What is the recommended dose of imipenem (Imipenem/Cilastatin) for patients with impaired renal function?

Imipenem-Cilastatin Dosing in Renal Impairment

For patients with impaired renal function, imipenem-cilastatin requires dose reduction based on creatinine clearance, with a maximum dose of 500 mg every 12 hours for severe renal failure (CrCl <15 mL/min), and supplemental dosing of 500 mg after each hemodialysis session. 1, 2

Dosing Algorithm by Renal Function

Normal Renal Function (CrCl >70 mL/min)

• Adults >50 kg: 1 g twice daily or 500-1000 mg every 6-8 hours 3, 1
• Adults <50 kg: 15 mg/kg twice daily 3
• Pediatric dosing:
  • Neonates 0-4 weeks and <1200 g: 20 mg/kg every 18-24 hours 3
  • Neonates >7 days and >1500 g: 75 mg/kg/day divided every 8 hours 3
  • Infants <3 months: 100 mg/kg/day divided every 6 hours 3
  • Infants ≥3 months and children: 60-100 mg/kg/day divided every 6 hours 3

Severe Renal Impairment (CrCl <15 mL/min)

• Maximum dose: 500 mg every 12 hours 2, 4
• This dosing maintains therapeutic plasma levels (≥4 mg/L) for 8-10 hours after administration 4
• Alternative regimen: 1000 mg twice daily (though 500 mg four times daily may be considered) 2

End-Stage Renal Disease on Hemodialysis

• Maintenance dose: 500 mg every 12 hours 5
• Supplemental dose: 500 mg after each dialysis session 6, 2
• Both imipenem and cilastatin are efficiently removed by hemodialysis during a 4-hour session 2
• Peak concentrations average 29 ± 5 mcg/mL and trough concentrations 10 ± 3 mcg/mL with this regimen 5

Pharmacokinetic Rationale

Imipenem half-life increases from 52 minutes in normal renal function to 173 minutes in end-stage renal failure, while cilastatin half-life increases dramatically from 54 minutes to 798 minutes. 2

• Approximately 70% of imipenem is recovered in urine within 10 hours in normal renal function 1
• The plasma half-life of imipenem in elderly patients with normal renal function for their age is 91 ± 7 minutes 1
• In severe renal failure, imipenem clearance is controlled by a metabolic pathway unaffected by cilastatin, preventing excessive accumulation 6
• Cilastatin accumulates more significantly than imipenem in renal failure, with AUC increasing on repeated dosing, though trough levels stabilize after the third injection 4

Critical Safety Considerations

Seizure Risk

• Seizures occur in 1-3% of treated patients, with increased risk in renal insufficiency and underlying CNS disease 7
• The risk is particularly elevated when doses are not appropriately reduced for renal function 7

Cilastatin Accumulation

• Moderate accumulation of cilastatin occurs in neonates and patients with severe renal failure 1, 4
• The safety of cilastatin accumulation in neonates is unknown 1
• Dose reduction serves to prevent accumulation of cilastatin and circulating metabolites of imipenem while maintaining therapeutic imipenem concentrations 6

Monitoring Parameters

• Monitor renal function throughout treatment 1
• Observe patients with any degree of renal insufficiency carefully for adverse effects 2
• The 500 mg every 12 hours regimen in severe renal failure is well tolerated without notable clinical side effects for 2-14 days 5

Common Pitfalls to Avoid

• Do not use standard dosing in renal impairment: Failure to reduce doses in CrCl <15 mL/min increases seizure risk and cilastatin accumulation 7, 2
• Do not skip post-dialysis supplementation: Both drugs are efficiently cleared by hemodialysis, requiring replacement dosing 6, 2
• Do not exceed 500 mg every 12 hours in severe renal failure: Higher doses lead to excessive cilastatin accumulation without improving imipenem efficacy 2, 4
• Avoid in patients with CNS disease and renal failure: The combination significantly increases seizure risk 7