What is the recommended dose and frequency of meropenem (Merrem) for patients with Chronic Kidney Disease (CKD) and impaired renal function?

Meropenem Dosing in Chronic Kidney Disease

In patients with CKD, meropenem requires dose reduction when creatinine clearance falls below 50 mL/min, with the standard dose of 500 mg or 1 gram given every 12 hours for CrCl 26-50 mL/min, half the recommended dose every 12 hours for CrCl 10-25 mL/min, and half the recommended dose every 24 hours for CrCl <10 mL/min. 1

Dosing Algorithm Based on Renal Function

For CrCl >50 mL/min

• Standard dosing applies: 500 mg every 8 hours for complicated skin and skin structure infections, or 1 gram every 8 hours for intra-abdominal infections 1
• No dose adjustment necessary 1

For CrCl 26-50 mL/min (Moderate Impairment)

• Administer the full recommended dose every 12 hours (instead of every 8 hours) 1
• This represents extending the dosing interval while maintaining the same individual dose 1

For CrCl 10-25 mL/min (Severe Impairment)

• Reduce dose to one-half the recommended dose every 12 hours 1
• For example: 250 mg every 12 hours for skin infections, or 500 mg every 12 hours for intra-abdominal infections 1

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

• Administer one-half the recommended dose every 24 hours 1
• The elimination half-life extends dramatically from approximately 1 hour in healthy individuals to up to 13.7 hours in anuric patients 2
• Pharmacokinetic studies confirm half-lives of 7.0 hours in end-stage renal disease patients not on dialysis 3

Hemodialysis Considerations

The FDA label states there is inadequate information regarding meropenem use in patients on hemodialysis or peritoneal dialysis 1, creating a critical knowledge gap in official guidance. However, research evidence provides important insights:

During Hemodialysis

• Approximately 50% of meropenem is removed by intermittent hemodialysis 2
• Hemodialysis significantly shortens the elimination half-life from 7.0 hours to 2.9 hours 3
• Dosing after each hemodialysis session is recommended based on pharmacokinetic studies 3
• Peak plasma levels after 500 mg dosing reach up to 53 mg/L in hemodialysis patients 2

Continuous Renal Replacement Therapy (CRRT)

• For patients on continuous venovenous hemofiltration (CVVHF), the recommended dose should be increased by 100% to avoid underdosing 4
• CVVHF removes 25-50% of meropenem, with hemofiltration clearance of 22.0 ± 4.7 mL/min 2, 4
• Total clearance in anuric patients on CVVHF is approximately 52.0 ± 8.4 mL/min 4
• The elimination half-life during CVVHF is 8.7 ± 3.5 hours 4
• A dosing regimen of 500 mg every 8-12 hours maintains adequate plasma concentrations (trough 7.3-11.9 mg/L, peak 38.9-44.7 mg/L) 4

Continuous Venovenous Hemodiafiltration (CVVHDF)

• Removes 13-53% of meropenem, showing high variability based on treatment parameters 2

Calculating Creatinine Clearance

Use the Cockcroft-Gault equation when only serum creatinine is available 1:

• Males: CrCl (mL/min) = [Weight (kg) × (140 - age)] / [72 × serum creatinine (mg/dL)]
• Females: 0.85 × male calculation 1

Recent pharmacokinetic modeling confirms that Cockcroft-Gault creatinine clearance best describes meropenem clearance in critically ill patients 5.

Pharmacokinetic Considerations

Progressive Accumulation with Declining Renal Function

• Meropenem exposure increases substantially as kidney function declines 6
• Elimination half-life increases progressively: 1.54 hours (CrCl >50 mL/min) → 3.36 hours (CrCl 30-50 mL/min) → 5.00 hours (CrCl <30 mL/min) 3
• Cumulative urinary excretion decreases from 48.5% in mild impairment to minimal amounts in severe CKD 3

Metabolite Accumulation

• The main metabolite H-4295 accumulates in renal failure, with peak levels occurring 0.5-1.0 hours after dosing 3
• This metabolite is also removed by hemodialysis 3

Critical Pitfalls to Avoid

The most common error is underdosing in patients receiving renal replacement therapy due to conflicting recommendations in the literature 2. The excellent tolerability profile of meropenem means such underadministration should be avoided 2.

Do not use the same dosing for all forms of renal replacement therapy—the treatment modality (intermittent hemodialysis versus CVVHF versus CVVHDF) has a profound influence on drug elimination, with removal rates varying from 13% to 50% 2.

In critically ill patients with fluctuating renal function, more frequent monitoring and dose adjustments may be necessary to maintain therapeutic concentrations while avoiding toxicity 6.

Administration Considerations

• Administer as intravenous infusion over 15-30 minutes 1
• Doses of 1 gram may be given as bolus injection over 3-5 minutes 1
• Do not mix with or add to solutions containing other drugs 1