Imipenem/Cilastatin Dosing in Renal Impairment
For patients with renal impairment, imipenem/cilastatin requires specific dose adjustments based on creatinine clearance, with a recommended dose of 500 mg every 12 hours for patients with severe renal impairment (CrCl <15 mL/min) and post-hemodialysis supplemental dosing. 1, 2
Dosing Recommendations Based on Renal Function
Normal to Moderate Renal Impairment
- Normal renal function: Standard dosing (500-1000 mg every 6-8 hours)
- Moderate renal impairment (CrCl 30-50 mL/min): Dose reduction may be necessary
Severe Renal Impairment
- CrCl <15 mL/min: 500 mg every 12 hours 2, 3
- This regimen maintains therapeutic plasma levels of imipenem (≥4 mg/L) for 8-10 hours after administration 3
- The half-life of imipenem increases from approximately 1 hour in normal renal function to about 4 hours in severe renal failure 4
Hemodialysis Patients
- Recommended dose: 500 mg every 12 hours 5
- Supplemental dose: 500 mg after each hemodialysis session 4
- Imipenem is efficiently removed by hemodialysis 6, 4
- Administer after hemodialysis on dialysis days to avoid premature removal of the drug 2
Pharmacokinetic Considerations
Imipenem Clearance
- Imipenem's plasma half-life increases from approximately 52 minutes in normal renal function to 173 minutes in end-stage renal failure 6
- Non-renal clearance pathways for imipenem remain functional even in severe renal impairment 4
Cilastatin Considerations
- Cilastatin's half-life increases significantly more than imipenem's in renal failure (from 54 minutes to 798 minutes) 6
- Cilastatin accumulates with repeated dosing in severe renal impairment, but trough levels stabilize after the third dose 3
- Dose reduction in severe renal failure prevents excessive cilastatin accumulation while maintaining therapeutic imipenem levels 4
Monitoring Recommendations
- No routine drug level monitoring is required for imipenem/cilastatin 2
- Monitor for clinical response and adverse effects
- Pay particular attention to potential neurological side effects (seizures) which may be more common in patients with renal impairment
Special Considerations
- Both imipenem and cilastatin are well cleared by hemodialysis, necessitating supplemental dosing post-dialysis 4
- For patients on continuous renal replacement therapies (CVVH/CAVHD), a regimen of 500 mg twice daily is appropriate 7
- Administration after hemodialysis facilitates directly observed therapy and prevents premature drug removal 2
The 500 mg every 12 hours regimen for severe renal impairment has been shown to be well-tolerated and maintains effective antimicrobial activity without significant drug accumulation 3, 5.