Meropenem Dose Adjustment in Renal Impairment
For adults with impaired renal function, meropenem dosing must be reduced based on creatinine clearance: use the recommended dose (500 mg for cSSSI, 1 gram for intra-abdominal infections) 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 thresholds for adjustment 1:
CrCl >50 mL/min: No adjustment needed—use standard dosing (500 mg every 8 hours for complicated skin/soft tissue infections; 1 gram every 8 hours for intra-abdominal infections or Pseudomonas aeruginosa) 1
CrCl 26-50 mL/min: Maintain the full recommended dose but extend the interval to every 12 hours 1
CrCl 10-25 mL/min: Reduce to half the recommended dose every 12 hours 1
CrCl <10 mL/min: Reduce to half the recommended dose every 24 hours 1
Pharmacokinetic Rationale
The elimination half-life of meropenem increases dramatically with declining renal function 2, 3:
- Normal renal function: approximately 1 hour 4, 2
- Moderate impairment (CrCl 30-50 mL/min): 3.4 hours 5
- Severe impairment (CrCl <30 mL/min): 5-7 hours 5, 3
- End-stage renal disease: 10-13.7 hours 2, 4
Approximately 70% of meropenem is renally eliminated in patients with normal kidney function, with renal clearance directly proportional to creatinine clearance 2, 3. As renal function declines, nonrenal clearance becomes proportionally more important, accounting for up to 50% of elimination in severe impairment 3.
Hemodialysis Considerations
Meropenem is significantly removed by hemodialysis (approximately 50% of the drug), so doses should be administered after dialysis sessions to avoid premature drug removal. 4, 6
- Hemodialysis clearance: 79-81 mL/min 2, 3
- Elimination half-life during dialysis: reduced from 7 hours to 2.9 hours 5
- Recommended approach: Administer the scheduled dose after each dialysis session 5, 6
Continuous Renal Replacement Therapy (CRRT)
For patients on CRRT, use 1 gram every 8 hours to compensate for continuous drug removal, as CRRT removes 25-50% of meropenem. 6, 4
The elimination during CRRT varies by modality 4:
- CVVHF (continuous venovenous hemofiltration): removes 25-50% 4
- CVVHDF (continuous venovenous hemodiafiltration): removes 13-53% 4
- Hemofiltration clearance: approximately 22 mL/min 7
- Terminal half-life during CVVHF: 8.7 hours 7
Critical Pitfalls to Avoid
Never reduce the individual milligram dose below the recommended amount when adjusting for renal impairment—instead, extend the dosing interval to preserve meropenem's concentration-dependent bactericidal activity. 6
- Maintain adequate peak concentrations (38-45 mg/L) to ensure efficacy 7
- Avoid administering doses before dialysis, as this leads to subtherapeutic levels 6
- Consider therapeutic drug monitoring in critically ill patients with renal impairment to ensure adequate exposure 6
- Be aware that neurological toxicity typically occurs when trough concentrations exceed 64 mg/L 6
Special Considerations for Resistant Organisms
When treating infections with organisms having MIC ≥4-8 mg/L, use extended 3-hour infusions even in renal impairment to maximize time above MIC. 6
For carbapenem-resistant Enterobacterales with meropenem MIC ≥8 mg/L, extended 3-hour infusion of 1 gram every 8 hours is specifically recommended 6.
Metabolite Accumulation
The inactive open-ring metabolite (ICI 213,689) accumulates significantly in renal impairment 2, 3: