From the FDA Drug Label
Pharmacokinetic studies with meropenem for injection in patients with renal impairment have shown that the plasma clearance of meropenem correlates with creatinine clearance. Dosage adjustments are necessary in subjects with renal impairment (creatinine clearance 50 mL/min or less) [ see Dosage and Administration (2. 2) and Use in Specific Populations (8. 6)]. Meropenem IV is hemodialyzable.
The dosing of Meropenem during Renal Replacement Therapy (RRT) is not directly stated in the provided drug labels. However, it is mentioned that Meropenem IV is hemodialyzable.
- Dosage adjustments are necessary in subjects with renal impairment (creatinine clearance 50 mL/min or less).
- The FDA drug label does not provide specific guidance on dosing during RRT. 1
From the Research
Meropenem dosing during renal replacement therapy (RRT) should be adjusted to 750 mg every 8 hours for most patients, as this regimen achieves the pharmacodynamic target of 40% of free drug above 4 times the minimum inhibitory concentration (MIC) 2.
Key Considerations
- The type of RRT being used (continuous vs. intermittent hemodialysis) and the patient's residual kidney function can affect meropenem dosing, but the optimal dose of 750 mg every 8 hours is recommended for pre-dilution continuous venovenous hemofiltration and continuous venovenous hemodialysis modality using two effluent rates (25 and 35 mL/kg/h) 2.
- For patients on continuous renal replacement therapy (CRRT), a loading dose may not be necessary, but therapeutic drug monitoring may be beneficial in critically ill patients to ensure adequate drug levels while avoiding toxicity.
- Meropenem is moderately removed by dialysis due to its low protein binding and molecular weight, and its pharmacokinetics are altered in renal failure, with decreased clearance leading to drug accumulation if not properly adjusted 3, 4.
Monitoring and Adjustments
- Monitor the patient for seizures, which can occur with excessive meropenem levels, especially in those with CNS disorders or prior seizure history.
- Adjust the dose based on the patient's residual kidney function and the type of RRT being used, and consider therapeutic drug monitoring to ensure adequate drug levels and minimize the risk of toxicity.
Evidence Summary
- A systematic review and Monte Carlo simulations study found that a meropenem dose of 750 mg every 8 hours achieved the pharmacodynamic target of 40% of free drug above 4 times the MIC for most patients on CRRT 2.
- Other studies have reported varying dosing regimens, but the optimal dose of 750 mg every 8 hours is supported by the most recent and highest-quality evidence 5, 6.