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: 6

• Hemofiltration clearance: 22.0 ± 4.7 mL/min 6
• Total clearance: 52.0 ± 8.4 mL/min 6
• Amount removed: Approximately 47% of the dose is removed through CVVHF 6
• Recommended dose: The dose should be increased by 100% compared to standard renal failure dosing (i.e., 500 mg every 8-12 hours rather than every 12-24 hours) to avoid underdosing 6, 4

The elimination varies by CRRT modality: 25-50% by CVVHF, 13-53% by continuous venovenous hemodiafiltration (CVVHDF). 4

Critical Considerations for Target Attainment

Augmented renal clearance and mild renal impairment are significant risk factors for subtherapeutic meropenem levels, particularly when treating pathogens with MIC values ≥2 mg/L. 7 A hyperbolic relationship exists between creatinine clearance (25-255 mL/min) and meropenem serum concentrations at the end of the dosing interval. 7

For infections caused by Pseudomonas aeruginosa, higher doses are required: 1

• Adults: 1 gram every 8 hours (adjusted for renal function as above) 1
• Pediatric patients >50 kg: 1 gram every 8 hours 1
• Pediatric patients <50 kg: 20 mg/kg every 8 hours 1

Metabolite Accumulation

The open-ring metabolite (ICI 213,689) accumulates significantly in renal impairment, 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 the context of overall drug safety. 3

Common Pitfalls to Avoid

• Do not reduce the dose per administration in mild-to-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 higher doses due to significant drug removal 6, 4
• Do not forget to dose after hemodialysis sessions, as approximately 50% of the drug is removed 2, 3
• Be aware that standard dosing may be insufficient even with dose adjustments in critically ill patients with augmented renal clearance or when treating organisms with MIC ≥2 mg/L 7