Meropenem Dosage Adjustments in Renal Impairment
Meropenem dosage must be reduced based on creatinine clearance, with frequency adjustment being the primary modification strategy in patients with renal impairment. 1
Recommended Dosing Schedule Based on Renal Function
| Creatinine Clearance (mL/min) | Dose | Dosing Interval |
|---|---|---|
| Greater than 50 | Standard dose (500 mg for cSSSI or 1 gram for intra-abdominal infections) | Every 8 hours |
| 26 to 50 | Standard dose | Every 12 hours |
| 10 to 25 | One-half standard dose | Every 12 hours |
| Less than 10 | One-half standard dose | Every 24 hours |
Pharmacokinetic Considerations
Meropenem is predominantly eliminated by the kidneys, with approximately 70% recovered in urine in patients with normal renal function 2. The elimination half-life increases significantly with declining renal function:
- Normal renal function: ~1 hour
- Moderate impairment: 3-5 hours
- End-stage renal disease: Up to 13.7 hours 3
This prolongation of half-life necessitates the adjustment of dosing intervals rather than just dose reduction to prevent drug accumulation while maintaining therapeutic efficacy.
Special Considerations for Renal Replacement Therapies
Hemodialysis
- Meropenem is readily dialyzable with approximately 50% removed during hemodialysis 3
- Hemodialysis shortens the elimination half-life from about 7 hours to 2.9 hours 4
- Recommendation: Administer dose after hemodialysis session 4
Continuous Renal Replacement Therapy (CRRT)
- For patients on continuous venovenous hemofiltration (CVVHF), approximately 25-50% of meropenem is eliminated 3
- For continuous venovenous hemodiafiltration (CVVHDF), 13-53% is eliminated 3
- Dosing may need to be increased by up to 100% compared to standard renal dosing to avoid underdosing in critically ill patients on CRRT 5
Clinical Application
When treating infections in patients with renal impairment:
- Determine the patient's creatinine clearance
- Select appropriate dose based on infection type (500 mg for skin/soft tissue or 1 gram for intra-abdominal infections)
- Adjust dosing interval according to the renal function table above
- For Pseudomonas aeruginosa infections, use 1 gram as the standard dose (before adjustment) 1
- For patients on dialysis, administer after dialysis session
Common Pitfalls to Avoid
- Underdosing: Particularly in CRRT patients where drug clearance may be higher than expected
- Failure to reassess: Renal function may change during critical illness; regular monitoring and dose adjustment are essential
- Overlooking infection severity: For severe infections, using the higher end of the dosing range may be necessary despite renal impairment
- Ignoring drug interactions: Concomitant nephrotoxic drugs may further impair renal function and affect meropenem clearance
By following these guidelines, clinicians can optimize meropenem therapy in patients with renal impairment, balancing efficacy against the risk of adverse effects from drug accumulation.