Imipenem Dosing in Renal Impairment
For patients with impaired renal function, imipenem/cilastatin requires dose reduction to prevent accumulation of cilastatin and imipenem metabolites, with the maximum recommended dose being 500 mg every 6 hours (or 1000 mg every 12 hours) in severe renal failure (CrCl <15 mL/min), and supplemental 500 mg doses should be given after hemodialysis sessions. 1, 2
Standard Dosing in Normal Renal Function
For context, the standard dosing in patients with normal renal function includes:
- Standard infections: 500 mg every 6 hours or 1000 mg every 8 hours 3, 4
- Severe infections: 1000 mg every 6 hours for suspected Pseudomonas or resistant organisms 5
- Critically ill patients with healthcare-associated infections: 1000 mg every 8 hours 6, 4
Dose Adjustments for Renal Impairment
Severe Renal Failure (CrCl <15 mL/min)
The maximum dose should be limited to either 1000 mg twice daily OR 500 mg four times daily to prevent accumulation of cilastatin, which has a dramatically prolonged half-life (up to 798 minutes compared to 54 minutes in normal function). 1
The pharmacokinetic rationale is critical here: while imipenem's half-life increases from 52 minutes to 173 minutes in end-stage renal disease, cilastatin's half-life increases much more dramatically (from 54 minutes to 798 minutes), making cilastatin accumulation the primary concern. 1
Hemodialysis Patients
For patients on hemodialysis, administer 500 mg every 12 hours, with a supplemental 500 mg dose after each dialysis session. 1, 2, 7
This schedule maintains effective trough antibiotic activity with peak concentrations averaging 29 ± 5 mcg/mL and trough concentrations of 10 ± 3 mcg/mL. 7 Both imipenem and cilastatin are efficiently removed during a 4-hour hemodialysis session, necessitating post-dialysis supplementation. 1, 2
Pharmacokinetic Considerations
The elimination pathways differ significantly between the two components:
- Imipenem: 60-70% renal clearance (glomerular filtration + active tubular secretion) when given with cilastatin; metabolic clearance pathway remains unaffected by renal dysfunction 2
- Cilastatin: Primarily renal elimination with marked accumulation in renal failure 1, 2
Therapeutic imipenem levels are maintained for 8-10 hours after a 500 mg dose in normal renal function. 3, 2
Critical Safety Monitoring
Seizure risk increases substantially in renal insufficiency, occurring in 1-3% of treated patients overall but with higher incidence in those with both renal impairment and underlying CNS disease. 3, 8
Additional monitoring requirements include:
- Periodic complete blood count, renal function tests, and liver function tests during prolonged treatment 3, 5, 4
- Avoid concomitant use with valproic acid/divalproex sodium, as imipenem reduces valproate concentrations below therapeutic range 3, 5, 4
- Increased seizure risk with concurrent ganciclovir 3, 5, 4
Common Pitfalls
The most important pitfall is failing to reduce the dose in severe renal impairment, which leads to cilastatin accumulation even though imipenem itself has a metabolic clearance pathway that partially compensates. 1, 2 Another critical error is forgetting post-dialysis supplementation, as both drugs are efficiently dialyzed. 1, 2, 7