Meropenem Dosing in Adults with Impaired Renal Function
The recommended dose of meropenem for adults with impaired renal function should be adjusted based on creatinine clearance, with 1 gram every 8 hours for patients with creatinine clearance >50 mL/min, 1 gram every 12 hours for those with creatinine clearance 26-50 mL/min, 500 mg every 12 hours for those with creatinine clearance 10-25 mL/min, and 500 mg every 24 hours for those with creatinine clearance <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 |
|---|---|---|
| Greater than 50 | Recommended dose (500 mg for cSSSI and 1 gram for intra-abdominal infections) | Every 8 hours |
| 26 to 50 | Recommended dose | Every 12 hours |
| 10 to 25 | One-half recommended dose | Every 12 hours |
| Less than 10 | One-half recommended dose | Every 24 hours |
Calculating Renal Function
When only serum creatinine is available, the Cockcroft and Gault equation can be used to estimate creatinine clearance:
- Males: Creatinine Clearance (mL/min) = Weight (kg) × (140 - age) / (72 × serum creatinine [mg/dL])
- Females: 0.85 × above value
Special Considerations for Renal Replacement Therapy
For patients on hemodialysis or peritoneal dialysis, the FDA label notes that there is inadequate information regarding meropenem dosing 1. However, research studies provide additional guidance:
- Approximately 50% of meropenem is eliminated by intermittent hemodialysis 2
- For continuous renal replacement therapy (CRRT), 25-50% is eliminated by continuous venovenous hemofiltration (CVVHF) and 13-53% by continuous venovenous hemodiafiltration (CVVHDF) 2
Pharmacokinetic Considerations
Meropenem's half-life increases significantly in patients with renal impairment:
- Normal renal function: approximately 1 hour
- End-stage renal disease: up to 13.7 hours 2
This prolonged half-life necessitates the dosing adjustments outlined above to prevent drug accumulation while maintaining efficacy.
Target Attainment and Clinical Efficacy
Recent research has shown that standard meropenem dosing may result in insufficient drug exposure in critically ill patients, particularly those with augmented renal clearance 3. For infections with pathogens having minimum inhibitory concentrations (MICs) of 2 mg/L or higher, patients with mild renal impairment up to augmented renal function are at risk for target non-attainment 3.
Safety Profile in Renal Impairment
Meropenem has an excellent safety profile in renally impaired patients. A study of 436 patients with creatinine clearance <51 mL/min showed that the pattern and frequency of adverse events were similar to those in patients with normal renal function 4. Importantly, meropenem-related seizures were rare (0.1%), even in patients with renal impairment 4.
Common Pitfalls to Avoid
Failing to adjust doses based on renal function: This can lead to drug accumulation and potential toxicity in patients with impaired renal function.
Underdosing in critical infections: For serious infections with less susceptible pathogens (higher MICs), standard dosing may be insufficient, especially in patients with augmented renal clearance 3.
Not reassessing renal function: Renal function can change during the course of therapy, requiring dose adjustments.
Inappropriate dosing in renal replacement therapy: Different modalities of renal replacement therapy affect meropenem clearance differently 2, 5.
By following the recommended dosing adjustments based on creatinine clearance, clinicians can optimize meropenem therapy in adults with impaired renal function, balancing efficacy against the risk of adverse effects.