Drug Interactions between belzutifan and ivacaftor / lumacaftor

MONITOR: Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations of ivacaftor, which is primarily metabolized by the isoenzyme. In study subjects, administration of a single 150 mg dose of ivacaftor with the potent CYP450 3A4 inducer rifampin (600 mg once daily) decreased ivacaftor peak plasma concentration (Cmax) and systemic exposure (AUC) by 80% and 89%, respectively, compared to administration of ivacaftor alone. When lumacaftor/ivacaftor was coadministered with rifampin, lumacaftor pharmacokinetics were minimally affected, but ivacaftor Cmax and AUC decreased by an average of 50% and 57%, respectively. No pharmacokinetic data are available for elexacaftor or tezacaftor, but decreased exposures are expected according to prescribing information.

MANAGEMENT: The potential for diminished pharmacologic effects of ivacaftor-containing medications should be considered during coadministration with CYP450 3A4 inducers. Alternative treatments may be required if an interaction is suspected.

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 Pharmacologic response to belzutifan should be monitored more closely whenever a CYP450 2C19 inducer is added to or withdrawn from therapy.