What is the dose adjustment of meropenem (generic name) for patients with impaired renal function based on creatinine (Cr) clearance?

Meropenem Dosing in Renal Impairment

For patients with impaired renal function, meropenem requires dose reduction based on creatinine clearance: use the recommended dose (500 mg for cSSSI or 1 gram for intra-abdominal infections) 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

Standard Dosing in Normal Renal Function

• 500 mg every 8 hours intravenously for complicated skin and skin structure infections (cSSSI) in adults 1
• 1 gram every 8 hours for cSSSI caused by Pseudomonas aeruginosa 1
• 1 gram every 8 hours for complicated intra-abdominal infections 1
• Infusion should be administered over 15-30 minutes, or as bolus injection over 3-5 minutes 1

Dose Adjustments for Renal Impairment

Adults with Renal Dysfunction

The FDA-approved dosing schedule stratifies by creatinine clearance 1:

• CrCl >50 mL/min: No adjustment needed - use recommended dose every 8 hours 1
• CrCl 26-50 mL/min: Use recommended dose (500 mg or 1 gram depending on indication) every 12 hours 1
• CrCl 10-25 mL/min: Use half the recommended dose every 12 hours 1
• CrCl <10 mL/min: Use half the recommended dose every 24 hours 1

Pharmacokinetic Rationale

The elimination half-life of meropenem increases dramatically with declining renal function 2, 3:

• Normal renal function: approximately 1 hour 2
• CrCl 50-30 mL/min: 3.36 hours 3
• CrCl <30 mL/min: 5.00 hours 3
• Anuric patients: up to 13.7 hours 2

Meropenem is predominantly excreted unchanged in the urine (63% of dose), making dose adjustment essential in renal impairment 4

Dosing During Renal Replacement Therapy

Intermittent Hemodialysis (IHD)

• Dose after each hemodialysis session is recommended 3
• Hemodialysis removes approximately 50% of meropenem 2
• The elimination half-life shortens from 7.0 hours to 2.9 hours during dialysis 3
• Use the dose appropriate for CrCl <10 mL/min and administer post-dialysis 1, 3

Continuous Venovenous Hemofiltration (CVVH)

• 1 gram every 8 hours is recommended for critically ill patients on CVVH 5
• CVVH removes 25-50% of meropenem, contributing significantly to drug elimination 2
• The total clearance during CVVH is approximately 143.7 mL/min, with hemofiltration clearance of 22.0 mL/min 6, 5
• Peak concentrations of 28-45 mg/L and trough levels of 6.6-11.9 mg/L are achieved with this dosing 6, 5

Continuous Venovenous Hemodiafiltration (CVVHDF)

• 1 gram every 12 hours is appropriate for patients on CVVHDF 4
• CVVHDF removes 13-53% of meropenem, less than CVVH 2
• This dosing maintains trough levels above MIC90 for most pathogens 4

Continuous Ambulatory Peritoneal Dialysis (CAPD)

• Limited data available; use caution and consider dosing similar to CrCl <10 mL/min 2

Pediatric Dosing Considerations

Children ≥3 Months with Normal Renal Function

• cSSSI: 10 mg/kg every 8 hours (maximum 500 mg per dose) 1
• cSSSI caused by P. aeruginosa: 20 mg/kg every 8 hours (maximum 1 gram per dose) 1
• Intra-abdominal infections: 20 mg/kg every 8 hours (maximum 1 gram per dose) 1
• Meningitis: 40 mg/kg every 8 hours (maximum 2 grams per dose) 1

Infants <3 Months with Intra-Abdominal Infections

Dosing varies by gestational age (GA) and postnatal age (PNA) 1:

• <32 weeks GA, PNA <2 weeks: 20 mg/kg every 12 hours 1
• <32 weeks GA, PNA ≥2 weeks: 20 mg/kg every 8 hours 1
• ≥32 weeks GA, PNA <2 weeks: 20 mg/kg every 8 hours 1
• ≥32 weeks GA, PNA ≥2 weeks: 30 mg/kg every 8 hours 1

Pediatric Renal Impairment

• No established dosing recommendations exist for pediatric patients with renal impairment 1
• Extrapolation from adult dosing adjustments may be necessary with careful monitoring 1

Critical Pitfalls to Avoid

Underdosing in CRRT: The literature contains varying recommendations for continuous renal replacement therapy, creating risk of inadequate dosing 2. Given meropenem's excellent tolerability profile, err toward higher doses (1 gram every 8 hours for CVVH) rather than risk therapeutic failure 2, 5.

Ignoring hemofiltration contribution: Hemofiltration clearance (22 mL/min) represents a substantial portion of total drug clearance (52 mL/min) in anuric patients on CVVH 6. Standard renal failure dosing without accounting for CRRT will result in subtherapeutic levels 6.

Timing with hemodialysis: Always administer meropenem after hemodialysis sessions, as dialysis removes approximately 50% of the drug 2, 3. Pre-dialysis dosing wastes medication and leaves patients undertreated 3.

Seizure risk: High doses of meropenem are associated with seizures, particularly in patients with renal impairment where drug accumulation occurs 1. Adhere strictly to dose reduction guidelines based on creatinine clearance 1.