What is the recommended dosing of meropenem for patients with impaired renal function?

Meropenem Dosing in Renal Impairment

For patients with impaired renal function, meropenem dosing should be adjusted based on creatinine clearance, with recommended dosage reductions as follows: normal dose every 12 hours for CrCl 26-50 mL/min, half the recommended dose every 12 hours for CrCl 10-25 mL/min, and half the recommended dose every 24 hours for CrCl <10 mL/min. 1

Dosing Algorithm Based on Renal Function

Adult Patients:

• For creatinine clearance >50 mL/min: Standard dose (500 mg for cSSSI or 1 gram for intra-abdominal infections) every 8 hours 1
• For creatinine clearance 26-50 mL/min: Standard dose every 12 hours 1
• For creatinine clearance 10-25 mL/min: Half the standard dose every 12 hours 1
• For creatinine clearance <10 mL/min: Half the standard dose every 24 hours 1

Special Considerations:

• When treating Pseudomonas aeruginosa infections, a higher dose of 1 gram (rather than 500 mg) every 8 hours is recommended in patients with normal renal function, with appropriate adjustments for renal impairment 1
• The half-life of meropenem increases significantly with declining renal function, from approximately 1 hour in patients with normal renal function to up to 13.7 hours in anuric patients with end-stage renal disease 2
• Maintaining the standard dose per administration when possible while extending the dosing interval is recommended to take advantage of the concentration-dependent bactericidal effect 3

Patients on Renal Replacement Therapy

Hemodialysis:

• Hemodialysis significantly shortens the elimination half-life of meropenem from approximately 7 hours to 2.9 hours 4
• Approximately 50% of meropenem is eliminated by intermittent hemodialysis 2
• Dosing after each hemodialysis session is recommended for patients receiving intermittent hemodialysis 4

Continuous Renal Replacement Therapy (CRRT):

• For patients on continuous venovenous hemofiltration (CVVHF), approximately 25-50% of meropenem is eliminated 2
• For patients on continuous venovenous hemodiafiltration (CVVHDF), approximately 13-53% of meropenem is eliminated 2
• For critically ill patients with septic shock on CRRT, residual diuresis should be considered when determining dosing regimens 5
• For patients with preserved residual diuresis on CRRT, extended infusions (over 3 hours) may be beneficial for treating less susceptible organisms (MICs 2-4 mg/L) 5

Pediatric Considerations:

• There is limited experience with meropenem dosing in pediatric patients with renal impairment 1
• For pediatric patients with normal renal function, dosing is weight-based:
  • 10 mg/kg every 8 hours for complicated skin and skin structure infections (maximum 500 mg) 1
  • 20 mg/kg every 8 hours for intra-abdominal infections (maximum 1 gram) 1
  • 40 mg/kg every 8 hours for meningitis (maximum 2 grams) 1

Clinical Pearls and Pitfalls:

• Underdosing is a common pitfall due to varying recommendations in the literature; because of meropenem's excellent tolerability profile, this should be avoided 2
• For critically ill patients with acute renal failure undergoing CRRT, consider that approximately 47% of the dose may be removed through continuous venovenous hemofiltration 6
• A significant linear relationship exists between total body clearance and creatinine clearance, making creatinine clearance a reliable parameter for dose adjustment 7
• The volume of distribution is not significantly altered in uremic patients, so loading doses generally do not need adjustment 7