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, as reducing the milligram dose amount may compromise the concentration-dependent bactericidal effect 2. This approach is supported by pharmacokinetic data showing:
The elimination half-life of meropenem increases from approximately 1 hour in healthy volunteers to 7-13.7 hours in anuric patients with end-stage renal disease 3, 4
Total body clearance and renal clearance correlate linearly with creatinine clearance 4
Approximately 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 hemodialysis, there is inadequate FDA-approved dosing information 1. However, research evidence provides guidance:
Hemodialysis removes approximately 50% of meropenem, shortening the elimination half-life from 7.0 hours to 2.9 hours 3, 6
Dosing after each hemodialysis session is recommended to facilitate directly observed therapy and avoid premature drug removal 6
The dialysis clearance of meropenem is approximately 81 ± 22 mL/min 4
Continuous Renal Replacement Therapy (CRRT)
For critically ill patients receiving CRRT, standard renal dosing may result in underdosing 7:
Continuous venovenous hemofiltration (CVVHF) removes 25-50% of meropenem, contributing significantly to drug elimination 3
The recommended dose should potentially be increased by 100% in anuric patients receiving CVVHF to avoid underdosing 7
Hemofiltration clearance averages 22.0 ± 4.7 mL/min, with total clearance of 52.0 ± 8.4 mL/min 7
Pediatric Renal Dosing
There is no established experience or dosing guidance for pediatric patients with renal impairment 1. The FDA label explicitly states this limitation for both pediatric patients 3 months and older and those less than 3 months of age 1.
Monitoring Considerations
Serum drug concentrations should be monitored in patients with severe renal impairment to avoid toxicity 8
The metabolite ICI 213,689 (H-4295) accumulates significantly in uremic patients, with an apparent half-life of approximately 35 hours in severe renal insufficiency 4, 6
Baseline and regular monitoring of renal parameters are necessary to detect early signs of further renal deterioration 8
Common Pitfalls
Avoid reducing the milligram dose amount when possible, as this compromises the concentration-dependent bactericidal effect; instead, extend the dosing interval 2
Do not administer meropenem before hemodialysis, as this will result in premature drug removal and subtherapeutic levels 6
Be aware that CRRT dosing differs significantly from intermittent hemodialysis dosing, and standard renal dosing tables may lead to underdosing in CRRT patients 3, 7
Remember that the FDA label provides no guidance for peritoneal dialysis patients 1