Meropenem Renal Dose Adjustment
For patients with renal impairment, reduce meropenem dosing frequency while maintaining the full gram dose per administration to preserve concentration-dependent bactericidal activity. 1
Standard Renal Dosing Algorithm
The FDA-approved dosing adjustments based on creatinine clearance are: 1
- CrCl >50 mL/min: Standard dose (500 mg or 1 g depending on infection) every 8 hours 1
- CrCl 26-50 mL/min: Recommended dose every 12 hours 1
- CrCl 10-25 mL/min: One-half recommended dose every 12 hours 1
- CrCl <10 mL/min: One-half recommended dose every 24 hours 1
Critical principle: The half-life of meropenem increases from approximately 1 hour in normal renal function to up to 13.7 hours in anuric patients, necessitating interval extension rather than dose reduction when possible. 2, 3
Dialysis-Specific Dosing
Intermittent Hemodialysis (IHD)
- Administer meropenem after dialysis sessions to prevent premature drug removal, as approximately 50% of the drug is eliminated during a dialysis session 4, 2
- The FDA label notes inadequate information for specific hemodialysis dosing recommendations 1
Continuous Renal Replacement Therapy (CRRT)
- Dose: 1 gram every 8 hours for patients on CVVHF or CVVHDF 4
- CRRT removes 25-50% of meropenem via CVVHF and 13-53% via CVVHDF, requiring higher doses than standard renal impairment adjustments 4, 2
- The elimination half-life during CRRT is approximately 2.5-8.7 hours 4, 5
Sustained Low-Efficiency Dialysis (SLED)
- Maintain the full 1 gram dose every 12 hours rather than reducing individual doses 4, 6
- This preserves the concentration-dependent bactericidal effect critical for efficacy 6
Special Considerations for Resistant Organisms
When treating infections with organisms having MIC ≥4-8 mg/L: 4
- Use extended infusion over 3 hours, even in renal impairment, to maximize time above MIC 4
- For carbapenem-resistant Enterobacterales with MIC ≥8 mg/L, use 1 g every 8 hours as a 3-hour infusion 4
Critical Pitfalls to Avoid
- Never reduce individual doses below 1 gram when treating serious infections, even in renal impairment—instead extend the dosing interval 6
- Avoid administering meropenem before dialysis sessions, as this leads to premature drug removal and subtherapeutic levels 4
- Do not underdose patients on CRRT by using standard renal impairment adjustments, as continuous drug removal requires higher doses than intermittent renal dysfunction 2, 5
Therapeutic Drug Monitoring
- Consider therapeutic drug monitoring in critically ill patients with renal impairment to ensure adequate exposure 4
- Target trough concentrations below 64 mg/L to prevent neurological toxicity, which is the primary concern in renal dysfunction 4, 6
- Meropenem has lower pro-convulsive activity compared to imipenem, making it safer in renal dysfunction 4
Pharmacokinetic Rationale
The time-dependent bactericidal activity of meropenem requires maintaining free-drug concentrations above the MIC for approximately 40% of the dosing interval (%T>MIC) 7. In renal impairment, maintaining adequate peak concentrations through full gram doses while extending intervals preserves this pharmacodynamic target better than reducing individual doses 6.