Is meropenem dialyzable, and how should its dose be adjusted in an adult patient undergoing intermittent high‑flux hemodialysis, continuous renal replacement therapy, or peritoneal dialysis?

Is Meropenem Dialyzable?

Yes, meropenem is significantly dialyzable and requires dose adjustment in patients undergoing any form of dialysis, with approximately 50% removed during intermittent hemodialysis and 13-53% removed during continuous renal replacement therapy. 1

Dialyzability Characteristics

Meropenem is predominantly excreted unchanged in the urine, making it highly susceptible to removal by dialysis 1:

• Intermittent hemodialysis (IHD) removes approximately 50% of meropenem during a typical session 1
• Continuous venovenous hemofiltration (CVVHF) removes 25-50% of the drug 1
• Continuous venovenous hemodiafiltration (CVVHDF) removes 13-53% 1
• Sustained low-efficiency dialysis (SLED) produces a mean reduction of 79.1% in plasma concentration over an 8-hour session, with significantly more removal occurring in the first 4 hours 2

The half-life of meropenem extends from approximately 1 hour in healthy volunteers to 13.7 hours in anuric patients with end-stage renal disease 1. During SLED, the mean half-life is 3.6 hours 2.

Dosing Adjustments for Intermittent Hemodialysis

For patients on intermittent high-flux hemodialysis:

• Standard dosing: 500 mg every 12 hours maintains adequate plasma concentrations 1
• Timing: Administer the dose after dialysis to prevent premature drug removal and facilitate directly observed therapy 3
• Peak plasma concentrations reach up to 53 mg/L after 500 mg administration in hemodialysis patients 1

This post-dialysis timing follows the established principle used for other dialyzable medications and ensures the full therapeutic dose is retained 4.

Dosing Adjustments for Continuous Renal Replacement Therapy (CRRT)

For critically ill patients undergoing CRRT, dosing must account for both the type of therapy and patient characteristics:

• Standard CRRT dosing: 1 g every 12 hours is commonly used 1, 5
• Higher doses may be needed: Patients with conserved renal function or polytrauma may require increased dosing or continuous infusion to achieve adequate efficacy 5
• Continuous infusion is recommended for septic patients and polytraumatized patients when treating pathogens with MIC ≥4 mg/L 5

Population pharmacokinetic modeling shows that creatinine clearance and patient type (septic versus polytraumatized) significantly influence meropenem clearance during CRRT 5. The population clearance is 15 L/h, with apparent volume of distribution varying from 15.7 L in septic patients to 69.5 L in polytraumatized patients 5.

Dosing for Sustained Low-Efficiency Dialysis (SLED)

• Recommended dose: 1 g every 12 hours during typical 8-hour SLED sessions maintains adequate plasma concentrations 2
• Mean plasma trough concentration of 4 mg/L is achieved with this regimen, which exceeds the MIC of 2 mg/L for most susceptible pathogens 2

Dosing for Peritoneal Dialysis

While specific dosing recommendations for continuous ambulatory peritoneal dialysis (CAPD) are limited in the evidence, meropenem requires dosage adjustment in these patients due to its renal excretion 1.

Special Considerations for Augmented Renal Clearance

Critical pitfall: Standard meropenem regimens are suboptimal in ICU patients with normal or augmented renal clearance 6:

• Patients with creatinine clearance 60-90 mL/min need 6 g/day to achieve appropriate MIC coverage 6
• Patients with creatinine clearance ≥90 mL/min require increased dose, frequency, extended infusion duration, or continuous infusion 6
• Recommended regimens appropriately cover MIC90 only in patients with creatinine clearance <60 mL/min 6

Therapeutic Target

The goal is to maintain meropenem plasma concentration above the pathogen's MIC over 100% of the dosing interval (100% ƒT>MIC), which is a determinant of outcome in severe infections 6. For meropenem-susceptible pathogens (MIC90 of 2 mg/L), the dosing strategies above achieve this target in 90% of patients 6.