Meropenem Dosing in Adults with Impaired Renal Function
For adults with impaired renal function, reduce the standard meropenem dose (500 mg or 1 gram) based on creatinine clearance while maintaining the same individual dose strength when possible and extending the dosing interval to every 12 or 24 hours. 1
Dose Adjustment Algorithm by Creatinine Clearance
The FDA-approved dosing schedule provides clear cutoffs based on renal function 1:
- CrCl >50 mL/min: Use recommended dose (500 mg for cSSSI, 1 gram for intra-abdominal infections) every 8 hours 1
- CrCl 26-50 mL/min: Use recommended dose every 12 hours 1
- CrCl 10-25 mL/min: Use one-half recommended dose every 12 hours 1
- CrCl <10 mL/min: Use one-half recommended dose every 24 hours 1
Pharmacokinetic Rationale
The strategy of maintaining full individual doses while extending intervals is preferred over dose reduction because meropenem exhibits concentration-dependent bactericidal activity. 2 The elimination half-life increases significantly as renal function declines—from approximately 1 hour in normal function to substantially longer in renal impairment 2, 3. This prolonged half-life supports interval extension rather than dose reduction 3.
Special Considerations for Dialysis Patients
Intermittent Hemodialysis
- Approximately 50% of meropenem is removed during a hemodialysis session 4
- Administer doses after dialysis sessions to prevent premature drug removal 4
Continuous Renal Replacement Therapy (CRRT)
- CRRT removes 25-50% of meropenem, while CVVHDF removes 13-53% 4
- For patients on SLED, maintain the full 1 gram dose every 12 hours rather than reducing individual doses below 1 gram 4
- The dosing interval of every 12 hours is appropriate given the prolonged elimination half-life in renal impairment 4
- Residual diuresis significantly impacts clearance: patients with preserved diuresis (>100 mL/24h) have higher clearance than oligoanuric patients 5
Therapeutic Drug Monitoring
TDM is strongly recommended in critically ill patients with renal impairment to ensure adequate exposure while avoiding toxicity. 4, 6
- Monitor renal function indicators throughout treatment 4
- Target trough concentrations should remain below 64 mg/L to prevent neurological toxicity 4, 6
- TDM is particularly valuable for patients on renal replacement therapy where pharmacokinetic variability is high 6
Critical Pitfalls to Avoid
- Do not reduce individual doses below 1 gram when treating serious infections, even in renal impairment—instead extend the dosing interval 4
- Meropenem has lower pro-convulsive activity than imipenem, making it safer in renal dysfunction, but neurological toxicity can still occur when trough concentrations exceed 64 mg/L 4, 6
- For infections caused by organisms with MIC ≥4 mg/L, consider extended infusion (3 hours) or continuous infusion, particularly in patients with preserved diuresis 5
- Consult nephrology for patients on dialysis or with severely decreased kidney function for individualized dosing guidance 7