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 dialysis clearance is approximately 81 mL/min, and hemodialysis shortens the elimination half-life from 7.0 hours to 2.9 hours 3, 5
• The FDA label notes inadequate information for specific dosing recommendations in hemodialysis patients, but research supports post-dialysis dosing 1, 5

Continuous Renal Replacement Therapy (CRRT)

• For patients on continuous venovenous hemofiltration (CVVHF), increase the standard renal failure dose by 100% to avoid underdosing 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

Pharmacokinetic Rationale

• The preferred strategy is extending the dosing interval while maintaining dose strength rather than reducing the milligram amount, as this preserves the concentration-dependent bactericidal effect 2
• Meropenem is predominantly renally excreted (up to 70% recovered unchanged in urine), making dosage adjustment essential in renal impairment 7
• Total body clearance and renal clearance correlate linearly with creatinine clearance 3
• The metabolite ICI 213689 (ring-opened form) accumulates significantly in uremic patients, with a half-life of 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 reduce the milligram dose amount without extending the interval, as this compromises bactericidal efficacy 2
• Do not administer meropenem before hemodialysis, as this results in significant drug removal and potential therapeutic failure 5
• Do not use standard dosing in patients with CrCl <50 mL/min, as this leads to drug accumulation and potential toxicity 1
• Avoid underdosing in CRRT patients by recognizing that hemofiltration contributes significantly to drug elimination 6

Monitoring

• While not explicitly required by the FDA label, serum drug concentration monitoring may be considered in critically ill patients with severe renal impairment to optimize dosing 4
• Calculate creatinine clearance using the Cockcroft-Gault equation when only serum creatinine is available 1