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

Meropenem Dosing in Renal Failure

For patients with renal impairment, meropenem dosing should be reduced according to creatinine clearance levels, with specific adjustments 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 Recommendations Based on Renal Function

• For patients with creatinine clearance >50 mL/min: standard dosing of 500 mg every 8 hours for skin/skin structure infections or 1 gram every 8 hours for intra-abdominal infections 1
• For patients with creatinine clearance 26-50 mL/min: maintain recommended dose but extend interval to every 12 hours 1
• For patients with creatinine clearance 10-25 mL/min: reduce to one-half the recommended dose every 12 hours 1
• For patients with creatinine clearance <10 mL/min: reduce to one-half the recommended dose every 24 hours 1

Special Considerations for Dialysis Patients

• The FDA label notes there is inadequate information regarding meropenem use in patients on hemodialysis or peritoneal dialysis 1
• However, research indicates that approximately 50% of meropenem is eliminated by intermittent hemodialysis, suggesting the need for post-dialysis dosing 2
• For patients undergoing continuous renal replacement therapies (CRRT), studies show that 25-50% of meropenem is removed by continuous venovenous hemofiltration (CVVHF) and 13-53% by continuous venovenous hemodiafiltration (CVVHDF) 2
• Research suggests that for critically ill anuric patients receiving continuous venovenous hemofiltration, the dose should be increased by 100% to avoid potential underdosing 3

Pharmacokinetic Considerations

• Meropenem is predominantly excreted unchanged in the urine, making dosage adjustments necessary in renal impairment 2
• The elimination half-life of meropenem increases from approximately 1 hour in healthy volunteers to up to 13.7 hours in anuric patients with end-stage renal disease 2
• In patients with end-stage renal disease (CrCl <5 mL/min), the elimination half-life is approximately 7 hours without dialysis and decreases to 2.9 hours during hemodialysis 4
• The volume of distribution is approximately 12.4-21 L, indicating predominantly extracellular distribution 3, 5

Monitoring Recommendations

• When using meropenem in patients with severe renal impairment, monitor for signs of toxicity 6
• For patients on dialysis, consider administering the dose after the dialysis session to prevent premature removal of the drug, similar to recommendations for other antibiotics 7
• The Cockcroft-Gault equation can be used to estimate creatinine clearance when only serum creatinine is available 1

Common Pitfalls to Avoid

• Underdosing is a significant risk in patients on renal replacement therapy due to varying elimination rates across different modalities 2
• Failure to adjust dosing based on the specific type of renal replacement therapy (intermittent hemodialysis vs. CRRT) may lead to inadequate antimicrobial coverage 2
• Not considering the potential for increased clearance in critically ill patients with augmented renal clearance, even when baseline renal function appears impaired 3

Meropenem dosing in renal impairment requires careful consideration of the degree of renal dysfunction and the presence of renal replacement therapy to ensure adequate antimicrobial coverage while avoiding toxicity.