Ajuste de Dosis de Medicamentos en Paciente Renal

Paediatric Drug Dosage Adjustments
in Patients with Renal Impairment or

on Renal Replacement Therapies for
use on the Intensive Care and Renal
Units
Drug Dosage Adjustments in Renal Impairment & CVVH 2011

Document updated 01/11/11. Next review due Nov 2013
Author: Rachelle Booth (PICU Senior Specialist Pharmacist)
Checked by: Sue Patey (Renal Senior Specialist Pharmacist) and Quen Mok (Consultant Paediatric Intensivist)
Gt Ormond St Hospital for Children NHS Trust. While all care has been taken in the preparation of this guide, no responsibility will be
taken by the authors for the drug doses, which should always be confirmed independently by the prescriber.
Introduction
When adjusting drug doses for patients with renal impairment or on renal replacement
therapies, drug doses should be adjusted taking into account all of the following:
the usual mechanism of clearance of the drug

the degree of renal failure
the potential nephrotoxicity of the drug
the degree of removal of the drug by renal replacement therapies, and
the severity of the condition being treated.
Limitations of this guideline

1. Wherever possible, drug doses as per the British National Formulary for Children
have been used, however in some instances antibiotic doses and references as per
GOSH local guidelines have been utilised.
2. GFR has been used as a substitute for CrCL and for eGFR. The variations in local
assays may make these difficult to determine and interpret.
3. Differentiations between the different modalities of haemofiltration (CVVH, CVVHD,
CVVHDF) have not been specified.
4. Supplementary doses for patients undergoing haemofiltration for non-renal reasons
(such as drug overdose) have not been specified.
Notes regarding dose adjustment in PICU patients undergoing haemofiltration

1. It is important to determine the indication for which the patient is being filtered. Not
all patients that are haemofiltered have severe renal impairment for example
patients may undergo haemofiltration because of drug overdose, for reasons of fluid
overload, or for removal of high levels of ammonia, lactate or other toxins. In these
cases it may be inappropriate to reduce drug doses where renal textbooks say for
CVVH to dose as per GFR of <10ml/minute; dosing as per normal renal function
may be more appropriate. Remember to check the patients degree of residual
kidney function before recommending any drug dose reductions.
2. In patients with septic shock, the risk of mortality from sepsis may often outweigh
any risk of toxicity or further kidney damage from antibiotic accumulation, in which
case initial drug dosing may be more aggressive than the usual recommended dose
reductions. It should always be discussed with the consultant looking after the
patient and a senior pharmacist who specialises in CVVH before any dosage
reductions are recommended in any patient with sepsis.
3. For drugs for which CVVH dosage adjustment information is not available, it may be
useful to consider the properties of the drug in order to determine whether it is likely
that the drug will be removed by the filter or not, as listed below.

4. It is important to remember that once the patient is stabilised on haemofiltration, the

patients urea and creatinine may begin to return back to within the normal range.
This does not imply that all other drugs will be also be cleared, or that the patient
can be treated as having normal renal function; the filter will remove urea and
creatinine because of their small molecular weight and because they are water
soluble molecules, so serum creatinine and urea values cannot be used to
determine a patients renal function once they are undergoing haemofiltration.
Drug properties to consider in order to determine likelihood of drug removal by

haemofiltration
The following drug properties are required in order for a drug to be removed by
haemofiltration:
Low molecular weight (< 10000 daltons)

Low volume of distribution (< 1L/kg)
High degree of water solubility
Low degree of protein binding
Small, water soluble molecules with low volume of distribution and low protein binding are
more likely to be removed by the filter; however it is important to remember that there are
other factors such as stearic hindrance at the membrane site which may affect drug
clearance and which may be difficult to predict.

Drug:
ACICLOVIR
Usual route of
clearance:
Aciclovir is predominantly renally cleared (75-80% excreted unchanged in

the urine)1,2 by glomerular filtration and tubular secretion.3 There is only one
significant metabolite, which accounts for 10-15% of the dose excreted in the
urine.1,4
Protein binding:
9-33%1,3,4
Molecular Wt:
225.20 daltons5
Vd:
Adults: 0.7 L/kg6
Children: 1.01 0.282
Half-life (t):
Adults: approximately 3 hours1
Children 1-12 years old: 2-3 hours7
Neonates: approximately 4 hours1,7
t in renal imp:
Approximately 20 hours1,3,4
<3 months:
20mg/kg iv every 8 hours8,9
>3 months-12 yrs: 500mg/m2 iv every 8 hours8
>12 years:
10mg/kg iv every 8 hours8
GFR 25-50ml/min: Give normal dose iv every 12 hours1,4,6,8,10
GFR 10-25ml/min: Give normal dose iv every 24 hours1,4,6,8,10
GFR <10ml/min:
Give half the normal dose iv every 24 hours6,11
6
Dialysed. HD removes approximately 60% of a dose.7 Give half the normal
dose iv every 24 hours,1,4,10,11,12 administered after dialysis session.7,12
Not dialysed.6 Give half the normal dose iv every 24 hours.1,4,10,11,12
Pharmacokinetic
parameters:
Normal dose:
(meningoencephalitis):
Dose adjustment
in renal
impairment:
Dose adjustment
in HD:
Dose adjustment
in PD
Intraperitoneal
dose:
Dose adjustment
in CVVH:
Notes:
No information
Filtered. Give normal dose iv every 24hours.2,6 Increase to every 12 hours7,12
if severe infection eg herpes encephalitis.
Nephrotoxic decrease risk by infusing over one hour and ensuring patient
is well hydrated.1,6 Polyuric renal failure may occur with high dose therapy,
especially when administered with concurrent nephrotoxic drugs. This
generally responds rapidly to hydration and reduction/withdrawal of
aciclovir.9 The risk of neurological toxicity is increased in renal impairment.6,7
Monograph reviewed: 16/12/10
References:
1. Summary of Product Characteristics: EMC/Package Insert, Last updated: 28/07/09 Manufacturer: Hospira UK Ltd
2. Veltri MA, Neu AM, Fivush BA, et al. Drug dosing during intermittent hemodialysis and continuous renal replacement
therapy, special considerations in pediatric patients. Pediatr Drugs 2004; 6 (1): 45-65
3. McEvoy GK et al. American Hospital Formulary Service (AHFS) Drug Information, 2009. American Society of
Health-System Pharmacists, Bethesda, 2009. Accessed online 25/03/10.
4. Summary of Product Characteristics: EMC/Package Insert, Last updated: 20/05/08 Manufacturer: Wockhardt UK
Ltd
5. Budavari ES. The Merck Index. 2009. The Merck Research Laboratories, Whitehouse Station (NJ), 2009. Accessed
online 04/08/09
6. Ashley C, Currie A. The Renal Drug Handbook. 3rd edn. Radcliffe Medical Press Ltd, Oxon UK, 2009
7. Lexi-comp online accessed via www.crlonline.com, accessed 16/12/10
8. Martin J et al. British National Formulary for Children 2011-2012. Pharmaceutical Press, London, UK 2011
9. Hey E. Neonatal formulary 6: drug use in pregnancy and the first year of life. 6th edn. Malden, Mass.; Oxford:
Blackwell; 2011.
10. Guy's, St Thomas' and Lewisham Hospitals Trust. Paediatric Formulary, 8th edn. London, UK, 2010
rd
11. Levy J, Brown E, Daley C, Lawrence A. Oxford Handbook of Dialysis, 3 edn. Oxford University Press, Oxford, UK,
2009
12. Aronoff GR, Bennett WM, Berns JS et al. Drug Prescribing in Renal Failure, Dosing Guidelines for Adults and
th
Children, 5 edn. American College of Physicians, US, 2007.

Drug:
AMIKACIN
Usual route of
clearance:
Pharmacokinetic
parameters:
94-98% of a dose of amikacin is excreted in the urine unchanged within 24

hours,1,2 primarily by glomerular filtration.3
Protein binding:
<20%3
Molecular Wt:
585.60 daltons4
Vd:
Adults: 0.22-0.29 L/kg5
Paediatrics: 0.2-0.7 L/kg6
Half-life (t):
Adults: 2-3 hours1-3
Adolescents: 1.5 1 hour2
Children: 1.6-2.5 hours2
Term neonates >7 days old: 4-5 hours1,2
Pre-term neonates 1-3 days old: 7-8 hours1,2
t in renal imp:
17-150 hours5
<2kg <4wks of life: 10mg/kg iv every 24 hours7
<2kg >4wks of life: 15mg/kg iv every 24 hours7
>2kg <4wks of life: 15mg/kg iv every 24 hours7
Prophylaxis:
10mg/kg iv every 12 hours for 3 doses (use ideal body
weight)7
Cystic fibrosis:
30mg/kg (max 1.5g) iv every 24 hours7
All other patients: 20mg/kg (max 1.5g) iv every 24 hours (use ideal body
weight) 7
Give 10mg/kg iv, take trough level after 24 hours, and hold dose until trough
level is available. Adjust dosage interval according to serum levels aim to
keep trough <10mg/L and peak 20-30mg/L.7
Dialysed.1,2,5 Give 10mg/kg iv, take trough level after 24 hours, and hold
dose until trough level is available. Adjust dosage interval according to
serum levels aim to keep trough <10mg/L and peak 20-30mg/L.8
Dialysed.1,2,5 Give 10mg/kg iv, take trough level after 24 hours, and hold
dose until trough level is available. Adjust dosage interval according to
serum levels aim to keep trough <10mg/L and peak 20-30mg/L.8
Loading dose: 25mg/L, maintenance dose: 12mg/L9
Normal dose:
Dose adjustment
in renal
impairment:
Dose adjustment
in HD:
Dose adjustment
in PD:
Intraperitoneal
dose:
Dose adjustment
in CVVH:
Notes:
Give 10mg/kg iv, take trough level after 24 hours, and hold dose until trough
level is available. Adjust dosage interval according to serum levels10 aim to
Peak levels are only required for doses <20mg/kg.7
Repeat levels daily in renal impairment or if on any form of dialysis or
haemofiltration.7
Take care not to underdose; ensure that a therapeutic peak level is
maintained.
References:
th
Children, 5 edn. American College of Physicians, US, 2007
online 04/08/09
7. Gt Ormond St Hospital for Children NHS Trust Antibiotic Policy Amikacin Guidelines V2.0 Feb 2008
8. Gt Ormond St Hospital for Children NHS Trust - Local Practice as at December 2010
9. Daschner M. Drug Dosage in Children with Reduced Renal Function. Pediatr Nephrol 2005; 20: 1675-1686
rd
2009

Drug:
AMPHOTERICIN LIPOSOMAL (AMBISOME)
Usual route of
clearance:
2-5% of a dose is excreted unchanged in the urine.1

The excretion of liposomal amphotericin has not been studied and the
metabolic pathways are unknown, however due to the size of the liposomes
the degree of glomerular filtration and renal elimination is very low.2
Liposomal amphotericin exhibits nonlinear kinetics (an increase in dose may
result in a greater than proportional increase in serum concentration).3
Protein binding:
90%1,4
Molecular Wt:
924.08 daltons5
Vd:
Adults: 0.1-0.44 L/kg1
Half-life (t):
Adults: 6.3-10.7 hours1
t in renal imp:
Unchanged1
Prophylaxis:
Treatment:
3-5mg/kg iv every 24 hours6
Give test dose of 100mcg/kg (max 1mg) over 10
minutes prior to first dose, followed by the rest of the
dose one hour later if no reaction.6
GFR 20-50ml/min: No dosage adjustment required - give normal dose1,7-9
GFR 10-20ml/min: No dosage adjustment required - give normal dose1,7-9
GFR <10ml/min:
No dosage adjustment required - give normal dose1,7-9
1
Not dialysed. No dosage adjustment required - give normal dose,
administered after dialysis session1,2
Not dialysed.1 No dosage adjustment required - give normal dose2,9
Pharmacokinetic
parameters:
Normal dose:
Dose adjustment
in renal
impairment:
Dose adjustment
in HD:
Dose adjustment
in PD:
Intraperitoneal
dose:
Dose adjustment
in CVVH:
Notes:
No information
Not filtered but no dosage adjustment required - give normal dose.1,9
Administer into the venous return of the of the filtration circuit as liposomal
preparations may increase the risk of the filter clotting.1,9
Liposomal amphotericin is less nephrotoxic than conventional amphotericin,
due to the size of the liposomes preventing interaction of amphotericin B with
the cells of the distal tubules.1,2,6
References:
2. Summary of Product Characteristics: EMC/Package Insert, Last updated: 21/05/09 Manufacturer: Gilead Sciences
Ltd
online 04/08/09
rd
2009

