Drug Interaction Report

MONITOR: Coadministration of belzutifan with inducers of CYP450 2C19 may decrease the plasma concentrations and pharmacologic effects of belzutifan. The proposed mechanism is induction of CYP450 2C19, one of the primary pathways for the metabolic clearance of belzutifan. Clinical data are not available.

MANAGEMENT: Caution and clinical monitoring are recommended whenever belzutifan is prescribed in combination with a CYP450 2C19 inducer. Pharmacologic response to belzutifan should be monitored more closely whenever a CYP450 2C19 inducer is added to or withdrawn from therapy.

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.