ANTIMICROBIAL DOSES FOR ADULTS IN RENAL IMPAIRMENT

ANTIMICROBIAL DOSES FOR ADULTS IN RENAL IMPAIRMENT
Version
3.0
Date ratified
March 2009 updated January 2010
Review date
January 2012
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 with advice on calculating renal function and whether to use eGFR as reported on NOTIS or creatinine clearance using Cockcroft-gault equation.
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/antibiotics
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.

ANTIMICROBIAL DOSES FOR ADULTS IN RENAL IMPAIRMENT

Assessing Renal Function
Renal function in adults is now commonly reported via NOTIS on the basis of estimated glomerular filtration rate (eGFR) normalised to a body surface area of 1.73m2 and derived from the Modification of Diet in Renal Disease (MDRD) formula. Published information on the effects of renal impairment on drug elimination has historically been stated in terms of creatinine clearance (not normalised for body surface area). The Cockgroft-Gault formula has been used to estimate this and in recent years the advice has been to continue to use Cockcroft-Gault estimates for drug dosing in renal impairment. The Cockcroft Gault equation is shown below and there is a calculator on the antibiotic website.
CrCl (ml/min)    =                 F   x            (140-age)  x  weight (kg)                    
                                                serum creatinine (micromol/L)

The latest edition of the British National Formulary gives dosage adjustments for many drugs expressed in terms of eGFR rather than creatinine clearance. Although the two equations are not interchangeable, there is relatively good correlation between the two for calculating renal function in patients of average build and height, and either could be used for the majority of drugs. However, eGFR should not be used for calculating drug doses in patients at extremes of body weight (BMI of less than 18.5 kg/m2 or greater than 30 kg/m2), nor for potentially toxic drugs of a narrow therapeutic index. In these cases, the correlation between the two measures can be significant and potential drug over/under doses could arise.
BMI =    Weight (kg)
         Height (m2)
·         eGFR should not be used for calculating drug doses in patients at extremes of body weight (BMI of less than 18.5 kg/m2 or greater than 30 kg/m2)therefore for those who are obese (>20% above IBW) ideal body weight should be calculated and then used to create a creatinine clearance using Cockcroft-Gault.
  • IBW for males = 50 + (2.3 x (height in inches - 60))
  • IBW for female = 45 + (2.3 x (height in inches - 60))
  • Equally for those patients who have a BMI<18.5kg/m2 creatinine clearance using Cockcroft-Gault should be calculated.
  • eGFR should not be used for calculating drug doses for potentially toxic drugs of a narrow therapeutic index.  For the purposes of this guideline creatinine clearance using Cockcroft-Gault should always be used for vancomycin, gentamicin, foscarnet, ganciclovir, valganciclovir.
  • Neither equation is a perfect marker of renal function. When using the equation, creatinine levels should be stable and the clinical picture should always be taken into account.
  • Patients that are oligoanuric (dialysis dependency/acute kidney injury) should be assumed to have a GFR <10 ml/min and neither equation is valid.
Renal dosing monographs
  • The doses recommended are derived from the references stated and represent those commonly used in Nottingham (these may vary from the SPC)
  • 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: refer to Renal Pharmacist (bleep 80-7078)
  • For dosing advice in continuous veno-venous haemofiltration (CVVH): refer to Critical Care Pharmacist
  • 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.

Antimicrobial
Creatinine clearance (ml/min)
Comments
50-20
20-10 
<10 
*Aciclovir IV
Normal dose every 12h
Normal dose
every 24h
50% of normal dose every 24h
Give post HD
Aciclovir po
Normal
Simplex: 200mg qds
 Zoster: 800mg tds
Simplex: 200mg bd
Zoster: 800mg bd
Give post HD
*Amikacin
5-6 mg/kg 12h
3-4 mg/kg 24h
2mg/kg 24-48h

HD: 5mg/kg post HD and monitor levels
Give post HD
Monitor blood levels & adjust dose as req’d
Amoxicillin 
Normal
Normal
250mg-1g 8h
Endocarditis (refer to microbiology):max 6g per day
Give post HD
Lipid associated Amphotericin IV 
 (Abelcet© and Ambisome©)
Normal- see note below
Normal- see note below
Normal- see note below
For further advice on dosing and administration see antibiotic website, local guidelines and Trust IV guide
Amphotericin is highly NEPHROTOXIC.  
Daily monitoring of renal function is essential
Azithromycin
Normal
Normal
Normal

Benzylpenicillin
Normal
600mg-2.4g every 6 hours
600mg-1.2g every 6 hours
Endocarditis (refer to microbiology): max 4.8g per day
Give post HD
Caspofungin
Normal
Normal
Normal

Cefalexin
Normal
Normal
250-500mg tds
Give post HD
Cefradine
Normal
Normal
250mg-500mg 6h
Give post HD
Ceftazidime
CrCl 30-50 ml/min
1-2g 12h
CrCl 20-30 ml/min
1-2g 24h
CrCl 5-20 ml/min
500mg-1g 24h
CrCl<5 ml/min
500mg-1g 48h
Give post HD
Ceftriaxone
Normal
Normal
Normal
Max 2g/day

Cefuroxime IV
Normal
750mg – 1.5g 12h
750mg 12h
Give post HD
Chloramphenicol
Normal
Normal
Normal

Ciprofloxacin IV+po
Normal
PO 250-500mg bd
IV 200mg-400mg  bd
PO 250-500mg bd
IV 200mg-400mg bd

Clarithromycin 
IV + po
Normal
Normal
250-500mg bd
Give post HD
Clindamycin 
IV +po
Normal
Normal
Normal

Co-Amoxiclav IV
(Augmentin) 
CrCl 30-50
Normal
CrCl 10-30
1.2g 12h
1.2g stat then 600-1.2g 12h
Give post HD
Co-Amoxiclav po
(Augmentin) 
Normal
Normal
Normal
Give post HD
Colistin IV
Normal
50% of normal dose
30% of normal dose

*Co-trimoxazole IV + po
(Treatment doses  only)
CrCl 30–50 ml/min

        Normal
CrCl 15-30 ml/min PCP: Normal for 3/7  then 50%
Other infections: 50%
CrCl <15ml/min

All infections: 50%
Give post HD
Monitor sulfamethoxazole levels
Daptomycin
CrCl 30-50ml/min
Normal
CrCl<30ml/min 4mg/kg every 48 hours
Not dialysed
Antimicrobial
Creatinine clearance (ml/min)
Comments
50-20
20-10
<10
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

*Ethambutol
Normal
7.5-15mg/kg/day
5-7.5mg/kg/day
Give post HD
Monitor levels  if Crcl < 30ml/min (contact Micro)
Flucloxacillin IV+po
Normal
Normal
Normal Max 4g/day

Fluconazole
Normal
Normal
              50%
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
BOTH METHODS:
Give post HD
Monitor blood levels & U&Es. see antibiotic website. In the obese use a dose determining weight- see antibiotic website.
2) Gentamicin
 
Multiple daily dosing regimen
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
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: 75mg stat then 75mg after each dialysis session
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%

Antimicrobial
Creatinine Clearance (ml/min)
Comments
50-20
20-10
<10
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
                  

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