Meropenem Dosage Adjustment in Renal Impairment
For patients with renal impairment, meropenem dosage should be adjusted based on creatinine clearance, with half the recommended dose given every 12 hours for patients with CrCl of 10-25 mL/min and half the recommended dose every 24 hours for patients with CrCl <10 mL/min. 1
Dosing Algorithm Based on Renal Function
The FDA-approved dosing recommendations for meropenem in adults with renal impairment are as follows:
| Creatinine Clearance (mL/min) | Dose | Dosing Interval |
|---|---|---|
| >50 | Standard dose (500 mg for cSSSI, 1 g for intra-abdominal infections) | Every 8 hours |
| 26-50 | Standard dose | Every 12 hours |
| 10-25 | Half standard dose | Every 12 hours |
| <10 | Half standard dose | Every 24 hours |
Hemodialysis Considerations
Meropenem is effectively removed by hemodialysis, with approximately 50% of the drug eliminated during a standard hemodialysis session 2. For patients on hemodialysis:
- Administer the dose after dialysis to avoid premature removal of the drug
- Use half the standard dose every 24 hours
- The dialysis clearance of meropenem is approximately 81 ± 22 mL/min 3
Continuous Renal Replacement Therapy (CRRT)
For patients receiving CRRT, dosage adjustments are also necessary:
- Approximately 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 CVVHF, consider 500 mg every 12 hours or 1 g every 12 hours depending on the severity of infection
Pharmacokinetic Changes in Renal Impairment
Renal impairment significantly alters meropenem pharmacokinetics:
- The half-life increases from approximately 1 hour in patients with normal renal function to up to 13.7 hours in anuric patients 2
- Total body clearance and renal clearance of meropenem are linearly related to creatinine clearance 3, 4
- The volume of distribution is not significantly altered in uremic patients 4
Clinical Considerations
When using meropenem in patients with renal impairment:
- Monitor for clinical response and potential adverse effects
- Consider that underdosing may lead to treatment failure, especially in critically ill patients
- For severe infections caused by Pseudomonas aeruginosa, higher doses may be needed (adjusted according to renal function)
- The metabolite concentrations (open-ring metabolite) increase significantly in uremic patients 3
Common Pitfalls
- Failing to adjust the dose in patients with renal impairment can lead to drug accumulation and potential toxicity
- Underdosing may occur when treating critically ill patients with renal replacement therapy due to varying recommendations in literature 2
- Not accounting for the significant removal of meropenem during hemodialysis can result in subtherapeutic concentrations
- Administering the dose before dialysis rather than after can lead to premature drug removal
By following these dosing recommendations based on creatinine clearance and considering the specific renal replacement therapy being used, clinicians can optimize meropenem therapy in patients with renal impairment.