Drug Interactions between elagolix and mefloquine

MONITOR: Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations of mefloquine, which is primarily metabolized by the isoenzyme. In seven healthy, nonsmoking male volunteers, administration of a single 500 mg oral dose of mefloquine on day 7 of treatment with the potent CYP450 3A4 inducer rifampin (600 mg orally once daily on days 1 through 7, followed by 600 mg twice weekly on days 8 through 56) decreased mean mefloquine peak plasma concentration (Cmax) and systemic exposure (AUC) by 19% and 68%, respectively, compared to mefloquine administered alone. The mean elimination half-life of mefloquine was also decreased by 63% (from 305 to 113 hours) in the presence of rifampin, while mean apparent oral clearance increased by 281%. The interaction has not been studied with other, less potent CYP450 3A4 inducers.

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