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 P. aeruginosa, use 1 gram every 8 hours 1

CrCl 26-50 mL/min

• Recommended dose every 12 hours (maintain full dose strength, extend interval) 1
• This means 500 mg every 12 hours for cSSSI, or 1 gram every 12 hours for intra-abdominal infections 1

CrCl 10-25 mL/min

• One-half recommended dose every 12 hours 1
• This translates to 250 mg every 12 hours for cSSSI, or 500 mg every 12 hours for intra-abdominal infections 1

CrCl <10 mL/min

• One-half recommended dose every 24 hours 1
• This means 250 mg every 24 hours for cSSSI, or 500 mg every 24 hours for intra-abdominal infections 1

Pharmacokinetic Rationale

The preferred strategy is to extend the dosing interval while maintaining dose strength, rather than reducing the milligram amount, to preserve the concentration-dependent bactericidal effect. 2

• Meropenem elimination half-life increases from approximately 1 hour in healthy volunteers to 8.7 hours in anuric patients with acute renal failure, and up to 13.7 hours in end-stage renal disease 3, 4
• Total body clearance and renal clearance correlate linearly with creatinine clearance 4
• Up to 70% of meropenem is recovered unchanged in urine under normal conditions 5

Hemodialysis Considerations

The FDA label states there is inadequate information regarding meropenem use in patients on hemodialysis or peritoneal dialysis. 1

However, research evidence demonstrates:

• Approximately 50% of meropenem is removed by intermittent hemodialysis 3
• Dialysis clearance averages 81 ± 22 mL/min 4
• Hemodialysis shortens the elimination half-life from 7.0 hours to 2.9 hours 6
• Dosing after each hemodialysis session is recommended based on pharmacokinetic studies 6

Continuous Renal Replacement Therapy (CRRT)

For critically ill patients on CRRT:

• Hemofiltration clearance contributes 22.0 ± 4.7 mL/min to total clearance 7
• Approximately 25-50% is eliminated by continuous venovenous hemofiltration (CVVHF), and 13-53% by continuous venovenous hemodiafiltration (CVVHDF) 3
• The recommended dose should be increased by 100% (e.g., 500 mg every 8 hours instead of every 12 hours) to avoid underdosing in anuric patients receiving CVVHF 7

Pediatric Renal Dosing

The FDA label notes there is no experience in pediatric patients with renal impairment, and no specific dosing recommendations are provided. 1

Critical Pitfalls to Avoid

• Do not reduce the milligram dose amount without extending the interval, as this compromises bactericidal efficacy 2
• Do not use standard dosing in patients with CrCl <50 mL/min, as this leads to drug accumulation and potential toxicity 1, 4
• Do not underdose patients on CRRT, as significant drug removal occurs and standard renal failure dosing may be insufficient 7
• Avoid administering meropenem before hemodialysis, as this results in premature drug removal; dose after dialysis 6

Estimating Creatinine Clearance

When only serum creatinine is available, use the Cockcroft-Gault equation 1:

Males: CrCl (mL/min) = [Weight (kg) × (140 - age)] / [72 × serum creatinine (mg/dL)]

Females: 0.85 × above value 1