23. Dose adjustments to commonly used antimicrobials in renal impairment

The available data on dose reduction in patients with renal impairment is based on the estimation of absolute glomerular filtration rate (GFR) using the traditional creatinine clearance based on the Cockcroft and Gault equation below. Please note that that this is not interchangeable with GFR normalized to body surface area (1.73m2) derived from the MDRD (Modification of Diet in Renal Disease) formula.

Clearance (ml/min ) = (140 - age (years)) x N x weight (kg)
  Serum creatinine (micromol/l)

Where N = 1.04 for female patients
  N = 1.23 for male patients

DRUG NAME	NORMAL DOSE	GFR 20-50 ml/min	GFR 10-20 ml/min	GFR <10 ml/min
AMOXICILLIN	500 mg every 8hrs(max 6g per day)	NORMAL	NORMAL	250mg every 8hrs
BENZYLPENICILLIN NOTE: increased risk of seizures in severe renal impairment	2.4 - 14.4g per day in divided doses	NORMAL	75% of normal	20-50% of normal MAX 2.4-3.6g daily
CEFALEXIN	500mg every 8-12 hours (maximum 6g daily)	500mg every 8-12 hours (maximum 6g daily)	500mg every 8-12 hours	250-500mg every 12 hours
CEFOTAXIME	1g every 12 hours 8-12g daily in severe infection	NORMAL	NORMAL	500mg-1g every  8-12 hours
CEFTAZIDIME	1-2g every 8-12 hours	GFR 31-50 1g every 12 hours	GFR 16-30 1g every 24 hours	GFR < 15 1g every 24-48 hours
CEFTRIAXONE	1-2g daily (4g daily in meningitis)	NORMAL	NORMAL	NORMAL MAX 2g
CEFUROXIME	750mg - 1.5g every 6-8 hrs (total dose 3-6g/day)	750mg - 1.5g every 8 hrs	750mg - 1.5g  every 8-12 hrs	750mg - 1.5g every 24 hrs
CIPROFLOXACIN	Oral: 250-750mg every 12 hrs IV: 100-400mg every 12 hrs	NORMAL	50% of normal eg. 200mg IV every 12 hours	50% of normal
CLARITHROMYCIN (parenteral)	500mg every 12 hrs	NORMAL	250-500mg every 12 hrs	250 mg  every 12 hrs
CO-AMOXICLAV	Oral: 375-625mg every 8 hours IV: 1.2g every 8 hours	NORMAL	IV: 1.2g every 12 hours Oral: NORMAL	IV: 1.2g stat then 600mg-1.2g every 12 hours Oral: 375mg every 8 hours
DOXYCYCLINE	200mg on day one then 100mg daily. 200mg daily in severe infections	NORMAL	NORMAL	NORMAL
ERYTHROMYCIN (oral)	Erymax: 500mg every 12 hrs	NORMAL	NORMAL	50-75% of normal dose
FLUCLOXACILLIN	Oral: 500mg - 1g every 6 hrs IV: 250mg - 2g every 4-6 hrs	NORMAL	NORMAL	NORMAL up to total daily dose of 4g
GENTAMICIN	5mg/kg daily ideal body weight	Refer to separate policy
IMIPENEM Plus cilastatin (PRIMAXIN)	Severe Infection: 500 mg every 6 hrs	GFR 31-70 500mg every 8 hrs	GFR 10-30 Use meropenem 500mg every 12 hrs	GFR <10 Use meropenem 500mg every 24 hrs
LEVOFLOXACIN	500mg every 12 hrs	500mg stat then 250mg every 12 hours	500mg stat then 125mg every 12 hours	500mg stat then 125mg daily
MEROPENEM	500mg-1g every 8 hours (Higher doses in CF and meningitis)	500mg-1g every 12 hours	250mg-1g every 12 hours or 500mg every 8 hours	250mg-1g every 24 hours
METRONIDAZOLE	IV: 500mg every 8 hrs Oral: 400mg every 8 hours	NORMAL	NORMAL	Normal dose every 12 hrs
RIFAMPICIN	Up to 1200mg daily	NORMAL	NORMAL	50-100% of normal dose
TAZOCIN (piperacillin/ tazobactam)	4.5g every 8hrs	NORMAL	4.5g every 12 hrs	4.5g every 12 hrs
TEICOPLANIN	400mg daily or 6mg/kg (up to 12mg/kg in severe infection) All patients should receive a loading dose of 400mg (or 6mg/kg) every 12 hours for 3 doses	100% of normal dose every 48 hours	100% of normal dose every 72 hours	100% of normal dose every 72 hours
		Reduce doses on Day 4 Adjust doses according to levels
TIMENTIN (ticarcillin/ clavulanic acid)	3.2g every 6 hours	GFR 30-50 3.2g every 8 hours	GFR 10-30 1.6g every 8 hours	GFR <10 1.6g every 12 hours
TRIMETHOPRIM	200mg every 12 hours	NORMAL	GFR 16-30 normal dose for 3 days then 100mg every 12 hours	GFR <15 normal dose for 3 days then 100mg every 12 hours
VANCOMYCIN (parenteral)	750mg-1g every 12 hrs See separate policy	750mg-1g every 24 hrs	750mg-1g every 48 hrs	750-1g every 3-7 days
		Guide only - doses adjusted on the basis of levels Do not give subsequent doses until levels <1mg/l

Antivirals

DRUG NAME	NORMAL DOSE	GFR 20-50 ml/min	GFR 10-20 ml/min	GFR <10 ml/min
ACICLOVIR (IV)	5mg/kg every 8 hrs 10mg/kg every 8 hrs if immunocompromised / encephalitis	5-10mg/kg every 12 hrs	5-10 mg/kg every 24 hrs	2.5-5 mg/kg every 24hrs
ACICLOVIR (PO)	See BNF	NORMAL	Simplex: 200mg tds/qds Zoster: 400-800mg every 8 hrs	Simplex: 200mg every 12 hrs Zoster: 400-800mg every 12 hrs

Antifungals

DRUG NAME	NORMAL DOSE	GFR 20-50 ml/min	GFR 10-20 ml/min	GFR <10 ml/min
FLUCONAZOLE	50-400mg daily	NORMAL	NORMAL	50-100% of normal dose

If a patient is having renal replacement therapy, eg haemofiltration, please contact Medicines Information

References

       1. Ashley C and Currie A (Eds). The Renal Drug Handbook. 2nd Ed. Abingdon: Radcliffe Medical Press 2004
       2. ww.medicines.org.uk

       November 2006