)
Level A
Clinical trial (Drug-herb
interaction was not directly Variable
May increase drug May have additive effect studied. The ingestion of bilberry Theoretical (depending Use with caution under supervision of a
Hypoglycaemic drugs effect to drug on drug healthcare professional and monitor
extract significantly decreased
and disease
the incremental AUC for both state)
glucose and insulin compared to
placebo)
May increase or May increase cytotoxicity

Chemotherapeutic agents decrease drug effect of docetaxel and Level D
(Docetaxel, doxorubicin, depending in vitro study on mouse breast Moderate
Black cohosh doxorubicin or may Theoretical Avoid concomitant use
cisplatin) on chemotherapeutic cancer cell line -High
Cimicifuga decrease cytotoxicity
racemosa agents of cisplatin
May increase or decrease Variable

May increase or Level B Use with caution under supervision of a
CYP2D6 substrates blood levels of drug via Possible (depending
decrease drug effect Human study healthcare professional and monitor
inhibition of this enzyme on drug and
activity disease state)
Pg.6 Pg.7
DRUG, DRUG CLASS,
SEVERITY
of of
of RECOMMENDATIONS
RECOMMENDATION
INTERACTION OUTCOME
CYP450 enzyme substrates May increase or decrease Variable

(CYP1A2, CYP2C9, May increase or Level D Use with caution under supervision of a
Boswellia substrate blood levels via Theoretical (depending
Boswellia serrata CYP2C19, CYP2D6 and decrease drug effect inhibition of these enzyme in vitro study on drug and healthcare professional and monitor
CYP3A4) disease state)
activities
May have opposing effect Level D Moderate

Immunosuppressants May decrease drug Theoretical Avoid concomitant use
to drug in vitro study -High
effect
May increase effect

Brahmi Acetylcholinesterase (AChE) of AChE inhibitor and May increase acetylcholine
Bacopa monnieri inhibitor, anticholinergic cholinergic drug. levels due to inhibition of Level A Use with caution under supervision of a
drug, cholinergic drug Clinical trials Likely Moderate healthcare professional and monitor
May decrease acetylcholinesterase
effectiveness of
anticholinergic drug
CYP450 enzyme substrates May increase or decrease Variable

(CYP1A2, CYP2C19, May increase or blood levels of drug via Level D Theoretical (depending Use with caution under supervision of a
CYP2C9, CYP3A4) decrease drug effect inhibition of these enzyme in vitro study on drug and healthcare professional and monitor
activities disease state)
Thyroid hormone May increase drug May have additive effect Level D Use with caution under supervision of a
Theoretical Moderate
effect to drug Animal study healthcare professional and monitor
Level A
Bromelain May increase levels of Clinical trials (160 mg bromelain
amoxicillin in tissue and appreared to increase intra- Use with caution under supervision of a
Amoxicillin May increase drug blood by increasing the operative amoxicillin levels in Possible Moderate healthcare professional and monitor
effect absorption and enhancing tissue, serum and skin samples.
its penetration into tissues The effect persisted 3 hours after
surgery)
Level D
May increase retention Animal and in vitro study (Oral
Drug effect on No evidence from human studies to
Antacids of proteolytic effect bromelain retained substantial
nutrient (May Low support clinical recommendations
of bromelain when in proteolytic activity throughout the Theoretical
increase nutrient
combination with antacids gastrointestinal tract when in com-
effect)
bination with antacids)
Level B
Anticoagulants and May increase risk of May have additive effect Human study (Drug-herb interaction Use with caution under supervision of a
Theoretical Moderate -
antiplatelet agents bleeding to drug was not directly studied. Bromelain High healthcare professional and monitor
showed antiplatelet and
anticoagulant effect)
Level D
in vitro study (Bromelain 25-50mg/
May increase drug Bromelain may increase mL decreased IC50 value of Moderate - Use with caution under supervision of a
Cisplatin Theoretical
effect apoptosis and autophagy cisplatin in malignant peritoneal High healthcare professional and monitor
mesothelioma cells)
Level C
May increase drug Case report (Ecchymosis devel- Moderate - Use with caution under supervision of a
NSAIDs (Naproxen) side effect Mechanism unclear Possible
oped on forearms after taking High healthcare professional and monitor
naproxen with bromelain)
Pg.8 Pg.9
DRUG, DRUG CLASS,
SEVERITY
of of
of RECOMMENDATIONS
RECOMMENDATION
INTERACTION OUTCOME
Calcium may reduce blood Avoid concomitant use. If indicated,

Antiretrovirals (Integrase Level A Moderate -
Calcium May decrease drug levels of dolutegravir, Possible interaction may be minimised by taking
inhibitors - dolutegravir, Clinical trials High
effect elvitegravir and raltegravir 2 hours before or 6 hours after taking
elvitegravir, raltegravir)
through chelation calcium
Level B
Calcium may decrease Small human study. Calcium-rich Interaction may be minimised by
Beta Blockers (Atenolol, May decrease drug
absorption of atenolol food considered to be the major Possible Moderate separating dose of medication and
sotolol) effect
sotalol reason for reduced absorption calcium by at least 2 hours
Bisphosphonates, Level A (quinolones)

May decrease drug Calcium may decrease the Interaction may be minimised by
tetracycline or quinolone Level B (bisphosphonates)
absorption and efficacy of Possible Moderate separating dose of medication and
antibiotics, thyroid effect Level C (tetracyclines, thyroid
these drugs calcium by at least 2 hours
hormones hormones)
Calcium may decrease Level B Use with caution under supervision of a
Calcium channel blockers May decrease drug Possible Moderate
the hypotensive effect of Study in arrhythmic patients healthcare professional and monitor
(verapamil) effect verapamil using IV calcium and case report
IV calcium and IV
ceftriaxone may result Level C
Ceftriaxone May increase drug Possible High Avoid concomitant use
in precipitation of a Case reports
side effect
ceftriaxone-calcium salt in
the lungs and kidneys
Calcium may increase the Use with caution under supervision of a
May increase drug Level C
Thiazide diuretics risk of hypercalcaemia Possible Moderate
side effect Case reports healthcare professional and monitor
with these drugs
Celery CYP1A2 substrates May increase or blood levels of drug via Level D Theoretical (depending Use with caution under supervision of a
Apium decrease drug effect inhibition of this enzyme Animal and in vitro study on drug and healthcare professional and monitor
graveolens activity disease state)
May decrease drug May decrease blood levels Level C Use with caution under supervision of a
Thyroid hormone Case reports Possible Moderate
effect of drug healthcare professional and monitor
Celery may increase blood Level C
Venlafaxine May increase drug Possible Moderate -
levels of venlafaxine by Case report Avoid concomitant use
effect High
inhibition of CYP2D6
Chaste Tree See “Vitex”
May have additive effect

Chondroitin to drug. Chondroitin is
sulfate Anticoagulant and May increase drug Level C Moderate -
a small component of a Possible Avoid concomitant use
antiplatelet agents effect Case report High
heparinoid and might
(warfarin)
have weak anticoagulant
activity
Drug effect on May decrease absorption

Level D
Chromium Antacids (Aluminium of chromium by forming
nutrient (May Animal study (Chromium levels Use with caution under supervision of a
hydroxide and magnesium insoluble complex when Theoretical Moderate
decrease blood levels in blood were lower when in healthcare professional and monitor
hydroxide) pH is raised in gastroin-
of nutrient) combination with antacids)
testinal tract by antacids
Level A
Nutrient effect on Multiple mechanisms pro- Clinical trials (Evidence based
drug (May increase posed (addressing dietary on sulfonylureas. Combination of
Hypoglycaemic drugs drug effect but intake, skeletal muscle glipizide and chromium improved Use with caution under supervision of a
Possible Low
decrease associated fat oxidation, and insulin glycaemic control, increased insulin healthcare professional and monitor
side effects) signalling) with studies sensitivity and significantly
ongoing attenuated body weight gain
induced by glipizide)
Pg.10 Pg.11
DRUG, DRUG CLASS,
SEVERITY
of of
of RECOMMENDATIONS
RECOMMENDATION
INTERACTION OUTCOME
May decrease blood Level B

Chromium May decrease drug Human study (Chromium picolinate Avoid concomitant use. If chromium is
Levothyroxine levels of drug by reducing Possible Moderate
effect significantly decreased the AUC of indicated, interaction may be minimized
absorption
serum thyroxine) by separating the dose by 2 hours
Drug effect on Level D

NSAIDs (Aspirin and nutrient (May May increase the absorp- Animal studies (Chromium levels
Use with caution under supervision of a
indomethacin) increase blood levels tion of chromium in blood, urine and tissues were Theoretical Moderate healthcare professional and monitor
of nutrient) higher when in combination with
aspirin or indomethacin)
May increase drug Level A

Co-enzyme Q10 May have additive Moderate - Use with caution under supervision of a
Antihypertensive drugs effect Meta-analyses in patients taking Likely
(CoQ10) hypotensive effect High healthcare professional and monitor
anti-hypertensive drugs
Drug effect on Level D
Beta-blocker adrenergic nutrient (May CoQ10 levels may be in vitro studies found beta blockers Theoretical Assess nutrient status and supplement if
Low
agents decrease nutrient decreased by these drugs inhibited mitochondrial CoQ10 indicated
effect) enzymes
Despite the potential

benefits of CoQ10 in CoQ10 does not elicit its protective
Chemotherapeutic agents Nutrient effect on preventing cardiotoxicity, Level A effect against doxorubicin-induced
(Anthracyclines such as drug (May decreases it is unknown if Clinical trial in leukemia and Possible Low cardiotoxicity by reducing the drug
daunorubcin, doxorubicin) drug side effect) CoQ10 diminishes the lymphoma patients levels in the blood or by inhibiting
antineoplastic effect of the formation of doxorubicinol
doxorubicin therapy
Level A
Drug effect on
HMG-CoA reductase CoQ10 levels may be Several studies in hyperlipidaemic
nutrient (May Likely Low Assess nutrient status and supplement if
inhibitors (statins) depleted by these drugs patients; statins decreased plasma
decrease nutrient indicated
CoQ10 levels (effect on tissue levels
effect)
not established)
Level A
Conflicting data
Nutrient effect on CoQ10 may decrease Clinical trials show conflicting Inadequate evidence to support
HMG-CoA reductase Low
drug (May decrease myalgia associated with results. Systematic review Possible supplementation in all patients taking
inhibitors (statins)
drug side effect) statin use found inadequate evidence to statins
recommend routine use with
statins
Level A
Hypoglycaemic drugs May increase drug May have additive Moderate - Use with caution under supervision of a
Conflicting data Possible
effect hypoglycaemic effect High healthcare professional and monitor
Clinical trials
Level A
CoQ10 may have Conflicting data
Anticoagulants and May increase or Moderate -
procoagulant or Clinical trial found no interaction. Possible Avoid concomitant use
antiplatelet agents decrease drug effect High
anticoagulant effect Multiple case reports of changes
to INR
Anticoagulants and May increase drug May have additive Level D Moderate - Use with caution under supervision of a
Coleus antiplatelet agents effect to drug Theoretical
effect Animal studies High healthcare professional and monitor
Coleus forskohlii
Level B
May have additive No significant adverse effect expected.
May increase drug Human and animal studies using
Antihypertensive drugs
effect to drug Theoretical Moderate - Use with caution uder supervision of a
effect IV extracts High health care professional and monitor
Relevance to oral doses unknown
Pg.12 Pg.13
DRUG, DRUG CLASS,
SEVERITY
of of
of RECOMMENDATIONS
RECOMMENDATION
INTERACTION OUTCOME
Level A
Cranberry
Conflicting data.
Vaccinium
Clinical trials suggest no evidence
macrocarpon Anticoagulant and May increase Moderate - Use with caution under supervision of a
May increase drug of increasing drug affects with Unlikely
antiplatelet agents effect blood levels of drug cranberry juice. Case reports exist. High healthcare professional and monitor
in vitro studies suggest cranberry
effect warfarin metabolism
(CYP3A4 minor metaboliser)