Drug:
AMPICILLIN
Usual route of
clearance:
Pharmacokinetic
parameters:
Ampicillin is excreted mainly in the bile and urine;1 60-80% is excreted

unchanged in the urine.2
Protein binding:
17-20%3
Neonates: 10%4
Molecular Wt:
349.40 daltons5
Vd:
Adults: 0.17-0.31 L/kg2
Paediatrics: 0.32 L/kg3
Half-life (t):
Adults: 1-2 hours4
Children: 1-1.8 hours4
Neonates 8-14 days old: 2.8 hours4
Neonates 2-7 days old: 4 hours4
t in renal imp:
7-20 hours2
Meningitis,
1 week of life and 2kg: 50mg/kg iv 12 hourly6
enterococcal &
> 1 week of life and 2kg: 50mg/kg iv 8 hourly6
Group B
1 week of life and > 2kg: 50mg/kg iv 8 hourly6
streptococcal
> 1 week of life and > 2kg: 50mg/kg iv 6 hourly6
infection:
Highly suspected/ 1 week of life: 50mg/kg 6 hourly4,7
confirmed listeria
> 1 week of life: 50mg/kg 4 hourly4,7
meningitis:
GFR 20-50ml/min: No dosage adjustment required - give normal dose2
GFR 10-20ml/min: Give normal dose every 6-12 hours3,4
GFR <10ml/min:
Give normal dose every 12 hours3,4
Dialysed, approximately 40% of a dose is removed by HD.4,8
Give normal dose every 12 hours, administered after dialysis session.8
Not dialysed.2 Give normal dose every 12 hours.8
Normal dose:
(see notes
below)
Dose adjustment
in renal
impairment:
Dose adjustment
in HD:
Dose adjustment
in PD:
Intraperitoneal
dose:
Dose adjustment
in CVVH:
Notes:
125mg/L9
Filtered, give normal dose every 68 to 83 hours
The neonatal dose for meningitis and Group B streptococcal infection is lower
than that specified in the BNF-C, as it is Trust policy that ampicillin is always
used in combination with cefotaxime for empirical treatment of suspected
meningitis. If being used as monotherapy, the dose should always be
discussed with microbiology/infectious diseases.
For monotherapy of highly suspected/confirmed listeria meningitis, the dose
has been extrapolated from that used in Lexi-comp for Group B streptococcal
meningitis. Again, these patients should be discussed with
microbiology/infectious diseases.
References:
1. Summary of Product Characteristics: EMC/Package Insert, Last updated: March 2005 Manufacturer: Essential
Generics
online 04/08/09
th
6. Bradley JS and Nelson JD. Nelsons Pocket Book of Pediatric Antimicrobial Therapy, 2010-2011 18 Edition.
American Academy of Pediatrics.
7. Gt Ormond St Hospital for Children NHS Trust Antibiotic Policy Neonatal Antibiotic Doses V3.0 November 2010
th

Drug:
BENZYLPENICILLIN
Usual route of
clearance:
60-90% of a dose is excreted by renal elimination, 10% of which is by

glomerular filtration and 90% of which is by tubular secretion.1
10-30% of a dose is metabolised in the liver to penicilloic acid.2
Biliary excretion accounts for only a minor fraction of the dose.1
Protein binding:
60%1,3
Molecular Wt:
334.39 daltons4
Vd:
Half-life (t):
Adults: 30 minutes1,3,5
Infants and Children: 0.5-1.2 hours2
Neonates >14 days old: 0.9-1.9 hours2
Neonates 7-13 days old: 1.2-2.2 hours2
Neonates < 6 days old: 3.2-3.4 hours2
t in renal imp:
10 hours3
Meningitis,
<4 weeks:
meningococcal
>4 weeks:
50mg/kg (max 2.4g) iv every 4-6
disease:
hours6
Bacterial
<1 week of life:
endocarditis,
1-4 weeks of life: 50mg/kg iv every 8 hours6
treatment or
>4 weeks of life: 50mg/kg (max 2.4g) iv every 4-6
prevention of
hours6
neonatal group B
streptococcus
infection, NEC,
other severe
infection:
Mild-moderate
<1 week of life:
infection:
1-4 weeks of life: 25mg/kg iv every 8 hours6
>4 weeks of life: 25mg/kg iv every 6 hours6
GFR 10-50ml/min: Give normal dose q8-12h2,6,7
GFR <10ml/min:
Give normal dose q12h2,6,7
Maximum adult dose in severe renal impairment is
4.8g/day3
3
Dialysed. Give normal dose every 12 hours, administered after dialysis.3,8
Pharmacokinetic
parameters:
Normal dose:
Dose adjustment
in renal
impairment:
Dose adjustment
in HD:
Dose adjustment
in PD:
Intraperitoneal
dose:
Dose adjustment
in CVVH:
Notes:
Dialysed.3 Give normal dose every 12 hours (or 50% of dose at same
frequency).3,7,8
No information
Give normal dose every 82,7,8 to 12 hours3,7
Increased incidence of neurotoxicity (seizures) with benzylpenicillin in renal
impairment.3,6
Further dose reductions are required if advanced hepatic impairment is
associated with severe renal failure1 discuss with pharmacy.
References:
1. Summary of Product Characteristics: EMC/Package Insert, Last updated: 16/09/08 Manufacturer: Genus
Pharmaceuticals
online 04/08/09
8.
rd
Levy J, Brown E, Daley C, Lawrence A. Oxford Handbook of Dialysis, 3 edn. Oxford University Press, Oxford, UK,
2009

Drug:
CASPOFUNGIN
Usual route of
clearance:
Caspofungin undergoes spontaneous degradation to an open-ring

compound.1 Further metabolism involves peptide hydrolysis and N-acetylation
in the liver.1
Distribution is the dominant mechanism affecting plasma clearance, with a
short alpha phase of distribution, followed by a beta phase with a half-life of 911 hours, then a terminal gamma phase with a half-life of 45 hours.1,2
35% of a dose is excreted in faeces primarily as metabolites and 41% of a
dose is excreted in urine primarily as metabolites.3 Only 1.4% of a dose is
excreted unchanged in the urine.1
Caspofungin exhibits non-linear pharmacokinetics.1
Protein binding:
92.4-96.5%1
Molecular Wt:
1093.31 daltons4
Vd:
Unknown1,2
Half-life (t):
Adults: 12-15 days1,2
Beta phase half-life is 32% to 43% lower in paediatric
patients than in adult patients3
t in renal imp:
Increased but not significantly2
1-3 months:
25mg/m2 iv every 24 hours5
3months-1 year:
50mg/m2 iv every 24 hours5
1-18 years:
70mg/m2 (max 70mg) iv on Day 1, then 50mg/m2 (max
70mg) iv every 24 hours.5
May be increased to 70mg/m2 (max 70mg) every 24
hours if lower dose is tolerated but there is an
inadequate response. 5
GFR 20-50ml/min: No dosage adjustment required - give normal dose1-3,6,7
GFR 10-20ml/min: No dosage adjustment required - give normal dose1-3,6,7
GFR <10ml/min:
No dosage adjustment required - give normal dose1-3,6,7
2,3
Not dialysed. No dosage adjustment required - give normal dose1,2,6,7
Pharmacokinetic
parameters:
Normal dose:
Dose adjustment
in renal
impairment:
Dose adjustment
in HD:
Dose adjustment
in PD:
Intraperitoneal
dose:
Dose adjustment
in CVVH:
Notes:
Not dialysed.2,3 No dosage adjustment required - give normal dose1,2,6,7

No information
Unlikely to be removed by haemofiltration due to high degree of protein
binding.
No dosage adjustment required - give normal dose2,6,7
Adverse effects include renal failure although this is uncommon.1
Dose reduction is required in patients with moderate hepatic impairment
reduce dose by 30%.3,5
References:
1. Summary of Product Characteristics: EMC/Package Insert, Last updated: 20/07/09 Manufacturer: Merck Sharpe
and Dohme Ltd
online 04/08/09
th
rd
2009

Drug:
CEFOTAXIME
Usual route of
clearance:
Cefotaxime is partially metabolised prior to excretion. Elimination is

predominantly by renal excretion; approximately 60% of a dose is excreted
unchanged in the urine, while approximately 24% is excreted as the
microbiologically active metabolite desacetyl-cefotaxime.1,2,3
Protein binding:
40%4
Molecular Wt:
455.47daltons5
Vd:
Adults: 0.15-0.55 L/kg4,6
Half-life (t):
Adults: 0.9-1.14 hours; metabolite 1.3 hours1
Children: 1.5 hours3
Neonates 1-4 weeks old: 2 hours3
Full-term neonates <1 week old: 2-3.4 hours3
Premature neonates <1 week old: 5-6 hours3
t in renal imp:
Adults: 2.5 hours; metabolite approximately 10 hours4
Meningitis:
<1 week of life: 50mg/kg iv every 12 hours7,8
1-3 weeks of life: 50mg/kg iv every 8 hours7,8
>3 weeks of life: 50mg/kg iv (max 3g) every 6 hours7,8
GFR 20-50ml/min: No dosage adjustment required - give normal dose4,7
GFR 5-20ml/min:
No dosage adjustment required - give normal dose7
GFR <5ml/min:
Give 1x normal dose initially, then give half the normal
dose and keep the frequency the same1,7,9
4,9
Dialysed. Give 1x normal dose initially, then give half the normal dose and
keep the frequency the same4
Not dialysed.4 Give 1x normal dose initially, then give half the normal dose
and keep the frequency the same4
Loading dose 500mg/L then maintenance 12511 to 250mg/L10
Pharmacokinetic
parameters:
Normal dose:
Dose adjustment
in renal
impairment:
Dose adjustment
in HD:
Dose adjustment
in PD:
Intraperitoneal
dose:
Dose adjustment
in CVVH:
Notes:
>3 weeks of life: give normal dose every 8 hours6

Administration of high-dose cephalosporins in patients with renal impairment
may result in encephalopathy (decreased consciousness, dyskinesias,
convulsions).1
Because of extra-renal elimination, it is only necessary to decrease the dose
in severe renal failure where GFR<5ml/min.1,7,9
Reduce dose further if the patient has concomitant hepatic and renal failure4
discuss with pharmacy.
References:
1. Summary of Product Characteristics: EMC/Package Insert, Last updated: 15/08/07 Manufacturer: sanofi-aventis
Health-System Pharmacists, Bethesda, 2009. Accessed online 22/10/09
online 04/08/09
Blackwell; 2011.
th

Drug:
CEFTAZIDIME
Usual route of
clearance:
Pharmacokinetic
parameters:
80-90% of a dose of ceftazidime is excreted unchanged in the urine by

glomerular filtration.1,2,3 Less than 1% of a dose is excreted via the bile.2
Protein binding:
<10%1
Molecular Wt:
546.58 daltons4
Vd:
Half-life (t):
Neonates: 5.4-8.8 hours2
t in renal imp:
13-25 hours6
<1 week of life:
25mg/kg iv every 24 hours, double in severe
infection7,8
1-3 weeks of life:
25mg/kg iv every 12 hours, double in severe
infection7,8
>3 weeks of life:
25mg/kg iv every 8 hours, double in severe infection
(max 2g every 8 hours, cystic fibrosis max 3g every 8
hours)7
GFR 30-50ml/min: Give 1x normal dose initially, followed by 50-100% of
normal dose every 12 hours2,6,9
GFR 15-30ml/min: Give 1x normal dose initially, followed by 50-100% of
GFR 5-15ml/min:
Give 1x normal dose initially, followed by 25-50% of
GFR <5ml/min:
Give 1x normal dose initially, followed by 25-50% of
Dialysed.6 Give 1x normal dose initially, followed by 50% of the normal dose
every 24 hours, administered after dialysis5,10
Dialysed.6 Give 50% of the normal dose every 24 hours6,10
Normal dose:
Dose adjustment
in renal
impairment:
Dose adjustment
in HD:
Dose Adjustment
in PD:
Intraperitoneal
dose:
Dose adjustment
in CVVH:
Notes:
Loading dose: 250mg/L, maintenance dose: 125mg/L11,12

