Meropenem Dosing in Creatinine Clearance <30 mL/min
For adults with creatinine clearance less than 30 mL/min, reduce meropenem to half the standard dose and extend the dosing interval to every 12 hours for CrCl 10-25 mL/min, or every 24 hours for CrCl <10 mL/min. 1
FDA-Approved Dosing Algorithm for Renal Impairment
The FDA prescribing information provides clear dose adjustments based on creatinine clearance 1:
For CrCl 10-25 mL/min:
- Dose: One-half of the recommended dose (250 mg for cSSSI, 500 mg for intra-abdominal infections)
- Interval: Every 12 hours 1
For CrCl <10 mL/min:
- Dose: One-half of the recommended dose (250 mg for cSSSI, 500 mg for intra-abdominal infections)
- Interval: Every 24 hours 1
For patients on hemodialysis:
- Meropenem is significantly removed by dialysis, with the elimination half-life shortening from 9.7 hours pre-dialysis to 1.4 hours during dialysis 2
- Administer the dose after hemodialysis sessions to prevent premature drug removal 3
- Use the same reduced dose as for CrCl <10 mL/min (every 24 hours), timing it post-dialysis 1, 2
Critical Pharmacokinetic Considerations
The principle of maintaining full individual doses while extending intervals does not apply to meropenem. Unlike fluoroquinolones or aminoglycosides, meropenem requires actual dose reduction in severe renal impairment because 1, 2:
- Peak plasma concentrations (28-40 mcg/mL) remain unchanged regardless of renal function 2
- Terminal half-life increases proportionately with declining renal function (from ~1 hour in normal function to ~10 hours in severe impairment) 2
- Total body clearance correlates linearly with creatinine clearance 2
- Mean urinary recovery decreases from 77% in healthy volunteers to significantly lower amounts in renal impairment 2
Special Populations Requiring Adjusted Approach
Continuous Renal Replacement Therapy (CRRT):
- Hemofiltration contributes significantly to meropenem elimination, removing approximately 47% of the dose 4
- For critically ill anuric patients on continuous venovenous hemofiltration, the recommended dose should be increased by 100% compared to standard renal failure dosing to avoid underdosing 4
- Hemofiltration clearance averages 22.0 ± 4.7 mL/min, with total clearance of 52.0 ± 8.4 mL/min 4
- Consider 500 mg every 8-12 hours rather than the reduced doses used in non-CRRT renal failure 4
Augmented Renal Clearance (CrCl ≥90 mL/min):
- Standard dosing regimens are suboptimal in ICU patients with normal or augmented renal clearance 5
- These patients may require increased doses, more frequent administration, prolonged infusion duration (≥2 hours), or continuous infusion to achieve adequate MIC coverage 6, 5
Common Pitfalls to Avoid
Do not use creatinine-based eGFR equations alone in critically ill patients. Creatinine is a suboptimal GFR marker in the ICU setting, and equations incorporating both creatinine and cystatin C provide superior prediction of meropenem clearance 7. When available, use combined biomarker equations for more accurate dosing decisions 7.
Do not assume stable renal function. In critically ill patients with acute kidney injury or fluctuating renal function, reassess creatinine clearance frequently and adjust doses accordingly 5. The pharmacokinetic variability is substantial in ICU patients 5.
Do not underdose patients with severe infections caused by less susceptible organisms. For pathogens with MIC >1 mcg/mL, even with dose adjustments for renal impairment, consider prolonged infusions (≥2 hours) to maximize time above MIC, which is the key pharmacodynamic parameter for meropenem efficacy 6, 5.