What is the recommended dosage adjustment for ertapenem (a carbapenem antibiotic) in patients with impaired renal function?

Ertapenem Dosage Adjustment in Renal Impairment

For patients with creatinine clearance ≤30 mL/min/1.73 m², reduce ertapenem to 500 mg once daily; if hemodialysis occurs within 6 hours of dosing, give a supplementary 150 mg dose post-dialysis. 1

Standard Dosing by Renal Function

Normal to Moderate Renal Impairment (CrCl >30 mL/min/1.73 m²)

• No dose adjustment required - continue standard 1 gram once daily dosing 1
• This applies to patients with mild renal insufficiency (CrCl >90 mL/min) and moderate renal insufficiency (CrCl 31-90 mL/min) 2

Advanced Renal Impairment (CrCl ≤30 mL/min/1.73 m²)

• Reduce dose to 500 mg once daily for both advanced renal insufficiency and end-stage renal disease 1
• This recommendation is based on pharmacokinetic data showing 158% increase in drug exposure in advanced renal insufficiency and 192% increase in ESRD 2

Hemodialysis Patients

• Maintain 500 mg daily dosing 1
• Critical timing consideration: If ertapenem is administered within 6 hours prior to hemodialysis, give a supplementary 150 mg dose after the dialysis session 1
• If administered ≥6 hours before hemodialysis, no supplementary dose is needed 1
• Hemodialysis removes approximately 30% of the ertapenem dose, justifying the supplementary dosing 2

Important Safety Considerations and Pitfalls

Neurotoxicity Risk in Advanced CKD

The recommended 500 mg daily dose may still be excessive for some patients with Stage 5 CKD, particularly those not yet on dialysis. 3, 4

• Neurotoxic manifestations include confusional states, hallucinations, asterixis, myoclonic jerks, cognitive impairment, and peripheral neuropathy 3, 4, 5
• Symptoms can develop within 4-7 days of treatment even with dose-adjusted regimens 3, 5
• Neurotoxicity can be insidious and prolonged - symptoms may persist for 2 weeks despite drug cessation and high-flux hemodialysis 3
• Plasma levels can remain markedly elevated (53.7 mg/L vs therapeutic MIC90 of 2 mg/L) 24 hours after the last dose in advanced CKD 3

High-Risk Patient Characteristics

Monitor closely in patients with: 4

• CrCl <50 mL/min/1.73 m² (90% of neurotoxicity cases)
• Hypoalbuminemia (present in all reported neurotoxicity cases)
• Dynamic changes in renal function during treatment

Monitoring Strategy

• Re-evaluate creatinine clearance during treatment, especially if behavioral changes occur 4
• If CrCl drops to ≤30 mL/min/1.73 m² during therapy, immediately reduce to 500 mg daily 4
• Consider dose reduction or alternative therapy if unexplained neurologic symptoms develop 4
• Confirm neurotoxicity with EEG/EMG if peripheral neuropathy suspected 5

Pharmacokinetic Rationale

The dose adjustments are based on progressive increases in drug exposure: 2

• Half-life prolongation: 4.5 hours (normal) → 6.1 hours (moderate RI) → 10.6 hours (advanced RI) → 14.1 hours (ESRD)
• AUC increases: 7% (mild RI) → 53% (moderate RI) → 158% (advanced RI) → 192% (ESRD)
• Ertapenem's high lipophilicity and CNS penetration contribute to sustained neurotoxicity even after drug cessation 3

Special Populations

Pediatric Patients

• No data available for dose adjustment in pediatric patients with renal impairment 1
• Standard pediatric dosing (15 mg/kg twice daily, max 1 g/day) applies only to those with normal renal function 1

Peritoneal Dialysis and Hemofiltration

• No data available for dosing recommendations in these modalities 1

Hepatic Impairment

• No dose adjustment recommendations can be made due to insufficient data 1