Give 50-100% of normal dose every 12 hours5,6,10,12
There have been reports of neurological sequelae including tremor,
myoclonia, convulsions, encephalopathy, and coma in patients with renal
impairment in whom the dose of ceftazidime has not been appropriately
reduced.2
References:
1. Summary of Product Characteristics: EMC/Package Insert, Last updated: 21/12/09 Manufacturer: Sandoz Ltd
2. Summary of Product Characteristics: EMC/Package Insert, Last updated: 12/08/09 Manufacturer: GlaxoSmithKline
UK
online 04/08/09
Blackwell; 2011.
rd
2009
th

Drug:
CEFTRIAXONE
Usual route of
clearance:
Ceftriaxone is eliminated mainly as unchanged drug, with approximately 60%

of a dose being excreted in the urine, almost exclusively by glomerular
filtration.1 The remainder of the dose is excreted via the biliary and intestinal
tracts.1
Protein binding:
85-95%1-3
Molecular Wt:
554.58 daltons4
Vd:
Adults: 0.12-0.18 L/kg5
Half-life (t):
Adults: approximately 8 hours1
t in renal imp:
Adults: 14.7 hours2
Meningitis:
>4 weeks of life: 80mg/kg (max 4g) iv every 24 hours7
Pharmacokinetic
parameters:
Normal dose:
Dose adjustment
in renal
impairment:
Dose adjustment
in HD:
Dose adjustment
in PD:
Intraperitoneal
dose:
Dose adjustment
in CVVH:
Notes:

GFR <10ml/min:
Give 50mg/kg (max 2g) every 24 hours5,6
Not dialysed.2,5,8 Give 50mg/kg (max 2g) every 24 hours3,5
Not dialysed.2,5,8 Give 50mg/kg (max 2g) every 24 hours3,5,6
Loading dose: 250mg/L; maintenance dose: 125mg/L9
No dosage adjustment required - give normal dose5,6 (unless concomitant
hepatic impairment, see below)1
In patients with renal or hepatic dysfunction, the pharmacokinetics of
ceftriaxone are only minimally altered and the half-life only slightly increased;
if renal function alone is impaired then biliary excretion is increased, if liver
function alone is impaired then renal elimination is increased.1
If both renal and hepatic function are impaired then dosage adjustment will be
necessary discuss with pharmacy.1
The policy on the intensive care units is to change patients admitted on
ceftriaxone to cefotaxime at the earliest convenient time, due to the risk of
ceftriaxone and calcium interactions, as per the MHRA Drug Safety Bulletin
Oct 2009.10
References:
Ltd
th
online 04/08/09
10. MHRA Drug Safety Update October 2009

Drug:
CIDOFOVIR
Usual route of
clearance:
The major route of elimination of cidofovir is by renal excretion of unchanged

drug via glomerular filtration and tubular secretion.1,2 80-100% of a dose is
excreted unchanged in the urine within 24 hours.1,3 No metabolites have been
detected in the serum or urine of patients receiving cidofovir.1
Protein binding:
<10%1
Molecular Wt:
279.19 daltons4
Vd:
Adults: 0.388 0.125 L/kg1
Half-life (t):
Adults: 2.2 hours1
t in renal imp:
Adults: 16-25 hours2
Adenovirus, CMV: 5mg/kg iv once per week for two weeks (induction),
then 5mg/kg iv every two weeks (maintenance)5,6
Administer with concomitant hyperhydration and
probenecid in order to minimise potential
nephrotoxicity.1
GFR >55ml/min:
No dosage adjustment required - give normal dose3
GFR 10-55ml/min: 1mg/kg iv three times per week for two weeks
(induction), then 1mg/kg iv every two weeks
(maintenance)5,6
GFR <10ml/min:
0.5mg/kg iv once per week for two weeks (induction),
then 0.5mg/kg iv every two weeks (maintenance)2
1,2,7
Dialysed.
Give 2mg/kg iv once per week for two weeks (induction), then
2mg/kg iv every two weeks (maintenance).
Administer dose 2 hours before dialysis session to benefit from peak
concentration without having delayed clearance.2,3
High-flux HD has been shown to reduce serum concentrations of cidofovir by
52% 11%.1,2
Not dialysed.2 Give 0.5mg/kg iv once per week for two weeks (induction),
then 0.5mg/kg iv every two weeks (maintenance)2,3
No information
Pharmacokinetic
parameters:
Normal dose:
Dose adjustment
in renal
impairment:
Dose adjustment
in HD:
Dose adjustment
in PD:
Intraperitoneal
dose:
Dose adjustment
in CVVH:
Notes:
Give 2mg/kg iv weekly for two weeks (induction), then 2mg/kg iv every two
weeks (maintenance).8
The manufacturers state that renal insufficiency or proteinuria >100mg/dL is a
contraindication for the use of cidofovir.1
Dose-dependent nephrotoxicity is the major dose-limiting toxicity related to
cidofovir administration.1
Constant serum levels of cidofovir are not required as it is the intracellular
levels which provide antiviral effect.2
Probenecid is unlikely to be effective in patients with GFR<30ml/minute.5
Patients on CAPD or HD should not receive hyperhydration or probenecid as
the risk of fluid overload and probenecid adverse effects does not outweigh
the benefit of administering these medications.2
References:
1. Summary of Product Characteristics: EMC/Package Insert, Last updated: 10/11/09 Manufacturer: Gilead Sciences
Ltd
2. Brody S, Humphreys M, Gambertoglio J, Schoenfeld P, Cundy K, Aweeka F. Pharmacokinetics of cidofovir in renal
insufficiency and in continuous ambulatory peritoneal dialysis or high-flux hemodialysis. Clin Pharmacol Ther. 1999
Jan; 65(1):21-8.
online 04/08/09
6. Yusuf U, Hale GA, Carr J, et al. Cidofovir for the Treatment of Adenoviral Infection in Pediatric Hematopoietic Stem
Cell Transplant Patients. Transplantation. 2006; 81(10):1398-404.
th
Drug:
CIPROFLOXACIN
Usual route of
Clearance:
Ciprofloxacin and its active metabolites are eliminated primarily by the kidney,
with approximately 40-70% of a dose being excreted unchanged in the urine.1
Non-renal clearance of ciprofloxacin is mainly due to active trans-intestinal
secretion and metabolism, with approximately 1% of a dose eliminated via the
biliary route.2
PB:
20-40%1,3
Mol Wt:
331.34 daltons4
Vd:
Adults: 2-3 L/kg1,2
t:
Adults: 3-5 hours5
Paediatrics: 4-5 hours2
t in renal imp:
Adults: up to 12 hours2
<4 weeks of life:
iv: 10mg/kg every 12 hours6,7
po/ng: 15mg/kg every 12 hours6
>4 weeks 18yrs
(including patients iv: 10mg/kg (max 400mg) every 8 hours6
with cystic
po/ng: 20mg/kg (max 750mg) every 12 hours6
fibrosis):
GFR 30-50ml/min: No dosage adjustment required give normal dose.1
GFR 10-30ml/min: Give 502-100%1 of the normal dose iv/po/ng every 12
hours1
GFR <10ml/min:
Give 50% of the normal dose iv/po/ng every 12
hours1,3,8
<10% removed by dialysis.9 Give 50% of the normal dose iv/po/ng every 12
hours,3,8 administered after dialysis session
OR give 100% of the normal dose iv/po/ng every 24 hours, administered after
dialysis session2,9
<10% removed by dialysis.9 Give 100% of the normal dose iv/po/ng every 24
hours9
Pharmacokinetic
parameters:
Normal dose
(severe GI or
respiratory tract
infection):
Dose adjustment
in renal
impairment:
Dose adjustment
in HD:
Dose adjustment
in PD:
Intraperitoneal
dose:
Dose adjustment
in CVVH:
Notes:
25-100mg/L1
Give 753-100%1,8,9 of the dose iv/po/ng every 12 hours
Licensed for children over 1 year for specific indications.2
The bioavailability of the oral suspension is 70-80%.1,2
References:
2. Summary of Product Characteristics: EMC/Package Insert, Last updated: 12/11/08 Manufacturer: Bayer PLC
online 04/08/09
Blackwell; 2011.
rd
2009
th

Drug:
CLARITHROMYCIN
Usual route of
clearance:
Clarithromycin undergoes first-pass metabolism to form a microbiologicallyactive metabolite (14-hyroxyclarithromycin).1,2 Bioavailability of the active
metabolite is reduced following iv administration.1 Approximately 33% of
clarithromycin and 11% of the active metabolite is excreted unchanged in the
urine.1
Elimination of clarithromycin appears to follow non-linear pharmacokinetics,
possibly due to saturable metabolism.2
Protein binding:
80%3
Molecular Wt:
747.95 daltons4
Vd:
Adults: 2-4 L/kg3
Half-life (t):
Adults: 3-7 hours3
t in renal imp:
Prolonged2,3
<4 weeks of life:
iv: 7.5mg/kg every 12 hours5
po/ng: 7.5mg/kg every 12 hours6
>4 weeks - 12yrs:
iv: 7.5mg/kg (max 500mg) every 12 hours2,6,7
po/ng: <8kg: 7.5mg/kg every 12 hours; >8kg: dose band
as per BNF-C6
12-18 years:
iv: 500mg every 12 hours6
po/ng: 250-500mg every 12 hours6
GFR 30-50ml/min: No dosage adjustment required - give normal
dose1,3,6,8,9,10
GFR <30ml/min:
Give 50% of normal dose iv/po/ng every 12 hours1,2,6,7,8
3
Dialysed. po/ng: no dosage adjustment required - give normal dose3
iv: give 5010-100%3 of dose every 24 hours10 after dialysis session8
Unknown dialysability.3
po/ng: no dosage adjustment required - give normal dose3
iv: give 5010-100%3 of dose every 24 hours10
No information
Pharmacokinetic
parameters:
Normal dose:
Dose adjustment
in renal
impairment:
Dose adjustment
in HD:
Dose adjustment
in PD:
Intraperitoneal
dose:
Dose adjustment
in CVVH:
Notes:
po/ng: no dosage adjustment required - give normal dose3

iv: give 50-100% of dose every 12 hours3
Vomiting may occur in patients with severe renal impairment receiving high
doses.3
Patients with hepatic impairment alone do not usually require a dosage
adjustment as renal clearance of clarithromycin is increased in these
patients,2 however a dosage reduction will be required if patient has both
renal and hepatic impairment, dose as per GFR <30ml/min.2
References:
1. Summary of Product Characteristics: EMC/Package Insert, Last updated: 08/01/10 Manufacturer: Abbott
Laboratories Ltd
online 04/08/09.
5. Sharland M. Manual of Childhood Injections the Blue Book. Oxford University Press, UK, 2011
6. Martin J et al. British National Formulary for Children 2011-2012. Pharmaceutical Press, London, UK, 2011
th

Drug:
CLINDAMYCIN
Usual route of
clearance:
Clindamycin phosphate is biologically inactive and is hydrolysed to

clindamycin, which undergoes metabolism to both active and inactive
metabolites.1,2 High concentrations occur in bile.1 Approximately 10% is
excreted in the urine as active drug or metabolites, approximately 4% is
excreted in the faeces and the remainder is excreted as inactive metabolites.1
Protein binding:
>90%1,3,4,5
Molecular Wt:
424.98 daltons6
Vd:
Half-life (t):
Adults and children: 2-3 hours1,3,5
Infants 1month1 year: 3 hours4
Term neonates: 3.6 hours2,4
Pre-term neonates: 8.7 hours2,4
t in renal imp:
Adults: 3-5 hours3
<2 weeks of life:
2-4 weeks of life:
5mg/kg iv every 8 hours (may increase to 6 hourly if
hepatic function is normal)7
>4 weeks - 12yrs:
15-25mg/kg/day iv in 3-4 divided doses1,8,9
Severe infection: 25-40mg/kg/day iv in 3-4 divided
doses (max 1.2g iv every 6 hours) 1,8,9
12-18 years:
150-675mg iv every 6 hours (or total daily dose may be
given in 3 divided doses)9
Severe infection: up to 1.2g iv every 6 hours9
dose3,5,10,11
dose3,5,10,11
GFR <10ml/min:
1,2,3,4
Not dialysed.
Pharmacokinetic
parameters:
Normal dose:
Dose adjustment
in renal
impairment:
Dose adjustment
in HD:
Dose adjustment
in PD:
Intraperitoneal
dose:
Dose adjustment
in CVVH:
Notes:
Not dialysed.1,2,3,4 No dosage adjustment required - give normal dose3,5,11

