Drug Interaction Report

MONITOR: Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations of macitentan, which is primarily metabolized by the isoenzyme. In ten healthy male subjects pretreated with macitentan (30 mg initially, followed by 10 mg once daily) for 5 days, coadministration with the potent CYP450 3A4 inducer rifampin (600 mg once daily) on days 6 through 12 reduced macitentan systemic exposure (AUC) by 79% and trough plasma concentration (Cmin) by 93% compared to macitentan administered alone. There was no significant effect on the AUC of the active metabolite, which has been reported to be approximately 5-fold less potent than macitentan in vitro, but whose systemic exposure in human is 2.5-fold higher than that of macitentan.

MANAGEMENT: Caution is advised when macitentan is used with CYP450 3A4 inducers. The possibility of diminished therapeutic effects should be considered.