Drug Interactions between istradefylline and vibegron

Coadministration with moderate or potent inhibitors of CYP450 3A4 and/or P-glycoprotein (P-gp) may increase the plasma concentrations (AUC) of vibegron, which has been shown in vitro to be a substrate of the isoenzyme and transporter. Although CYP450 3A4 is the predominant enzyme in vibegron metabolism, metabolic pathways have only a minor role in the elimination of vibegron. In a phase 3 Japanese study, coadministration of vibegron (100 mg) with moderate (diltiazem) and potent (ketoconazole) inhibitors of CYP450 3A4, resulted in a 1.6- and 2.1-fold increase in vibegron AUC, respectively, which was not considered clinically significant. No dosage adjustment is recommended when vibegron is administered in combination with moderate or potent CYP450 3A4 and/or P-gp inhibitors.