What is the recommended dose, frequency, and length of treatment of ertapenem (Invanz) for patients with Impaired renal function undergoing Hemodialysis (HD)?

Ertapenem Dosing for Hemodialysis Patients

For patients on hemodialysis, administer ertapenem 500 mg once daily, with a supplementary 150 mg dose given after hemodialysis if the daily dose was administered within 6 hours prior to the dialysis session. 1

Standard Dosing Regimen

• Daily dose: 500 mg once daily for adult hemodialysis patients with end-stage renal disease (creatinine clearance ≤10 mL/min/1.73 m²) 1
• Supplementary dose: 150 mg post-dialysis is required only when ertapenem is given within 6 hours before hemodialysis, as approximately 30% of the drug is cleared during a dialysis session 1, 2
• No supplementary dose needed if ertapenem is administered at least 6 hours prior to hemodialysis 1

Route and Administration

• Intravenous infusion over 30 minutes is the standard route for hemodialysis patients 1
• Intramuscular administration is not recommended for this population given the need for precise dosing adjustments 1

Treatment Duration

Treatment duration depends on the specific infection being treated 1:

• Complicated intra-abdominal infections: 5-14 days 1
• Complicated skin/skin structure infections (including diabetic foot): 7-14 days 1
• Community-acquired pneumonia: 10-14 days (may switch to oral after ≥3 days parenteral if clinically improved) 1
• Complicated UTI/pyelonephritis: 10-14 days (may switch to oral after ≥3 days parenteral if clinically improved) 1
• Acute pelvic infections: 3-10 days 1

Critical Safety Considerations

The FDA-recommended 500 mg daily dose may still pose significant neurotoxicity risk in hemodialysis patients, particularly those with smaller body size. 3, 4

Neurotoxicity Warning

• Multiple case reports document severe CNS toxicity (hallucinations, seizures, myoclonic jerks, cognitive impairment) occurring with the recommended 500 mg daily dose in hemodialysis patients after only 3-7 consecutive doses 3, 4
• Plasma ertapenem levels can reach 53.7 mg/L (far exceeding therapeutic MIC90 of 2 mg/L) even with dose reduction, due to ertapenem's high lipophilicity and CNS penetration 3
• Neurotoxic symptoms may persist for 2 weeks after discontinuation, even with high-flux hemodialysis, due to the drug's large volume of distribution 3
• Asian patients and those with smaller body size appear at particularly high risk 4

Alternative Dosing Strategy

• Thrice-weekly dosing (500 mg after each hemodialysis session) has been proposed as a safer alternative that maintains plasma concentrations above 2 mg/L while reducing accumulation risk 5
• This approach may be more practical and safer than daily dosing, though it is not yet FDA-approved 5

Monitoring Recommendations

• Monitor closely for CNS symptoms including confusion, hallucinations, tremors, or seizures, especially in patients with smaller body size or those not yet established on regular dialysis 3, 4
• Consider measuring plasma ertapenem levels if neurotoxicity is suspected, though this is not routinely available 3, 4
• If CNS toxicity develops, discontinue ertapenem immediately and initiate high-flux hemodialysis; symptoms may take up to 2 weeks to resolve 3, 4

Key Pharmacokinetic Data

• Half-life increases from 4.5 hours in normal renal function to 14.1 hours in ESRD 2
• Area under the curve increases by 192% in ESRD compared to patients with normal renal function 2
• Hemodialysis removes approximately 30% of the administered dose 1, 2