What is the recommended dosing of meropenem for a patient with End-Stage Renal Disease (ESRD)?

Meropenem Dosing in End-Stage Renal Disease (ESRD)

For patients with ESRD (creatinine clearance <10 mL/min), administer meropenem at one-half the recommended dose (250 mg for skin/soft tissue infections or 500 mg for intra-abdominal infections) every 24 hours. 1

Standard ESRD Dosing (Not on Dialysis)

• The FDA-approved dosing for ESRD patients with creatinine clearance <10 mL/min is one-half the standard recommended dose given every 24 hours 1
• For complicated skin and skin structure infections: 250 mg IV every 24 hours 1
• For complicated intra-abdominal infections: 500 mg IV every 24 hours 1
• Administer as IV infusion over 15-30 minutes, or as IV bolus over 3-5 minutes for doses ≥1 gram in patients with normal renal function 1

Critical Pharmacokinetic Considerations in ESRD

• The half-life of meropenem is dramatically prolonged in ESRD, extending from approximately 1 hour in healthy volunteers to up to 13.7 hours in anuric patients 2
• Meropenem is predominantly excreted unchanged in the urine, making dosage adjustments essential in renal insufficiency 2
• Peak plasma concentrations after 500 mg dosing in hemodialysis patients reach approximately 53 mg/L 2

Hemodialysis Patients: Timing is Critical

The FDA label states there is inadequate information regarding meropenem use in patients on hemodialysis 1, however research provides important guidance:

• Hemodialysis removes approximately 50% of meropenem from the body 2
• Administer meropenem at least 2 hours before hemodialysis initiation, or immediately after completion of hemodialysis 3
• Completing infusion right before HD initiation substantially reduces drug exposure and may lead to treatment failure 3
• In pediatric hemodialysis patients, the median drug half-life off dialysis is 7.3 hours (range 4.9-11.7 hours) 4

Specific Hemodialysis Dosing Recommendations

• For adult ESRD patients on intermittent hemodialysis: administer one-half the recommended dose every 24 hours, timed appropriately relative to dialysis sessions 1
• The standard 20 mg/kg pediatric dose may be insufficient; dosing simulations suggest 25 mg/kg daily or 40 mg/kg on alternate days for adequate interdialytic coverage 4

Continuous Renal Replacement Therapy (CRRT)

The FDA label provides no specific guidance for CRRT 1, but research demonstrates critical dosing considerations:

• CRRT significantly contributes to meropenem elimination, removing 25-50% via continuous venovenous hemofiltration (CVVHF) and 13-53% via continuous venovenous hemodiafiltration (CVVHDF) 2
• For critically ill anuric patients on CRRT, increase the standard dose by 100% to avoid underdosing 5
• Recommended dosing for CRRT patients: 500 mg every 8-12 hours 5
• Total meropenem clearance during CVVHF is approximately 52 mL/min, with hemofiltration clearance contributing 22 mL/min 5

Residual Diuresis Impact on CRRT Dosing

• Residual diuresis is a critical modifier of meropenem clearance in CRRT patients 6
• The clearance equation: CL = 3.68 + 0.22 × (residual diuresis/100) liters/hour 6
• CRRT intensity itself was NOT identified as a clearance modifier 6

For oligoanuric CRRT patients (minimal residual urine output):

• 500 mg every 8 hours as 30-minute bolus achieves 40% ƒuT>MIC for susceptible organisms (MIC <2 mg/L) 6
• For 100% ƒuT>MIC target: 500 mg every 8 hours as 30-minute bolus 6
• For resistant organisms (MIC 2-4 mg/L): 500 mg every 6 hours as 30-minute bolus 6

For CRRT patients with preserved diuresis (>100 mL/24h):

• For 100% ƒuT>MIC target: 500 mg every 8 hours as 3-hour infusion 6
• For resistant organisms (MIC 2-4 mg/L): 500 mg every 6 hours as 3-hour infusion 6

Peritoneal Dialysis

There is inadequate information regarding meropenem use in patients on peritoneal dialysis 1

• Approximately 13% of meropenem is eliminated by continuous ambulatory peritoneal dialysis (CAPD) 2
• Begin with ESRD dosing (one-half recommended dose every 24 hours) and monitor closely 1

Common Pitfalls to Avoid

• Do not administer meropenem immediately before hemodialysis - this timing substantially reduces drug exposure and risks treatment failure 3
• Do not use standard dosing in CRRT patients - the combination of renal failure and extracorporeal clearance requires dose increases, not decreases 5
• Do not ignore residual diuresis in CRRT patients - preserved urine output significantly increases drug clearance and may require higher doses or extended infusions 6
• Do not assume CRRT intensity affects dosing - residual renal function is more important than CRRT parameters 6