Meropenem Dosage Adjustments Based on Creatinine Clearance
Meropenem dosing must be reduced in patients with renal impairment according to specific creatinine clearance (CrCl) thresholds, with patients having CrCl <10 mL/min requiring half the recommended dose every 24 hours. 1
Standard Dosing and Renal Adjustment Guidelines
Adult Dosing Based on Renal Function
- For CrCl >50 mL/min: Standard dose (500 mg for complicated skin infections, 1 gram for intra-abdominal infections) every 8 hours 1
- For CrCl 26-50 mL/min: Standard dose every 12 hours 1
- For CrCl 10-25 mL/min: Half the recommended dose every 12 hours 1
- For CrCl <10 mL/min: Half the recommended dose every 24 hours 1
Hemodialysis Considerations
- Meropenem is significantly removed by hemodialysis, with approximately 50% eliminated during dialysis sessions 2
- For patients on hemodialysis, administer the dose after the dialysis session to avoid premature removal of the drug 2
- The elimination half-life is shortened from approximately 7 hours to 2.9 hours during hemodialysis 3
Pharmacokinetic Considerations in Renal Impairment
- Meropenem is predominantly excreted unchanged in the urine, making dosage adjustments necessary in renal impairment 2
- The half-life of meropenem increases from approximately 1 hour in healthy volunteers to up to 13.7 hours in anuric patients 2
- There is a hyperbolic relationship between creatinine clearance and meropenem serum concentrations, with lower CrCl resulting in higher drug levels 4
Continuous Renal Replacement Therapy (CRRT)
- For patients on CRRT, meropenem clearance is affected by the specific modality used 2:
- For patients on CVVHF, approximately 47% of the dose is removed through filtration 5
- Consider increasing the dose by up to 100% in critically ill anuric patients on CVVHF to avoid underdosing 5
Clinical Pitfalls and Considerations
- Underdosing is a significant risk in patients with varying degrees of renal function, especially in critically ill patients with severe infections 4
- Large inter- and intra-patient variability in meropenem concentrations has been observed in critically ill populations 4
- Patients with augmented renal clearance (CrCl >130 mL/min) may require higher doses or more frequent administration to maintain therapeutic levels 4
- Monitor for clinical response and consider therapeutic drug monitoring in critically ill patients with severe infections to ensure adequate drug exposure 4
Special Populations
- For pediatric patients with renal impairment, there is limited data available, but similar principles of dose adjustment should be applied 1
- Elderly patients often have decreased renal function and may require dose adjustments based on their calculated creatinine clearance 3
By following these dosing guidelines based on creatinine clearance, clinicians can optimize meropenem therapy to achieve therapeutic efficacy while minimizing potential toxicity in patients with renal impairment.