Renal Dosing of Meropenem
For patients with impaired renal function, meropenem dosing should be adjusted by maintaining the standard dose strength (500 mg or 1 gram depending on infection type) while extending the dosing interval based on creatinine clearance, rather than reducing the dose per administration. 1
Standard Dosing Adjustments by Creatinine Clearance
The FDA-approved dosing schedule for adult patients with renal impairment is structured as follows 1:
- 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: One-half the standard dose every 12 hours
- CrCl <10 mL/min: One-half the standard dose every 24 hours
Rationale for Interval Extension Over Dose Reduction
The pharmacokinetic principle underlying this approach is that meropenem exhibits concentration-dependent bactericidal activity, making it preferable to maintain adequate peak concentrations while adjusting for the prolonged half-life seen in renal impairment. 2 The elimination half-life increases from approximately 1 hour in normal renal function to 5 hours with CrCl <30 mL/min, and up to 10-13.7 hours in end-stage renal disease 3, 4.
Special Populations and Clinical Considerations
Hemodialysis Patients
Meropenem is significantly removed by hemodialysis (approximately 50% of the drug), with dialysis clearance of 81 ± 22 mL/min. 4, 5 The elimination half-life shortens from 7.0 hours to 2.9 hours during dialysis 3. Dosing after each hemodialysis session is recommended 3, though the FDA label notes inadequate information for specific dosing recommendations in hemodialysis patients 1.
Continuous Renal Replacement Therapy (CRRT)
For critically ill patients on CVVHF, meropenem clearance is approximately 22 mL/min through hemofiltration, with 47% of the dose removed 6. The recommended dose should be increased by 100% (to 500 mg every 8-12 hours or 1 gram every 12 hours) to avoid underdosing in anuric patients receiving CVVHF 6. Different CRRT modalities remove 13-53% of meropenem, creating substantial variability 5.
Augmented Renal Clearance
A critical pitfall is that patients with augmented renal clearance (CrCl >130 mL/min) or even mild renal impairment may fail to achieve therapeutic targets with standard dosing. 7 In a prospective study, only 48.4% of critically ill patients achieved the target of 100%T>MIC for pathogens with MIC 2 mg/L, and only 20.6% for MIC 8 mg/L 7. Patients with CrCl 25-255 mL/min showed a hyperbolic relationship between renal function and meropenem trough concentrations, with mild renal impairment through augmented renal clearance identified as risk factors for target non-attainment 7.
Pediatric Dosing Adjustments
There is no established experience or dosing recommendations for pediatric patients with renal impairment 1. Standard pediatric dosing should not be extrapolated to renally impaired children without therapeutic drug monitoring.
Key Clinical Pitfalls
- Do not assume standard dosing is adequate in critically ill patients: Large inter- and intra-patient variability exists, with considerable risk of subtherapeutic levels even with normal renal function 7
- Avoid underdosing in CRRT: The significant drug removal during continuous hemofiltration necessitates dose increases, not decreases 6
- Monitor for metabolite accumulation: The inactive metabolite ICI 213,689 accumulates significantly in renal failure (half-life up to 35 hours in severe impairment), though clinical significance is unclear 4
- Consider extended or continuous infusions: Given the time-dependent killing of beta-lactams and high risk of target non-attainment, extended infusions may be preferable in critically ill patients with variable renal function 7