No dosage adjustment required - give normal dose1,3,5,11
References:
1. Summary of Product Characteristics: EMC/Package Insert, Last updated: 08/09/09 Manufacturer: Pharmacia Ltd
th
online 04/08/09
Blackwell; 2011.
rd
2009

Drug:
CO-AMOXICLAV (AMOXICILLIN+CLAVULANIC ACID)
Usual route of
clearance:
The pharmacokinetics of amoxicillin and clavulanic acid are similar.1

Amoxicillin is largely excreted through the kidneys (52 15% in unchanged
form within 7 hours) with a small fraction excreted in the bile.2 Clavulanic acid
is 50-70% metabolised, with approximately 40% eliminated via the kidneys,
primarily by glomerular filtration,3 of which 18-38% is in the unchanged form.2
Protein binding:
amoxicillin:
~17-20%2,3
clavulanic acid: ~22-30%3
Molecular Wt:
amoxicillin:
365.40 daltons4
clavulanic acid: 199.16 daltons4
Vd:
amoxicillin:
Adults: ~0.3-0.4 L/kg2
clavulanic acid: Adults: ~0.2 L/kg2
Half-life (t):
amoxicillin:
Children 2-15 years: 1.2 hours3
clavulanic acid: Adults: ~1 hour2
Children 2-15 years 0.8 hours3
t in renal imp:
amoxicillin:
Adults: 6 hours if CrCl 10-30ml/min2
and 10-15 hours in anuric patients2
clavulanic acid: Adults: 2.6 hours if CrCl 20-70ml/min2
and 3-4 hours in anuric patients2,5
Intravenous:
<1week of life & 30mg/kg iv every 12 hours6
pre-term babies:
>1wk of life30mg/kg iv every 8 hours6
3mths:
>3mths-18 yrs: 30mg/kg iv (max 1.2g) every 8 hours
(increased to every 6 hours in severe
infections)6
Enteral:
<4 weeks of life: 0.25ml/kg of 125/31 suspension
every 8 hours7
>4 weeks 0.25ml/kg of 125/31 suspension
1year:
every 8 hours (dose doubled in
severe infection)7
1-6 years:
5ml of 125/31 suspension every 8
hours or 0.25ml/kg of 125/31
suspension every 8 hours (dose
doubled in severe infection)7
6-12 years:
5ml of 250/62 suspension every 8
hours or 0.15ml/kg of 250/62
suspension every 8 hours (dose
doubled in severe infection)7
12-18 years:
One 250/125 strength tablet every 8
hours, increase in severe infection to
one 500/125 strength tablet every 8
hours7
dose1,2,3,7,8
GFR 10-30ml/min: iv: Use normal initial dose, followed by 50% of dose
every 12 hours1,2,7,9
po/ng: give normal dose every 12 hrs7,9
GFR <10ml/min:
iv: Use normal initial dose, followed by 50% of dose
every 24 hours1,2,7,9
po/ng: give 100% of the normal mild/moderate infection
dose every 12 hours7
iv: give normal initial dose, followed by 50% of dose every 24 hours5
po/ng: give 50% of normal dose every 12 hrs10
iv: give normal initial dose, followed by 50% of dose every 24 hours4
po/ng: give 50% of normal dose every 12 hrs10
Pharmacokinetic
parameters:
Normal dose:
Dose adjustment
in renal
impairment:
Dose adjustment
in HD:
Dose adjustment
in PD:

Intraperitoneal
dose:
Dose adjustment
in CVVH:
Notes:
No information
iv: Use normal initial dose, followed by 50% of dose every 12 hours5
po/ng: give normal dose every 12 hours5
References:
UK
Ltd
online 04/08/09
rd
2009

Drug:
CO-TRIMOXAZOLE (TRIMETHOPRIM +
SULFAMETHOXAZOLE)
Usual route of
clearance:
Trimethoprim: principal route of excretion is renal with approximately 50% of

a dose excreted unchanged in the urine within 24 hours.1
Sulfamethoxazole: principal route of excretion is renal with approximately 1530% excreted unchanged in the urine.1
Both trimethoprim and sulfamethoxazole undergo hepatic metabolism.2
Protein binding:
trimethoprim:
~50%1
sulfamethoxazole: ~66%1
Molecular Wt:
trimethoprim:
290.32 daltons3
sulfamethoxazole: 253.28 daltons3
Vd:
trimethoprim:
sulfamethoxazole: Adults: 0.28-0.38 L/kg4
Half-life (t):
trimethoprim:
Adults: 8.6-17 hours1
Children 1-10 years old: 5.5
hours2
Infants <1 year old: 7.7 hours2
sulfamethoxazole: Adults: 9-11 hours1
t in renal imp:
trimethoprim:
sulfamethoxazole: No change in the t of
sulfamethoxazole in renal
impairment but the t of the major
metabolite is increased when CrCl
<25ml/min.1
Treatment of PCP: >4 weeks of life-18 years: 60mg/kg every 12 hours
iv/po/ng for 14-21 days, total daily dose may
alternatively be given in 3-4 divided doses5
Stenotrophomonas
maltophilia:
>4 weeks of life: 45mg/kg every 12 hours iv/po/ng6
Prophylaxis:
See individual protocols as prophylactic regimens vary.
GFR >30ml/min:
GFR 15-30ml/min: Give 50% of normal dose. 1,4,5
If treating PCP, give normal dose for 3 days then give
50% of normal dose ie 30mg/kg iv/po/ng every 12
hours.4,7
GFR <15ml/min:
Give 50% of normal iv/po/ng dose (no loading
dose).4,7,8,9
4
Dialysed. Give 50% of normal iv/po/ng dose.4,7,8
Pharmacokinetic
parameters:
Normal dose:
Dose adjustment
in renal
impairment:
Dose adjustment
in HD:
Dose adjustment
in PD:
Intraperitoneal
dose:
Dose adjustment
in CVVH:
Not dialysed.4,7 Give 50% of normal iv/po/ng dose.4,8

480mg/L10
Give 50% of normal iv/po/ng dose.2
If treating PCP, give normal dose for 3 days then give 50% of normal dose ie
30mg/kg iv/po/ng every 12 hours.4,8
Notes:
References:
UK
online 04/08/09
5.
6.
7.
8.
Martin J et al. British National Formulary for Children 2011-2012. Pharmaceutical Press, London, UK 2011
Personal communication from GOSH microbiologist James Soothill 28/01/10 (local policy)
Guy's, St Thomas' and Lewisham Hospitals Trust. Paediatric Formulary, 8th edn. London, UK, 2010
rd
2009
th

Drug:
COLISTIMETHATE (COLISTIN)
Usual route of
clearance:
Colistimethate is predominantly renally cleared with 80% of a dose recovered

unchanged in the urine at 24 hours.1,2 Colistimethate does not undergo biliary
excretion.1 The remainder of the dose is thought to be inactivated in the
tissues however the mechanism for this is unknown.1 The pharmacokinetics
of colistimethate in children appears to be similar to that of adults.1
Protein binding:
Low1
Molecular Wt:
1749.82 daltons3
Vd:
Adults: 0.09-0.34 L/kg2
Half-life (t):
Adults: 1.51,2-8 hours2
t in renal imp:
Cystic fibrosis:
1 month - 18 years old and <60kg: 25000 units/kg iv
every 8 hours4
>60kg: 2 million units iv every 8 hours4
GFR 10-20ml/min: Give 50% of normal dose iv every 12-18 hours1,2
GFR <10ml/min:
Give 50% of normal dose iv every 18-24 hours1,2
Not dialysed.2 Give 50% of normal dose iv every 18-24 hours2
Pharmacokinetic
parameters:
Normal dose:
Dose adjustment
in renal
impairment:
Dose adjustment
in HD:
Dose adjustment
in PD:
Intraperitoneal
dose:
Dose adjustment
in CVVH:
Notes:
Dialysed.2 Give 50% of normal dose iv every 18-24 hours2

No information
Give 50% of normal dose iv every 18-24 hours5
Serum levels should be monitored in children with renal impairment; peak
concentrations (30 minutes after the end of the infusion) should be
maintained between 10-15mg/L (125-200units/ml).4
References:
1. Summary of Product Characteristics: EMC/Package Insert, Last updated: 08/01/10 Manufacturer: Forest
laboratories UK Ltd
online 04/08/09
5. Local practice at GOSH as at 24/02/10

Drug:
ERYTHROMYCIN
Usual route of
clearance:
Erythromycin is metabolised principally by demethylation in the liver and

excreted in the bile.1,2,3 Approximately 12-15% is excreted in the active form
in the urine.2
Protein binding:
70-95%4
Molecular Wt:
733.93 daltons5
Vd:
Half-life (t):
Adults: ~2 hours2
t in renal imp:
Adults: 4-7 hours in severe renal impairment2,4
Gastric stasis:
3mg/kg po/ng every 6 hours (all ages)6,8
Chest infection:
12.5mg/kg (max 1g) iv every 6 hours (all ages)6,7,8
Meningitis:
25mg/kg (max 1g) iv every 6 hours8
GFR 20-50ml/min: No dosage adjustment required - give normal dose4,6,9
GFR <10ml/min:
Give 50-75% of normal total daily dose;4 max 1.5g in
24 hours10
4
Not dialysed. Give 50-75% of normal dose every 6 hours;4 max 1.5g in 24
hours10
Not dialysed.4 Give 50-75% of normal dose every 6 hours;4 max 1.5g in 24
hours10
No information
Pharmacokinetic
parameters:
Normal dose:
Dose adjustment
in renal
impairment:
Dose adjustment
in HD:
Dose adjustment
in PD:
Intraperitoneal
dose:
Dose adjustment
in CVVH:
Notes:
No dosage adjustment required - give normal dose;4,9,11 max 1.5g in 24

hours10 unless treating meningoencephalitis discuss with pharmacist
Despite being predominantly hepatically metabolised, toxicity (ototoxicity) has
been seen in patients with severe renal impairment.6
The iv route should always be used if treating meningoencephalitis.
Erythromycin may markedly elevate levels of other hepatically metabolised
drugs such as ciclosporin and tacrolimus12 ensure erythromycin drug
interactions are always checked with the pharmacist.
References:
1. Summary of Product Characteristics: EMC/Package Insert, Last updated: 18/09/07 Manufacturer: Amdipharm plc
4. Ashley C, Currie A. The Renal Drug Handbook. 3rd edn. Radcliffe Medical Press Ltd, Oxon UK, 2009.
online 04/08/09
Blackwell; 2011.
th
10. Martin J et al. British National Formulary 61 March 2011. Pharmaceutical Press, London, UK 2011
rd
2009
12. Stockleys Drug Interactions: Copyright 2010 The Pharmaceutical Press. Accessed online 26/04/10

