Drug Interaction Report

MONITOR: Coadministration with isavuconazonium sulfate (prodrug of isavuconazole) may increase the plasma concentrations of drugs that are substrates of CYP450 3A4 and/or P-glycoprotein (P-gp). The mechanism is decreased clearance due to inhibition of CYP450 3A4 activity and/or 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.

MANAGEMENT: Caution is advised when isavuconazonium sulfate is used concomitantly with drugs that are substrates of the CYP450 3A4 isoenzyme or the P-gp transport protein, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever isavuconazonium sulfate is added to or withdrawn from therapy.