Imipenem/Cilastatin Renal Dose Adjustment
In renal failure, dose reduction is necessary: consult a pharmacist for specific adjustments, but generally limit to 500 mg twice daily or 1000 mg twice daily maximum in severe renal impairment (CrCl <15 mL/min), with supplemental dosing after hemodialysis. 1, 2
Standard Dosing in Normal Renal Function
- Adults >50 kg: 1 g twice daily IV 1
- Adults <50 kg: 15 mg/kg twice daily IV 1
- Children: 20-40 mg/kg (max 2 g) three times daily IV 1
Dose Adjustment Principles in Renal Impairment
The key challenge with imipenem/cilastatin in renal failure is the differential accumulation of the two components. While imipenem maintains significant non-renal clearance pathways, cilastatin depends almost entirely on renal elimination, leading to marked accumulation in renal failure. 2, 3
Pharmacokinetic Considerations
- Imipenem half-life: Increases from 52 minutes (normal function) to 173 minutes (end-stage renal disease), but maintains metabolic clearance pathways 2
- Cilastatin half-life: Increases dramatically from 54 minutes (normal) to 798 minutes (end-stage renal disease) 2
- Both drugs are efficiently removed by hemodialysis 2, 3
Recommended Dosing Regimens in Severe Renal Failure
For patients with creatinine clearance <15 mL/min:
- Maximum dose: Either 1000 mg/1000 mg twice daily OR 500 mg/500 mg four times daily 2
- Preferred regimen: 500 mg/500 mg twice daily, which has been shown to maintain therapeutic imipenem levels (≥4 mg/L) for 8-10 hours while minimizing cilastatin accumulation 4
Critical Pitfall to Avoid
Do not use standard dosing in renal failure. The primary concern is cilastatin accumulation, as its clearance drops from 230 mL/min to only 3 mL/min in anuria, while imipenem clearance only decreases from 245 mL/min to 116 mL/min. 5 Although cilastatin accumulation occurs with twice-daily dosing, trough levels stabilize after the third injection and the regimen is well-tolerated. 4
Hemodialysis Considerations
- Both drugs are efficiently cleared by hemodialysis 2, 3
- Supplemental dose required: Give 500 mg/500 mg after each dialysis session 3
- Approximately 7% of imipenem and 30% of cilastatin dose is removed during continuous arteriovenous hemofiltration (CAVH) 6
Continuous Renal Replacement Therapy (CRRT)
For patients on CAVHD (continuous arteriovenous hemodiafiltration):
- Recommended dose: 500 mg/500 mg twice daily 5
- No additional dose adjustment needed beyond that for renal failure, as CRRT clearance partially corrects cilastatin accumulation 5
- CAVHD increases imipenem clearance by 15-25% and cilastatin clearance by 335-600%, helping to reverse cilastatin accumulation 5