Drug:
FLUCLOXACILLIN
Usual route of
clearance:
Flucloxacillin is metabolised to a limited extent and the metabolites are

excreted in the urine by glomerular filtration and renal tubular secretion.1
Approximately 60-76% of a dose is recovered in the urine within 8 hours.1
Only small amounts are excreted in the bile.1
Protein binding:
95%2
Molecular Wt:
453.87 daltons3
Vd:
Adults: 0.13 L/kg2
Half-life (t):
Adults: 1 hour1
Neonates: prolonged1
t in renal imp:
<7 days of life:
Infection due to -lactamase-producing Staphylococci:
25mg/kg iv every 12 hours, double dose in severe
infection4
Meningitis, osteomyelitis: 50-100mg/kg iv every 12
hours4
7-21 days of life:
infection4
hours4
21-28 days of life:
infection4
hours4
>4 weeks of life-18 Infection due to -lactamase-producing Staphylococci:
years:
12.5-25mg/kg (max 1g) iv every 6 hours, double dose
in severe infection4
Meningitis, osteomyelitis: 50mg/kg (max 2g) iv every 6
hours4
GFR <10ml/min:
Give normal dose iv every 8 hours4,5
2,5
Not dialysed. Give normal dose iv every 8 hours6
Pharmacokinetic
parameters:
Normal dose:
Dose adjustment
in renal
impairment:
Dose adjustment
in HD:
Dose adjustment
in PD:
Intraperitoneal
dose:
Dose adjustment
in CVVH:
Notes:
Not dialysed.1,2,5 Give normal dose iv every 8 hours6

No information
Not filtered. Give normal dose iv every 8 hours6
References:
Ltd
online 04/08/09
6. Local practice at GOSH as at 24/02/10

Drug:
FLUCONAZOLE
Usual route of
clearance:
Fluconazole is predominantly renally cleared, with approximately 80% of a

dose excreted unchanged in the urine. There is no evidence of circulating
metabolites.1
Protein binding:
11-12%1,2,3
Molecular Wt:
306.27 daltons4
Vd:
Paediatrics: 0.95 0.39 L/kg2
Half-life (t):
Adults: 30 hours3,5
Paediatrics: 15-25 hours3
t in renal imp:
Adults: 98 hours5
Prophylaxis:
<2 weeks of life: 3mg/kg every 72 hours po/iv6
2-4 weeks of life: 3mg/kg every 48 hours po/iv6
>4 weeks of life: 3mg/kg every 24 hours po/iv6
Treatment:
<2 weeks of life: 6-12mg/kg every 72 hours po/iv3,7
2-4 weeks of life: 6-12mg/kg every 48 hours po/iv7
>4 weeks of life: 6-12mg/kg every 24 hours po/iv7
GFR >50ml/min:
GFR <50ml/min:
Give 1x normal dose initially, followed by 50% of the
normal dose1,7,9
3,5,8
Dialysed.
Give 50% of the normal dose daily,5 or give 100% of the dose
three times a week, administered after dialysis session3,9,10,11
Dialysed.3,5 Give 50% of the normal dose daily5,10
Pharmacokinetic
parameters:
Normal dose:
Dose adjustment
in renal
impairment:
Dose adjustment
in HD:
Dose adjustment
in PD:
Intraperitoneal
dose:
Dose adjustment
in CVVH:
Notes:
Not recommended12
Filtered.5 No dosage adjustment required,10 but give upper range of normal
dose.2
References:
1. Summary of Product Characteristics: EMC/Package Insert, Last updated: 23/07/07 Manufacturer: Pfizer Ltd
online 04/08/09
6. Kaufman et al. Fluconazole prophylaxis against fungal colonisation and infection in preterm infants. N Engl J Med
345 (23): 1660-1666.
th
rd
2009
12. Correspondence from manufacturer (Pfizer Ltd).

Drug:
GANCICLOVIR
Usual route of
clearance:
The major route of elimination is renal excretion of unchanged drug by

glomerular filtration and active tubular secretion1 (approximately 80-100% of a
dose is excreted unchanged).2,3
Protein binding:
1-2%2,4-6
Molecular Wt:
255.237
Vd:
Adults: 0.54-0.87 L/kg2
Paediatrics: 0.64 0.22 L/kg2,3
Half-life (t):
Adults: 2.73 1.29 3.98 1.78 hours4
Children: 2.49 0.57 hours4
Neonates and infants up to 49 days old: 2.4 hours3
t in renal imp:
CMV, VZV:
>4 weeks of life: 5mg/kg iv every 12 hours6,8
Pharmacokinetic
parameters:
Normal dose:
Dose adjustment
in renal
impairment:
Dose adjustment
in HD:
Dose adjustment
in PD:
Intraperitoneal
dose:
Dose adjustment
in CVVH:
Notes:
GFR >70ml/min:
5mg/kg iv every 12 hours1,2,4
GFR 50-70ml/min: 2.5mg/kg iv every 12 hours1-5
GFR <10ml/min:
1.25mg/kg iv every 24 hours1,4,6,9
4
Dialysed. Approximately 40-50% is removed by a four-hour dialysis session.3
Give 1.25mg/kg iv every 24 hours, administered after dialysis session1,2,5,6,9
Dialysed.4 Give 1.25mg/kg iv every 24 hours6,9
No information
2.5mg/kg iv every 24 hours4,9,10
Nephrotoxic. Monitor for signs of myelosuppression.
References:
1. Summary of Product Characteristics: EMC/Package Insert, Last updated: 21/04/06 Manufacturer: Roche Products
Ltd
online 04/08/09
rd
2009
th

Drug:
GENTAMICIN
Usual route of
clearance:
Gentamicin does not undergo metabolism and is 90% excreted unchanged in

the urine by glomerular filtration.1,2,3 Small amounts of gentamicin appear in
the bile.2
Protein binding:
0-30%3,4,5
Molecular Wt:
463.97 daltons6
Vd:
Adults: 0.31 L/kg3,7
Adolescents: 0.3 0.1 L/kg5
Children: 0.35 0.15 L/kg5
Infants: 0.4 0.1 L/kg5
Neonates: 0.45 0.1 L/kg5
Half-life (t):
Adults: 2-3 hours1,2,3,7,8
Adolescents: 1.5 1 hour5
Children: 2 1 hour5
Infants: 4 1 hour5
Neonates 7-28 days: 3-6 hours5
Neonates <7days: 3-11.5 hours5
t in renal imp:
Prolonged2. 36-70 hours in anuric patients5
Neonate <32wks
postmenstrual age: 4-5mg/kg iv every 36 hours9,10
Neonate 32wks
postmenstrual age: 4-5mg/kg iv every 24 hours9,10
Cystic fibrosis:
10mg/kg (max 550mg) iv every 24 hours11
All other patients
>4 weeks of life:
7mg/kg iv every 24 hours (use ideal body weight)9
GFR 30-70ml/min: 3-5mg/kg iv3
GFR 10-30ml/min: 2-3mg/kg iv3
GFR <10ml/min:
2mg/kg iv3
Take trough level after 24hours, and hold next dose
until trough level is available.
Adjust dosage interval according to serum levels5,12
aim to keep trough <1mg/L and peak 5-10mg/L.9
2,5
Dialysed. Give 2mg/kg iv,3,13 take trough level after 24 hours, and hold next
dose until trough level is available. Adjust dosage interval according to serum
levels5,12,13 aim to keep trough <1mg/L and peak 5-10mg/L.9
Dialysed.2,5 Give 2mg/kg iv,3,13 take trough level after 24 hours, and hold next
dose until trough level is available. Adjust dosage interval according to serum
levels5,12,13 aim to keep trough <1mg/L and peak 5-10mg/L.9
Loading dose 8mg/L, maintenance dose 4mg/L13,14
Pharmacokinetic
parameters:
Normal dose:
(for endocarditis
see notes)
Dose adjustment
in renal
impairment:
Dose adjustment
in HD:
Dose adjustment
in PD:
Intraperitoneal
dose:
Dose adjustment
in CVVH:
Notes:
Give 4-5mg/kg iv,13 take trough level after 24 hours, and hold until trough
level is available. Adjust dosage interval according to serum levels13 aim to
Peak levels are only required for doses <7mg/kg.
Repeat levels daily in renal impairment or if on any form of
dialysis/haemofiltration.
Take care not to underdose; ensure that a therapeutic peak level is
maintained.
The above regimens are not suitable for patients with endocarditis; discuss
with pharmacist.
References:
1. Summary of Product Characteristics: EMC/Package Insert, Last updated: 11/09/08, Manufacturer: Sanofi-Aventis
2. Summary of Product Characteristics: EMC/Package Insert, Last updated: 28/04/09, Manufacturer: Hospira UK Ltd
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
Lexi-comp online accessed via www.crlonline.com, accessed 06/06/11

Budavari ES. The Merck Index 2009. The Merck Research Laboratories, Whitehouse Station (NJ), 2009. Accessed
online 31/07/09
Summary of Product Characteristics: EMC/Package Insert, Last updated: 24/09/08, Manufacturer: Winthrop
Pharmaceuticals Ltd
Summary of Product Characteristics: EMC/Package Insert, Last updated: 27/05/09, Manufacturer: Amdipharm
Hey E. Neonatal formulary 6: drug use in pregnancy and the first year of life. 6th edn. Malden, Mass.; Oxford:
Blackwell; 2011
Gt Ormond St Hospital for Children NHS Trust and the Institute of Child Health Handbook for the Management of
nd
Children with Cystic Fibrosis 2 edn March 2006
rd
2009
Aronoff GR, Bennett WM, Berns JS et al. Drug Prescribing in Renal Failure, Dosing Guidelines for Adults and
th
Daschner M. Drug Dosage in Children with Reduced Renal Function. Pediatr Nephrol 2005; 20: 1675-1686

Drug:
IMIPENEM + CILASTATIN
Usual route of
clearance:
Cilastatin is an enzyme inhibitor which blocks the metabolism of imipenem in

the kidney, increasing the plasma concentration, AUC, and urinary
concentration of imipenem.1,2
When imipenem and cilastatin are administered concurrently in a 1:1 ratio
approximately 50-70% of the imipenem dose and 75% of the cilastatin dose is
excreted unchanged in the urine within 10 hours by both glomerular filtration
and tubular secretion.2
Imipenem also undergoes a degree of non-renal metabolism with
approximately 20-30% of an imipenem dose undergoing hydrolysis of the
beta-lactam ring to form a microbiologically inactive metabolite.2
Approximately 12% of a dose of cilastatin undergoes metabolism in the
kidneys to N-acetylcilastatin; the remaining metabolic pathways of cilastatin
are unknown.2
Less than 1% of an imipenem dose and less than 2% of a cilastatin dose are
excreted in the faeces.2
Protein binding:
imipenem: 13-21%2,3
cilastatin:
~40%2,3,4
Molecular Wt:
imipenem: 299.35 daltons5
cilastatin:
358.45 daltons5
Vd:
imipenem: Adults: 0.23 L/kg4
Neonates 1-8 days old: 0.251-0.418 L/kg4
cilastatin:
Adults: 0.2 L/kg2
Half-life (t):
imipenem: Adults: 0.85-1.3 hours2
Children aged 2-12years: 1-1.3 hours2
Neonates 1-10 days old: 1.5-2.6 hours2
cilastatin:
Neonates: 3.1-8.8 hours2
t in renal imp:
imipenem: Adults: 2.1-3.7 hours2
cilastatin:
<1 week of life:
1-3 weeks of life:
3 wks - 3 months:
3 months - 18yrs:
<40kg: 15mg/kg (max 500mg) iv every 6 hours6
>40kg: 250-500mg iv every 6 hours; 6 less sensitive
organisms 12.5mg/kg (max 1g) iv every 6 hours6
Cystic fibrosis:
See doses in BNF-C6
GFR 30-70ml/min: >4 weeks of life: Give 80-100% of dose every 8 hours4
GFR 20-30ml/min: >4 weeks of life: Give 80-100% of dose every 12
hours4
GFR <20ml/min:
>4 weeks of life: Give 30-50% of dose every 12 hours4
GFR <5ml/min:
Do not start imipenem/cilastatin unless haemodialysis
or haemofiltration is to be started within 48 hours1
Give normal dose iv every 12 hours, administered after dialysis session1
Pharmacokinetic
parameters:
Normal dose:
Dose adjustment
in renal
impairment:
Dose adjustment
in HD:
Dose adjustment
in PD:
Intraperitoneal
dose:
Dose adjustment
in CVVH:
Notes:
Give 50% of the normal dose every 24 hours9

Give 80-100% of normal dose iv every 8-12 hours4
Increased risk of convulsions when imipenem/cilastatin is used in patients
with renal impairment10 (it may be more appropriate to change treatment to
meropenem).

