Meropenem Dosing in Patients with Impaired Renal Function
Meropenem dosage should be reduced in patients with renal impairment based on creatinine clearance, with specific adjustments as follows: for CrCl >50 mL/min use standard dose every 8 hours, for CrCl 26-50 mL/min use standard dose every 12 hours, for CrCl 10-25 mL/min use half the standard dose every 12 hours, and for CrCl <10 mL/min use half the standard dose every 24 hours. 1
Standard Dosing for Adults with Normal Renal Function
- Complicated skin and skin structure infections: 500 mg IV every 8 hours
- Intra-abdominal infections: 1 gram IV every 8 hours
- When treating infections caused by Pseudomonas aeruginosa: 1 gram IV every 8 hours
- Administration: 15-30 minute infusion or 3-5 minute IV bolus injection 1
Renal Dosing Adjustments for Adults
The FDA-approved dosing adjustments for meropenem in adult patients with renal impairment are as follows:
| Creatinine Clearance (mL/min) | Dose | Dosing Interval |
|---|---|---|
| >50 | Recommended dose (500 mg for cSSSI and 1 gram for intra-abdominal) | 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
Critically Ill Patients
- In critically ill patients with sepsis, higher initial doses may be needed due to increased clearance and volume of distribution, especially in those with preserved renal function 2
- Extended or continuous infusions may be beneficial for infections due to bacteria with high MICs to increase probability of achieving pharmacokinetic/pharmacodynamic targets 2
Continuous Renal Replacement Therapy
- For patients on continuous venovenous hemofiltration (CVVH), meropenem clearance is significantly affected
- Studies suggest that approximately 47% of the dose may be removed through CVVH 3
- For patients on CVVH, 500 mg IV every 12 hours has been shown to maintain adequate trough levels for susceptible organisms 4
Hemodialysis
- There is inadequate information regarding meropenem dosing in patients on hemodialysis or peritoneal dialysis in the FDA labeling 1
- However, as with other antibiotics, administration after dialysis is generally recommended to avoid premature removal of the drug
Pediatric Dosing with Renal Impairment
- There is no specific guidance for pediatric patients with renal impairment in the FDA labeling 1
- Clinical judgment and consultation with pediatric infectious disease specialists is recommended
Safety Considerations
- Meropenem has a relatively low risk of seizures compared to other carbapenems (relative pro-convulsive activity of 16 compared to imipenem's 71) 2
- Meropenem is generally well-tolerated in elderly and/or renally impaired patients, with rare occurrence of meropenem-related seizures (0.1%) even in patients with renal impairment 5
Monitoring Recommendations
- Regular assessment of renal function
- Clinical response to therapy
- Monitor for adverse effects, particularly neurological symptoms which may occur with excessive plasma concentrations
Practical Application
- Calculate the patient's creatinine clearance using the Cockcroft-Gault equation:
- Males: CrCl (mL/min) = Weight (kg) × (140 - age) / (72 × serum creatinine [mg/dL])
- Females: CrCl (mL/min) = 0.85 × above value 1
- Select the appropriate dose and interval based on the calculated CrCl and type of infection
- Reassess renal function regularly during therapy and adjust dosing as needed
Remember that these dosing recommendations are designed to maintain effective antimicrobial concentrations while minimizing the risk of adverse effects in patients with impaired renal function.