What is the dosage adjustment for meropenem in patients with impaired renal function (Renal Impairment)?

Meropenem Dosage Adjustment in Renal Impairment

For patients with renal impairment, meropenem dosage should be adjusted based on creatinine clearance, with specific dose reductions and extended dosing intervals as creatinine clearance decreases. 1

Standard Dosing in Normal Renal Function

• Standard adult dosing for meropenem in patients with normal renal function (CrCl >50 mL/min):
  • Complicated skin and skin structure infections: 500 mg every 8 hours 1
  • Intra-abdominal infections: 1 gram every 8 hours 1
  • Infections caused by Pseudomonas aeruginosa: 1 gram every 8 hours 1

Dosage Adjustment for Renal Impairment

The FDA-approved dosing schedule for adult patients with renal impairment is as follows:

Creatinine Clearance (mL/min)	Dose	Dosing Interval
>50	Recommended dose (500 mg for cSSSI and 1 gram for intra-abdominal)	Every 8 hours
26-50	Recommended dose	Every 12 hours
10-25	One-half recommended dose	Every 12 hours
<10	One-half recommended dose	Every 24 hours
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Pharmacokinetic Considerations

• Meropenem is predominantly excreted unchanged in the urine, making dosage adjustments necessary in patients with renal insufficiency 2
• The half-life of meropenem increases from approximately 1 hour in healthy volunteers to up to 13.7 hours in anuric patients with end-stage renal disease 2
• Total body clearance and renal clearance of meropenem are linearly related to creatinine clearance 3

Renal Replacement Therapy Considerations

• Approximately 50% of meropenem is eliminated by intermittent hemodialysis 2
• For patients on continuous renal replacement therapy:
  • 25-50% is eliminated by continuous venovenous hemofiltration (CVVHF) 2
  • 13-53% is eliminated by continuous venovenous hemodiafiltration (CVVHDF) 2
• Meropenem should be administered after dialysis to avoid premature removal of the drug 2

Monitoring Recommendations

• Therapeutic drug monitoring may be beneficial in patients with renal impairment to ensure adequate drug levels while avoiding toxicity 4
• Monitor for potential neurological adverse effects (seizures) with excessive plasma concentrations, particularly in patients with severe renal impairment 4

Clinical Considerations

• Because meropenem is excreted primarily by the kidneys, underdosing should be avoided to ensure adequate antimicrobial coverage 2
• The open-ring metabolite of meropenem (ICI 213,689) can accumulate in patients with renal impairment, with an apparent half-life of approximately 35 hours in patients with severe renal insufficiency 3
• Unlike imipenem, meropenem does not require co-administration with cilastatin (a dehydropeptidase inhibitor) as it is relatively stable to hydrolysis by the enzyme dehydropeptidase I 5, 6

Common Pitfalls and Caveats

• Underdosing is a common pitfall in patients with renal impairment, which may lead to treatment failure 2
• Excessive dosing in patients with severe renal impairment may lead to neurological toxicity 4
• Meropenem and its metabolite are effectively removed by hemodialysis, with a dialysis clearance of approximately 81 ± 22 mL/min for the unchanged drug 3