May increase or blood levels of drug via Level C (depending
CYP3A4 substrates Possible Use with caution under supervision of a
decrease drug effect on drug
inhibition of this enzyme Case report healthcare professional and monitor
and disease
activity state)
May decrease drug May decrease blood levels Level C

Tacrolimus Possible High Avoid concomitant use
effect of drug Case report
Level C
Dong quai Anticoagulant and May have additive effect Moderate -
May increase drug Several case reports and animal Possible Avoid concomitant use
Angelica antiplatelet agents to drug High
effect studies
polymorpha
May have additive effect Level A Use with caution under supervision of a
Aspirin May increase drug Unlikely High
to drug Clinical trials healthcare professional and monitor
effect
May increase blood levels Level C

Echinacea of drug via inhibition Case report involving concurrent Moderate -
Echinacea Chemotherapeutic agent May increase drug Possible Avoid concomitant use
of CYP1A2, CYP2C19, use of etoposide, cisplatin, and High
angustifolia (Etoposide) effect
CYP2C9, CYP3A4 echinacea. Patient developed
Echinacea profound thrombocytopenia
purpurea
CYP1A2 and CYP2D6 May increase or blood levels of drug Level B
Possible (depending Use with caution under supervision of a
substrates decrease drug effect via inhibition of these Human studies on drug and healthcare professional and monitor
enzyme activities disease state)

CYP3A4 substrates May increase or blood levels of drug via Level B (depending Use with caution under supervision of a
Human studies Possible
decrease drug effect induction of this enzyme on drug and healthcare professional and monitor
Level B
May increase drug Animal studies, in vitro and in vivo
May have opposing effect Moderate-
Immunosuppressants side effect evidence of immunomodulatory Possible Avoid concomitant use
to drug High
effect.
No case report evidence
Level C
Evening Case report in patient using
primrose oil Antiretrovirals May increase drug May increase blood levels Moderate -
lopinavir/ritonavir with evening Possible Avoid concomitant use
(Lopinavir/ritonavir) effect of drug High
primrose experiencing an increase
in blood levels of drugs
Level B
Conflicting data
Phenothiazine May increase drug May lower seizure Human study found no interaction Unlikely High Use with caution under supervision of a
side effect threshold Case reports of seizures in healthcare professional and monitor
schizophrenic patients exist
Pg.14 Pg.15
DRUG, DRUG CLASS,
SEVERITY
of of
of RECOMMENDATIONS
RECOMMENDATION
INTERACTION OUTCOME
Level C
Fenugreek Anticoagulant and May increase drug May have additive effect Case report in patients with Moderate -
Possible Avoid concomitant use
Trigonella antiplatelet agents effect to drug arrhythmia using fenugreek High
foenum-graecum capsule and warfarin
Level A
Hypoglycaemic drugs May increase drug May have additive effect Human studies and meta-analyses Use with caution under supervision of a
Likely Moderate - healthcare professional and monitor
effect to drug confirm blood glucose-lowering
High
effect in patients with type-2
diabetes
Level D
Theophylline May decrease drug May decrease blood levels Animal study (oral administration Use with caution under supervision of a
of theophylline 200 mg after Theoretical Moderate healthcare professional and monitor
effect of drug
fenugreek in male beagle dog)
Level B
Feverfew Conflicting data.
Tanacetum Anticoagulant and May increase drug May have additive effect in vitro and in vivo studies Moderate - Use with caution under supervision of a
Possible
parthenium antiplatelet agents effect to drug found feverfew inhibits platelet High healthcare professional and monitor
aggregation.
Human study found no such effect
CYP450 enzyme May increase or decrease Level D Variable No significant adverse effect expected.
substrates (CYP1A2, May increase or blood levels of drug via in vitro study found low inhibitory Theoretical (depending Use with caution under supervision of a
CYP2C8, CYP2C9, decrease drug effect inhibition of these enzyme on drug and
activity healthcare professional and monitor
CYP2C19 and CYP3A4) activities disease state)
Level A
Fish Oil Conflicting data.
High doses of fish oil (>3 Multiple clinical trials have found Possible
May increase drug
Anticoagulants and g/d omega-3 fatty acids) no increase in risk of bleeding (depending Moderate - Use with caution under supervision of a
effect depending on
antiplatelet agents may increase the risk of with antiplatelet or anticoagulant on fish oil High healthcare professional and monitor
fish oil dose
bleeding with these drugs drugs, however there are dose)
some studies that suggest an
interaction, particularly at higher
doses
May have additive Level A
May increase drug Moderate Blood pressure should be monitored
Antihypertensive drugs hypotensive effect Meta-analyses in patients taking Likely
effect when patient is on high dose of fish oil
depending on fish oil dose anti-hypertensive drugs
Chemotherapeutic agents Level C Moderate -

May decrease drug May cause compound Possible Avoid concomitant use
(Cisplatin, oxaliplatin, Case report High
effect resistance
irinotecan)
High doses (30-40 g/d) of Level A Unlikely Interaction unlikely at normal doses.
Flaxseed oil Anticoagulants and May increase drug
flaxseed oil may increase Conflicting data (possible Moderate - Use with caution under supervision of a
antiplatelet agents effect
the risk of bleeding with Human studies
with high High healthcare professional and monitor
these drugs doses)
May have additive Level A Blood pressure should be monitored

Antihypertensive drugs May increase drug Likely Moderate -
hypotensive effect. Dose Clinical trials when patient is on high dose of flaxseed
effect. Dose dependent High
dependent oil
Co-trimoxazole,
sulphazalazine, Drug effect on nutrient
May decrease folic Level C Moderate - Assess and monitor nutrient status and
Folic acid phenytoin, phenobarbital, (May decrease blood Possible
acid levels Multiple case reports High supplement if indicated
primidone and levels of nutrient)
methotrexate
Pg.16 Pg.17
DRUG, DRUG CLASS,
SEVERITY
of of
of RECOMMENDATIONS
RECOMMENDATION
INTERACTION OUTCOME
Fluorouracil and May increase drug Folic acid may increase the Level C Moderate -
Folic acid Possible Avoid concomitant use
capecitabine side effect toxicity of fluorouracil and Case reports High
capecitabine
Folic acid may

decrease the efficacy of
methotrexate for children
May decrease drug Level A Moderate - Follow Australian Medicines Handbook’s
Methotrexate with lymphoblastic Likely
effect Clinical trials High recommendations for concurrent use of
leukaemia
folic acid and methotrexate
Folic acid may decrease
drug side effect in
rheumatoid arthritis
May decrease drug Folic acid may decrease Level B Use only under supervision of healthcare
Phenytoin Likely High professional and monitor phenytoin
effect the efficacy of phenytoin Uncontrolled studies in epileptic
patients blood concentration
Level A
Garlic May increase drug May increase the risk Conflicting data
Anticoagulants and Moderate - Use with caution under supervision of a
Allium sativum effect depending on of bleeding with these Human studies show conflicting Possible
antiplatelet agents High healthcare professional and monitor
formulation and dose medications results. Interaction more likely at
higher doses (>7 g). Case reports
Level A
May increase drug May have additive Clinical trials indicate Use with caution under supervision of a
Antihypertensive drugs Moderate -
hypotensive effect to drug. Likely
effect antihypertensive activity with High healthcare professional and monitor
Dose dependent aged garlic extract (480-960 mg/d)
May increase blood levels Level B Variable

CYP2E1 substrates May increase drug (depending Use with caution under supervision of a
of substrates via inhibition in vitro and open studies using Possible
effect on drug and healthcare professional and monitor
of this enzyme activity chlorzoxazone disease state)
May increase or decrease Level C Variable

Hepatic CYP3A4 May increase or (depending Use with caution under supervision of a
blood levels of drug via Case report Possible
substrates decrease drug effect on drug and healthcare professional and monitor
inhibition of hepatic disease state)
CYP3A4 enzyme activity
May decrease blood levels Level B Variable

Intestinal CYP3A4 May decrease drug of drug via induction of (depending Use with caution under supervision of a
Human study Possible
substrates (Saquinavir) effect intestinal CYP3A4 enzyme on drug and healthcare professional and monitor
disease state)
activity
May decrease blood Level B

Variable
Intestinal P-glycoprotein May decrease drug levels of substrates via in vitro and human studies found (depending Use with caution under supervision of a
substrates effect upregulation of intestinal garlic decreased levels of the Possible on drug and healthcare professional and monitor
ABCB1 or ABCC2 activity protease inhibitors saquinivir and disease state)
ritonavir
Modeate
Metformin May increase drug May have additive Level B Use with caution under supervision of a
Possible - High
effect hypoglycemic effect Human study (depending
healthcare professional and monitor
on dose)
Pg.18 Pg.19
NATURE of LIKELIHOOD SEVERITY
SEVERITY
INGREDIENT DRUG, DRUG CLASS,
DRUG/CLASS/ENZYME/ MECHANISM of EVIDENCE LIKELIHOOD RECOMMENDATIONS
INTERACTION MECHANISM of of
of RECOMMENDATION
TRANSPORTER INTERACTION
INTERACTION OUTCOME
OUTCOME
Level A
Ginger Conflicting data.
Zingiber Clinical trials indicate normal Do not use high doses (≥4 g/d) in
officinale May increase the risk doses ≤4 g/d are unlikely to cause patients with bleeding disorders or
Anticoagulants and May increase drug Moderate -
antiplatelet agents of bleeding with these platelet dysfunction. Unlikely those taking antiocagulant medication.
effect High
medications Human study with high dose Use with caution under supervision of a
ginger (10 g) and in vitro studies healthcare professional and monitor
showed inhibition of platelet
aggregation
May decrease drug May decrease blood level Level D Moderate - Use with caution under supervision of a
Ciclosporin Theoretical
effect of drug Animal study High healthcare professional and monitor
May increase drug May increase absorption Level D Use with caution under supervision of a
Metronidazole Theoretical Moderate
effect and plasma half life Animal study healthcare professional and monitor
Tacrolimus May increase drug May increase blood levels Level D

