Drug Interaction Report

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.

ADJUST DOSING INTERVAL: Consumption of food has led to a 27% decrease in the bioavailability of orally administered tacrolimus.

MANAGEMENT: Tacrolimus should be administered at least one hour before or two hours after meals.

GENERALLY AVOID: Grapefruit juice has been reported to increase tacrolimus trough concentrations. Data are limited, but inhibition of the CYP450 enzyme system appears to be involved.

MANAGEMENT: The clinician may want to recommend that the patient avoid ingesting large amounts of grapefruit juice while taking tacrolimus.