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Dosing Recommendations for Adults with Renal Impairment: Nottingham Guidelines, Study notes of Pharmacy

Guidelines for calculating creatinine clearance and dosing antimicrobial agents for adults with renal impairment, including specific dosing recommendations for various antimicrobials and special considerations for haemodialysis, continuous ambulatory peritoneal dialysis, and continuous veno-venous haemofiltration patients.

What you will learn

  • What are the dosing recommendations for Aciclovir in renal impairment?
  • What is the dosing advice for Amikacin in haemodialysis patients?
  • What is the Cockcroft-Gault equation used for in the document?

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Nottingham Antimicrobial Guidelines Committee March 2009 Review March 2011
- 1 -
ANTIMICROBIAL DOSES FOR ADULTS IN RENAL IMPAIRMENT
Version 3.0
Date ratified March 2009
Review date March 2011
Ratified by Nottingham University Hospitals Antimicrobial
Guidelines Committee
Nottingham University Hospitals Joint Drugs and
Therapeutics Committee
Authors Annette Clarkson Microbiology pharmacist
Judith Gregory Renal pharmacist
Consultation Nottingham University hospitals Antibiotic
Guidelines Committee members
Nottingham University Hospitals NHS Trust Drugs
and Therapeutics Committee
Renal consultants
Evidence base Renal drug handbook 3rd Edition 2009
Summary of product characteristics for the
individual drugs
Recommended best practice based on clinical
experience of guideline developers
Changes from previous
Guideline
Updated dosing advice for a number of
antibiotics in line with the updated renal drug
handbook 2009
Removal of the definitions mild, moderate and
severe renal failure in line with the BNF
Addition of azithromycin, daptomycin,
posaconazole, foscarnet, ganciclovir,
valganciclovir, valaciclovir, chloramphenicol and
cefalexin
Inclusion criteria Adult patients with renal impairment
Distribution - Pharmacists/Medicines Information
- Clinical Effectiveness Database
- Renal Unit doctors handbook distributed to all
SHOs and SpRs
- Junior doctors handbook available via the
intranet
- NUH Antibiotic Guidelines intranet site
http://nuhnet/diagnostics_clinical_support/antibio
tics
Local contacts Dr V Weston Consultant Microbiologist
Annette Clarkson Microbiology pharmacist
Judith Gregory Renal pharmacist
This guideline has been registered with the Trust.
Clinical guidelines are guidelines only. The interpretation and application of clinical
guidelines will remain the responsibility of the individual clinician. If in doubt contact a
senior colleague. Caution is advised when using guidelines after a review date.
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Nottingham Antimicrobial Guidelines Committee March 2009 Review March 2011

ANTIMICROBIAL DOSES FOR ADULTS IN RENAL IMPAIRMENT

Version 3.

Date ratified March 2009

Review date March 2011

Ratified by • Nottingham University Hospitals Antimicrobial

Guidelines Committee

• Nottingham University Hospitals Joint Drugs and

Therapeutics Committee

Authors Annette Clarkson Microbiology pharmacist

Judith Gregory Renal pharmacist

Consultation Nottingham University hospitals Antibiotic

Guidelines Committee members

Nottingham University Hospitals NHS Trust Drugs

and Therapeutics Committee

Renal consultants

Evidence base • Renal drug handbook 3

rd

Edition 2009

• Summary of product characteristics for the

individual drugs

• Recommended best practice based on clinical

experience of guideline developers

Changes from previous

Guideline

• Updated dosing advice for a number of

antibiotics in line with the updated renal drug

handbook 2009

• Removal of the definitions mild, moderate and

severe renal failure in line with the BNF

• Addition of azithromycin, daptomycin,

posaconazole, foscarnet, ganciclovir,

valganciclovir, valaciclovir, chloramphenicol and

cefalexin

Inclusion criteria Adult patients with renal impairment

Distribution - Pharmacists/Medicines Information

- Clinical Effectiveness Database

- Renal Unit doctors handbook distributed to all

SHOs and SpRs

- Junior doctors handbook available via the

intranet

- NUH Antibiotic Guidelines intranet site

http://nuhnet/diagnostics_clinical_support/antibio

tics

Local contacts Dr V Weston Consultant Microbiologist

Annette Clarkson Microbiology pharmacist

Judith Gregory Renal pharmacist

This guideline has been registered with the Trust.

