What is the recommended renal dose of meropenem for patients with impaired renal function?

Meropenem Renal Dosing

For patients with renal impairment, meropenem dosing must be adjusted based on creatinine clearance, with the standard dose per administration maintained when possible while extending the dosing interval to preserve its concentration-dependent bactericidal activity. 1

Standard Dosing Adjustments by Creatinine Clearance

The FDA-approved dosing schedule for adults with renal impairment is as follows: 1

• CrCl >50 mL/min: Full dose (500 mg for cSSSI, 1 gram for intra-abdominal infections) every 8 hours 1
• CrCl 26-50 mL/min: Full recommended dose every 12 hours 1
• CrCl 10-25 mL/min: Half the recommended dose every 12 hours 1
• CrCl <10 mL/min: Half the recommended dose every 24 hours 1

Pharmacokinetic Rationale

The elimination half-life of meropenem increases dramatically with declining renal function, from approximately 1 hour in patients with normal renal function to 5-10 hours in severe renal impairment and up to 13.7 hours in anuric patients with end-stage renal disease. 2, 3, 4 This prolongation necessitates dosing interval adjustments rather than dose reductions to maintain adequate peak concentrations for bactericidal activity. 5

Total body clearance and renal clearance of meropenem are linearly related to creatinine clearance, with approximately 48.5% of the dose excreted unchanged in urine in patients with normal renal function, decreasing progressively as renal function declines. 2, 3

Special Populations Requiring Dose Modification

Hemodialysis Patients

Meropenem and its metabolite are effectively removed by hemodialysis, with dialysis clearance of approximately 81 mL/min and approximately 50% of the drug eliminated during a dialysis session. 3, 4 The elimination half-life shortens from 7.0 hours to 2.9 hours during hemodialysis. 2

• Dosing recommendation: Administer meropenem after each hemodialysis session 2
• The standard dose should be given post-dialysis to ensure adequate drug levels 3

Continuous Renal Replacement Therapy (CRRT)

For critically ill anuric patients receiving continuous venovenous hemofiltration (CVVHF), hemofiltration contributes significantly to meropenem elimination with a hemofiltration clearance of 22.0 ± 4.7 mL/min, removing 47.2% of the dose. 6

• The recommended dose should be increased by 100% compared to standard dosing for anuric patients to avoid underdosing 6
• Dosing intervals of 8-12 hours are appropriate during CVVHF 6
• CVVHDF removes 13-53% of meropenem, while CVVHF removes 25-50% 4

Critical Considerations for Target Attainment

Augmented renal clearance and mild renal impairment paradoxically represent high-risk scenarios for subtherapeutic meropenem levels. In critically ill patients with creatinine clearance ranging from 25-255 mL/min, standard dosing (1000 mg every 8 hours) achieved the target of 100%T>MIC in only 48.4% of patients for pathogens with MIC 2 mg/L and 20.6% for MIC 8 mg/L. 7

Patients with mild renal impairment up to augmented renal function (CrCl >50 mL/min) are at highest risk for target non-attainment and may require higher doses or extended infusions, particularly when treating Pseudomonas aeruginosa or other pathogens with MIC ≥2 mg/L. 7

Metabolite Accumulation

The open-ring metabolite (ICI 213,689) accumulates significantly in uremic patients, with an apparent half-life of approximately 35 hours in severe renal insufficiency compared to very low concentrations in healthy subjects. 3 While this metabolite is microbiologically inactive, its accumulation should be considered in patients with prolonged severe renal impairment.

Pediatric Renal Dosing

There is no established experience or dosing recommendations for pediatric patients with renal impairment. 1 Standard pediatric dosing should not be extrapolated to renally impaired children without therapeutic drug monitoring or nephrology consultation.

Common Pitfalls to Avoid

• Do not reduce the dose per administration in mild-moderate renal impairment—extend the interval instead to maintain concentration-dependent killing 5, 1
• Do not underdose patients on CRRT by using standard renal failure dosing; these patients require dose increases due to significant drug removal 6
• Do not assume standard dosing is adequate for critically ill patients with normal or augmented renal clearance when treating resistant organisms (MIC ≥2 mg/L) 7
• Do not forget to dose after hemodialysis sessions as approximately 50% of the drug is removed 3, 4