What is the recommended dose of imipenem (Imipenem/Cilastatin) for a patient with mild impaired renal function, specifically a creatinine clearance of 65?

Imipenem Dosing for Creatinine Clearance of 65 mL/min

For a patient with a creatinine clearance of 65 mL/min, the recommended dose of imipenem is 400 mg every 6 hours or 500 mg every 6 hours depending on the severity of infection. 1

Dosing Algorithm for Imipenem Based on Renal Function

The dosing of imipenem requires adjustment based on creatinine clearance levels:

• For patients with creatinine clearance ≥90 mL/min:

  • 500 mg every 6 hours for susceptible infections
  • 1000 mg every 8 hours for susceptible infections (alternative)
  • 1000 mg every 6 hours for infections with intermediate susceptibility 1

• For patients with creatinine clearance <90 to ≥60 mL/min (applies to our patient):

  • 400 mg every 6 hours for susceptible infections
  • 500 mg every 6 hours for susceptible infections (alternative)
  • 750 mg every 8 hours for infections with intermediate susceptibility 1

• For patients with creatinine clearance <60 to ≥30 mL/min:

  • 300 mg every 6 hours for susceptible infections
  • 500 mg every 8 hours for susceptible infections (alternative)
  • 500 mg every 6 hours for infections with intermediate susceptibility 1

Pharmacokinetic Considerations

• Imipenem is partially hydrolyzed during excretion by renal brush border dehydropeptidase, which is why it's co-administered with cilastatin (a dehydropeptidase inhibitor) 2
• The mean plasma half-life of imipenem increases as renal function decreases, from approximately 52 minutes in subjects with normal renal function to 173 minutes in those with end-stage renal failure 2
• Drug exposure increases significantly as renal function declines, with studies showing progressive increases in plasma imipenem levels and area under the curve (AUC) as creatinine clearance decreases 3

Important Clinical Considerations

• Imipenem should be administered intravenously, with doses ≤500 mg infused over 20-30 minutes and doses >500 mg infused over 40-60 minutes 1
• For patients who develop nausea during infusion, the rate of infusion may be slowed 1
• Routine drug level monitoring is not required for imipenem 4
• The maximum total daily dosage should not exceed 4 g/day 1

Potential Adverse Effects to Monitor

• Common adverse effects include:

  • Dermatological: rash and urticaria (3%), injection site pain 4
  • Gastrointestinal: nausea, vomiting, diarrhea 4
  • Hematological: thrombophlebitis (3%), eosinophilia (4%) 4
  • Hepatic: transient mild increases in liver function tests 4
  • Renal: transient increases in urea and/or serum creatinine concentrations (<2%) 4

• Serious adverse effects include:

  • Seizures (risk increases with renal impairment and underlying CNS disease) 1, 5
  • Immunological reactions including anaphylaxis 4
  • Clostridium difficile-associated diarrhea and colitis 4
  • Hematological abnormalities including pancytopenia, neutropenia, and thrombocytopenia 4

Special Considerations

• The Cockcroft-Gault formula is recommended for calculating creatinine clearance for drug dosing purposes rather than eGFR equations 6
• For patients on hemodialysis, imipenem should be administered after the dialysis session to avoid premature clearance of the drug 1
• Drug interactions to be aware of include increased risk of seizures with ganciclovir and reduced serum concentrations of valproate 4

Remember that dosing should be adjusted based on both renal function and the suspected or confirmed pathogen susceptibility to ensure optimal therapeutic outcomes while minimizing the risk of adverse effects.