What is the dosing recommendation for imipenem (Imipenem)/cilastatin (Cilastatin) in patients with impaired renal function?

Imipenem-Cilastatin Dosing in Renal Impairment

In patients with severe renal impairment (creatinine clearance <15 mL/min), limit the maximum dose to either 1000 mg twice daily or 500 mg four times daily to prevent cilastatin accumulation, and provide a supplemental 500 mg dose after hemodialysis sessions. 1

Dosing Algorithm Based on Renal Function

Normal Renal Function (CrCl >70 mL/min)

• Standard dosing: 500 mg every 6 hours, 1000 mg every 8 hours, or 1000 mg every 6 hours for severe infections 2
• For adults >50 kg: 1 g twice daily or 500-1000 mg every 6-8 hours 3
• For adults <50 kg: 15 mg/kg twice daily 3, 4

Severe Renal Impairment (CrCl <15 mL/min)

• Maximum dose limitation: Either 1000 mg twice daily OR 500 mg four times daily 1
• This restriction specifically prevents accumulation of cilastatin, which has a dramatically prolonged half-life (up to 798 minutes vs. 54 minutes in normal function) in end-stage renal disease 1
• Imipenem half-life increases from 52 minutes to 173 minutes in end-stage renal failure, but remains manageable 1

Hemodialysis Patients

• Both imipenem and cilastatin are efficiently cleared by hemodialysis 5, 1
• Provide supplemental 500 mg dose after each dialysis session 5
• The 4-hour dialysis session effectively removes both components 1

Pharmacokinetic Rationale for Dose Adjustment

The differential accumulation pattern between imipenem and cilastatin drives renal dosing adjustments:

• Imipenem: Plasma half-life increases modestly (52 min → 173 min) with renal failure, controlled by metabolic clearance pathways unaffected by cilastatin 5
• Cilastatin: Plasma half-life increases dramatically (54 min → 798 min) in end-stage renal disease, with significant accumulation risk 1
• Therapeutic imipenem levels (≥4 mg/L) are maintained for 8-10 hours after a 500 mg dose even in severe renal failure 6

Critical Safety Monitoring in Renal Impairment

Seizure risk increases substantially in renal insufficiency patients 2, 7:

• Baseline seizure incidence: 1-3% of treated patients 2, 7
• Risk factors include renal insufficiency, underlying CNS disease, and higher doses 2, 7
• Strict adherence to reduced dosing schedules is essential in renal impairment 8

Practical Implementation

For patients with severe renal failure receiving repeated doses:

• The twice-daily 500 mg regimen has been validated as well-tolerated with stable pharmacokinetics after multiple doses 6
• Cilastatin AUC increases on day 5 due to accumulation, but trough levels stabilize after the third injection 6
• Imipenem parameters remain consistent without accumulation 6