Drug Interaction Report

CONTRAINDICATED: Coadministration with potent inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of isavuconazole, which is primarily metabolized by CYP450 3A4 and 3A5 and subsequently by uridine diphosphate glucuronosyltransferases (UGT). When a single dose of isavuconazonium sulfate (equivalent to 200 mg of isavuconazole) was administered to healthy volunteers following multiple dosing of the potent CYP450 3A4 inhibitor ketoconazole (200 mg twice daily for 24 days), isavuconazole peak plasma concentration (Cmax) increased by 9% and systemic exposure (AUC) increased by 422%.

MANAGEMENT: Concomitant use of isavuconazonium sulfate with potent CYP450 3A4 inhibitors is considered contraindicated. Ritonavir given at low dosages as a pharmacokinetic booster may be used with caution, but is contraindicated at high dosages (e.g., 400 mg every 12 hours).