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

Meropenem Renal Dosing

For patients with renal impairment, reduce meropenem dosing frequency while maintaining the full milligram dose strength: administer the recommended dose (500 mg for skin infections, 1 gram for intra-abdominal infections) every 12 hours for creatinine clearance 26-50 mL/min, and half the recommended dose every 12 hours for CrCl 10-25 mL/min, or every 24 hours for CrCl <10 mL/min. 1

Dosing Algorithm by Creatinine Clearance

CrCl >50 mL/min

• Standard dosing: 500 mg every 8 hours for complicated skin/skin structure infections (cSSSI), or 1 gram every 8 hours for intra-abdominal infections 1
• For cSSSI caused by Pseudomonas aeruginosa, use 1 gram every 8 hours 1

CrCl 26-50 mL/min

• Administer the full recommended dose every 12 hours (500 mg or 1 gram depending on infection type) 1
• This maintains adequate peak concentrations while accounting for reduced renal clearance 2

CrCl 10-25 mL/min

• Administer one-half the recommended dose every 12 hours 1
• Example: 250 mg every 12 hours for cSSSI, or 500 mg every 12 hours for intra-abdominal infections 1

CrCl <10 mL/min (End-Stage Renal Disease)

• Administer one-half the recommended dose every 24 hours 1
• The elimination half-life extends from 1 hour in healthy patients to 10-13.7 hours in anuric patients 3, 4

Hemodialysis Considerations

• Meropenem is significantly removed by hemodialysis (approximately 50% of the drug is eliminated during a dialysis session) 4
• Administer doses after hemodialysis sessions to avoid premature drug removal 5
• The FDA label notes inadequate information for specific hemodialysis dosing recommendations, but research supports post-dialysis administration 1, 5
• Dialysis clearance averages 81 ± 22 mL/min, shortening the elimination half-life from 7.0 hours to 2.9 hours during dialysis 3, 5

Continuous Renal Replacement Therapy (CRRT)

• For patients on continuous venovenous hemofiltration (CVVHF), increase the standard dose by 100% to compensate for significant drug removal 6
• CVVHF removes 25-50% of meropenem, with hemofiltration clearance of approximately 22 mL/min 4, 6
• Recommended dosing: 500 mg every 8-12 hours for critically ill anuric patients on CVVHF 6
• Continuous venovenous hemodiafiltration (CVVHDF) removes 13-53% of the drug 4

Key Pharmacokinetic Principles

The preferred dosing strategy is to extend the dosing interval while maintaining dose strength, rather than reducing the milligram amount 2

• Reducing the dose amount may compromise the concentration-dependent bactericidal effect 2, 7
• Total body clearance and renal clearance correlate linearly with creatinine clearance 3, 8
• The metabolite ICI 213689 (ring-opened form) accumulates significantly in renal failure, with a half-life extending to approximately 35 hours in severe renal insufficiency 3

Administration Method

• Administer as intravenous infusion over 15-30 minutes 1
• Doses of 1 gram may also be given as IV bolus over 3-5 minutes 1

Critical Pitfalls to Avoid

• Do not administer meropenem before hemodialysis, as this results in substantial drug removal and potential therapeutic failure 5
• Avoid reducing the milligram dose when possible, as this compromises bactericidal activity; instead extend the dosing interval 2
• Do not use the same dosing for all forms of renal replacement therapy—CRRT requires higher doses than intermittent hemodialysis due to continuous drug removal 4, 6
• The FDA label provides limited guidance for dialysis patients, so clinicians must rely on pharmacokinetic data showing significant dialytic removal 1, 4