Meropenem Renal Dosing
For patients with renal impairment, meropenem dosing must be adjusted based on creatinine clearance: maintain the standard dose (500 mg or 1 gram) but extend the dosing interval to every 12 hours for CrCl 26-50 mL/min, reduce to half-dose every 12 hours for CrCl 10-25 mL/min, and half-dose every 24 hours for CrCl <10 mL/min. 1
Standard Renal Dose Adjustments
The FDA-approved dosing schedule for adults with renal impairment follows a clear algorithm based on creatinine clearance 1:
CrCl >50 mL/min: Use standard dosing (500 mg for complicated skin/soft tissue infections or 1 gram for intra-abdominal infections) every 8 hours 1
CrCl 26-50 mL/min: Maintain the full recommended dose but extend interval to every 12 hours 1
CrCl 10-25 mL/min: Reduce to one-half the recommended dose every 12 hours 1
CrCl <10 mL/min: Reduce to one-half the recommended dose every 24 hours 1
Pharmacokinetic Rationale
The dosing strategy prioritizes extending the dosing interval while maintaining dose strength when possible, rather than reducing the milligram amount, to preserve the concentration-dependent bactericidal effect 2. This approach is critical because:
Meropenem's terminal elimination half-life increases dramatically from approximately 1 hour in healthy volunteers to 8-14 hours in anuric patients with end-stage renal disease 3, 4
Total body clearance and renal clearance correlate linearly with creatinine clearance 4
Up to 70% of meropenem is recovered unchanged in urine under normal conditions, making renal function the primary determinant of drug elimination 5
Hemodialysis Considerations
For patients on intermittent hemodialysis:
Approximately 50% of meropenem is removed during a hemodialysis session 3
Hemodialysis clearance averages 81 ± 22 mL/min, significantly shortening the elimination half-life from 7.0 hours to 2.9 hours 4, 6
Administer meropenem after each hemodialysis session to avoid premature drug removal and facilitate directly observed therapy 6
The FDA label notes inadequate information for specific dosing recommendations in hemodialysis patients, but research supports post-dialysis dosing 1, 6
Continuous Renal Replacement Therapy (CRRT)
For critically ill patients receiving CRRT:
Hemofiltration contributes significantly to meropenem elimination, removing 25-50% of the drug during continuous venovenous hemofiltration (CVVHF) and 13-53% during continuous venovenous hemodiafiltration (CVVHDF) 3
In anuric patients on CVVHF, approximately 47% of the dose is removed through hemofiltration, with a total clearance of 52 mL/min 7
The recommended dose should be increased by 100% (to 500 mg every 8-12 hours or 1 gram every 8-12 hours) for critically ill anuric patients receiving CVVHF to avoid underdosing 7
Peak and trough concentrations for 500 mg every 12 hours are approximately 39 mg/L and 7 mg/L, respectively, while every 8 hours dosing achieves 45 mg/L and 12 mg/L 7
Pediatric Renal Dosing
The FDA label provides no specific guidance for pediatric patients with renal impairment, stating "there is no experience in pediatric patients with renal impairment" 1
In the absence of data, extrapolation from adult dosing principles (extending intervals while maintaining mg/kg dose) would be the most prudent approach 2
Critical Monitoring Points
Calculate creatinine clearance using the Cockcroft-Gault equation for accurate dosing decisions (multiply by 0.85 for females) 1
Monitor for accumulation of the inactive metabolite ICI 213,689, which has an apparent half-life of approximately 35 hours in severe renal insufficiency 4
Serum drug concentration monitoring should be considered in patients with severe renal impairment to avoid toxicity, though meropenem has an excellent tolerability profile 8, 3
Common Pitfalls to Avoid
Do not reduce the milligram dose amount when extending intervals in moderate renal impairment (CrCl 26-50 mL/min), as this compromises bactericidal efficacy 2, 1
Avoid administering meropenem before hemodialysis, as this results in significant drug removal and subtherapeutic levels 6
Do not assume standard dosing is safe in elderly patients, as renal function declines with age and creatinine may not accurately reflect true clearance 1
Physicians risk underdosing in CRRT patients due to variable recommendations in the literature; err on the side of higher dosing given meropenem's safety profile 3