Meropenem Dosing in Adults with Impaired Renal Function
Dose adjustments for meropenem in renal impairment should maintain the standard dose per administration (500 mg or 1 gram depending on infection type) while extending the dosing interval based on creatinine clearance, rather than reducing the dose itself, to preserve the concentration-dependent bactericidal effect. 1, 2
FDA-Approved Dosing Algorithm by Creatinine Clearance
The FDA label provides the following specific adjustments 2:
- CrCl >50 mL/min: Standard dose (500 mg for cSSSI, 1 gram for intra-abdominal infections) every 8 hours
- CrCl 26-50 mL/min: Standard dose every 12 hours
- CrCl 10-25 mL/min: Half the standard dose every 12 hours
- CrCl <10 mL/min: Half the standard dose every 24 hours
Pharmacokinetic Rationale
The half-life of meropenem increases significantly as renal function declines, from approximately 1 hour in normal renal function to substantially longer in severe impairment 1, 3. Up to 70% of meropenem is eliminated unchanged in urine, making renal function the primary determinant of clearance 3. The elimination half-life correlates well with creatinine clearance, allowing for predictable dose adjustments 3.
Special Considerations for Dialysis Patients
For patients on intermittent hemodialysis, approximately 50% of meropenem is removed during a dialysis session 4. Doses should be administered after dialysis to avoid premature drug removal and facilitate directly observed therapy 4.
For continuous renal replacement therapy (CRRT), the approach differs 4, 5:
- CRRT removes 25-50% of meropenem, with CVVHDF removing 13-53% 4
- Therapeutic drug monitoring is strongly recommended for patients on CRRT to ensure adequate exposure 4
- Population pharmacokinetic studies show that residual diuresis (not CRRT intensity) is the primary modifier of meropenem clearance in CRRT patients 6
Therapeutic Drug Monitoring
TDM is recommended in critically ill patients with renal impairment to ensure adequate exposure while avoiding toxicity 4, 7. Key monitoring parameters include:
- Target trough concentrations should remain above the MIC of the suspected pathogen 8
- Neurological toxicity typically occurs when trough concentrations exceed 64 mg/L 8, 4
- Monitor renal function indicators throughout treatment 4
Critical Safety Considerations
Meropenem has lower pro-convulsive activity compared to imipenem, making it safer in renal dysfunction 4, 9. However, neurological adverse effects (seizures) can still occur with excessive plasma concentrations, particularly in patients with CNS infections or severe renal impairment 8.
The key pitfall to avoid is underdosing by reducing the individual dose rather than extending the interval, which compromises the concentration-dependent killing effect essential for carbapenem efficacy 1.