Dose Adjustment Required for Primaxin in Severe Renal Impairment
Yes, you can continue imipenem-cilastatin (Primaxin) in this patient with a creatinine clearance of approximately 28 mL/min, but a significant dose reduction is mandatory to prevent drug accumulation and reduce seizure risk. 1
Recommended Dosing for CrCl 28 mL/min
Based on the FDA-approved prescribing information, for a patient with creatinine clearance of 28 mL/min (which falls in the "less than 30 to greater than or equal to 15 mL/min" category): 1
For infections due to susceptible organisms:
- 200 mg every 6 hours (if previously on 500 mg every 6 hours regimen) 1
- OR 500 mg every 12 hours (if previously on 1000 mg every 8 hours regimen) 1
For infections due to organisms with intermediate susceptibility:
- 500 mg every 12 hours 1
Critical Safety Considerations
Seizure Risk
- Patients with creatinine clearance less than 30 mL/min have an increased risk of seizures with imipenem-cilastatin 1
- This risk is particularly elevated in patients with background CNS disease 1
- Careful neurological monitoring is essential during therapy 1
Pharmacokinetic Rationale
The dose reduction is necessary because: 2, 3
- Imipenem half-life increases from 52 minutes in normal renal function to 173-220 minutes in severe renal failure 2, 4
- Cilastatin half-life increases dramatically from 54 minutes to 798-1,020 minutes (13-17 hours) in end-stage renal disease 2, 3
- Cilastatin undergoes an 87% reduction in nonrenal clearance with renal disease, leading to significant accumulation 3
- While imipenem has alternative metabolic pathways, cilastatin relies heavily on renal elimination 4, 5
Infusion Guidelines
- Doses ≤500 mg: infuse over 20-30 minutes 1
- Doses >500 mg: infuse over 40-60 minutes 1
- If nausea develops during infusion, slow the infusion rate 1
Monitoring Requirements
- Monitor for CNS adverse effects including seizures, particularly given the increased risk in this renal function range 1
- Observe for signs of drug accumulation (confusion, myoclonus, tremor) 2
- Consider therapeutic drug monitoring if available, though not routinely required 6
Contraindications
Do not use imipenem-cilastatin if: 1
- Creatinine clearance is <15 mL/min unless hemodialysis will be instituted within 48 hours 1
- The patient is undergoing peritoneal dialysis (inadequate data) 1
Common Pitfall to Avoid
The most critical error is continuing standard dosing without adjustment. 1 Research demonstrates that twice-daily dosing of 500/500 mg in severe renal failure (CrCl ~10 mL/min) maintains therapeutic levels while preventing excessive accumulation, but your patient with CrCl 28 mL/min requires the specific dosing outlined above based on their renal function category and infection severity. 6