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

Imipenem/Cilastatin Dosing in Adults with Impaired Renal Function

For adults with impaired renal function, imipenem/cilastatin dosage must be reduced based on creatinine clearance, with 500 mg every 12 hours recommended for patients with creatinine clearance less than 30 to greater than or equal to 15 mL/min. 1

Dosage Recommendations Based on Renal Function

The dosage of imipenem/cilastatin should be adjusted according to the patient's creatinine clearance as follows:

• Normal renal function (CrCl ≥90 mL/min): 1

  • 500 mg every 6 hours OR
  • 1000 mg every 8 hours

• Mild renal impairment (CrCl <90 to ≥60 mL/min): 1

  • 400 mg every 6 hours OR
  • 500 mg every 6 hours

• Moderate renal impairment (CrCl <60 to ≥30 mL/min): 1

  • 300 mg every 6 hours OR
  • 500 mg every 8 hours

• Severe renal impairment (CrCl <30 to ≥15 mL/min): 1

  • 200 mg every 6 hours OR
  • 500 mg every 12 hours

Calculation of Creatinine Clearance

The Cockcroft-Gault formula should be used to calculate creatinine clearance: 1

• Males: (weight in kg) × (140-age in years) ÷ (72 × serum creatinine [mg/100 mL])
• Females: 0.85 × (value calculated for males)

Special Considerations

Hemodialysis Patients

• For patients with CrCl <15 mL/min undergoing hemodialysis, use the dosage for severe renal impairment (CrCl <30 to ≥15 mL/min) 1
• Administer after hemodialysis and time intervals from the end of the session 1
• Both imipenem and cilastatin are efficiently removed during hemodialysis 2, 3
• A supplementary dose after dialysis is recommended 2
• For hemodialysis patients, 500 mg every 12 hours has been shown to maintain effective antibiotic activity without notable clinical side effects 3

Risk of Seizures

• Patients with creatinine clearance <30 mL/min have an increased risk of seizures 1
• Careful monitoring is especially important for dialysis patients with background CNS disease 1
• Imipenem/cilastatin should only be used when benefits outweigh the potential risk of seizures in hemodialysis patients 1

Contraindications

• Patients with creatinine clearance <15 mL/min should not receive imipenem/cilastatin unless hemodialysis is instituted within 48 hours 1
• There is inadequate information to recommend usage for patients undergoing peritoneal dialysis 1

Administration Guidelines

• Doses ≤500 mg: Administer by intravenous infusion over 20-30 minutes 1
• Doses >500 mg: Administer by intravenous infusion over 40-60 minutes 1
• For patients who develop nausea during infusion, the rate may be slowed 1
• Maximum total daily dosage should not exceed 4 g/day 1

Pharmacokinetic Considerations

• The half-life of imipenem increases from approximately 1 hour in normal renal function to about 4 hours in severe renal failure 4, 2
• Cilastatin half-life increases more dramatically, from 1 hour to approximately 16 hours in end-stage renal failure 4, 2
• Dose adjustments in renal failure prevent accumulation of cilastatin and imipenem metabolites while maintaining therapeutic imipenem concentrations 4

By following these dosing guidelines based on renal function, clinicians can optimize the efficacy of imipenem/cilastatin while minimizing the risk of adverse effects, particularly seizures, which are more common in patients with renal impairment.