Theoretical High Avoid concomitant use
effect of drug via unknown Animal study
mechanism
Anticonvulsants May decrease drug May increase risk of Level C Moderate - Use with caution under supervision of a
Ginkgo (Phenylbarbitone, sodium Possible
effect seizure Case reports High healthcare professional and monitor
Ginkgo biloba valproate, phenytoin)
Ginkgo may add

to the beneficial
Herb effect on drug
Chlorpromazine and effect of haloperidol, Level A Likely Low No significant adverse effect expected
(May increase drug
haloperidol chlorpromazine and Meta-analysis and studies
efficacy)
olanzapine in the
treatment of schizophrenia

CYP450 enzyme May increase or Use with caution under supervision of a
blood levels of drug via Level D Theoretical (depending
substrates (CYP 1A2, decrease drug effect healthcare professional and monitor
weak inhibition of these in vitro study on drug and
CYP2C9, CYP3A)
enzyme activities disease state)
Level B
May increase or Conflicting data. Use with caution under supervision of a
CYP2C19 substrates blood levels of drug via (depending
decrease drug effect Human studies found ginkgo Possible healthcare professional and monitor
induction of this enzyme on drug and
decreased levels of omeprazole,
but had no effect on voriconazole
May increase blood levels

May decrease drug of drug due to possible Level C Moderate -
Efavirenz Possible Avoid concomitant use
effect induction of CYP3A4 and Case report High
P-glycoprotein
Level B
Conflicting data.
Ginkgo may increase or Clinical trials and human studies
Hypoglycaemic drugs May increase or decrease blood glucose Moderate - Use with caution under supervision of a
decrease drug effect found ginkgo had a variable effect Possible
levels High healthcare professional and monitor
on drug activity. Animal and in
vitro studies suggest ginkgo may
reduce insulin resistance
May increase drug May increase blood level Level B Moderate - Use with caution under supervision of a
Nifedipine Human studies Possible healthcare professional and monitor
effect of drug High
Pg.20 Pg.21
SEVERITY
DRUG, DRUG CLASS,
DRUG/CLASS/ENZYME/ MECHANISM of
of of
of RECOMMENDATIONS
RECOMMENDATION
TRANSPORTER INTERACTION INTERACTION
INTERACTION OUTCOME
OUTCOME
Level A
Ginkgo
Conflicting data.
Ginkgo biloba Ginkgo may increase risk
Anticoagulants and May increase drug Clinical trials find ginkgo does not
of bleeding with these have a significant effect on platelet Moderate - Use with caution under supervision of a
antiplatelet agents effect Unlikely
medications function and does not interact with High healthcare professional and monitor
warfarin, aspirin or clopidogrel.
Case reports suggest an
interaction is possible
May increase drug May increase blood level Level B Moderate -

Raltegravir Possible Avoid concomitant use
effect of drug Human studies High
May increase drug May have an effect on Level C Moderate - Use with caution under supervision of a
Ginseng (Korean) Amitriptyline Possible
effect neurochemical system Case report High healthcare professional and monitor
Panax ginseng
Level A
Conflicting data.
Possible CYP450 enzymes Clinical trial results suggest no
Anticoagulant and May increase or Moderate - Use with caution under supervision of a
interaction and Vitamin K interaction. Possible
antiplatelet agents decrease drug effect High healthcare professional and monitor
effect on ginseng Case reports exist
in vitro studies suggest possible
interaction

CYP2D6 substrates May increase or Level A
blood level of drugs via Possible (depending Use with caution under supervision of a
decrease drug effect Clinical trials on drug and
inhibition of this enzyme healthcare professional and monitor
disease state)
activity
May interfere with the Korean ginseng may Level B

Digoxin accuracy of a range of falsely elevate or decrease in vitro, animal and human ex vivo Possible High Avoid concomitant use
tests measuring serum assays for blood digoxin studies
digoxin levels
Herb effect on drug May enhance susceptibility
Docetaxel Level D No evidence from human studies to
(May increase drug of colon cancer cells to Theoretical Low
in vitro study support clinical recommendations
efficacy) docetaxel
Herb effect on drug May have a protective Level D No evidence from human studies to
Doxorubicin (May decrease drug effect on doxorubicin- Theoretical Low
Animal study support clinical recommendations
side effect) induced toxicity
May increase drug Level A Use with caution under supervision of a

Hypoglycaemic drugs May have additive Moderate -
effect Clinical trials in NIDDM patients Likely healthcare professional and monitor
hypoglycaemic effect High
and healthy subjects
May increase drug May increase blood levels Level C

Imatinib of drugs possibly due to Possible High Avoid concomitant use
side effect Case report
inhibition of CYP3A4
May decrease blood levels Level A Moderate -
Midazolam May decrease drug Possible Use with caution under supervision of a
of drugs possibly due to Clinical trials High
effect healthcare professional and monitor
induction of CYP3A4
Monoamine Oxidase Korean ginseng may Level C Use with caution under supervision of a
May increase drug Unlikely Moderate
Inhibitors (MAOI) increase the side effect of Case reports (ginseng type not healthcare professional and monitor
side effect
(Phenelzine) phenelzine or other MAOIs specified)
May increase or Korean ginseng may cause Level D Theoretical Low - Use with caution under supervision of a
Oestrogen decrease drug effect a phytoestrogenic effect in vitro study Moderate healthcare professional and monitor
Pg.22 Pg.23
SEVERITY
DRUG, DRUG CLASS,
of of
of RECOMMENDATIONS
RECOMMENDATION
INTERACTION OUTCOME
OUTCOME
Level B
Ginseng in vivo study found anticoagulant
(Siberian) Siberian ginseng may activity for an isolated constituent. Moderate -
Elutherococcus Anticoagulant and May increase drug Human study in athletes Possible Avoid concomitant use
increase risk of bleeding High
senticosus antiplatelet agents effect with this medication adminstered a preparation of
Siberian ginseng and andrographis
found reduced coagulation
Level A
Siberian ginseng may Human trials in women with
Nutrient effect on drug increase tolerance for Use with caution under supervision of a
Chemotherapeutic agents breast and ovarian cancer Likely Low
(May decrease drug chemotherapy and improve healthcare professional and monitor
side effect) undergoing chemotherapy
immune response treatment

CYP3A4 and CYP2D6 May increase or Level B (depending Use with caution under supervision of a
blood levels of drug via Human studies Possible on drug and healthcare professional and monitor
substrates decrease drug effect
inhibition of these enzyme disease state)
activities
May interfere with the Siberian ginseng may Level B

accuracy of a range of falsely elevate or decrease High Avoid concomitant use
Digoxin in vitro, animal and human ex vivo Possible
tests measuring serum assays for blood digoxin studies
digoxin levels levels
May increase drug May have additive Level A Use with caution under supervision of a
Hypoglycaemic drugs Likely Moderate -
effect hypoglycaemic effect to Clinical trials healthcare professional and monitor
High
drug
Monoamine Oxidase Siberian ginseng may Level C

May increase drug Use with caution under supervision of a
Inhibitors (MAOI) increase side effect of Two case reports (ginseng type Unlikely Moderate
side effect healthcare professional and monitor
(Phenelzine) phenelzine or other MAOIs not specified)
Variable
May increase drug May increase blood level of Level D (depending Use with caution under supervision of a
P-glycoprotein substrates Possible
effect drug via inhibition of P-gp in vitro study on drug and healthcare professional and monitor
disease state)
May increase drug Glucosamine may increase Level C

Anticoagulant and Moderate - Avoid concomitant use
Glucosamine effect risk of bleeding with this Case reports Possible
antiplatelet agents High
medication
Level A
Clinical trials indicate no Interaction unlikely but use with caution
May decrease drug Glucosamine may affect Moderate -
Hypoglycaemic drugs interaction. under supervision of a healthcare
blood glucose levels in Unlikely
effect Lower-level studies reports High professional and monitor
people with diabetes
changes to glucose and insulin
levels
Grape seed Anticoagulants and May increase risk of May decrease platelet Level D Moderate - Use with caution under supervision of a
bleeding adhesion to fibrinogen Theoretical healthcare professional and monitor
Vitis vinifera antiplatelet agents in vitro studies High
Level A
Clinical trial (6 weeks treatment
Antihypertensive drugs + May have opposing Moderate - Avoid combination of vitamin C and
Unknown mechanism with both vitamin C 500 mg and Possible
vitamin C effect to drug High grape seed in hypertensive pateints
grape seed polyphenol 1000 mg
daily increased blood pressure in
hypertensive patients)
Pg.24 Pg.25
SEVERITY
DRUG, DRUG CLASS,
of of
of RECOMMENDATIONS
RECOMMENDATION
INTERACTION OUTCOME
OUTCOME
Grape seed Unclear mechanism. May Level D

Vitis vinifera Herb effect on drug suppress free radicals and Animal study (400 mg/kg of grape
(May reduce cisplatin- rescue the down-regulated seed extract showed protective Theoretical Low No evidence from human studies to
Cisplatin
induced oxidative/ expression of testosterone effects on the testicular toxicity support clinical recommendations
nitrative stress) synthesis induced by induced by cisplatin (10 mg/kg)
cisplatin in rats)
Level B
Human study (300 mg of grape
seed did not significantly
May increase or decrease change metabolic rates of Variable
May increase or blood levels of drug dextromethorphan (CYP2D6 (depending Use with caution under supervision of a
CYP2D6 substrates Unlikely
decrease drug effect via inhibition of this substrate) in healthy volunteers) on drug and healthcare professional and monitor
enzyme activity Level D disease state)
In vitro study (100 mg of grape
seed extract inhibited CYP2D6
activity)
Level D
in vitro study (100 mg of grape
seed extract inhibited CYP2C9
CYP450 enzyme May increase or Variable
and intestinal CYP3A4 activity) in (depending
substrates (CYP2C9, May increase or decrease blood levels Use with caution under supervision of a
vitro and animal study (Wild grape Theoretical on drug and
CYP2E1, Intestinal decrease drug effect of drug via inhibition healthcare professional and monitor
seed procyanidins diminished disease state)
CYP3A4) of these enzyme activities
CYP2E1 expression in vitro
and downregulated the protein
expression level of liver CYP2E1
in rats)
Level D
Herb effect on drug Unclear mechanism. May Animal study (100 mg/kg grape
(May attenuate seed extract showed cardio- No evidence from human studies to
Doxorubicin protect DNA from oxidative Theoretical Low
doxorubicin-induced protective effect without affecting support clinical recommendations
damage
toxicity) antitumor effects of 2mg/kg
doxorubicin)
Level D
Animal study (1 week treatment
May increase or decrease of grape seed extract (80 mg/ Variable
May increase or blood levels of drug via kg) with the administration of (depending Use with caution under supervision of a
Hepatic CYP3A4
decrease drug effect induction of hepatic intravenous midazolam (10mg/kg) Theoretical on drug and healthcare professional and monitor
substrates disease state)
CYP3A4 enzyme activity increased the effect of midazolam)
Midazolam is bio-transformed to
the active metabolite via hepatic
CYP3A4 enzyme
Level B
Green-lipped Green-lipped mussel Conflicting data.
mussel Anticoagulant and May increase drug may increase the risk Several case reports of raised INR. Moderate - Use with caution under supervision of a
effect Small human study found no Theoretical healthcare professional and monitor
antiplatelet agents of bleeding with this High
medication effect on platelet aggregation,
prothrombin time, APTT,
fibrinogen or factor VII
Hawthorn
Anticoagulants and May increase drug May have additive effect Level C Moderate - Use with caution under supervision of a
Crataegus Possible
antiplatelet agents effect to drug Case report High healthcare professional and monitor
monogyna
Pg.26 Pg.27
SEVERITY
DRUG, DRUG CLASS,
of of
of RECOMMENDATIONS
RECOMMENDATION
INTERACTION OUTCOME
OUTCOME
Hawthorn May increase drug May have additive Level A

