What is the recommended dosage adjustment of meropenem (generic name) for a patient with impaired renal function based on creatinine clearance?

Meropenem Dosing in Renal Impairment

For patients with impaired renal function, meropenem requires dose reduction when creatinine clearance falls below 50 mL/min, with specific adjustments based on CrCl ranges: full dose every 12 hours for CrCl 26-50 mL/min, half dose every 12 hours for CrCl 10-25 mL/min, and half dose every 24 hours for CrCl <10 mL/min. 1

Standard Dosing in Normal Renal Function

• Adults with CrCl >50 mL/min: 500 mg IV every 8 hours for complicated skin/soft tissue infections; 1 gram IV every 8 hours for intra-abdominal infections 1
• Infusion time: 15-30 minutes for standard doses; 1 gram doses may be given as IV bolus over 3-5 minutes 1
• Pseudomonas aeruginosa infections: Use 1 gram every 8 hours regardless of infection site 1

Dose Adjustments for Renal Impairment

Adults with Reduced Creatinine Clearance

The FDA-approved dosing schedule provides clear cutoffs 1:

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

Pharmacokinetic Rationale

• The elimination half-life increases dramatically with declining renal function: from approximately 1 hour in healthy volunteers to 5-7 hours in severe renal impairment (CrCl <30 mL/min), and up to 13.7 hours in anuric patients 2, 3
• Urinary excretion accounts for approximately 48.5% of the dose in patients with normal renal function, decreasing progressively as renal function declines 3
• Nonrenal clearance accounts for approximately 20% of elimination in normal renal function but increases to about 50% in patients with severe impairment 4

Hemodialysis Patients

The FDA label states there is inadequate information for specific dosing recommendations in hemodialysis patients 1, however research evidence provides guidance:

• Hemodialysis removes approximately 50% of meropenem from the body 2
• The elimination half-life shortens from 7.0 hours to 2.9 hours during hemodialysis 3
• Recommended approach: Administer the dose after each hemodialysis session 3
• Dialysis clearance: Approximately 79 mL/min, making meropenem readily dialyzable 4

Continuous Renal Replacement Therapy (CRRT)

For critically ill patients receiving CRRT, standard renal dosing may result in subtherapeutic levels:

• CVVHF (continuous venovenous hemofiltration): Removes 25-50% of meropenem; hemofiltration clearance is approximately 22 mL/min 2, 5
• CVVHDF (continuous venovenous hemodiafiltration): Removes 13-53% of meropenem 2
• Recommended dosing for CVVHF: 500 mg every 8 hours or 1 gram every 12 hours to avoid underdosing 5, 6
• The terminal elimination half-life during CVVHF is approximately 8.7 hours 5

Critical Consideration for CRRT

Because hemofiltration contributes significantly to meropenem elimination, doses should be increased by 100% compared to standard renal failure dosing to avoid therapeutic failure 5. Peak and trough concentrations with 500 mg every 12 hours are 38.9 mg/L and 7.3 mg/L respectively, maintaining levels above MIC for most pathogens 5.

Peritoneal Dialysis

• The FDA label provides no specific recommendations for peritoneal dialysis patients 1
• Limited data exists for CAPD (continuous ambulatory peritoneal dialysis) patients 2

Pediatric Dosing Adjustments

• Children ≥3 months with normal renal function: 10 mg/kg every 8 hours (cSSSI), 20 mg/kg every 8 hours (cIAI), or 40 mg/kg every 8 hours (meningitis), up to maximum adult doses 1
• No established pediatric renal dosing guidelines exist - the FDA label explicitly states there is no experience in pediatric patients with renal impairment 1

Monitoring and Safety

Key Monitoring Parameters

• Calculate creatinine clearance using the Cockcroft-Gault equation when only serum creatinine is available 1
• Monitor renal function regularly, as meropenem accumulation can occur even with appropriate dose adjustments 2
• The open-ring metabolite (ICI 213,689) accumulates significantly in renal failure, with half-life increasing from 2.3 hours in healthy volunteers to 23.6 hours in severe impairment 4

Important Caveats

• Underdosing risk: The excellent tolerability profile of meropenem should not lead to conservative underdosing, particularly in CRRT patients where standard renal dosing may be insufficient 2
• Variable CRRT parameters: Different CRRT modalities and settings significantly affect drug clearance, potentially requiring individualized dosing based on treatment intensity 2
• Meropenem should not be mixed with other drugs in solution 1