Meropenem Dosage Adjustments in Acute Kidney Injury
Meropenem dosage should be reduced in patients with acute kidney injury based on creatinine clearance, with 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
Dosage Adjustment Algorithm Based on Renal Function
The FDA-approved meropenem dosing recommendations for patients with renal impairment are as follows:
| Creatinine Clearance (mL/min) | Dose | Dosing Interval |
|---|---|---|
| >50 mL/min | Standard dose (500 mg for cSSSI or 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
For patients receiving renal replacement therapy, the dosing should be adjusted as follows:
- Hemodialysis: Administer dose after dialysis session to prevent premature drug removal 1
- Continuous Venovenous Hemofiltration (CVVH): Consider 500 mg every 12 hours or 1 gram every 12 hours depending on infection severity 2
- Continuous Hemodiafiltration (CHDF): 500 mg every 8 hours or 1 gram every 12 hours for susceptible bacteria 3
Clinical Pharmacokinetics in AKI
Meropenem is primarily excreted unchanged by the kidneys (approximately 70% of the dose within 12 hours), with only 2% eliminated via fecal route 1. In patients with renal impairment:
- Terminal elimination half-life increases from ~1 hour (normal renal function) to up to 13.7 hours in anuric patients 4
- Plasma clearance correlates directly with creatinine clearance 1
- Meropenem is hemodialyzable, with approximately 50% of the drug removed during hemodialysis sessions 4
Monitoring Recommendations
- Assess renal function before initiating therapy and regularly during treatment
- Monitor for signs of drug accumulation in patients with severe AKI (seizures, CNS effects)
- Consider therapeutic drug monitoring in critically ill patients with AKI if available
Common Pitfalls to Avoid
- Underdosing: Despite renal impairment, maintaining adequate antimicrobial coverage is essential, particularly for serious infections. Don't reduce doses excessively in critically ill patients.
- Timing with renal replacement therapy: For patients on intermittent hemodialysis, administer meropenem after dialysis sessions to prevent premature drug removal 1
- Failure to reassess: Renal function may improve or worsen during treatment, requiring dose adjustments
- Drug interactions: Probenecid inhibits renal excretion of meropenem and should be avoided 1
Special Populations
For pediatric patients with AKI, limited data exists on specific dosing recommendations. The principles of dose reduction based on creatinine clearance should be applied, but close monitoring is essential.
In elderly patients with AKI, the age-associated reduction in creatinine clearance should be considered when determining appropriate dosing regimens 1.
By following these evidence-based dosing recommendations, clinicians can optimize meropenem therapy in patients with AKI, ensuring adequate antimicrobial coverage while minimizing the risk of adverse effects from drug accumulation.