Does Invanz (ertapenem) require renal dosing adjustments in patients with impaired renal function?

Does Invanz Require Renal Dosing?

Yes, Invanz (ertapenem) requires dose reduction in patients with severe renal impairment (creatinine clearance ≤30 mL/min/1.73 m²) and end-stage renal disease, but no adjustment is needed for mild to moderate renal dysfunction.

Specific Dosing Recommendations by Renal Function

Normal to Moderate Renal Impairment

• No dose adjustment is necessary when creatinine clearance is >30 mL/min/1.73 m² 1
• The standard dose of 1 gram daily remains appropriate for patients with mild to moderate renal insufficiency 2

Severe Renal Impairment and ESRD

• Reduce dose to 500 mg daily in patients with creatinine clearance ≤30 mL/min/1.73 m² 1
• The same 500 mg daily dose applies to end-stage renal disease patients (creatinine clearance ≤10 mL/min/1.73 m²) 1

Hemodialysis Considerations

Supplemental Dosing Protocol

• Administer a 150 mg supplementary dose if ertapenem is given within 6 hours prior to hemodialysis 1
• No supplementary dose is needed if ertapenem is administered at least 6 hours before hemodialysis 1
• Hemodialysis removes approximately 30% of the ertapenem dose 2

Timing Rationale

• The supplementary dose compensates for drug removal during dialysis, as hemodialysis clears a significant portion of the medication 2

Pharmacokinetic Basis for Dose Adjustment

Drug Accumulation in Renal Failure

• Area under the curve (AUC) increases by 158% in advanced renal insufficiency and 192% in ESRD compared to normal renal function 2
• Half-life extends from 4.5 hours in normal function to 10.6 hours in advanced renal insufficiency and 14.1 hours in ESRD 2

Clinical Implications

• The substantial increase in drug exposure necessitates dose reduction to prevent toxicity 2

Critical Safety Concerns

Neurotoxicity Risk in Advanced CKD

• Even the recommended 500 mg daily dose may be excessive for patients with Stage 5 CKD not yet on dialysis 3, 4
• Neurotoxicity can manifest as hallucinations, asterixis, myoclonic jerks, cognitive impairment, and peripheral neuropathy within 4-7 days of treatment 3, 4
• Plasma levels can reach 53.7 mg/L (far exceeding therapeutic MIC90 of 2 mg/L) even with dose-adjusted regimens in severe renal failure 3

Prolonged Toxicity Duration

• Neurologic manifestations may persist for 2 weeks despite drug cessation and high-flux hemodialysis, due to ertapenem's high lipophilicity and CNS penetration 3
• Complete clinical recovery typically occurs within 2 weeks of stopping ertapenem 4

Practical Clinical Algorithm

Step 1: Calculate Creatinine Clearance

• Use the Cockcroft-Gault equation if only serum creatinine is available 1

Step 2: Determine Dose Based on Renal Function

• CrCl >30 mL/min/1.73 m²: Standard 1 gram daily 1
• CrCl ≤30 mL/min/1.73 m²: Reduced to 500 mg daily 1

Step 3: Adjust for Hemodialysis

• If dialysis occurs within 6 hours of dosing: Add 150 mg post-dialysis 1
• If dialysis occurs ≥6 hours after dosing: No supplementation needed 1

Step 4: Monitor for Neurotoxicity

• Exercise heightened caution in Stage 5 CKD patients, particularly those not yet on dialysis 3, 4
• Consider alternative antibiotics or further dose reduction if neurologic symptoms develop 4

Important Caveats

Pediatric Patients

• No data exist for dose adjustments in pediatric patients with renal impairment 1

Peritoneal Dialysis and Hemofiltration

• No dosing data are available for these modalities 1

Hepatic Impairment

• No dose adjustment recommendations can be made for hepatic impairment 1