Crataegus Antihypertensive drugs Clinical trials suggest hypotensive Moderate - Use with caution under supervision of a
effect hypotensive effect Likely
monogyna effect High healthcare professional and monitor
May increase drug May have additive Level B Possible Moderate - Use with caution under supervision of a
Nitrate
effect vasodilation effect Human studies High healthcare professional and monitor
Phosphodiesterase-5- May increase drug May have additive Level D Use with caution under supervision of a
Theoretical High
Inhibitors effect vasodilation effect Animal study healthcare professional and monitor
Anticoagulant and May increase drug May inhibit platelet Level D Use with caution under supervision of a
Holy basil Animal study Theoretical Moderate -
antiplatelet agents effect aggregation High healthcare professional and monitor
Ocimum
tenuiflorum
Level A
May increase drug May have additive Clinical trial in NIDDM patients Moderate - Use with caution under supervision of a
Hypoglycaemic drugs Possible
effect hypoglycaemic effect found holy basil may decrease High healthcare professional and monitor
blood glucose levels
May potentiate Level D

May increase drug Use with caution under supervision of a
Phenobarbital phenobarbitone - induced Animal study Theoretical High
sleeping time
CYP450 enzyme
Hops May increase or decrease Variable
substrates (CYP1A1, May increase or Level D Use with caution under supervision of a
Humulus lupulus CYP1A2, CYP1B1, blood levels of drug via Theoretical (depending
decrease drug effect in vitro studies on drug and healthcare professional and monitor
CYP2C8, CYP2C9, inhibition of these enzyme
disease state)
CYP2C19, CYP3A4) activities
May decrease drug May bind to estrogen Level D Low - Use with caution under supervision of a
Oestrogen Theoretical
effect receptor site in vitro studies Moderate healthcare professional and monitor
May decrease blood levels

Horsetail of drug by increasing renal
Antiretrovirals Level C
Equisetum excretion of drug due to its
(Lamivudine, zidovudine, May decrease drug Case reports (2 patients had
arvense diuretic properties or via Possible High Avoid concomitant use
emtricitabine, efavirenz, effect detectable viral loads)
flavonoids and phenols in
tenofovir)
horsetail that could induce
CYP450 enzyme activity
May increase or decrease Level D Variable
CYP450 enzyme May increase or blood levels of drug via Use with caution under supervision of a
in vitro study (Horsetail extract (depending
substrates (CYP1A2, decrease drug effect inhibition of these enzyme Theoretical on drug and healthcare professional and monitor
CYP2D6) from 800 mg of horsetail)
activities disease state)
May increase adverse May increase blood levels Level C Use with caution under supervision of a
Iodine Amiodarone effect on thyroid Possible Moderate
of iodine Case reports healthcare professional and monitor
function
May increase drug Iodine may precipitate Level D Use with caution under supervision of a
Antithyroid drugs Theoretical Moderate
effect hypothyroidism in vitro studies healthcare professional and monitor
Iodine at high doses may Level C

May increase drug increase the hypothyroid Use with caution under supervision of a
Lithium Case reports and open study in Possible Moderate
side effect activity of lithium healthcare professional and monitor
patients taking lithium
carbonate
Iodine (at very high Level B
Thyroid hormone May increase drug doses) may precipitate Use with caution under supervision of a
Studies in euthyroid subjects - Possible Moderate
effect or exacerbate hyper or healthcare professional and monitor
thyroid function inhibited
hypothyroidism
Pg.28 Pg.29
SEVERITY
DRUG, DRUG CLASS,
of of
of RECOMMENDATIONS
RECOMMENDATION
INTERACTION OUTCOME
OUTCOME
May decrease drug May decrease the Level B Avoid concomitant use. If indicated,
Iron Bisphosphonates effect Possible Moderate interaction may be minimised by taking
absorption of drug Human studies
2 hours before or 6 hours after drug
Use with caution under supervision

of a healthcare professional and
May decrease drug May decrease blood level Level A monitor. Avoid concomitant use. If iron
Captopril Possible Moderate
effect of drug Clinical trials is indicated, interaction may be reduced
by taking 4-6 hour before or 2 hours after
drug
Avoid concomitant use. If iron is

May decrease drug May decrease the Level A indicated, interaction may be minimised
Dolutegravir Likely High
effect absorption of drug Clinical trials by taking 2 hours before or 6 hours after
drug
Level B Avoid concomitant use. If iron is

Methyldopa, levadopa, May decrease drug May decrease the Moderate -
Studies in patients (carbidopa, Likely indicated, interaction may be minimised
carbidopa and effect absorption of drug High
levodopa, methyldopa) and healthy by taking 2 hours before or 6 hours after
penicillamine
subjects (penicillamine) drug
May decrease drug May decrease the Level B High indicated, interaction may be minimised
Mycophenolate Possible
effect absorption of drug Human studies by taking 2 hours before or 6 hours after
drug

Tetracycline and May decrease drug May decrease the Level B Moderate - indicated, interaction may be minimised
Likely
quinolone effect absorption of drug Human studies High by taking 2 hours before or 6 hours after
drug
May decrease drug May decrease the Level B indicated, interaction may be minimised
Thyroid hormone Likely Moderate
effect absorption of drug Human studies by taking 2 hours before or 6 hours after
drug
May increase or May increase or decrease Level C Moderate - Use with caution under supervision of a
Kelp Lithium Possible
decrease drug effect blood level of drug Case reports High healthcare professional and monitor
Fucus vesiculosus
Level A
May increase or Taking kelp may Clinical trial found T3 decreased
Thyroid hormone Use with caution under supervision of a
decrease drug effect precipitate or exacerbate and TSH increased. Possible Moderate healthcare professional and monitor
hyper or hypothyroidism Case reports of hyperthyroidism
and hypothyroidism
Additive effect to drug

Liquorice classes, however may
Glycyrrhiza glabra induce CYP3A4 and Level A
Anticoagulants and May increase or Moderate - Use with caution under supervision of a
CYP2C9 (metabolisers in vitro and in vivo studies and Possible
antiplatelet agents decrease drug effect High healthcare professional and monitor
of warfarin) which may systematic review
decrease blood levels of
warfarin
May have opposing May have hypertensive Level B Moderate - Use with caution under supervision of a
Antihypertensive drugs Possible
effect to drug effect (at high doses 50- Open studies and case report High healthcare professional and monitor
200 g/d)
May decrease drug May decrease blood level Level D Use with caution under supervision of a
Cisplatin
effect of drug Theoretical Moderate -
Animal study High healthcare professional and monitor
Pg.30 Pg.31
SEVERITY
DRUG, DRUG CLASS,
of of
of RECOMMENDATIONS
RECOMMENDATION
INTERACTION OUTCOME
OUTCOME
Corticosteroids May increase drug May increase blood levels Level B Use with caution under supervision of a
Possible Moderate
Liquorice (Prednisolone) effect of drug Open human studies healthcare professional and monitor
Glycyrrhiza glabra
May increase or Level B (depending
CYP3A4 substrates blood levels of drug via Possible
decrease drug effect Human studies on drug and healthcare professional and monitor
inhibition or induction of
disease state)
this enzyme activity
CYP450 enzyme May increase or decrease Variable
May increase or Level D Use with caution under supervision of a
substrates (CYP2C9, blood levels of drug via Theoretical (depending
decrease drug effect in vitro studies on drug and healthcare professional and monitor
CYP2C19, CYP2B6, inhibition of these enzyme
disease state)
CYP2C8) activities
Liquorice may increase Level C
May increase drug the risk of digoxin toxicity High Avoid concomitant use
Digoxin Case report, in vitro study and Possible
side effect (possibly via hypokalaemia animal study
and/or inhibition of P-gp)
Liquorice (at high doses -
over 100 g/d) may increase Level B
Potassium-depleting May increase drug the risk of electrolyte Use with caution under supervision of a
Open human studies (dosage 100- Possible Moderate
diuretics, laxatives side effect disturbances, especially healthcare professional and monitor
200 g/d) and case reports
hypokalaemia, with these
medications
Nutrient effect on drug Level D

Lutein (May prevent cisplatin- May have antioxidant and Animal study (Co-administration No evidence from human studies to
Cisplatin Theoretical Low
induced retinal anti-inflammatory effects of Lutein 0.5 mg/kg and cisplatin support clinical recommendations
damage) 5mg/kg in rats) 
Level D
May increase or decrease in vitro studies showed dose- Variable
CYP3A4 substrates May increase or blood levels of drug via dependent effects. (Lutein (5- Use with caution under supervision of a
Theoretical (depending
decrease drug effect inhibition of this enzyme 100mg/L) had inhibitory effects on on drug and healthcare professional and monitor
activity CYP3A4. Lutein (2.8 mg/L) did not disease state)
inhibit CYP3A4 activity)
May have additive effect Level D

Nutrient effect on
to drug on reactive in vitro study study showed
oxygen species-mediated enhanced cytotoxic effect in
drug (May enhance No evidence from human studies to
Doxorubicin apoptosis. May reduce breast cancer cells. Another in Moderate -
cytotoxicity and Theoretical
doxorubicin-induced vitro and animal study showed High support clinical recommendations
reduce cancer
inflammatory response that the combination of lutein and
resistance)
via inhibition of NF-kB doxorubicin reduced sarcoma cell
expression proliferation and tumour growth.
Nutrient effect on Level D

drug (May prevent May have antioxidant and Animal study (Co-administration No evidence from human studies to
Ethambutol + isoniazid Theoretical Low
isoniazid-induced toxic anti-inflammatory effects of lutein 0.5 mg/kg, ethambutol support clinical recommendations
optic neuropathy) 50 mg/kg and isoniazid 50 mg/kg
in rats) 
Magnesium May have additive

May increase drug
Aminoglycosides inhibitory effects on Level C Moderate -
side effect such as Possible Avoid concomitant use
presynaptic acetylcholine Case report High
muscle weakness
release
Pg.32 Pg.33
SEVERITY
DRUG, DRUG CLASS,
of of
of RECOMMENDATIONS
RECOMMENDATION
INTERACTION OUTCOME
OUTCOME
Electrolyte disturbances,
Magnesium including low serum
magnesium levels, may
Drug effect on nutrient occur with this medication.
Amphotericin-B Level B Assess nutrient status and supplement
(May decrease blood This has been association Possible Moderate
Human studies and case reports if indicated
levels of nutrient) with nephrotoxicity, and
may necessitate stopping
the drug and giving
intravenous electrolyte
replacement
Nutrient effect on drug Magnesium may have Level A