Clinical guidelines are guidelines only. The interpretation and application of clinical

guidelines will remain the responsibility of the individual clinician. If in doubt contact a

senior colleague. Caution is advised when using guidelines after a review date.

Nottingham Antimicrobial Guidelines Committee March 2009 Review March 2011

ANTIMICROBIAL DOSES FOR ADULTS IN RENAL IMPAIRMENT

Assessing Renal Function

The Cockcroft-Gault equation (below) should be used to calculate creatinine clearance and gives an

estimate of kidney function for the purposes of drug dosing in renal impairment. Cockcroft-Gault

CrCl estimates should be used for drug dosing rather than the automated MDRD eGFR

produced by the clinical chemistry laboratory available on NOTIS/HISS. There can be a

significant difference between the results of the two calculations.

CrCl (ml/min) = F x (140-age) x weight (kg)

serum creatinine (micromol/L)

  • If patient is anuric, morbidly obese or in acute renal failure (ARF), this equation will NOT give a

true reflection of creatinine clearance.

  • For those who are morbidly obese, ideal body weight should be calculated

o IBW for males = 50 + (2.3xheight in inches >60inches);

o IBW for female = 45 + (2.3xheight in inches>60inches)

  • Anuric and oliguric (<500ml/day) patients can be assumed to have a CrCl < 10ml/min (severe

renal impairment)

† Many elderly patients have a CrCl below 50ml/min, which, because of reduced muscle mass, may

not be indicated by a raised creatinine level. It is therefore especially prudent to calculate the CrCl

as outlined above for this patient group.

Renal dosing monographs

  • The doses recommended are derived from the references stated and represent those commonly used in Nottingham (these may vary from Data Sheet recommendations)
  • If 50% quoted, give half the dose but retain the normal frequency
  • For dosing advice in haemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) patients at both QMC and NCH: refer to Renal Pharmacist (bleep 80-7078)
  • For dosing advice in continuous veno-venous haemofiltration (CVVH): refer to Critical Care Pharmacist (City campus bleep 80-6914 or QMC campus bleep 80-6315)
  • Drugs marked * = Contact microbiologist for advice on assays where appropriate.
  • The sodium content of some IV antibiotic preparations may be significant (refer to ward pharmacist or Medicines Information)
  • Give post HD (haemodialysis): If patient is on daily or alternate day therapy this advice refers only to administration on dialysis days: ie on non-dialysis days the drug is given at the normal time. Contact microbiology or pharmacy for advice on dosing in renal impairment for any antimicrobial agents that are not included in the table below

where F

= 1.23 (male)

= 1.04 (female)

Nottingham Antimicrobial Guidelines Committee March 2009 Review March 2011

Creatinine clearance (ml/min)

Antimicrobial

Comments

Doxycycline Normal Normal Normal

All other tetracyclines contraindicated in renal impairment

Ertapenem CrCl 30-50 ml/min Normal

CrCl 10-30 ml/min 50-100% of dose

50% of dose or 1g three times a week

Give post HD

Erythromycin po Normal Normal 250-500mg qds

Normal 7.5-15mg/kg/day 5-7.5mg/kg/day

*Ethambutol Monitor levels if Crcl < 30ml/min (contact Micro)

Give post HD

Flucloxacillin IV+po Normal Normal Normal Max 4g/day

Fluconazole Normal Normal

Oral dose min 50mg

Give post HD No adjustments for single doses required

*Flucytosine 50mg/kg 12h 50mg/kg 24h 50mg/kg stat then dose according to levels.

