Meropenem Administration in Renal Impairment
Dose Adjustment Based on Creatinine Clearance
In patients with impaired renal function, meropenem dosing must be reduced according to creatinine clearance, with the specific dose and interval determined by both the severity of renal impairment and the type of infection being treated. 1
Standard Dosing Algorithm for Adults
The FDA-approved dosing schedule for adults with renal impairment follows this protocol 1:
- CrCl >50 mL/min: Full recommended dose (500 mg for cSSSI, 1 gram for intra-abdominal infections) every 8 hours 1
- CrCl 26-50 mL/min: Full recommended dose every 12 hours 1
- CrCl 10-25 mL/min: Half the recommended dose every 12 hours 1
- CrCl <10 mL/min: Half the recommended dose every 24 hours 1
Route and Infusion Time
Meropenem can be administered via two methods 1:
- Intravenous infusion: 15-30 minutes for standard dosing 1
- Intravenous bolus injection: 3-5 minutes (5-20 mL volume) 1
Special Considerations for Pseudomonas aeruginosa
When treating infections caused by P. aeruginosa, use 1 gram every 8 hours in adults with normal renal function, with proportional adjustments for renal impairment. 1 This higher dose is critical because P. aeruginosa requires higher drug concentrations for adequate bacterial killing 1.
Pharmacokinetic Rationale
The necessity for dose adjustment stems from meropenem's renal elimination profile 2, 3:
- Approximately 70% of meropenem is excreted unchanged in urine 4
- Half-life increases from ~1 hour in healthy volunteers to 10-13.7 hours in anuric patients with end-stage renal disease 2, 3
- Total body clearance and renal clearance are linearly related to creatinine clearance 3, 5
Patients on Renal Replacement Therapy
Hemodialysis
Meropenem is significantly removed by hemodialysis (approximately 50% eliminated per session), requiring supplemental dosing after dialysis. 2, 3
- Dialysis clearance averages 81 ± 22 mL/min 3
- Half-life shortens from ~9.7 hours pre-dialysis to 1.4 hours during dialysis 5
- Administer the scheduled dose after completing the dialysis session to prevent premature drug removal 3, 5
Continuous Renal Replacement Therapy (CRRT)
For patients on CVVHDF, initiate meropenem 1 gram IV every 12 hours, as this maintains trough levels above MIC90 for most pathogens. 6
- CVVHF removes 25-50% of meropenem 2
- CVVHDF removes 13-53% of meropenem 2
- Meropenem clearance during CVVHDF is approximately 129-141 mL/min 6
Critical Pitfalls to Avoid
The most common error is underdosing due to conflicting recommendations in the literature regarding renal replacement therapy. 2 Given meropenem's excellent tolerability profile, err on the side of adequate dosing rather than underdosing, particularly in critically ill patients 2.
Metabolite Accumulation
The open-ring metabolite (ICI 213,689) accumulates significantly in renal impairment, with half-life increasing to ~35 hours in severe renal insufficiency 3. While this metabolite has minimal antibacterial activity, its accumulation is not associated with toxicity 3.
Pediatric Dosing in Renal Impairment
There is no established experience or dosing guidance for pediatric patients with renal impairment. 1 Consultation with pediatric infectious disease and nephrology specialists is essential when treating children with compromised renal function requiring meropenem 1.