Antiarrythmic drugs (May increase drug additive antiarrythmic Clinical trial using high dose of Use with caution under supervision of a
Possible Low
efficacy) effect magnium (3204 mg/d magnesium healthcare professional and monitor
chloride)
Level B
Anticoagulant and May decrease drug Magnesium may reduce in vitro study and human Moderate -
antiplatelet agents effect the efficacy of warfarin Possible Avoid concomitant use
study based on IV route of High
administration
Antihypertensive drugs May increase drug Magnesium may have Level A Moderate - Use with caution under supervision of a
(calcium channel blockers) Possible High
effect additive hypotensive effect Meta-analysis healthcare professional and monitor
Bisphosphonates may
May decrease drug form complexes with Level A
Bisphosphonates Likely Moderate Avoid concomitant use
effect multivalent cations such as Clinical trials
magnesium
Digoxin, chlorpromazine, Level A (tetracycline and

Magnesium may decrease quinolone antibiotics) Interaction may be minimised by
penicillamine,
May decrease drug the absorption and efficacy Level B (chlorpromazine) separating the administration of
tetracycline, Possible Low
effect of these drugs Level B (penicillamine) medication and magnesium by at least
nitrofurantoin and
Level D (digoxin) 2 hours
quinolone antibiotics
Level D (nitrofurantoin)
May decrease drug May decrease blood level Level B Moderate -
Gabapentin Possible Avoid concomitant use
effect of drug Human studies High
Loop diuretics and, to a

lesser extent, thiazide
Drug effect on nutrient diuretics, interfere with Likely
Loop and thiazide Level B
(May decrease blood magnesium reabsorption (with long Assess nutrient status and supplement
diuretics Multiple studies and case reports Moderate
levels of nutrient) in the kidneys, which term use) if indicated
increase urinary losses
and may reduce serum
magnesium levels
Proguanil may form Level B

May decrease drug
Proguanil complexes with Human studies Possible High Avoid concomitant use
effect
magnesium
Drug effect on nutrient Proton pump Level B Likely

(May decrease blood inhibitors may cause Multiple case reports, case series, (with long Assess nutrient status and supplement
Proton pump inhibitors Moderate
levels of nutrient) hypomagnesaemia if taken reviews term use) if indicated
long-term (usually >1 year)
May have additive Level A

Rocuronium May increase drug Moderate Use with caution under supervision of a
inhibitory effects on Clinical trial using IV Possible
acetylcholine release administration
Pg.34 Pg.35
SEVERITY
DRUG, DRUG CLASS,
of of
of RECOMMENDATIONS
RECOMMENDATION
INTERACTION OUTCOME
OUTCOME
Methionine may decrease Level B

L-methionine May decrease drug Use with caution under supervision of a
Levodopa the efficacy of levodopa in Open study in patients with Possible Low
Parkinson’s disease Parkinson’s disease
Herb effect on drug Milk thistle may have

Milk thistle/St Chemotherapeutic agents cardioprotective activity No significant adverse effect expected.
(Cisplatin, doxorubicin) (May decrease drug Level A
Mary’s thistle against doxorubicin and Possible Low Use with caution uder supervision of a
side effect) Clinical trials
Silybum marianum nephroprotective activity health care professional and monitor
against cisplatin
May increase or blood levels of substrate Level A (depending Use with caution under supervision of a
CYP3A4 substrates Unlikely
decrease drug effect via inhibition or induction Clinical trials on drug and healthcare professional and monitor
disease state)
of this enzyme activity
Variable
May increase or May inhibit or induce P-gp Level D Theoretical (depending Use with caution under supervision of a
P-glycoprotein substrates
decrease drug effect activity in vitro study on drug and healthcare professional and monitor
disease state)
May increase blood levels Level D Use with caution under supervision of a
Raloxifene May increase drug
of drug by inhibiting in vitro study Theoretical Moderate healthcare professional and monitor
effect
glucuronidation of drug
May increase drug May decrease drug hepatic Level B

Sirolimus Possible High Avoid concomitant use
effect clearance Human studies
May increase blood level
May increase or of drug via inhibition of Level B Avoid concomitant use depending on
Tamoxifen Possible High
decrease drug effect CYP2CP, CYP3A4 and P-gp Human studies severity of disease state
activity
Anticoagulant and May increase drug May have additive effect Level C Moderate -
Nicotinic acid Possible Avoid concomitant use
antiplatelet agents effect to drug Case reports (Warfarin) High
Drug effect on nutrient

May reduce the clearance
(May increase or Level B Possible Moderate - Use with caution under supervision of a
Aspirin of niacin by competing for
decrease niacin side Human studies High healthcare professional and monitor
glycine conjugation
effect)
Bile acid sequestrants May increase drug Level C Use with caution under supervision of a
Mechanism unknown Possible Moderate
side effect Case report healthcare professional and monitor
May increase drug May increase risk of Level C Possible Moderate Use with caution under supervision of a
Gemfibrozil
side effect myopathy Case report healthcare professional and monitor
High dose nicotinic acid
HMG-CoA reductase (1500 mg/d) may increase Level C Possible Low - Use with caution under supervision of a
May increase drug
inhibitors (statins) the risk of rhabdomyolysis Case report Moderate healthcare professional and monitor
side effect
and myopathy with statins
May decrease drug May decrease blood levels Level A Use with caution under supervision of a
Thyroid hormone Possible Moderate
effect of drug Clinical trials healthcare professional and monitor
Drug effect on nutrient Low -
May have additive effect to Level C Possible Use with caution under supervision of a
Transdermal nicotine (May increase nutrient Moderate
nutrient Case reports healthcare professional and monitor
side effect)
Level A
Oats Clinical trials find oats decrease
(Avena sativa) Antihypertensive drugs May increase drug May have additive Moderate - Use with caution under supervision of a
effect hypotensive effect blood pressure. In one trial, 73% Likely
High healthcare professional and monitor
of patients were able to stop or
reduce their medication
Pg.36 Pg.37
SEVERITY
DRUG, DRUG CLASS,
of of
of RECOMMENDATIONS
RECOMMENDATION
INTERACTION OUTCOME
OUTCOME
Oats May decrease drug May reduce intestinal Level D Low - Use with caution under supervision of a
Atorvastatin Theoretical
(Avena sativa) effect absorption of atorvastatin Animal study Moderate healthcare professional and monitor
May increase drug May decrease metabolism Level B Use with caution under supervision of a
Intramuscular cortisone Possible Moderate
Para- effect of cortisone Human study healthcare professional and monitor
aminobenzoic
acid (PABA)
Sulphonamides and May decrease drug May inhibit antimicrobial Level B
sulphones (Dapsone) in vitro studies and human study Possible Moderate Avoid concomitant use
effect activities of drug
May have additive Level B

Pau d’Arco Anticoagulants and May increase drug One uncontrolled study found very Use with caution under supervision of a
anticoagulant effect (at Moderate -
antiplatelet agents effect very high doses) high dose of isolated constitutent Theoretical healthcare professional and monitor
High
prolonged prothrombin time
Pelargonium contains
Pelargonium coumarin which Level D Moderate - Use with caution under supervision of a
Anticoagulant and May increase drug
Pelargonium may reduce platelet Animal study suggests interaction Theoretical High healthcare professional and monitor
sidoides aggregation, additive unlikely
effect to drug
Level D
May decrease drug May have opposing effect Theoretical Moderate -
Immunosuppressants in vitro studies find pelargonium Avoid concomitant use
effect to drug High
has immune modulatory activity
May increase drug May increase blood levels Level D

Ciclosporin Theoretical High Avoid concomitant use
Peppermint effect of drug Animal study
Mentha x piperita
May increase or decrease Level B
blood levels of drug via Open study using felodipine,
CYP450 enzyme inhibition of CYP1A2, Variable
simvastatin (CYP3A4 substrates) Use with caution under supervision of a
substrates (CYP3A4, May increase or CYP2C9 and CYP2C19 Possible (depending
Level D on drug and healthcare professional and monitor
CYP1A2, CYP2C9, decrease drug effect enzyme activities and Animal study (CYP1A2, CYP2C0 disease state)
CYP2C19) induction of intestinal and CYP2C19 substrates)
CYP3A4 enzyme activity
Phytosterols / Level A No significant adverse effect expected.

Lipid-lowering agents May increase drug May have additive LDL-c Low -
Plant sterols Clinical trials and systematic Likely Use with caution uder supervision of a
(Statins and ezetimibe) effect lowering effect Moderate
reviews health care professional and monitor
Potassium ACE inhibitors,

angiotensin receptor Potassium may increase Likely
May increase drug Level C (dose- Moderate -
blockers and potassium- Avoid concomitant use
side effect the risk of hyperkalaemia Multiple case reports dependant) High
sparing diuretics
Nutrient effect on May restore gut flora Level A

Probiotics No significant adverse effects expected.
Antibiotics drug (May decrease and reduce diarrhoea Multiple trials in adults and Likely Low
secondary to antibiotic Supplementation may be beneficial
drug side effect) children taking antibiotics
therapy
Lactobacillus Nutrient effect on drug Level A

Combination therapy may
species including: Fluconazole (May increase drug Clinical trial in women with No significant adverse effects expected.
improve clinical outcome Likely Low
L. acidophilus efficacy) vulvovaginal candidiasis Supplementation may be beneficial
L. reuteri
L.Rhamnosus Possible
Immunosuppressants May predispose May predispose Level C (depending Moderate - Avoid concomitant use in critically ill and
GR-1 opportunistic infection due Case report immunocompromised patients
opportunistic infection on disease High
L. Reuteri RC-14 to immunosuppression state)
Pg.38 Pg.39
SEVERITY
DRUG, DRUG CLASS,
of of
of RECOMMENDATIONS
RECOMMENDATION
INTERACTION OUTCOME
OUTCOME
Psyllium husk Psyllium may decrease

Hypoglycaemic drugs May increase drug Level A Possible Moderate - Use with caution under supervision of a
post-prandial blood healthcare professional and monitor
effect Clinical trial High
glucose levels
Psyllium may decrease Variable

(depending Interaction may be minimised by
Oral drugs and nutritional May decrease drug the absorption of oral Level B separating dose of medication and
Possible on drug
supplements effect drugs if doses are taken Human studies and disease psyllium by at least 2 hours
comcommitantly state)
Quercetin Level A
Clinical trial found quercetin
supplementation reduced systolic,
diastolic and mean arterial
Antihypertensive May increase drug May have additive effect pressure in stage 1 hypertensive Moderate - Use with caution under supervision of a
drugs (Calcium channel effect to drug subjects Possible High healthcare professional and monitor
blockers) Level D
in vivo study found increased
bioavailability for diltiazem but
mechanism is unknown
May increase blood level

of drug by displacing
Anticoagulant and May increase drug Level D Moderate - Use with caution under supervision of a
warfarin from human Theoretical
serum albumin binding
in vitro study High healthcare professional and monitor
site and CYP2C9 inhibition

substrates (CYP1A1, May increase or blood levels of enzyme Level B (depending Use with caution under supervision of a
CYP1A2, CYP2C8, Human, animal and in vitro Possible on drug healthcare professional and monitor
decrease drug effect substrates via inhibition of and disease
CYP3A4, CYP2C9, these enzyme activities studies
state)
CYP2D6)
Organic anion Variable

