What is the recommended dose of Invanz (Ertapenem) for a patient with impaired renal function, specifically a creatinine clearance of 19 mL/min?

Ertapenem Dosing for Creatinine Clearance 19 mL/min

For a patient with CrCl 19 mL/min, reduce Invanz (ertapenem) to 500 mg once daily, as this falls below the 30 mL/min threshold requiring dose adjustment. 1

Dosing Recommendations Based on Renal Function

Standard Dose Adjustment

• Patients with CrCl ≤30 mL/min/1.73 m² require a reduced dose of 500 mg daily (compared to the standard 1 gram daily dose for normal renal function) 1
• No dosage adjustment is necessary when CrCl is >30 mL/min/1.73 m² 1

Hemodialysis Considerations

• If the patient is on hemodialysis and receives the 500 mg dose within 6 hours prior to dialysis, give a supplementary dose of 150 mg after the hemodialysis session 1
• If ertapenem is administered at least 6 hours before hemodialysis, no supplementary dose is needed 1
• Approximately 30% of ertapenem is cleared by a hemodialysis session 2

Critical Safety Concerns

Risk of CNS Toxicity

Even the recommended 500 mg daily dose may be excessive in patients with severe renal impairment, particularly those with CrCl <30 mL/min. Multiple case reports document serious neurotoxicity:

• CNS toxicity manifestations include: seizures, hallucinations, confusional states, cognitive dysfunction, asterixis, and myoclonic jerks 2, 3, 4
• Symptoms can develop after just 3-7 consecutive doses of the "recommended" 500 mg daily regimen 2
• Neurotoxicity can be prolonged, lasting up to 2 weeks even after drug discontinuation and initiation of hemodialysis 4
• Plasma ertapenem levels can accumulate to 53.7 mg/L (far exceeding the therapeutic MIC90 of 2 mg/L) even with dose reduction 4

Monitoring Requirements

• Monitor closely for early signs of neurotoxicity, as onset can be insidious and easily missed 3
• Consider checking plasma ertapenem levels if available, especially if unexplained behavioral changes occur 3, 4
• Re-evaluate renal function during treatment, as further deterioration may necessitate additional dose reduction or drug discontinuation 3
• Patients with hypoalbuminemia are at particularly high risk for neurotoxicity 3

Clinical Pitfalls to Avoid

• Do not assume 500 mg daily is always safe in severe renal impairment—this dose may still be too high for some patients, especially those not yet on dialysis 4
• The high lipophilicity and CNS penetration of ertapenem contribute to sustained neurotoxicity that persists even when plasma levels decline 4
• Consider alternative antibiotics if the patient has CrCl <30 mL/min and is not on dialysis, or if any signs of CNS toxicity emerge 3, 4
• Never mix or co-infuse ertapenem with other medications, and do not use diluents containing dextrose 1