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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