Meropenem Dosage Adjustments in Renal Impairment
Meropenem dosage must be reduced in patients with renal impairment based on creatinine clearance, with specific adjustments required for different levels of kidney function. 1
Standard Dosing and Renal Adjustment Guidelines
Meropenem is primarily eliminated by the kidneys, with approximately 63% excreted unchanged in urine, making dosage adjustments essential in renal impairment to prevent drug accumulation and potential toxicity.
According to the FDA-approved labeling, the following dosage adjustments are recommended for adult patients with renal impairment 1:
| Creatinine Clearance (mL/min) | Dose | Dosing Interval |
|---|---|---|
| >50 | Recommended dose (500 mg for cSSSI or 1 g for intra-abdominal infections) | Every 8 hours |
| 26-50 | Recommended dose | Every 12 hours |
| 10-25 | One-half recommended dose | Every 12 hours |
| <10 | One-half recommended dose | Every 24 hours |
Special Considerations for Dialysis Patients
For patients undergoing hemodialysis, meropenem is significantly removed during dialysis sessions:
- Approximately 50% of meropenem is eliminated by intermittent hemodialysis 2
- For patients on hemodialysis, dosing should occur after each dialysis session 3
- The elimination half-life of meropenem is shortened from approximately 7 hours to 2.9 hours during hemodialysis 3
Continuous Renal Replacement Therapy (CRRT)
For patients receiving CRRT, dosing adjustments differ from standard hemodialysis:
- 25-50% of meropenem is eliminated by continuous venovenous hemofiltration (CVVHF) 2
- 13-53% is eliminated by continuous venovenous hemodiafiltration (CVVHDF) 2
- For patients on CVVHDF, a dose of 1g intravenously every 12 hours has been recommended as an initial dose 4
Impact of Residual Diuresis
Recent research indicates that residual diuresis (remaining urine output) significantly impacts meropenem clearance in patients on CRRT:
- Meropenem clearance can be estimated as: CL = 3.68 + 0.22 × (residual diuresis/100) L/h 5
- Patients with preserved residual diuresis may require extended infusion times (3 hours) rather than bolus administration to maintain therapeutic levels 5
Risk Assessment for Target Non-Attainment
The risk of insufficient meropenem exposure increases with higher creatinine clearance:
- Patients with augmented renal function (high creatinine clearance >130 mL/min) are at risk for subtherapeutic levels with standard dosing 6
- For infections with pathogens having MICs of 2 mg/L or higher, standard dosing may be insufficient in patients with normal to augmented renal function 6
Clinical Application
- Assess the patient's renal function using creatinine clearance (Cockcroft-Gault equation)
- Select the appropriate dose and interval based on the FDA-approved recommendations
- For critically ill patients, consider therapeutic drug monitoring if available
- In patients with residual diuresis on CRRT, extended infusion times may be beneficial
- For patients on hemodialysis, administer the dose after the dialysis session
Remember that underdosing meropenem should be avoided due to the risk of treatment failure, while appropriate dose adjustments will help prevent drug accumulation and toxicity in patients with impaired renal function.