Quercetin may inhibit Use with caution under supervision of a
transporting polypeptide May increase drug Level B Possible (depending
OATP1B1-mediated on drug healthcare professional and monitor
(OATP) substrates effect Human studies
transport and disease
(OATP1B1) state)
Variable
May increase drug Quercetin may inhibit P-gp Level B (depending Use with caution under supervision of a
P-glycoprotein substrates pump efflux Possible on drug
effect Human studies healthcare professional and monitor
and disease
state)
Red clover/ Anticoagulant and May increase drug May have additive effect Level D Moderate - Use with caution under supervision of a
Isoflavones antiplatelet agents effect to drug Animal study and in vitro study Theoretical High healthcare professional and monitor
Trifolium pratense
substrates (CYP1A2, May increase or blood levels of drug via Level D (depending Use with caution under supervision of a
in vitro study Theoretical on drug
CYP2C9,CYP2C19, decrease drug effect inhibition of these enzyme healthcare professional and monitor
and disease
CYP3A4) activities
state)
May decrease drug
May increase drug Level D Use with caution under supervision of a
Daunorubicin metabolism due to Theoretical Moderate -
side effect in vitro study High healthcare professional and monitor
decrease in glutathione
cellular concentration
May increase blood levels
May increase drug Level D Moderate -
Digoxin of drug via inhibition of Theoretical Avoid concomitant use
effect in vitro study High
P-gp expression
Pg.40 Pg.41
SEVERITY
DRUG, DRUG CLASS,
of of
of RECOMMENDATIONS
RECOMMENDATION
INTERACTION OUTCOME
OUTCOME
Red clover/ Red clover binds to Variable

Isoflavones May increase or estrogen receptors and is Level D Theoretical (depending Use with caution under supervision of a
Oestrogen capable of acting as both on drug
Trifolium pratense decrease drug effect Animal study healthcare professional and monitor
agonists and antagonists and disease
state)
May increase drug May have additive Level D Moderate Use with caution under supervision of a
Hypoglycaemic drugs Theoretical
effect hypoglycaemic effect to in vitro study - High healthcare professional and monitor
drug
May increase drug May have additive lipid- Level A Low - Use with caution under supervision of a
Lipid-lowering drugs Possible
effect lowering effect to drug Clinical trials Moderate healthcare professional and monitor
May increase drug Level C Moderate

Methotrexate Mechanism unknown Possible Avoid concomitant use
side effect Case report - High
Red clover may have

May increase drug oestrogenic activity and Level B
Tamoxifen Possible High Avoid concomitant use
effect may theoretically interfere Human studies
with tamoxifen efficacy
May increase blood levels Level D

May increase drug Moderate Avoid concomitant use
Vinblastine of drug via inhibition of Theoretical
effect in vitro study - High
P-gp expression
Saw palmetto Level D

Serenoa repens May have additive effect in vitro study (Drug-herb
5-alpha reductase May increase drug interaction was not directly Use with caution under supervision of a
to drug due to inhibitory Theoretical Moderate
inhibitors effect studied. Saw palmetto extract healthcare professional and monitor
effect on 5-alpha reductase
showed an inhibitory effect on
5-alpha reductase activity)
Level D
in vitro study (Drug-herb
interaction was not directly
Androgen (Testosterone May decrease drug May have inhibtory effect studied. Saw palmetto decreased Theoretical Moderate Use with caution under supervision of a
and dihydrotestosterone) effect on 5-alpha reductase the androgen-sensitive LNCaP healthcare professional and monitor
human prostate cancer cell number
in the presence of testosterone or
dihydrotestosterone)
Level C
May increase drug May have additive effect Case report (Drug-herb interaction
Anticoagulants and Use with caution under supervision of a
was not directly studied. Saw Theoretical Moderate -
antiplatelet agents effect to drug High healthcare professional and monitor
palmetto can lead to prolonged
bleeding time)
Level B
Human study (Study with 12
May increase or decrease volunteers showed interaction Variable
CYP450 enzyme with CYP1A2, 3A4, 2E1, 2D6 is (depending Use with caution under supervision of a
May increase or blood level of drugs via
substrates unlikely) Unlikely on drug healthcare professional and monitor
decrease drug effect inhibition of these enzyme
(CYP1A2,3A4,2E1,2D6) Level D and disease
activities state)
in vitro study (Saw palmetto
extract showed potent inhibition
of CY3A4, CYP2D6 and CYP2C9)
Soy/isoflavones May increase drug May have additive Level A Moderate - Use with caution under supervision of a
Glycine max Antihypertensive drugs hypotensive effect to drug Clinical trials Possible healthcare professional and monitor
effect High
Pg.42 Pg.43
SEVERITY
DRUG, DRUG CLASS,
of of
of RECOMMENDATIONS
RECOMMENDATION
INTERACTION OUTCOME
OUTCOME
Soy protein may decrease Level B

Soy/isoflavones Anticoagulant and May decrease drug Moderate -
the anticoagulant effect of Human study and case report Possible Avoid concomitant use
Glycine max antiplatelet agents effect High
warfarin (Warfarin)
May increase drug Level D Moderate - Avoid High doses (>7 g) prior to surgery.
Chemotherapeutic agents Mechanism unknown Theoretical Use with caution under supervision of a
effect in vitro study High
May increase or decrease
blood levels of drug via Level B Variable
CYP450 enzyme inhibition of CYP1A2 and Human studies (CYP2C9 and 3A4)
May increase or (depending
substrates (CYP2C9, CYP2E1 enzyme activities Level D Possible on drug
decrease drug effect healthcare professional and monitor
CYP2E1, CYP3A4) and induction of CYP2C9 in vitro studies (CYP1A2) and and disease
and CYP3A4 enzyme animal study (CYP2E1) state)
activities
Diuretic drugs May increase drug May have additive diuretic Level D Theoretical Use with caution under supervision of a
effect Moderate
effect to drug Animal study healthcare professional and monitor
Gemfibrozil May increase drug May increase blood levels Level D Theoretical Use with caution under supervision of a
side effect of drug Moderate
Animal study healthcare professional and monitor
May have additive Use with caution under supervision of a

May increase drug Level A Moderate -
Hypoglycaemic drugs hypoglycemic effect to Possible
effect Clinical trials High healthcare professional and monitor
drug
HMG-CoA reductase
inhibitors May increase drug May have additive effect Level A Low - Use with caution under supervision of a
Possible Moderate
(Atorvastatin, effect to drug Clinical trials healthcare professional and monitor
simvastatin)
Tyramine in fermented
Level D
Monoamine Oxidase May increase drug soy products may cause Moderate - Use with caution under supervision of a
in vitro studies (fermented soy Theoretical
Inhibitors (MAOI) effect additive blood pressure High healthcare professional and monitor
products contain tyramine)
effect
Variable
May increase drug May increase blood level of Level D (depending Use with caution under supervision of a
P-glycoprotein substrates Theoretical on drug
(daunorubicin) effect drug via inhibition of P-gp in vitro study and disease
state)
May increase drug May have additive effect Level A Use with caution under supervision of a
Progesterone Possible Moderate
side effect to drug Clinical trials healthcare professional and monitor
Soy may have estrogenic
May decrease drug activity and may Level D
Tamoxifen Moderate -
effect Animal study Possible Avoid concomitant use
theoretically interfere with High
tamoxifen activity
May decrease drug Soy may decrease blood Level B Use with caution under supervision of a
Thyroid hormone Possible Moderate
effect levels of drug Human study and case report healthcare professional and monitor
St John’s wort Level A

Hypericum Multiple studies with oral
perforatum contraceptives, warfarin, protease
Variable
May increase or decrease inhibitors, reverse transcriptase
CYP450 enzyme (depending
Avoid or consult with healthcare
May increase or blood levels of drug via inhibitors, simvastatin, on drug
substrates (CYP2C19, Likely professional before concomitant us
decrease drug effect induction of these enzyme atorvastatin, verapamil, irinotecan, and disease
CYP3A4)
activities imatinib, methadone, cyclosporin, state)
tacrolimus, fexofenadine,
nifedipine, midazolam,
omeprazole, voriconazole
Pg.44 Pg.45
SEVERITY
DRUG, DRUG CLASS,
of of
of RECOMMENDATIONS
RECOMMENDATION
INTERACTION OUTCOME
OUTCOME

St John’s wort Level B (depending
Hypericum substrates (CYP2B6, May increase or blood levels of drug via Possible Avoid or consult with healthcare
Human study of the various CYP on drug
perforatum CYP2C9, CYP2E1 and CYP decrease drug effect induction of these enzyme and disease
professional before concomitant use
enzymes
1A2) activities state)
May decrease drug St John’s wort may Level A

Digoxin decrease blood levels of Possible Moderate Avoid concomitant use
effect Clinical trials
this medication
Pethidine and May increase drug May have additive Level D

Theoretical Moderate Avoid concomitant use
dextromethorphan side effect serotonergic effect in vitro and animal studies
St John’s wort may Variable

decrease blood levels Level A
May decrease drug (depending Avoid or consult with healthcare
P-glycoprotein substrates of these medications Clinical trials - interaction seen at Possible
effect on drug professional before concomitant use
via induction of P-gp doses over 2 g/d (dried herb) and disease
expression state)
Hypericin content of Level C

May increase drug St John’s wort may Use with caution under supervision of a
Photosensitising drugs Case study of aminolevulinic acid. Possible Moderate
side effect increase the possibility of healthcare professional and monitor
in vitro study
photosensitivity reactions
St John’s wort has additive Level B

Prescription serotonergic effects that Multiple case reports of
antidepressants - May increase drug can lead to serotonin serotonergic syndrome. Human Moderate -
Likely Avoid concomitant use
tricyclics, SSRIs and effect toxicity when taking the study in patients taking High
SNRIs, MAOIs respective antidepressants amitriptyline. Case report of
concomitantly monoxidase activity
Triptans May increase drug May have additive Level C Possible Moderate - Avoid concomitant use
effect serotonergic effect Case report High
Tribulus Level D
Tribulus terrestris in vitro and animal studies (Drug-
Antihypertensive drugs May increase drug May have additive effect herb interaction was not directly Theoretical Moderate - Use with caution under supervision of a
(ACE inhibitors) effect to drug studied. 10 mg/kg of lyophilized High healthcare professional and monitor
aqueous extract of tribulus fruit
decreased ACE activity in rats)
Level D
Herb effect on drug Animal study (Tribulus fruit
May decrease cisplatin
(May decrease renal extract at dose 100, 300 and 500 No evidence from human studies to
Cisplatin accumulation in kidney via Theoretical Low
side effects induced by mg/kg body weight provided support clinical recommendations
diuretic effect of tribulus
cisplatin) protection against the cisplatin
induced renal toxicity in mice)
Herb effect on Level D

drug (May improve Animal study (Tribulus dry extract
May have antioxidative No evidence from human studies to
Cyclophosphamide reproductive ameliorated the damage induced Theoretical Low
effect support clinical recommendations
damage induced by by cyclophosphamide in mice
cyclophosphamide) testes)
Level A
Clinical trials (Drug-herb
interaction was not directly
Hypoglycaemic drugs May increase drug May have additive effect studied. Tribulus terrestris Theoretical Moderate -
effect to drug High healthcare professional and monitor
showed a significant blood
glucose-lowering effect in diabetic
women compared to placebo.)
Pg.46 Pg.47
SEVERITY
DRUG, DRUG CLASS,
of of
of RECOMMENDATIONS
RECOMMENDATION
INTERACTION OUTCOME
OUTCOME
Turmeric May have additive effect to Level D

