Meropenem Dosing in Renal Failure
For patients with renal impairment, reduce meropenem dosing frequency while maintaining the standard dose amount, with specific adjustments based on creatinine clearance: use the recommended 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
Standard Dosing Adjustments by Creatinine Clearance
The FDA-approved dosing schedule provides clear guidance based on renal function 1:
- CrCl >50 mL/min: Full dose (500 mg for cSSSI or 1 gram for intra-abdominal infections) every 8 hours 1
- CrCl 26-50 mL/min: Full recommended dose every 12 hours 1
- CrCl 10-25 mL/min: Half the recommended dose every 12 hours 1
- CrCl <10 mL/min: Half the recommended dose every 24 hours 1
Pharmacokinetic Rationale
The elimination half-life of meropenem increases substantially with declining renal function 2, 3:
- Normal renal function: approximately 1 hour 4
- Moderate renal impairment (CrCl 30-50 mL/min): 3.4 hours 3
- Severe renal impairment (CrCl <30 mL/min): 5 hours 3
- End-stage renal disease (anuric): up to 13.7 hours 2
Approximately 70% of meropenem is eliminated unchanged in urine, making dosage adjustment essential in renal impairment 4. The total body clearance and renal clearance correlate linearly with creatinine clearance 5.
Hemodialysis Considerations
For patients on intermittent hemodialysis 1, 3, 5:
- Administer meropenem after each hemodialysis session 3
- Hemodialysis removes approximately 50% of meropenem 2
- The elimination half-life shortens from 7.0 hours to 2.9 hours during dialysis 3
- Dialysis clearance averages 81 ± 22 mL/min 5
Continuous Renal Replacement Therapy (CRRT)
For critically ill anuric patients receiving continuous venovenous hemofiltration (CVVHF), increase the standard dose by 100% to avoid underdosing 6:
- CVVHF removes 25-50% of meropenem 2
- Hemofiltration clearance: 22.0 ± 4.7 mL/min 6
- Approximately 47% of the dose is removed through CVVHF 6
- Recommended dosing: 500 mg every 8 hours (rather than every 12 hours) 6
The elimination half-life during CVVHF is approximately 8.7 hours, and hemofiltration contributes significantly to drug elimination 6.
Important Clinical Caveats
Avoid reducing the milligram dose amount when possible, as this may compromise the concentration-dependent bactericidal effect 7, 8. The preferred approach is extending the dosing interval while maintaining dose strength 8.
For severe renal insufficiency, the guideline principle of maintaining dose amount (12-15 mg/kg per dose) while reducing frequency to 2-3 times weekly applies to concentration-dependent antibiotics, though meropenem's FDA label provides more specific guidance 8.
There is no clinical experience with meropenem dosing in pediatric patients with renal impairment, so consultation with pediatric nephrology and infectious disease specialists is advised 1.
Monitoring
The inactive metabolite ICI 213,689 accumulates significantly in renal failure, with a half-life of approximately 35 hours in severe renal insufficiency 5. While this metabolite has minimal antibacterial activity, its accumulation should be considered in the overall safety profile 5.