References:
1. Summary of Product Characteristics: EMC/Package Insert, Last updated: 05/03/09 Manufacturer: Merck Sharp &
Dohme Limited
online 31/07/09
Blackwell; 2011
th

Drug:
LINEZOLID
Usual route of
clearance:
The (s)-linezolid enantiomer is biologically active and is primarily metabolised

by oxidation to form two inactive metabolites;1 the predominant metabolite is
thought to be formed by a non-enzymatic process.2
Non-renal clearance accounts for approximately 65% of the total clearance of
linezolid.1,2
Protein binding:
Approximately 31%1,2,3,4
Molecular Wt:
337.35 daltons4
Vd:
Adults: 0.6 L/kg3
Half-life (t):
Adults: 5-7 hours2,3
Preterm neonates <7 days of life: 5.6 hours1
Full-term neonates <7 days of life: 3 hours1
Neonates 7-28 days of life: 1.5 hours1
Infants >28 days to 2 months: 1.8 hours1
Children 3 months to 11 years: 2.9 hours1
Adolescents 1217 years: 3.1 hours1
t in renal imp:
Unchanged3
<1 week of life:
10mg/kg iv/po/ng every 12 hours,1,5,6,7 increase to
every 8 hours if poor response6
>1 week 12yrs:
10mg/kg (max 600mg) iv/po/ng every 8 hours1,5,6,7
>12 years:
600mg iv/po/ng every 12 hours1,6,7
GFR 20-50ml/min: No dosage adjustment required - give normal dose2,3,8,9
GFR <10ml/min:
Dialysed.3,9 No dosage adjustment required - give normal dose, administered
after dialysis session 2,3,4
Likely to be dialysed. No dosage adjustment required - give normal dose3
Pharmacokinetic
parameters:
Normal dose:
Dose adjustment
in renal
impairment:
Dose adjustment
in HD:
Dose adjustment
in PD:
Intraperitoneal
dose:
Dose adjustment
in CVVH:
Notes:
No information
While no dosage adjustment is required in renal impairment, note that the
metabolites may accumulate if the estimated GFR is <30ml/min/1.73m2,1,6,7,8
and that these metabolites may have NAOI activity.3 Patients with severe
renal impairment may have 10-fold increases in serum levels of the inactive
metabolites, the clinical significance of which is unknown.2
As linezolid is metabolised by a non-enzymatic process, impairment of
hepatic function is not expected to significantly alter its metabolism.2
References:
2. Summary of Product Characteristics: EMC/Package Insert, Last updated: 14/10/09 Manufacturer: Pharmacia
Blackwell; 2011
th
rd
2009

Drug:
MEROPENEM
Usual route of
clearance:
Pharmacokinetic
parameters:
Approximately 70% of a dose is excreted unchanged in the urine over 12

hours.1,2 The only metabolite of meropenem is microbiologically inactive.1
Protein binding:
Approximately 2%1,2,3
Molecular Wt:
383.46 daltons4
Vd:
Adults: 0.35 L/kg2
Children: 0.43 0.06 L/kg3
Half-life (t):
Adults: 1 hour1,2
Children <2 years: 1.5-2.3 hours1
t in renal imp:
Adults: 6-13.7 hours2
<7 days:
20mg/kg (severe infection/meningitis 40mg/kg) iv every
12 hours5,6,7
7-28 days:
20mg/kg (severe infection/meningitis 40mg/kg) iv every
8 hours5,6,7
1 month-12 years
10-20mg/kg (severe infection/meningitis 40mg/kg) iv
and <50kg:
every 8 hours (up to max 6g/day)6
12-18 years or
0.5-1g (severe infection/meningitis 2g) iv every 8
>50kg:
hours6
GFR 20-50ml/min: Give normal dose iv every 12 hours1,6,7,8
GFR 10-20ml/min: Give 50% of dose iv every 12 hours1,6,7,8
GFR <10ml/min:
Give 50% of dose iv every 24 hours1,6,7,8,9,10
2,7
Dialysed. Give 50% of dose iv every 24 hours,2,3,7,9,10 administered after
dialysis session1,8,10
Dialysed.2,7 Give 50% of dose iv every 24 hours7,9,10
Normal dose:
Dose adjustment
in renal
impairment:
Dose adjustment
in HD:
Dose adjustment
in PD:
Intraperitoneal
dose:
Dose adjustment
in CVVH:
Notes:
100mg/L2
Give 100% of normal dose every 12 hours,2,10 or every 8 hours7 depending
upon severity of infection (eg for meningitis) discuss with pharmacist.
Meropenem has less potential to induce seizures than imipenem.2
Licensed for children over 3 months old.6
References:
1. Summary of Product Characteristics: EMC/Package Insert, Last updated: 13/08/07 Manufacturer: AstraZenica UK
Ltd
online 04/08/09
Blackwell; 2011.
rd
2009
th

Drug:
METRONIDAZOLE
Usual route of
clearance:
Metronidazole is predominantly metabolised by hepatic oxidation.1

Approximately 10%2 to 20%3 of a dose is excreted in the urine as unchanged
drug.
Protein binding:
<20%2,4-6
Molecular Wt:
171.15 daltons7
Vd:
Adults: 1.1 0.4 /kg1
Half-life (t):
Adults: 8.5 2.9 hours1
Children: 6-12 hours6
Neonates: 25-75 hours6
t in renal imp:
Unchanged1
<4 weeks of life:
7.5mg/kg iv/po/ng every 12 hours8
7.5mg/kg (max 400mg) po/ng every 8 hours9,10
>4 weeks of life:
7.5mg/kg (max 500mg) iv every 8 hours9,10
GFR 20-50ml/min: No dosage adjustment required - give normal dose2-4,12
GFR <10ml/min:
No dosage adjustment required - give normal dose4,13
Dialysed.4,6 No dosage adjustment required - give normal dose, administered
after dialysis session1,2,4,10,13
Dialysed.6 No dosage adjustment required - give normal dose1,4,10,13
Pharmacokinetic
parameters:
Normal dose:
Dose adjustment
in renal
impairment:
Dose adjustment
in HD:
Dose adjustment
in PD:
Intraperitoneal
dose:
Dose adjustment
in CVVH:
Notes:
No information
Although the elimination half-life is unchanged in the presence of renal
impairment, the clearance of the metabolites is reduced, the significance of
which is unknown.1
The incidence of gastrointestinal and vestibular toxicity is increased in
patients on metronidazole with renal impairment.4
A 50% to 67% decrease in dosage is required in patients with hepatic
impairment.6
References:
1. Summary of Product Characteristics: EMC/Package Insert, Last updated: 24/09/09 Manufacturer: Winthrop
Pharmaceuticals UK Ltd
online 04/08/09
Blackwell; 2011.
th
rd
2009

Drug:
MICAFUNGIN
Usual route of
clearance:
Micafungin exhibits linear pharmacokinetics.1 Elimination of micafungin is

primarily non-renal,1 with micafungin undergoing hepatic metabolism and then
excretion in the faeces.2 Less than 1% of a dose is eliminated renally.3
PB:
>99%1,2,3,4,5
Mol Wt:
1292.3 daltons4
Vd:
Adults: 18-19L1 or 0.39 0.11 L/kg3
Children 9-17 years: 0.28 0.09 L/kg3
Children 2-8 years: 0.35 0.18 L/kg3
Neonates: 0.34-0.76 L/kg3
t:
Children 9-17 years: 13.3 4.3 hours3
Children 2-8 years: 11.6 2.8 hours3
Neonates: 6.7 2.2 hours3
t in renal imp:
No information
<4 weeks of life:
2mg/kg iv once daily, increased to 4mg/kg iv once daily
if inadequate response.6
>4 wks and <40kg: 2mg/kg iv once daily, increased to 4mg/kg iv once daily
(max 200mg) if inadequate response. 6
>40kg:
100mg iv once daily (increased to 200mg/kg iv once
daily if inadequate response). 1,6
GFR <10ml/min:
Not dialysed.2,3 No dosage adjustment required - give normal dose5
Pharmacokinetic
parameters:
Normal dose:
Dose adjustment
in renal
impairment:
Dose adjustment
in HD:
Dose adjustment
in PD:
Intraperitoneal
dose:
Dose adjustment
in CVVH:
Notes:
Not dialysed.2,3 No dosage adjustment required - give normal dose5

No information
Unlikely to be filtered. No dosage adjustment required - give normal dose5
Mean values of clearance in younger children (2 11 years) are
approximately 1.3-fold greater than those in older children (12 17 years).
Older children exhibit mean clearance values similar to those adults. Mean
clearance in premature infants (gestational age approximately 26 weeks) is
approximately 5-fold greater than in adults.1
While no dosage adjustment is required in renal impairment, micafungin
should be used with caution, as it may cause a further deterioration in renal
function.6
No adjustment needed in mild-to-moderate hepatic impairment; the effect of
severe hepatic impairment on micafungin pharmacokinetics has not been
studied3
References:
1. Summary of Product Characteristics: EMC/Package Insert, Last updated: 03/12/09 Manufacturer: Astellas Pharma
Ltd
4. Martindale: The Complete Drug Reference. Pharmaceutical Press, London, UK, 2010. Accessed online 04/05/10
th

Drug:
Usual Route of
Clearance:
Pharmacokinetic
parameters:
Normal dose:
Dose adjustment
in renal
impairment:
Dose adjustment
in HD:
Dose adjustment
in PD:
Dose adjustment
in CVVH:
Notes:
OSELTAMIVIR
Oseltamivir is predominantly eliminated by conversion to oseltamivir
carboxylate, an active metabolite, by liver esterases.1 The active metabolite is
then eliminated entirely by renal excretion.1,2 Less than 20% of an oral dose is
excreted in the faeces.1
Protein binding:
42% (oseltamivir carboxylate: 3%)2
Molecular Wt:
312.40 daltons3
Vd:
Half-life (t):
Adults: 1-3 hours1 (oseltamivir carboylate: 6-10
hours)1,2
t in renal imp:
Adults: >20 hours2
Treatment:
Dose is given twice daily for 5 days or as clinically
indicated1,4,5
*Prem neonate (<38weeks): 1mg/kg orally twice daily6,7
*0-8months:
3mg/kg orally twice daily6,7
*9-23months: 3.5mg/kg orally twice daily6,7
Age 2-13 years and:
15kg:
30mg orally twice daily4,5
>15-23kg:
>23-40kg:
>40kg:
>13years:
Prophylaxis:
Dose is given once daily for 10 days1,4,5
*Prem neonate: 1mg/kg orally once daily6,7
*0-8months:
3mg/kg orally once daily6,7
*9-23months: 3.5mg/kg orally once daily6,7
Age 2-13 years and:
15kg:
30mg orally once daily4,5
>15-23kg:
>23-40kg:
>40kg:
>13years:
GFR >30ml/min:
Give normal dose8
GFR 10-30ml/min: Treatment: give 100% of the normal dose every 24 hrs8
Prophylaxis: give 100% of the normal dose every 48
hrs8
GFR <10ml/min:
Treatment: give 50% of the normal dose as a single stat
dose (for longer courses, maximum 10 days) 8
Prophylaxis: give 50% of the normal dose as a single
stat dose8
Treatment: give 50% of the normal dose after each dialysis session8
Prophylaxis: give 50% of the normal dose after each dialysis session8
Treatment: give 50% of the normal dose as a single dose once a week, after
dialysate exchange8
Prophylaxis: give 50% of the normal dose as a single stat dose. A second
dose may be given after one week8
Treatment: give 100% of the normal dose every 24 hours8
Prophylaxis: give 100% of the normal dose every 48 hours8
The use of oseltamivir in patients with CrCl<10ml/min and for patients
receiving renal replacement therapy is not recommended by the
manufacturer and there is no definitive dose guidance. Patients must be
monitored closely for efficacy, adverse effects and signs of toxicity.
Gastrointestinal side effects and dizziness are more common in renal
impairment.
In children on the intensive care units >2 years old with a GFR > 30ml/minute
who are H1N1 positive with pandemic strain confirmed, discuss with
microbiology or infectious diseases to consider doubling the dose of

oseltamivir.
*Neonatal and infant dosing has been updated in the light of published
pharmacokinetic data
See Trust Guidelines and discuss all use of oseltamivir with
microbiology.
References:
1. Summary of Product Characteristics: Electronic Medicines Compendium. Last updated: 04/11/09, Manufacturer:
Roche Products Ltd
online 04/08/09
5. Health Protection Agency. Summary of prescribing guidance for the treatment and prophylaxis of influenza-like
illness. v4.0 25 November 2009
6. Acosta EP, Jester P, Gal P et al. Oseltamivir Dosing For influenza Infection in Premature Neonates. J infect Dis,
2010;202:563-6.
7. Acosta EP & Kimberlin DW. Determination of Appropriate Dosing of Influenza Drugs in Pediatric Patients. Clin Pcol
Therap, 2010;88:704-7.
8. Gt Ormond St Hospital for Children NHS Trust Oseltamivir Treatment and Prophylaxis in Renal Impairment
Paediatric Nephrology Guideline July 2009, developed in conjunction with RCPCH, BAPN, UKRPG & Dept of Health
Guidelines.

