Meropenem Dosing for eGFR <10 mL/min
For patients with eGFR <10 mL/min not on dialysis, administer meropenem 500 mg every 24 hours (for standard infections) or 1 gram every 24 hours (for severe infections including those caused by P. aeruginosa). 1
FDA-Approved Dosing Recommendations
The FDA label provides explicit guidance for severe renal impairment 1:
- Creatinine clearance <10 mL/min: Administer one-half the recommended dose every 24 hours
- This translates to:
- 250 mg every 24 hours for complicated skin/soft tissue infections (cSSSI) with standard pathogens
- 500 mg every 24 hours for intra-abdominal infections or cSSSI caused by P. aeruginosa
Important caveat: The FDA label explicitly states "there is inadequate information regarding the use of meropenem in patients on hemodialysis or peritoneal dialysis," so the above dosing applies only to non-dialysis patients with eGFR <10 mL/min. 1
Pharmacokinetic Rationale
The dramatic dose reduction is necessary because 2:
- Terminal half-life increases from 1.2 hours (normal function) to 10-13.7 hours in end-stage renal disease 3, 2
- Meropenem is 63% renally excreted unchanged, making it highly dependent on kidney function 4
- Total body clearance correlates linearly with creatinine clearance 2
Practical Considerations for Severe Infections
For critically ill patients with eGFR <10 mL/min and severe infections (MIC ≥2 mg/L), the standard FDA dosing may result in subtherapeutic levels 5:
- Consider 500 mg every 12 hours as an alternative, particularly for:
- Infections with pathogens having MIC values of 2-8 mg/L
- Critically ill patients with augmented non-renal clearance
- Life-threatening infections requiring aggressive therapy
This higher dosing is supported by research showing that even with severe renal impairment, non-renal clearance remains at approximately 30 mL/min in critically ill patients 6, and standard dosing frequently fails to achieve pharmacodynamic targets. 5
Monitoring Recommendations
- Check renal function before initiating therapy and monitor every 2-3 days during treatment 7
- Target trough concentrations should remain above the MIC for the pathogen (typically >2 mg/L for most organisms, >8 mg/L for P. aeruginosa) 5
- Watch for CNS toxicity (seizures, confusion) as meropenem accumulation increases neurological adverse effects in severe renal impairment 8
Dialysis Patients
Do not use the above dosing for patients on hemodialysis or peritoneal dialysis 1. Meropenem is significantly removed by dialysis (approximately 50% by intermittent hemodialysis) 3, requiring post-dialysis supplementation, but specific FDA-approved dosing is not established. 1