Anticoagulants and May increase drug Moderate - Use with caution under supervision of a
Curcuma longa drug (antiplatelet effect) at in vitro studies find antiplatelet Theoretical
antiplatelet agents effect High healthcare professional and monitor
high doses (o ver 15 g/d) effect
May increase or Antioxidant effect of Level D Moderate -

Chemotherapeutic agents curcumin may inhibit Theoretical Avoid concomitant use
decrease drug effect Conflicting data in vitro study High
apoptosis

May increase or Level D (depending Use with caution under supervision of a
CYP1A1 substrates substrate blood levels via Theoretical on drug
decrease drug effect inhibition of this enzyme in vitro and animal studies healthcare professional and monitor
and disease
activity state)

May increase or substrate blood levels via Level B (depending Use with caution under supervision of a
CYP1A2 substrates Human studies Possible on drug
decrease drug effect inhibition of this enzyme and disease
activity state)

CYP2A6 substrates May increase or substrate blood levels via Level B (depending Use with caution under supervision of a
decrease drug effect Human studies Possible on drug
induction of this enzyme healthcare professional and monitor
and disease
activity state)

May increase or substrate blood levels via Level C (depending Use with caution under supervision of a
CYP3A4 substrates Case report on tacrolimus Possible on drug
decrease drug effect inhibition of this enzyme and disease
activity state)
Variable
May increase or May compete with Level D (depending Use with caution under supervision of a
Oestrogen estrogen binding sites Theoretical on drug
decrease drug effect in vitro study healthcare professional and monitor
(dose dependent) and disease
state)
May increase drug May have additive Level B Moderate - Use with caution under supervision of a
Hypoglycaemic drugs Possible
effect hypoglycaemic effect Human study (for glibenclamide) High healthcare professional and monitor
May increase drug May increase blood levels Level D Theoretical Use with caution under supervision of a
Norfloxacin Moderate
effect of drug Animal study healthcare professional and monitor
Variable
May increase drug May increase drug blood Level D Theoretical (depending Use with caution under supervision of a
P-glycoprotein substrates on drug
effect levels via inhibition of P-gp Animal study healthcare professional and monitor
and disease
state)
May increase drug blood Level D Use with caution under supervision of a
May increase drug Moderate -
Paclitaxel levels due to increased Animal study Theoretical healthcare professional and monitor
effect High
bioavailability
May increase drug May increase drug blood Level B Moderate -

Sulfasalazine Possible Avoid concomitant use
effect levels Human studies High
Valerian Level C
Valeriana May increase Case report (Case of patient
Benzodiazepines May have additive effect Moderate -
officinalis inhibitory activitiy of self-medicating with valerian and Possible Avoid concomitant use
(Lorazepam, alprazolam) to drug by binding to the High
drug and drug side passion flower while on 2 mg
GABA receptors
effect lorazepam)
Pg.48 Pg.49
SEVERITY
DRUG, DRUG CLASS,
of of
of RECOMMENDATIONS
RECOMMENDATION
INTERACTION OUTCOME
OUTCOME
Valerian Level A
Valeriana Clinical trial (1000 mg of valerian
officinalis tablet daily did not significantly
change CYP3A4 and CYP2D6
Variable
May increase or decrease activities) (depending
CYP450 enzyme Level D Use with caution under supervision of a
May increase or blood levels of drug via on drug
substrates (CYP3A4, Unlikely
decrease drug effect inhibition or induction of in vitro studies showed moderate and disease healthcare professional and monitor
CYP2D6) to potent CYP3A4 inhibitory state)
these enzyme activities
effects by valerian. Another in
vitro study showed an induction
of CYP3A4 and CYP2D6 activities
by valerian
Level A
Herb effect on Clinical trial (4 weeks treatment
drug (May prevent May act on GABA-A of valerian 530 mg at night 1 Use with caution under supervision of a
Efavirenz efavirenz-induced receptor and boost Possible Low
hour before sleep improved healthcare professional and monitor
neuropsychiatric melatonin release neuropsychiatric adverse effects
adverse effects) of efavirenz such as anxiety and
insomnia)
Level D Variable
UGT substrates (UGT1A1, May have inhibitory effects in vitro study (Inhibitory effects (depending
May decrease Use with caution under supervision of a
UGT2B7) (Paracetamol, on glucuronidation of valerian on the glucuronidation Theoretical on drug
excretion of drug healthcare professional and monitor
estradiol, morphine) of paracetamol, estradiol and and disease
morphine) state)
Vitamin A Assess nutrient status and supplement if

Orlistat Vitamin A absorption may Level A Likely Low indicated. Interaction may be minimised
(May decrease nutrient
be decreased by orlistat Clinical trials by separating dose of medication and
effect)
vitamin A by at least 2 hours
May increase drug May have additive effect Level A

Likely High Avoid concomitant use
Retinoids side effect to drug Systematic review
May increase risk of Level D

May have Vitamin A and tetracycline are in
Tetracycline benign intracranial Possible High Avoid concomitant use
additive effect to drug the list of medications that may
hypertension
produce intracranial hypertension
Vitamin B2 Vitamin B2 found to have

Nutrient effect on drug migraine preventive Level B
Migraine drugs Theoretical Low Supplementation may be beneficial
(May increase drug activity. No additive effect Human studies
effect) with antimigraine drugs
investigated
Vitamin C May increase drug

Vitamin C chelates Level B Moderate -
Aluminium-containing side effect (especially Possible Avoid concomitant use
alumium and may increase Case reports and human study High
antacids in renal failure
aluminium absorption
patients)
Level A
Clinical trial (6 weeks treatment
Antihypertensive drugs + May have opposing Unknown mechanism of with both vitamin C 500 mg and Moderate - Avoid combination of vitamin C and
grape seed polyphenol 1000 mg Possible
Grape seed effect to drug the interaction High grape seed in hypertensive patients
daily increased blood pressure in
hypertensive patients)
Pg.50 Pg.51
SEVERITY
DRUG, DRUG CLASS,
of of
of RECOMMENDATIONS
RECOMMENDATION
INTERACTION OUTCOME
OUTCOME
Drug effect on nutrient Calcium channel blockers
Vitamin C Calcium channel blockers may inhibit uptake of Level D Moderate - Assess nutrient status and supplement
(May decrease Theoretical
(Nifedipine) vitamin C by intestinal in vitro study High if indicated
nutrient effect)
cells
Antioxidants like vitamin C
may reduce the activity of
Chemotherapeutic agents May increase or chemotherapeutic drugs or Level D Moderate -
Theoretical Avoid concomitant use
decrease drug effect may make chemotherapy in vitro study High
more effective by reducing
oxidative stress
Vitamin C may cause

May have opposing transient deterioration Level C
Desferrioxamine Possible High Avoid concomitant use
effect to drug of cardiac function with Case reports
desferrioxamine
May increase drug May increase blood levels Level B Use with caution under supervision of a
Oestrogen Possible Moderate
effect of drug Human studies healthcare professional and monitor
High doses of vitamin

May increase drug C (>3 g) may decrease Level B Moderate - Use with caution under supervision of a
Paracetamol Possible
effect the elimination rate of Human studies High healthcare professional and monitor
paracetamol
Protease inhibitors May decrease drug May decrease blood levels Level B Moderate -
Open study Possible Avoid concomitant use
(Indinavir) effect of drug High
Vitamin D3 May increase drug May increase drug Level D Use with caution under supervision of a
Aluminium Theoretical Moderate
effect absorption Animal study healthcare professional and monitor
Vitamin D3 improves
Nutrient effect on No significant adverse effect expected.
bone mineral density and Level A Possible Low
Anticonvulsants drug (May decrease Assess nutrient status and supplement
decreases the risk of bone- Clinical trials
drug side effect) if indicated
related side effect
Vitamin D3 decreases
Antiretrovirals Nutrient effect on the risk of bone mineral No significant adverse effect expected
(Efavirenz, emtricitabine drug (May decrease Level A Low
density loss with the Possible in humans. Assess nutrient status and
and tenofovir) drug side effect) Clinical trials
initiation of antiviral supplement if indicated
agents
May decrease blood level Level B Low - Use with caution under supervision of a
Atorvastatin Nutrient effect on drug of drugs via induction of Possible
Human studies Moderate healthcare professional and monitor
CYP3A4
Nutrient effect on drug No significant adverse effect expected

Combination therapy may Level A Possible Low in humans. Use with caution under
Budesonide (oral) (May increase drug
improve clinical outcome Clinical trials supervision of a healthcare professional
efficacy)
and monitor
May have opposing

Calcium channel blockers May decrease effect to drug. Decrease Level C Moderate -
Possible
(Diltiazem and verapamil) drug effect (Dose drug effect by causing Case report High Avoid concomitant use
dependent) hypercalcemia with high
doses of vitamin D3
Drug effect on nutrient Level B

Chemotherapeutic agents Mechanism unknown Possible Moderate - Assess nutrient status and supplement
(May decrease Human study
High if indicated
nutrient effect)
Pg.52 Pg.53
SEVERITY
DRUG, DRUG CLASS,
of of
of RECOMMENDATIONS
RECOMMENDATION
INTERACTION OUTCOME
OUTCOME
Vitamin D3 Cimetidine inhibits an

enzyme involved in
Cimetidine conversion of vitamin D Level B Assess nutrient status and supplement
(May decrease Possible Moderate
to its active form in the Human study if indicated
nutrient effect)
liver and affect vitamin D
metabolism in men
Level B Use with caution under supervision of a
May increase drug May increase drug effect Moderate -
Digoxin Human study suggests no Possible healthcare professional and monitor
side effect via inhibition of P-gp High
significant interaction
Heparin and low- Drug effect on nutrient Heparin and LMWH

decrease the metabolism Level B Moderate - Assess nutrient status and supplement
molecular-weight heparin (May decrease Possible
of vitamin D to its active Human studies High if indicated
(LMWH) nutrient effect)
form
Assess nutrient status and supplement if
Drug effect on nutrient Vitamin D absorption may Level A
Orlistat indicated. Interaction may be minimised
(May decrease be decreased by orlistat Clinical trials Likely Low
by separating dose of medication and
nutrient effect)
vitamin D by at least 2 hours
Sirolimus May decrease drug May increase the Level B

effect metabolism of sirolimus Human study Theoretical High Avoid concomitant use
Vitamin D3 may increase Level A

the risk of hypercalcaemia Multiple case reports. Use with caution under supervision of a
Thiazide diuretics May increase drug Moderate
if taken with calcium Clinical trial in hypoparathyroid Likely
side effect healthcare professional and monitor
supplements and/or patients taking vitamin D and
thiazide diuretics thiazide diuretics
Level A
Vitamin E
Conflicting data.
Clinical studies have found no
Anticoagulants and May increase drug Vitamin E may increase interaction with warfarin or Moderate - Use with caution under supervision of a
antiplatelet agents effect risk of bleeding Unlikely
aspirin, or inhibition of platelet High healthcare professional and monitor
aggregation.
Case reports of interaction with
warfarin and reduced clotting exist
May decrease drug Antioxidant effects may Level D Moderate -