Drug:
PIPERACILLIN + TAZOBACTAM
Usual route of
clearance:
Piperacillin is excreted rapidly as unchanged drug, with 68% of the

administered dose appearing in the urine.1-5 Piperacillin also undergoes
metabolism to a minor microbiologically active desethyl metabolite.1-5
Tazobactam is metabolised to a single inactive metabolite, with 80% of a
dose appearing in the urine unchanged and the remainder as the inactive
metabolite.1-5 Both piperacillin and tazobactam are eliminated by the kidney
via glomerular filtration and tubular secretion.1-4 There is also some biliary
excretion of piperacillin, tazobactam, and the desethyl piperacillin
metabolite.1-5
Protein binding:
piperacillin:
20-30%1-5
tazobactam: 20-30%1-5
Molecular Wt:
piperacillin:
515.55 daltons6
tazobactam: 300.29 daltons6
Vd:
piperacillin:
Adults: 0.18-0.3 L/kg5,7
tazobactam: Adults: 0.18-0.33 L/kg5
Half-life (t):
piperacillin:
Adults: 0.7-1.2 hours1-5
Children 2-12 years: 0.7 hours1-4
tazobactam: Adults: 0.7-1.2 hours1-5
t in renal imp:
piperacillin:
Adults: 4-6 hours5
tazobactam: Adults: 7 hours5
<1 month:
>1 mth and <15kg: 90mg/kg iv every 6 hours8
15.01-20kg:
1575mg iv every 6 hours9
20.01-25kg:
25.01-30kg:
30.01-35kg:
35.01-40kg:
40.01-45kg:
45.01-50kg:
>50kg:
GFR 40-80ml/min: 12 years old: decrease frequency to every 8 hours8
<12 years old: no dosage adjustment required - give
normal dose1-4,8,10
GFR 20-39ml/min: >1month old: decrease frequency to every 8 hours1-
Pharmacokinetic
parameters:
Normal dose:
With dose
banding:
Dose adjustment
in renal
impairment:
4,8,10
GFR <20ml/min:
>1month old: decrease frequency to every 12 hours14,8,10
Dose Adjustment
in HD:
Dose Adjustment
in PD:
Intraperitoneal
dose:
Dose Adjustment
in CVVH:
Notes:
Dialysed.5,11 >1month old and <50kg: 45mg/kg iv every 8 hours4

>50kg: 4500mg iv every 12 hours and supplementary dose of 2250mg iv post
dialysis on dialysis days1-4,12 (haemodialysis removes 30-50% of piperacillin in
4 hours)1
Not dialysed.5 >1month old: decrease frequency to every 12 hours1-3,11,12
250mg/L5
>1 month old: decrease frequency to every 8 hours5
Licensed for children over 2 years old4
References:
1.
Summary of Product Characteristics: EMC/Package Insert, Last updated: 22/06/09 Manufacturer: Wockhardt UK
Ltd
3. Summary of Product Characteristics: EMC/Package Insert, Last updated: 26/06/09 Manufacturer: Wyeth
Pharmaceuticals
4. Summary of Product Characteristics: EMC/Package Insert, Last updated: 02/02/10 Manufacturer: Sandoz Ltd
online 04/08/09
9. Gt Ormond St Hospital for Children NHS Trust Antibiotic Policy Appendix 2 V3 July 2011
th
rd
2009

Drug:
RIBAVIRIN
Usual route of
clearance:
Ribavirin is metabolised principally to deribosylated ribavirin (1,2,4-triazole-3carboxamide), which is thought to probably occur in the liver. This metabolite
has a similar activity to the parent drug.1
Ribavirin also undergoes phosphorylation in erythrocytes.1
Ribavirin is excreted primarily in the urine, with a small amount also fecally
excreted.1
Protein binding:
Negligible2
Molecular Wt:
244.2 daltons3
Vd:
Paediatrics (after single iv dose only): 7.7 5.1 L/kg2
Half-life (t):
Paediatrics (after single iv dose only):18.6 10.2 hours2
t in renal imp:
Likely to be increased2
RSV / Paraflu /
>1 month old: 33mg/kg iv as a single dose,
Adenovirus
then 16mg/kg iv every 6 hours for 4 days, followed by
8mg/kg iv every 8 hours for 3 days then review4,5
GFR 30-50ml/min: iv: no dosage adjustment required - give normal dose3,5
GFR 10-30ml/min: iv: no dosage adjustment required (but see notes
below)3,5
GFR <10ml/min:
iv: no dosage adjustment required (but see notes
below)3,5
3
Not dialysed. iv: no dosage adjustment required (but see notes below)3
Pharmacokinetic
parameters:
Normal dose:
Dose adjustment
in renal
impairment:
Dose adjustment
in HD:
Dose adjustment
in PD:
Intraperitoneal
dose:
Dose adjustment
in CVVH:
Notes:
Unlikely to be dialysed.3 iv: no dosage adjustment required (but see notes

below)3
No information
iv: no dosage adjustment required - give normal dose (but see notes below)3
enteral: avoid if GFR<50ml/min3,5,6
Caution should be used if iv ribavirin is prescribed in patients with GFR
<30ml/minute.5 While the normal dosage regimen may be prescribed, patients
should be closely monitored for signs of toxicity such as anaemia.2,3 There is
no experience of iv ribavirin use in patients with end-stage renal disease or on
renal replacement therapies.3
The manufacturer recommends that the oral preparation should be avoided in
patients with GFR<50ml/min or on haemodialysis.3,5,6
References:
th
2. Investigational Drug Brochure: Virazole (Ribavirin USP) Injection 100mg/ml IND 9076, 4 Edition; August 2004.
Manufacturer: Valeant Pharmaceuticals International
6. Summary of Product Characteristics: EMC/Package Insert, Last updated: 23/12/09 Manufacturer: Schering-Plough

Drug:
RIFAMPICIN
Usual route of
clearance:
Rifampicin is rapidly eliminated in the bile and undergoes enterohepatic recirculation, during which it undergoes progressive deacetylation to an active
metabolite.1 Nearly all the drug in the bile is in this form within approximately
6 hours. Intestinal reabsorption is reduced by deacetylation, therefore
facilitating elimination.1 Up to 30% of a dose is excreted in the urine, with
about half of this being unchanged drug.1
Protein binding:
~80%1,2,3,4
Molecular Wt:
822.9 daltons2
Vd:
Adults: 0.64-0.66 L/kg2
Half-life (t):
Adults: ~2-3 hours1
Paediatrics: ~1-3.8 hours5
t in renal imp:
Possibly increased5
<4 weeks of life:
5-10mg/kg (meningitis 10mg/kg) iv/po/ng every 12
hours6
1-12 months:
5-10mg/kg (meningitis 10mg/kg) iv/po/ng every 12
hours6
1-18 years:
10mg/kg (max 600mg) iv/po/ng every 12 hours6
but use with caution if dose is above 10mg/kg daily6
but use with caution if dose is above 10mg/kg daily6
GFR <10ml/min:
Give 50-100% of normal dose2,8 but use with caution if
dose is above 10mg/kg daily6
Not dialysed.2,3 Give 50-100% of normal dose iv/po/ng2,5,8
Pharmacokinetic
parameters:
Normal dose:
Dose adjustment
in renal
impairment:
Dose adjustment
in HD:
Dose adjustment
in PD:
Intraperitoneal
dose:
Dose adjustment
in CVVH:
Notes:
Not dialysed.2 Give 50-100% of normal dose iv/po/ng2,5,8

No information
No dosage adjustment required - give normal dose2,3
Renal dysfunction has been noted with rifampicin.1,2
Rifampicin is excreted into PD fluid causing an orange-yellow colour.2
If patient has impaired hepatic function, avoid or do not exceed 8mg/kg iv/po
daily6,9
References:
th
rd
2009

10.
Drug:
TEICOPLANIN
Usual route of
clearance:
Greater than 97% of a dose of teicoplanin is excreted unchanged,

predominantly in the urine.1,2 No metabolites of teicoplanin have been
identified.1
Protein binding:
90-95%1,2
Molecular Wt:
1877.64 daltons3
Vd:
Adults: 0.94-1.4 L/kg1,2 (similar values in children)1
Half-life (t):
Adults: 150 hours1,2
t in renal imp:
62-230 hours2
<4 weeks of life:
16mg/kg iv stat, then 24 hours later 8mg/kg iv every 24
hours1,4,5,6
>4 weeks of life:
Severe infection: 10mg/kg (max 400mg) iv q12h for 3
doses, then 10mg/kg (max 400mg) iv q24h1,4,5,6
Moderate infection: 10mg/kg (max 400mg) iv q12h for
3 doses, then 6mg/kg (max 400mg) iv q24h1,4,6
GFR 40-60ml/min: Give normal regimen for the first three days, then
reduce dose on Day 4 to 50% of the dose once daily or
give 100% of the dose every second day.1,4,6
GFR <40ml/min:
Give normal regimen for the first three days, then
reduce dose on Day 4 to one third of the dose once
daily or give 100% of the dose every third day.1,4,6
Not dialysed.2 Give normal regimen for the first three days, then reduce dose
on Day 4 to one third of the dose once daily or give 100% of the dose every
third day.1,2,4,7
Not dialysed.2 Give normal regimen for the first three days, then reduce dose
on Day 4 to one third of the dose once daily or give 100% of the dose every
third day.2,7
Give 10mg/kg (max 400mg) IV stat dose, then 20mg/L per bag for 7 days,
then 20mg/L per alternate bag for 7 days, then 20mg/L per night-bag only for
7 days2
Give normal regimen for the first three days, then reduce dose on Day 4 to
one third of the dose once daily or give 100% of the dose every third day.7
Due to the long half-life of the drug, dose reduction is not required until the 4th
day of treatment.4
Pharmacokinetic
parameters:
Normal dose:
Dose adjustment
in renal
impairment:
Dose adjustment
in HD:
Dose adjustment
in PD:
Intraperitoneal
dose:
Dose adjustment
in CVVH:
Notes:
References:
online 04/08/09
Blackwell; 2011.
rd
2009
th