Give post HD. Monitor pre-dialysis levels

Foscarnet Dose reduction required seek further advice from pharmacy/renal drug handbook Fusidic acid Normal Normal Normal

Ganciclovir Dose reduction required seek further advice from pharmacy/renal drug handbook

1) Gentamicin

ONCE DAILY

CrCl 10–40ml/min 3mg/kg (max 300mg) Check levels 18-24 hours after first dose. Re-dose only when level < 1mg/L.

CrCl<10ml/min 2 mg/kg (max 200mg) re-dose according to levels

2) Gentamicin

CONVENTIONAL

80mg 12h (60mg if <60kg)

80mg 24h (60mg if <60kg)

80mg 48h (60mg if <60kg) HD:1-2 mg/kg post HD redose according to levels

BOTH METHODS:

Give post HD

Monitor blood levels & adjust dose as required. For further advice see monitoring guidance on the antibiotic website http://nuhweb/antibiotics Isoniazid Normal Normal 200mg-300mg 24h Give post HD Itraconazole Normal Normal Normal

Levofloxacin 500mg stat then 250mg bd**

500mg stat then 125mg bd**

500mg stat then 125mg od

** Applies if full dose is 500mg bd. If full dose 500mg od give the reduced dose daily Linezolid Normal Normal Normal Give post HD Meropenem Higher doses needed in CNS infection d/w micro

500mg-2g bd 500mg-1g bd 500mg-1g od Give post HD

Metronidazole Normal Normal Normal Give post HD

Nitrofurantoin Use at normal dose with caution Contraindicated Contraindicated

Monitor for toxicity e.g blood dyscrasias, neuropathy

Oseltamivir (treatment dose)

CrCl >30ml/min 75mg bd

CrCl 10-30ml/min 75mg od 30mg stat

HD: 30mg after alternate dialysis sessions Penicillin V Normal Normal Normal Give post HD Piperacillin/ Tazobactam (Tazocin)

Normal 4.5g 8-12h 4.5g 12h Give post HD

Posaconazole Normal Normal Normal

Pyrazinamide Normal Normal Normal

Rifampicin Normal Normal 50-100%

Nottingham Antimicrobial Guidelines Committee March 2009 Review March 2011

Creatinine Clearance (ml/min)

Antimicrobial

Comments

Teicoplanin* Normal

Normal loading dose then 200- 400mg every 24- 48h

Normal loading dose then 200-400mg every 48-72h

Normal Loading dose 400mg every 12 hours for 3 doses Monitor levels

Tetracycline Use Doxycycline see above Tigecycline Normal Normal Normal

Trimethoprim Normal

Use alternative agent if possible Normal

Ineffective for UTI, other indications: Normal but use alternative agent if possible

Give post HD Consider short term folic acid supplementation. NB May cause temporary rise in creatinine due to reduced creatinine secretion rather than a fall in CrCl

Valaciclovir CrCl 30-50ml/min Normal

Dose reduction required for Crcl<30ml/min seek further advice from pharmacy/renal drug handbook Valganciclovir Dose reduction required seek further advice from pharmacy/renal drug handbook

Vancomycin

1g od Check pre dose level before 3rd^ dose.

1g 48 h Check pre dose level before 2nd^ dose

1g stat (or 15mg/kg max 2g). Check level after 4-5 days. ONLY re-dose when level <12mg/L. If deep seated when <15mg/L

Monitor blood levels & adjust dose as required

Voriconazole Normal Normal Normal

Give post HD Caution in the use of IV in renal impairment due to accumulation of vehicle-discuss with pharmacy

Evidence base of guideline

Information derived from standard reference sources:

1. BMA and RPSGB. British National Formulary. Number 57. March 2009

2. Summary of Product Characteristics from electronic Medicines Compendium for individual drugs.

Available from http://emc.medicines.org.uk Datapharm Communications Ltd.

3. Ashley C and Currie A. The Renal Drug Handbook. 3

rd

edition 2009. Radcliffe Publishing Ltd.

Oxford.