Drug Interaction Report

CONTRAINDICATED: Coadministration with potent inducers of CYP450 3A4 may significantly decrease the plasma concentrations of isavuconazole, which is primarily metabolized by CYP450 3A4 and 3A5 and subsequently by uridine diphosphate glucuronosyltransferases (UGT). When multiple doses of isavuconazonium sulfate (prodrug of isavuconazole) were administered to healthy volunteers with multiple doses of the potent CYP450 3A4 inducer rifampin (600 mg), mean isavuconazole peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 75% and 97%, respectively.

MANAGEMENT: Concomitant use of isavuconazonium sulfate with potent CYP450 3A4 inducers is considered contraindicated.

GENERALLY AVOID: Concurrent use of rifampin in patients who ingest alcohol daily may result in an increased incidence of hepatotoxicity. The increase in hepatotoxicity may be due to an additive risk as both alcohol and rifampin are individually associated with this adverse reaction. However, the exact mechanism has not been established.

ADJUST DOSING INTERVAL: Administration with food may reduce oral rifampin absorption, increasing the risk of therapeutic failure or resistance. In a randomized, four-period crossover phase I study of 14 healthy male and female volunteers, the pharmacokinetics of single dose rifampin 600 mg were evaluated under fasting conditions and with a high-fat meal. Researchers observed that administration of rifampin with a high-fat meal reduced rifampin peak plasma concentration (Cmax) by 36%, nearly doubled the time to reach peak plasma concentration (Tmax) but reduced overall exposure (AUC) by only 6%.

MANAGEMENT: The manufacturer of oral forms of rifampin recommends administration on an empty stomach, 30 minutes before or 2 hours after meals. Patients should be encouraged to avoid alcohol or strictly limit their intake. Patients who use alcohol and rifampin concurrently or have a history of alcohol use disorder may require additional monitoring of their liver function during treatment with rifampin.