What is the recommended dosing of meropenem for patients with impaired renal function?

Meropenem Dosing in Renal Impairment

For patients with impaired renal function, meropenem dosing should be adjusted based on creatinine clearance, with reduced frequency rather than reduced dose per administration to maintain efficacy while preventing toxicity.

Dosing Recommendations Based on Renal Function

Adult Patients

• Normal renal function (CrCl >50 mL/min): Standard dosing - 500 mg every 8 hours for skin/soft tissue infections or 1 gram every 8 hours for intra-abdominal infections 1
• Moderate renal impairment (CrCl 26-50 mL/min): Maintain standard dose but extend interval to every 12 hours 1
• Severe renal impairment (CrCl 10-25 mL/min): Half the recommended dose every 12 hours 1
• End-stage renal disease (CrCl <10 mL/min): Half the recommended dose every 24 hours 1

Hemodialysis Considerations

• Administer meropenem after hemodialysis sessions to avoid premature removal of the drug 1, 2
• Hemodialysis significantly shortens the elimination half-life of meropenem from approximately 7 hours to 2.9 hours 3
• Approximately 50% of meropenem is eliminated during hemodialysis 2

Pharmacokinetic Considerations

• Meropenem is predominantly excreted unchanged in the urine, making dosage adjustments essential in renal impairment 2
• The half-life of meropenem increases significantly with declining renal function:
  • Normal renal function: ~1 hour
  • Moderate impairment: ~3.4 hours
  • Severe impairment: ~5 hours
  • End-stage renal disease: up to 13.7 hours 2, 3

Special Considerations for Continuous Renal Replacement Therapy

• For patients on continuous venovenous hemofiltration (CVVHF), approximately 25-50% of meropenem is eliminated 2
• For patients on continuous venovenous hemodiafiltration (CVVHDF), approximately 13-53% of meropenem is eliminated 2
• In critically ill anuric patients receiving continuous venovenous hemofiltration, some experts recommend increasing the dose by 100% to avoid underdosing 4

Monitoring Recommendations

• For patients with fluctuating renal function, therapeutic drug monitoring may be beneficial to optimize dosing 5
• Target is to maintain drug levels above the minimum inhibitory concentration (MIC) for an adequate percentage of time 5
• Inadequate levels can lead to treatment failure and promote antimicrobial resistance 5

Clinical Pearls

• Maintain the standard dose per administration when possible, while extending the dosing interval, to take advantage of the concentration-dependent bactericidal effect 6
• When treating infections caused by Pseudomonas aeruginosa, a higher dose of 1 gram every 8 hours (adjusted according to renal function) is recommended 1
• For critically ill patients with severe infections, consider the higher end of the dosing range to ensure adequate antimicrobial coverage 5
• There is limited data for patients on peritoneal dialysis; consider consulting with a nephrologist for these patients 1

Remember that proper dosing of meropenem in renal impairment is crucial to balance efficacy against potential toxicity while preventing the development of antimicrobial resistance.