Chemotherapeutic agents Theoretical Avoid concomitant use
effect reduce activity of drug in vitro study High
Nutrient effect on drug Vitamin E may decrease Level A

the incidence and severity Use with caution under supervision of a
Cisplatin (May decrease drug Clinical trials in patients taking Likely Low
of neurotoxicity caused by healthcare professional and monitor
side effect) vitamin E and cisplatin
cisplatin
May increase or Level D (depending Use with caution under supervision of a
CYP3A4 substrates blood levels of drug via Theoretical
decrease drug effect in vitro study on drug healthcare professional and monitor
induction of this enzyme and disease
activity state)
Nutrient effect on drug Vitamin E may prevent

Nitroglycerine (May decrease drug nitrate tolerance when Level A Possible Use with caution under supervision of a
Low
side effect) given concurrently with Clinical trial healthcare professional and monitor
transdermal nitroglycerin
Drug effect on nutrient Assess nutrient status and supplement if

Orlistat Vitamin E absorption may Level A indicated. Interaction may be minimised
(May decrease Likely Low
be decreased by orlistat Clinical trial by separating dose of medication and
nutrient effect)
vitamin E by at least 2 hours
Pg.54 Pg.55
SEVERITY
DRUG, DRUG CLASS,
of of
of RECOMMENDATIONS
RECOMMENDATION
INTERACTION OUTCOME
OUTCOME
Vitamin K may decrease
Vitamin K
activity of warfarin and
Anticoagulant and May decrease drug other coumarin (oral) Level A Moderate -
Likely Avoid concomitant use
antiplatelet agents effect anticoagulants. Avoid Clinical trials and meta-analyses High
changes in vitamin K
intake whilst taking these
drugs
Level D
Human study that suggests higher
intake of vitamin K1 is associated
May increase drug May have additive with increased insulin sensitivity Use with caution under supervision of a
Hypoglycaemic drugs Theoretical Moderate -
effect hypoglycaemic effect and reduced postprandial glucose High healthcare professional and monitor
levels in adults but no direct
study between vitamin K and
hypoglycaemic drugs
Vitex Binding to dopamine-2 Level D

Vitex agnus- Dopamine receptor May increase or receptor and suppresses in vitro study (Drug-herb Use with caution under supervision of a
castus antagonist and agonist decrease drug effect prolactin release due to interaction was not directly Theoretical Moderate healthcare professional and monitor
dopamine agonistic effects studied)
of vitex
Level D
in vitro and animal studies
Oestrogen, contraceptive May increase or Via hormone modulating (Drug-herb interaction was not Use with caution under supervision of a
drugs decrease drug effect activity directly studied. Vitex may exhibit Theoretical Moderate healthcare professional and monitor
estrogen receptor binding effects
and induce progesterone receptor
expression)
Willow May have additive adverse

Salix alba effect to drug as willow
May increase drug contains salicin, a plant Level C Use with caution under supervision of a
Acetazolamide Possible Moderate healthcare professional and monitor
side effect salicylate which may Case report
increase unbound plasma
level of acetazolamide
Level B
May have additive effect Cohort study reported increased
Anticoagulants and May increase drug self-reported bleeding when taken Moderate -
to drug as willow contains Possible Avoid concomitant use
antiplatelet agents effect with warfarin. High
salicin, a plant salicylate
Clinical trial using herb alone
found a mild antiplatelet effect
Level D
Withania
Animal study (Co-administration
Withania
Hypoglycaemic drugs May increase drug May have additive effect of extract of withania coagulans Moderate - Use with caution under supervision of a
coagulans Theoretical
(Glipizide) effect to drug Dunal dried fruit (1000 mg/kg) and High healthcare professional and monitor
glipizide (1 mg/kg or 2.5 mg/kg) for
4 weeks in rats)
Withania See “Ashwagandha”

Withania somnifera
Zinc ACE inhibitors, Drug effect on nutrient Urinary zinc excretion may
angiotensin receptor (May decrease be increased with long- Level A Assess nutrient status and supplement
Possible Low
blockers, thiazide nutrient effect) term use of these drugs Clinical trials if indicated
diuretics
Pg.56 Pg.57
SEVERITY
DRUG, DRUG CLASS,
of of
of RECOMMENDATIONS
RECOMMENDATION
INTERACTION OUTCOME
OUTCOME
Zinc Zinc may decrease Level B Interaction may be minimised by

Cephalexin May decrease drug absorption of drug by Human study Possible High separating dose of zinc at least 3 hours
effect chelating with drug after taking cephalexin
Low zinc status is common
Nutrient effect on drug in diabetic patients. Zinc Assess nutrient status and supplement
Hypoglycaemic drugs supplementation and Level A if indicated. Monitor blood glucose level
(May increase drug Possible Low
normalisation of zinc Clinical trials and alter drug dose if required under the
efficacy)
levels has been shown to supervision of a healthcare professional
improve glycaemic control
May decrease drug May decrease blood level Level A

Integrase inhibitors of drug by chelating with Likely High Avoid concomitant use
effect Systematic review
drug
Interaction may be minimised by
May decrease drug Zinc may decrease the Level A
Penicillamine Possible Moderate separating dose of medication and zinc
effect activity of penacillamine Clinical trial
by at least 2 hours
Tetracycline or quinolone Interaction may be minimised by taking

May decrease drug Zinc may decrease the Level B
antibiotics (not Possible Moderate tetracycline at least 2 hours before, or
effect absorption and blood Multiple studies
doxycycline) 4-6 hours after zinc supplement
levels of these drugs
Pg.58 Pg.59
INDEX INDEX
A Echinacea L S
Acidophilus Echinacea purpurea Liquorice Saw palmetto
See “Probiotics” Evening primrose oil Glycyrrhiza glabra Serenoa repens
Alpha-lipoic acid (ALA) Lutein Soy/isoflavones
Andrographis Glycine max
Andorgraphis paniculata
F St John’s wort
Ashwagandha
Fenugreek M Hypericum perforatum
Trigonella foenum-graecum Magnesium
Withania somnifera
Feverfew L-methionine
Astragalus
Astragalus membranaceus
Tanacetum parthenium Milk thistle/St Mary’s thistle T
Fish oil Tribulus
Silybum marianum
Flaxseed oil Tribulus terrestris
B Folic acid Turmeric
Bacopa N Curcuma longa
See “Brahmi” Nicotinic acid
Betacarotene
G
Bilberry
Garlic V
Vaccinium myrtillus
Allium sativum O Valerian
Ginger Oats Valeriana officinalis
Black cohosh
Zingiber officinale (Avena sativa) Vitamin A
Cimicifuga racemosa
Ginkgo Vitamin B2
Boswellia
Ginkgo biloba Vitamin C
Boswellia serrata
Ginseng (Korean) P Vitamin D3
Brahmi Para-aminobenzoic acid
Panax ginseng Vitamin E
Bacopa monnieri (PABA)
Ginseng (Siberian) Vitamin K
Bromelain Elutherococcus senticosus Pau d’Arco
Vitex
Glucosamine Tabebuia avellanedae
Vitex agnus-castus
Pelargonium
C Green-lipped mussel
Pelargonium sidoides
Calcium Grape seed
Celery Vitis vinifera Peppermint W
Mentha x piperita Willow
Apium graveolens)
Phytosterols / Plant sterols Salix alba
Chaste Tree
See “Vitex”
H Potassium Withania
Hawthorn Probiotics Withania somnifera
Chondroitin sulfate
Crataegus monogyna Lactobacillus species See “Ashwagandha”
Chromium
Holy basil including: Withania
Co-enzyme Q10 (CoQ10)
Ocimum tenuiflorum L. acidophilus Withania coagulans
Coleus
Hops L. reuteri
Coleus forskohlii
Humulus lupulus L.Rhamnosus GR-1
Cranberry
Horsetail L. Reuteri RC-14 Z
Vaccinium macrocarpon Equisetum arvense Psyllium husk Zinc
D I Q
Dong quai Iodine
Quercetin
Angelica polymorpha Iron
E R
Echinacea
K Red clover/Isoflavones
Kelp Trifolium pratense
Echinacea angustifolia
Fucus vesiculosus
Pg.60 Pg.61
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10TH EDITION

Printed on FSC paper

Acidophilus See ‘Probiotics’

May decrease drug May have opposing Level C Moderate

Astragalus No significant adverse effect or reduction

Bacopa See “Brahmi”

Drug effect on Interaction may be minimised by

Herb effect on drug

May increase or May increase cytotoxicity

May increase or decrease Variable

CYP450 enzyme substrates May increase or decrease Variable

May have opposing effect Level D Moderate

May increase effect

CYP450 enzyme substrates May increase or decrease Variable

Calcium may reduce blood Avoid concomitant use. If indicated,

Bisphosphonates, Level A (quinolones)

Chaste Tree See “Vitex”

May have additive effect

Drug effect on May decrease absorption

May decrease blood Level B

Drug effect on Level D

May increase drug Level A

Despite the potential

May increase or decrease Variable

May decrease drug May decrease blood levels Level C

May increase blood levels Level C

May increase or decrease Variable

Chemotherapeutic agents Level C Moderate -

May have additive Level A Blood pressure should be monitored

Folic acid may

May increase blood levels Level B Variable

May increase or decrease Level C Variable

May decrease blood levels Level B Variable

May decrease blood Level B

Tacrolimus May increase drug May increase blood levels Level D

Ginkgo may add

May increase or decrease Variable

May increase blood levels

May increase drug May increase blood level Level B Moderate -

May increase or decrease Variable

May interfere with the Korean ginseng may Level B

May increase drug Level A Use with caution under supervision of a

May increase drug May increase blood levels Level C

May increase or decrease Variable

May interfere with the Siberian ginseng may Level B

Monoamine Oxidase Siberian ginseng may Level C

May increase drug Glucosamine may increase Level C

Grape seed Unclear mechanism. May Level D

Hawthorn May increase drug May have additive Level A

May potentiate Level D

May decrease blood levels

Iodine at high doses may Level C

Use with caution under supervision

Avoid concomitant use. If iron is

Level B Avoid concomitant use. If iron is

Avoid concomitant use. If iron is

Additive effect to drug

Nutrient effect on drug Level D