Meropenem Dosing in Chronic Kidney Disease
For CKD patients, reduce meropenem dose based on creatinine clearance: give 1 gram every 12 hours for CrCl 26-50 mL/min, 500 mg every 12 hours for CrCl 10-25 mL/min, and 500 mg every 24 hours for CrCl <10 mL/min. 1
Standard Dosing Algorithm by Renal Function
The FDA-approved dosing schedule provides clear guidance based on creatinine clearance 1:
CrCl >50 mL/min
- No adjustment needed: Use standard dosing of 500 mg every 8 hours for complicated skin/soft tissue infections or 1 gram every 8 hours for intra-abdominal infections 1
CrCl 26-50 mL/min (CKD Stage 3-4)
- Recommended dose every 12 hours: Maintain the full dose appropriate for the infection type, but extend the interval from every 8 hours to every 12 hours 1
- This maintains adequate drug exposure while preventing accumulation 2, 3
CrCl 10-25 mL/min (CKD Stage 5)
- Half the recommended dose every 12 hours: For example, 500 mg every 12 hours instead of 1 gram every 12 hours 1
- The elimination half-life extends to approximately 5 hours in this population 3
CrCl <10 mL/min (End-Stage Renal Disease)
- Half the recommended dose every 24 hours: For example, 500 mg every 24 hours 1
- Without dialysis, the half-life can extend up to 13.7 hours 2
- Plasma concentrations remain elevated significantly longer in anuric patients 4
Critical Considerations for Creatinine Clearance Calculation
Use the Cockcroft-Gault equation to estimate creatinine clearance, as this is the method validated in the FDA labeling and pharmacokinetic studies 1, 5:
- Males: CrCl (mL/min) = [Weight (kg) × (140 - age)] / [72 × serum creatinine (mg/dL)] 1
- Females: Multiply the male calculation by 0.85 1
This is particularly important because the Cockcroft-Gault equation best describes meropenem clearance in critically ill patients compared to other renal function estimates 5.
Special Populations Requiring Additional Attention
Hemodialysis Patients
- Inadequate data exists for specific dosing recommendations in the FDA label 1
- However, research demonstrates that approximately 50% of meropenem is removed during intermittent hemodialysis 2
- Dosing after each hemodialysis session is recommended based on pharmacokinetic studies 3
- The dialysis clearance is approximately 79 mL/min 4
Continuous Renal Replacement Therapy (CRRT)
- Standard CKD dosing guidelines do not apply to CRRT patients 2
- CVVHF removes 25-50% of meropenem, while CVVHDF removes 13-53% 2
- For anuric patients on continuous venovenous hemofiltration, doses should be doubled (e.g., 1 gram every 12 hours instead of 500 mg) to avoid underdosing 6
- Hemofiltration clearance averages 22 mL/min, contributing significantly to total drug elimination 6
Elderly Patients
- Calculate creatinine clearance rather than relying on serum creatinine alone, as elderly patients often have reduced muscle mass leading to falsely reassuring creatinine levels despite significant renal impairment 7
- Renal function may fluctuate during acute illness, requiring reassessment every 2-3 days 7
Common Pitfalls to Avoid
Do not use meropenem without dose adjustment in any patient with CrCl ≤50 mL/min, as this leads to drug accumulation and potential toxicity 1, 2. The elimination half-life increases progressively from 1 hour in normal renal function to over 6 hours in severe renal impairment 3, 4.
Do not assume peritoneal dialysis dosing is equivalent to hemodialysis dosing—there is inadequate information for peritoneal dialysis patients in the FDA labeling 1.
Avoid underdosing in CRRT patients by using standard CKD dosing schedules, as continuous therapies remove substantially more drug than expected 2, 6. The excellent tolerability profile of meropenem makes underdosing a greater clinical risk than modest overdosing 2.