What is the recommended renal dose of meropenem for a patient with impaired renal function?

Meropenem Renal Dosing

For patients with renal impairment, maintain the full individual dose of meropenem (500 mg or 1 gram depending on infection type) and extend the dosing interval rather than reducing the dose itself, to preserve concentration-dependent bactericidal activity. 1

Standard Renal Dosing Algorithm

The FDA-approved dosing adjustments based on creatinine clearance are: 1

• CrCl >50 mL/min: Use recommended dose (500 mg for cSSSI, 1 gram for intra-abdominal infections) every 8 hours 1
• CrCl 26-50 mL/min: Use full recommended dose every 12 hours (interval extended, dose unchanged) 1
• CrCl 10-25 mL/min: Use one-half recommended dose every 12 hours 1
• CrCl <10 mL/min: Use one-half recommended dose every 24 hours 1

Critical Consideration for Pseudomonas aeruginosa

• When treating infections caused by P. aeruginosa, start with 1 gram every 8 hours in patients with normal renal function, then apply the same renal adjustment algorithm to this higher base dose 1, 2
• This higher dosing is essential because P. aeruginosa typically has higher MIC values requiring increased meropenem exposure 2

Hemodialysis Dosing

• Intermittent hemodialysis removes approximately 50% of meropenem during each dialysis session 3, 4
• Administer meropenem immediately after each hemodialysis session to ensure adequate drug levels 2, 4
• The elimination half-life shortens from 7.0 hours to 2.9 hours during hemodialysis 4
• The FDA label notes inadequate information for specific hemodialysis dosing recommendations, but clinical practice supports post-dialysis administration 1

Continuous Renal Replacement Therapy (CRRT)

• For patients on CRRT, use 1 gram every 8-12 hours to compensate for continuous drug removal 2
• CRRT removes 25-50% of meropenem by continuous venovenous hemofiltration (CVVHF) and 13-53% by continuous venovenous hemodiafiltration (CVVHDF) 3
• The hemofiltration clearance of meropenem is approximately 22 mL/min, contributing significantly to total drug elimination 5
• Therapeutic drug monitoring is strongly recommended for all CRRT patients to ensure adequate exposure and prevent toxicity 2

Sustained Low-Efficiency Dialysis (SLED)

• For SLED patients, maintain the full 1 gram dose every 12 hours 2, 6
• The prolonged elimination half-life (2.5-8.7 hours) in this setting requires maintaining full doses rather than reducing individual doses below 1 gram 2, 6

Augmented Renal Clearance

• Patients with CrCl ≥90 mL/min are at high risk of subtherapeutic meropenem levels with standard dosing 7
• For CrCl 60-90 mL/min, increase total daily dose to 6 grams/day to achieve appropriate MIC coverage 7
• For CrCl ≥90 mL/min, consider increased dose, increased frequency, extended infusion duration (3 hours), or continuous infusion 7, 2

Extended Infusions for Resistant Organisms

• When treating organisms with MIC ≥4-8 mg/L, use extended 3-hour infusions even in renal impairment to optimize time above MIC 2
• Extended infusions maximize the percentage of time that free drug concentrations remain above the MIC, which is the critical pharmacodynamic parameter for beta-lactams 2

Pharmacokinetic Considerations

• The half-life of meropenem increases from approximately 1 hour in healthy volunteers to 3.36 hours with moderate renal impairment (CrCl 30-50 mL/min), 5.0 hours with severe impairment (CrCl <30 mL/min), and up to 13.7 hours in anuric patients 4, 3, 6
• Meropenem is predominantly excreted unchanged in the urine, making renal function the primary determinant of drug clearance 3
• A hyperbolic relationship exists between creatinine clearance and meropenem serum concentrations at the end of the dosing interval 8

Critical Pitfalls to Avoid

• Monitor for neurological toxicity in renal impairment, particularly when trough concentrations exceed 64 mg/L 2, 6
• Do not underdose in CRRT patients due to variable drug removal—when in doubt, use therapeutic drug monitoring 2
• Reassess renal function regularly (every 2-3 days in unstable patients) to adjust dosing appropriately 2
• Avoid reducing individual doses below 1 gram when treating serious infections, even in renal impairment; instead extend the dosing interval 6
• Standard dosing regimens result in insufficient meropenem exposure in a considerable fraction of critically ill patients, with target attainment of only 48.4% for MIC 2 mg/L and 20.6% for MIC 8 mg/L 8

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 × above value