What is the recommended dosage of Meropenem (generic name) for adults with impaired renal function?

Meropenem Dosing in Adults with Impaired Renal Function

For adults with renal impairment, meropenem dosing must be adjusted based on creatinine clearance (CrCl), with the standard dose maintained but the dosing interval extended, and post-dialysis administration is critical for patients on intermittent hemodialysis. 1

Standard Dose Adjustments by Creatinine Clearance

The FDA-approved dosing algorithm for renal impairment is straightforward and based on CrCl thresholds 1:

• CrCl >50 mL/min: Use the recommended dose (500 mg for complicated skin/soft tissue infections or 1 gram for intra-abdominal infections) every 8 hours 1
• CrCl 26-50 mL/min: Use the recommended dose every 12 hours 1
• CrCl 10-25 mL/min: Use one-half the recommended dose every 12 hours 1
• CrCl <10 mL/min: Use one-half the recommended dose every 24 hours 1

The key principle is to maintain the individual dose strength when possible and extend the dosing interval, rather than reducing the dose below 1 gram for serious infections, as this preserves the concentration-dependent bactericidal effect. 2, 3

Dialysis-Specific Considerations

Intermittent Hemodialysis

• Always administer meropenem after dialysis sessions, as approximately 50% of the drug is removed during a dialysis session 2
• Administering before dialysis leads to premature drug removal and subtherapeutic levels 2
• The elimination half-life is significantly prolonged in renal impairment (up to 6 hours compared to 1 hour in normal function) 4, 5

Continuous Renal Replacement Therapy (CRRT)

• Use 1 gram every 8-12 hours for patients on CRRT, as continuous therapy removes 25-50% of meropenem 2
• CVVHDF (continuous venovenous hemodiafiltration) removes 13-53% of the drug, necessitating higher doses than standard renal impairment adjustments 2
• Residual diuresis is a critical modifier of clearance: patients with preserved urine output require higher doses or extended infusions compared to oliguric patients 6

Sustained Low-Efficiency Dialysis (SLED)

• Maintain the full 1 gram dose every 12 hours rather than reducing individual doses 2, 3
• The 12-hour interval is supported by the prolonged elimination half-life in renal impairment 2

Optimizing Therapy for Resistant Organisms

When treating infections with organisms having higher MICs (≥4-8 mg/L), even in renal impairment 2:

• Use extended infusion over 3 hours to maximize the time that free drug concentrations remain above the MIC 2
• For carbapenem-resistant Enterobacterales with MIC ≥8 mg/L, use 1 gram every 8 hours by extended 3-hour infusion 2
• This approach optimizes pharmacokinetic/pharmacodynamic properties despite altered renal function 2

Therapeutic Drug Monitoring (TDM)

TDM is strongly recommended in critically ill patients with renal impairment to ensure adequate exposure while avoiding toxicity. 2, 7

• Target trough concentrations below 64 mg/L to prevent neurological toxicity, particularly seizures 3, 8
• Neurological deterioration occurs in approximately two-thirds of ICU patients when free trough concentrations exceed this threshold 8
• Meropenem has lower pro-convulsive activity compared to imipenem, making it safer in renal dysfunction, but monitoring remains essential 2

Critical Pitfalls to Avoid

• Never reduce individual doses below 1 gram when treating serious infections, even in severe renal impairment—instead, extend the dosing interval 3
• Never administer meropenem before dialysis sessions—this causes premature drug removal and treatment failure 2
• Do not ignore residual diuresis in CRRT patients—preserved urine output significantly increases drug clearance and may require dose escalation or extended infusions 6
• Avoid underdosing in the initial phase of treatment—inadequate levels lead to therapeutic failure and promote antimicrobial resistance 7
• Remember that approximately 50% of meropenem requires dose reduction when renal insufficiency is present, as the drug is primarily renally eliminated 9, 5

Administration Considerations

• Standard administration is by intravenous infusion over 15-30 minutes or bolus injection over 3-5 minutes 1
• Extended infusions (3 hours) should be used for resistant organisms or when optimizing pharmacodynamics 2
• Monitor renal function indicators throughout treatment, though meropenem does not cause clinically significant changes in renal function 2