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).

ADJUST DOSING INTERVAL: Food reduces the oral absorption and bioavailability of voriconazole. According to the product labeling, administration of multiple doses of voriconazole with high-fat meals decreased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) by 34% and 24%, respectively, when the drug is administered as a tablet, and by 58% and 37%, respectively, when administered as the oral suspension.

MANAGEMENT: To ensure maximal oral absorption, voriconazole tablets and oral suspension should be taken at least one hour before or after a meal.

The recommended maximum number of medicines in the 'antifungal agents' category to be taken concurrently is usually one. Your list includes two medicines belonging to the 'antifungal agents' category:

• isavuconazonium
• voriconazole

Note: In certain circumstances, the benefits of taking this combination of drugs may outweigh any risks. Always consult your healthcare provider before making changes to your medications or dosage.