Renal Dosing for Ertapenem
For patients with renal impairment, ertapenem requires specific dose adjustments based on creatinine clearance, with a recommended dose of 500 mg daily for patients with severe renal impairment (CrCl ≤30 mL/min/1.73 m²) and end-stage renal disease, plus a supplementary dose of 150 mg following hemodialysis if administered within 6 hours prior to the session. 1
Dosing Algorithm Based on Renal Function
| Renal Function | Creatinine Clearance | Recommended Dose |
|---|---|---|
| Normal to moderate impairment | >30 mL/min/1.73 m² | 1 g once daily |
| Severe impairment | ≤30 mL/min/1.73 m² | 500 mg once daily |
| End-stage renal disease | ≤10 mL/min/1.73 m² | 500 mg once daily |
| Hemodialysis | - | 500 mg once daily + 150 mg supplementary dose after hemodialysis if administered within 6 hours prior |
Pharmacokinetic Considerations
The FDA-approved labeling for ertapenem clearly outlines the need for dose adjustment in renal impairment based on pharmacokinetic data 1. This is supported by research showing that the area under the concentration-time curve (AUC) increases significantly with declining renal function:
- 7% increase in mild renal impairment
- 53% increase in moderate renal impairment
- 158% increase in advanced renal impairment
- 192% increase in end-stage renal disease 2
The elimination half-life of ertapenem is also prolonged with worsening renal function:
- 4.5 hours in patients with normal renal function
- 14.1 hours in patients with end-stage renal disease 2
Hemodialysis Considerations
Hemodialysis removes approximately 30% of the ertapenem dose 1, 2. Therefore:
- If ertapenem is administered at least 6 hours before hemodialysis, no supplementary dose is needed
- If administered within 6 hours prior to hemodialysis, a supplementary dose of 150 mg should be given after the hemodialysis session 1
Important Safety Considerations
Several case reports have documented neurotoxicity in patients with advanced renal failure receiving the recommended adjusted dose of 500 mg daily:
- Patients with Stage 5 CKD have developed hallucinations, asterixis, myoclonic jerks, and cognitive impairment after receiving the recommended dose for 4-5 days 3
- Plasma levels in these patients were significantly higher than the therapeutic minimum inhibitory concentration 3
- Symptoms of neurotoxicity may persist for up to 2 weeks despite drug discontinuation and initiation of hemodialysis 3, 4
Special Populations
Pediatric Patients
- No data are available for pediatric patients with renal impairment 1
Peritoneal Dialysis
- No data are available for patients undergoing peritoneal dialysis or hemofiltration 1
Monitoring Recommendations
Given the risk of neurotoxicity in patients with severe renal impairment, close monitoring for:
- Neurological symptoms (seizures, hallucinations, cognitive dysfunction)
- Signs of drug accumulation
- Changes in renal function during therapy
Calculation of Creatinine Clearance
When only serum creatinine is available, the Cockcroft-Gault equation can be used to estimate creatinine clearance 1:
- Males: (weight in kg) × (140-age in years) ÷ [(72) × serum creatinine (mg/100 mL)]
- Females: 0.85 × (value calculated for males)
The serum creatinine should represent a steady state of renal function.