Meropenem Dosing in End-Stage Renal Failure
For patients with end-stage renal failure (ESRF) not on dialysis, administer meropenem 500 mg every 24 hours; for patients on intermittent hemodialysis, administer 500 mg after each dialysis session. 1, 2
Dosing Based on Renal Function
ESRF Without Dialysis (CrCl <10 mL/min)
- Administer one-half the recommended dose (500 mg for most infections) every 24 hours 1
- The elimination half-life extends dramatically from 1 hour in healthy patients to 6.8-13.7 hours in anuric ESRF patients 3, 4
- Total plasma clearance drops to approximately 19 mL/min/1.73 m² compared to 186 mL/min/1.73 m² in normal renal function 4
ESRF on Intermittent Hemodialysis
- Administer 500 mg after each hemodialysis session 2
- This timing is critical because hemodialysis removes approximately 50% of meropenem from the body 3
- Hemodialysis shortens the elimination half-life from 7.0 hours to 2.9 hours during the dialysis session 2
- Never administer before dialysis, as this wastes drug and reduces efficacy 5
- Post-dialysis administration prevents premature drug removal and ensures therapeutic concentrations 5
Continuous Renal Replacement Therapy (CRRT)
CVVH/CVVHDF Dosing
- For critically ill patients on CVVH, administer 500 mg every 8-12 hours 6, 7
- CVVH removes 25-50% of meropenem, while CVVHDF removes 13-53% 3
- The recommended dose should be increased by 100% compared to standard ESRF dosing to avoid underdosing 6
- Total meropenem clearance during CVVH is approximately 52 mL/min, with hemofiltration contributing 22 mL/min 6
- For severe infections, 1 gram every 8 hours may be appropriate during CVVH 7
Critical Safety Considerations
Neurotoxicity Monitoring
- Keep trough concentrations below 64 mg/L to minimize neurotoxicity risk 5, 8
- Renal failure is the primary risk factor for beta-lactam accumulation and subsequent neurotoxicity 5, 8
- When free minimum concentration normalized to MIC (fCmin/MIC) exceeds 8, approximately two-thirds of ICU patients experience significant neurological deterioration 5, 8
- Monitor trough levels if available, particularly in ESRF patients 5, 8
- Meropenem has relatively favorable neurotoxicity profile (pro-convulsive activity of 16) compared to cefepime or imipenem 8
Practical Dosing Algorithm
Step 1: Determine renal replacement status
- No dialysis → 500 mg every 24 hours 1
- Intermittent hemodialysis → 500 mg post-dialysis 2
- CVVH/CVVHDF → 500 mg every 8-12 hours 6, 7
Step 2: Adjust for infection severity
- For severe infections or P. aeruginosa, consider doubling the dose 1
- Maximum dose should not exceed 1 gram per administration in ESRF without CRRT 1
Step 3: Monitor for toxicity
- Check trough levels if available, targeting <64 mg/L 5
- Watch for neurological symptoms (confusion, seizures, myoclonus) 5, 8
Common Pitfalls to Avoid
- Do not use standard dosing (500 mg every 8 hours) in ESRF without dialysis - this leads to dangerous drug accumulation 1, 4
- Do not administer before hemodialysis - dialysis will remove the drug before therapeutic effect 5, 2
- Do not underdose patients on CRRT - hemofiltration significantly removes meropenem, requiring higher doses than standard ESRF dosing 3, 6
- Do not ignore the metabolite ICI 213,689 - it accumulates extensively in renal failure (half-life up to 23.6 hours) and may contribute to toxicity 4