Drug:
TICARCILLIN + CLAVULANIC ACID
Usual route of
clearance:
The major route of elimination for both ticarcillin and clavulanic acid is renal
excretion.1 Approximately 60-77% of a dose of ticarcillin and 35-45% of
clavulanic acid is excreted unchanged in the urine within 6 hours.2,3 The
metabolic fate of clavulanic acid has not been completely elucidated.3
Protein binding:
ticarcillin:
Approximately 45-60%2,3
clavulanic acid: Approximately 22-30%3
Molecular Wt:
ticarcillin:
384.43 daltons4
clavulanic acid: 199.16 daltons4
Vd:
ticarcillin:
Adults: ~0.17 L/kg3
Paediatrics: 0.22 L/kg2,5
clavulanic acid: Adults: ~0.315-0.342 L/kg3
Paediatrics: 0.4 L/kg2,5
Half-life (t):
ticarcillin:
Adults: 1.1-1.2 hours3,5
Neonates: 4.4 hours5
clavulanic acid: Adults: 1.1-1.5 hours3,5
Neonates: 1.9 hours5
t in renal imp:
ticarcillin:
Adults: 4.9 hours if CrCl = 1137ml/min3
Adults: 8.5 hours if CrCl <8ml/min3
clavulanic acid: Adults: 2.3 hours if CrCl = 1137ml/min3
Adults: 2.9 hours if CrCl <8ml/min3
Pre-term neonates: <2kg: 80mg/kg iv every 12 hours1,6
>2kg: 80mg/kg iv every 8 hours, increase to every 6
hours in severe infections1,6
Term neonates:
80mg/kg iv every 8 hours, increase to every 6 hours in
severe infections1,6
>4 wks and <40kg: 80mg/kg (max 3.2g) iv every 8 hours, increase to every
6 hours in severe infections1,6
>4 wks and >40kg: 3.2g iv every 6-8 hours, increase to every 4 hours in
severe infections6
GFR 30-60ml/min: >2kg: Give normal dose but reduce frequency to every
8 hours2,6,7
GFR 10-30ml/min: >2kg: Give 50%1,6-100%2,8 of normal dose every 8
hours2,6,8
GFR <10ml/min:
>2kg: Give 50%1,6,9-100%2,8 of normal dose every 12
hours2,6,8,9
5,7
1,9
Dialysed. Give 50% -100%8 of normal dose and reduce frequency to every
12 hours1,8,9
Not dialysed.7 Give 50%1-100%8,9 of normal dose and reduce frequency to
every 12 hours1,8
No information
Pharmacokinetic
parameters:
Normal dose:
Dose adjustment
in renal
impairment:
Dose adjustment
in HD:
Dose adjustment
in PD:
Intraperitoneal
dose:
Dose adjustment
in CVVH:
Notes:
Give 100% of normal dose but consider reducing frequency to every 8

hours,2,8 depending on the severity of the infection.
If patient has concomitant hepatic impairment then dose should be reduced to
every 24 hours8
References:
UK
3.
4.
5.
6.
7.
8.
9.
McEvoy GK et al. American Hospital Formulary Service (AHFS) Drug Information, 2009. American Society of
Budavari ES. The Merck Index. 2009. The Merck Research Laboratories, Whitehouse Station (NJ), 2009. Accessed
online 04/08/09
Lexi-comp online accessed via www.crlonline.com, accessed 10/06/11
Ashley C, Currie A. The Renal Drug Handbook. 3rd edn. Radcliffe Medical Press Ltd, Oxon UK, 2009
Aronoff GR, Bennett WM, Berns JS et al. Drug Prescribing in Renal Failure, Dosing Guidelines for Adults and
th
rd
2009

Drug:
VANCOMYCIN
Usual route of
clearance:
Pharmacokinetic
parameters:
At least 75% of a vancomycin dose is excreted in the urine by glomerular

filtration within 24 hours.1,2
Protein binding:
55%1,3,4
Molecular Wt:
1449.25 daltons5
Vd:
Adults: 0.39-0.97 L/kg1
Paediatrics: 0.4-0.75 L/kg (inversely related to age)6
Half-life (t):
Adults: 4-6 hours1
Children 2.5-11 years: 5.6 hours2
Infants 1-12 months: 4.1 hours2
Term neonates: 6.7 hours2
t in renal imp:
<2kg <4ks of life:
15mg/kg iv, frequency dependent upon levels7
>2kg <4wks of life: 15mg/kg iv every 12 hours7
>2kg >4wks of life: 15mg/kg iv every 8 hours7
Central nervous system infection: 15mg/kg iv every 6
hours6,7
(NB Maximum total daily dose is 2g)8
GFR 10-50ml/min: Give 10mg/kg iv every 12 hours, take trough level after
12 hours, give the next dose, and adjust regimen if
necessary in order to maintain serum trough level
between 5-10mg/L.7
GFR <10ml/min:
Give 10mg/kg iv every 24 hours, take trough level after
24 hours and hold dose until the serum trough level is
between 5-10mg/L.7
Minimally removed by HD.2,9 Give 10mg/kg3 iv as determined by serum
levels.3 Hold dose until the serum level is between 5-10mg/L.
Minimally removed by PD. 2,9 Give 10mg/kg3 iv as determined by serum
levels.3 Hold dose until the serum level is between 5-10mg/L.
12.5-25mg/L9
Normal dose:
Dose adjustment
in renal
impairment:
Dose adjustment
in HD:
Dose adjustment
in PD:
Intraperitoneal
dose:
Dose adjustment
in CVVH:
Notes:
Substantially removed by haemofiltration.2 Give 10mg/kg3 iv every 12 hours,

take trough level after 12 hours, give the next dose, and adjust regimen if
necessary in order to maintain serum trough level between 5-10mg/L.
Repeat levels daily in renal impairment or if on any form of
dialysis/haemofiltration.
Take care not to underdose; ensure that the trough level is maintained above
5mg/L otherwise treatment will be subtherapeutic.
For patients with normal renal function, aim for trough levels 5-15mg/L.7
For patients with central nervous system infection, aim for trough levels 1015mg/L.7
References:
1. Summary of Product Characteristics: EMC/Package Insert, Last updated: 10/11/08 Manufacturer: Flynn Pharma Ltd
th
online 04/08/09
7. Gt Ormond St Hospital for Children NHS Trust Antibiotic Policy Vancomycin Guidelines v2.0 July 2008

Drug:
VORICONAZOLE
Usual route of
clearance:
Voriconazole is metabolised by the cytochrome P450 2C19, 2C9 and 3A4

isoenzymes and exhibits non-linear pharmacokinetics due to its saturable
metabolism.1,2 Less than 2% of a dose is excreted unchanged in the
urine.1,2,3,4
Inter-individual variability of pharmacokinetics is high.1
Protein binding:
58%1,2,3
Molecular Wt:
349.31 daltons5
Vd:
Adults: ~4.6 L/kg1,2,3
Half-life (t):
Variable and dose-dependent due to saturable
metabolism1
t in renal imp:
Variable and dose-dependent due to saturable
metabolism1
<2 years old:
iv/po/ng: Loading dose of 6mg/kg every 12 hours for
two doses, followed by 4mg/kg every 12 hours6
2-12 years old:
iv: 7mg/kg every 12 hours,1,7 if not tolerated reduce to
4mg/kg every 12 hours, for maximum of 6 months7
po/ng: 200mg every 12 hours,1,7 if not tolerated use
dose as for <2 years of age6
>12 years old:
iv: Loading dose of 6mg/kg every 12 hours for two
doses, followed by 4mg/kg every 12 hours (reduced to
3mg/kg every 12 hours if not tolerated), for maximum
of 6 months1,7
po/ng: <40kg: Loading dose of 200mg every 12 hours
for 2 doses, followed by 100mg every 12 hours (may
be increased to 150mg every 12 hours)1,7
po/ng: >40kg: Loading dose of 400mg every 12 hours
for 2 doses, followed by 200mg every 12 hours (may
be increased to 300mg every 12 hours)1,7
GFR <50ml/min:
po/ng: no dosage adjustment required - give normal
dose1,2,4,7
iv: No dosage adjustment required - give normal
dose,3,4 however iv use is not recommended2,4,8
therefore only use if benefit outweighs risk (see notes
below).
3
Dialysed. No dosage adjustment required - give normal dose,3,4 however iv
use is not recommended4,8 therefore only use if benefit outweighs risk (see
notes below)
Probably dialysed.3 No dosage adjustment required - give normal dose,3,4
however iv use is not recommended4,8 therefore only use if benefit outweighs
risk (see notes below)
No information
Pharmacokinetic
parameters:
Normal dose:
Dose adjustment
in renal
impairment:
Dose adjustment
in HD:
Dose adjustment
in PD:
Intraperitoneal
dose:
Dose adjustment
in CVVH:
Notes:
No dosage adjustment required - give normal dose, 3,4 however iv use is not
recommended4,8 therefore only use if benefit outweighs risk (see notes below)
In patients with GFR <50ml/minute, the oral route is preferred, as
accumulation of the iv vehicle sulphobutylether beta cyclodextrin sodium
(SBECD) occurs,2,7,9 therefore the iv route should only be used if the riskbenefit justifies its use.1,3,7,9,10
Voriconazole may cause acute renal failure.1
References:
1. Summary of Product Characteristics: EMC/Package Insert, Last updated: 23/09/09 Manufacturer: Pfizer Ltd
th
5.
Budavari ES. The Merck Index. 2009. The Merck Research Laboratories, Whitehouse Station (NJ), 2009. Accessed
online 04/08/09
6. Gt Ormond St Hospital for Children NHS Trust Prescribing Guidelines for Individual Medicines Guideline for the
use of voriconazole in fungal infections v4.0 February 2008
rd
2009


Ajuste de Dosis de Medicamentos en Paciente Renal

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Paediatric Drug Dosage Adjustments

in Patients with Renal Impairment or

Drug Dosage Adjustments in Renal Impairment & CVVH 2011

the usual mechanism of clearance of the drug

Limitations of this guideline

Notes regarding dose adjustment in PICU patients undergoing haemofiltration

Drug Dosage Adjustments in Renal Impairment & CVVH 2011

4. It is important to remember that once the patient is stabilised on haemofiltration, the

Drug properties to consider in order to determine likelihood of drug removal by

Low molecular weight (< 10000 daltons)

Drug Dosage Adjustments in Renal Impairment & CVVH 2011

Aciclovir is predominantly renally cleared (75-80% excreted unchanged in

Monograph reviewed: 16/12/10

Drug Dosage Adjustments in Renal Impairment & CVVH 2011

94-98% of a dose of amikacin is excreted in the urine unchanged within 24

Monograph reviewed: 16/12/10

Drug Dosage Adjustments in Renal Impairment & CVVH 2011

AMPHOTERICIN LIPOSOMAL (AMBISOME)

2-5% of a dose is excreted unchanged in the urine.1

Monograph reviewed: 16/12/10

Drug Dosage Adjustments in Renal Impairment & CVVH 2011

Ampicillin is excreted mainly in the bile and urine;1 60-80% is excreted

Monograph reviewed: 15/04/11

Drug Dosage Adjustments in Renal Impairment & CVVH 2011

60-90% of a dose is excreted by renal elimination, 10% of which is by

Monograph reviewed: 22/12/10

Drug Dosage Adjustments in Renal Impairment & CVVH 2011

Caspofungin undergoes spontaneous degradation to an open-ring

Not dialysed.2,3 No dosage adjustment required - give normal dose1,2,6,7

Monograph reviewed: 24/05/11

Drug Dosage Adjustments in Renal Impairment & CVVH 2011

Cefotaxime is partially metabolised prior to excretion. Elimination is

>3 weeks of life: give normal dose every 8 hours6

Monograph reviewed: 23/12/10

Drug Dosage Adjustments in Renal Impairment & CVVH 2011

80-90% of a dose of ceftazidime is excreted unchanged in the urine by

Loading dose: 250mg/L, maintenance dose: 125mg/L11,12

Monograph reviewed: 24/12/10

Drug Dosage Adjustments in Renal Impairment & CVVH 2011

Ceftriaxone is eliminated mainly as unchanged drug, with approximately 60%

GFR 20-50ml/min: No dosage adjustment required - give normal dose1,5

Monograph reviewed: 24/12/10

Drug Dosage Adjustments in Renal Impairment & CVVH 2011

The major route of elimination of cidofovir is by renal excretion of unchanged

Monograph reviewed: 30/12/10

Monograph reviewed: 24/05/11

Drug Dosage Adjustments in Renal Impairment & CVVH 2011

po/ng: no dosage adjustment required - give normal dose3

Monograph reviewed: 14/10/11

Drug Dosage Adjustments in Renal Impairment & CVVH 2011

Clindamycin phosphate is biologically inactive and is hydrolysed to

Not dialysed.1,2,3,4 No dosage adjustment required - give normal dose3,5,11

Monograph reviewed: 15/02/10

Drug Dosage Adjustments in Renal Impairment & CVVH 2011

CO-AMOXICLAV (AMOXICILLIN+CLAVULANIC ACID)

The pharmacokinetics of amoxicillin and clavulanic acid are similar.1

Drug Dosage Adjustments in Renal Impairment & CVVH 2011

Monograph reviewed: 14/10/11

Drug Dosage Adjustments in Renal Impairment & CVVH 2011