Drug Interaction Report

MONITOR: Coadministration with potent P-glycoprotein inhibitors may theoretically increase the plasma concentrations of ticagrelor, which is a substrate of the efflux transporter. However, the interaction has not been studied.

MANAGEMENT: Until more data are available, caution is recommended if ticagrelor must be used with potent P-glycoprotein inhibitors. It may be advisable to monitor pharmacologic response to ticagrelor more closely following the addition and withdrawal of these agents. Discontinuation of the concomitant medication may be required if an interaction is suspected.

GENERALLY AVOID: In a small, randomized, crossover study, the administration of quinidine with grapefruit juice (compared to water) to healthy volunteers significantly prolonged the time to reach peak plasma quinidine concentrations and decreased the plasma concentrations of its major metabolite, 3-hydroxyquinidine. These changes were associated pharmacodynamically with both a delay and a reduction in the maximal effect on QTc interval. The proposed mechanism is delay of gastric emptying as well as inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruits.

MANAGEMENT: Given the drug's narrow therapeutic index, patients receiving quinidine therapy should avoid the consumption of grapefruits and grapefruit juice to prevent any undue fluctuations in plasma drug levels.