Drug Interactions between isavuconazonium and Oncovin

GENERALLY AVOID: Coadministration with isavuconazonium sulfate (prodrug of isavuconazole) may increase the plasma concentrations of vinca alkaloids, which are substrates of the CYP450 3A4 isoenzyme and the P-glycoprotein (P-gp) transporter. The mechanism is decreased clearance due to inhibition of CYP450 3A4 activity and P-gp-mediated efflux of these drugs by isavuconazole. In pharmacokinetic studies, isavuconazole increased the systemic exposure (AUC) of sensitive CYP450 3A4 substrates midazolam, sirolimus, and tacrolimus by approximately 2-fold, thus it can be considered a moderate inhibitor of the isoenzyme. Vincristine exposure is predicted to increase by less than 2-fold following concomitant administration with isavuconazonium.

MANAGEMENT: Concomitant use of vinca alkaloids with isavuconazonium should generally be avoided. However, some authorities recommend close monitoring for toxicity and dose reduction of the antineoplastic if required. Based on the known half-life of vinca alkaloids (24 to 48 hours), the time course of interaction is expected to be approximately 5 to 7 days. Patients should be advised to seek medical attention if they experience symptoms that could indicate neuro- or myelotoxicity, including constipation, abdominal pain or bloating, urinary retention, paraesthesia, paralysis, muscle weakness, hearing loss, seizures, erratic blood pressure changes, unusual or excessive bleeding, easy bruising, pallor, fatigue, dizziness, lightheadedness, fever, chills, and sore throat.