Meropenem Dosage Adjustments in Renal Failure
Meropenem dosage must be reduced in patients with renal impairment according to their creatinine clearance (CrCl), with specific adjustments required for different levels of renal dysfunction. 1
Dosage Adjustment Algorithm Based on Creatinine Clearance
| Creatinine Clearance (mL/min) | Dose Adjustment | Dosing Interval |
|---|---|---|
| > 50 mL/min | Standard dose (500 mg for cSSSI, 1 g for intra-abdominal infections) | Every 8 hours |
| 26-50 mL/min | Standard dose | Every 12 hours |
| 10-25 mL/min | Half standard dose | Every 12 hours |
| < 10 mL/min | Half standard dose | Every 24 hours |
Special Considerations for Renal Replacement Therapy
Hemodialysis
- Meropenem is readily dialyzable with approximately 50% eliminated during hemodialysis 2
- Administer dose after each hemodialysis session 3
- For patients on hemodialysis, the infusion rate should be reduced to account for decreased drug clearance
Continuous Renal Replacement Therapy (CRRT)
- For patients on CVVHF (continuous venovenous hemofiltration): 25-50% of meropenem is eliminated 2
- For patients on CVVHDF (continuous venovenous hemodiafiltration): 13-53% of meropenem is eliminated 2
- Dosing may need to be individualized based on the specific CRRT modality and flow rates
Pharmacokinetic Considerations
The elimination half-life of meropenem increases significantly with declining renal function:
- Normal renal function: ~1 hour
- Moderate renal impairment: 3.36 hours
- Severe renal impairment: 5.00 hours
- End-stage renal disease: Up to 13.7 hours 2, 3
Monitoring Recommendations
- Monitor clinical response and signs of infection resolution
- Consider therapeutic drug monitoring in critically ill patients with fluctuating renal function
- Assess renal function regularly during treatment to adjust dosing as needed
- Monitor for adverse effects, which may be more common with accumulated drug levels
Pitfalls and Caveats
- Underdosing is a common risk in patients on renal replacement therapy due to varying recommendations in the literature 2
- Given meropenem's excellent safety profile, it's better to err on the side of adequate dosing to ensure antimicrobial efficacy
- The standard dose should be maintained while extending the dosing interval rather than reducing the dose itself in most cases of renal impairment
- For critically ill patients with severe infections, consider the higher end of the dosing range to ensure adequate antimicrobial coverage, particularly for pathogens with higher MICs
By following these specific dosage adjustments based on creatinine clearance and renal replacement modality, clinicians can optimize meropenem therapy in patients with renal impairment while minimizing the risk of toxicity and treatment failure.