Drug Interactions between Plavix and selexipag

ADJUST DOSE: Coadministration with moderate inhibitors of CYP450 2C8 may increase exposure to the active metabolite of selexipag. According to the prescribing information, selexipag is hydrolyzed to its active metabolite in the liver and intestine by carboxylesterases, and the active metabolite subsequently undergoes oxidative metabolism catalyzed primarily by CYP450 2C8 and to a lesser extent by CYP450 3A4. Coadministration of selexipag with the moderate to potent CYP450 2C8 inhibitor clopidogrel, given at 300 mg loading dose or 75 mg once daily maintenance dose, had no relevant effect on exposure to selexipag but increased exposure to the active metabolite by approximately 2.2- and 2.7-fold following the loading and maintenance doses, respectively.

MANAGEMENT: The dosing frequency of selexipag should be reduced to once daily when coadministered with a moderate CYP450 2C8 inhibitor. Patients should be monitored for potentially increased side effects such as diarrhea, nausea, vomiting, flushing, anemia, and decreased appetite. If selexipag is not tolerated at a given dosage, some authorities recommend that symptomatic treatment and/or a reduction to the next lower dose be considered. The selexipag dosing frequency should return to twice daily after the moderate CYP450 2C8 inhibitor is withdrawn from therapy.