Drug Interaction Report

GENERALLY AVOID: Coadministration with potent inducers of CYP450 3A4 may significantly decrease the plasma concentrations of ticagrelor, which is primarily metabolized by the isoenzyme. In 14 healthy volunteers, administration of a single 180 mg oral dose of ticagrelor on day 12 of treatment with the potent CYP450 3A4 inducer rifampin (600 mg once daily for 14 days) decreased mean ticagrelor peak plasma concentration (Cmax), systemic exposure (AUC) and plasma half-life by 73%, 86% and 67%, respectively, compared to administration of ticagrelor alone. Mean Cmax of the major active metabolite was unchanged in the presence of rifampin, but mean AUC decreased by 46% and plasma half-life by 50%. Inhibition of platelet aggregation (IPA) was also assessed in the study. Mean IPA at 12 hours was 87% with ticagrelor alone versus 63% in combination with rifampin; corresponding values at 24 hours were 70% and 15%, respectively.

MANAGEMENT: Concomitant use of ticagrelor with potent CYP450 3A4 inducers should generally be avoided.