Drug Interaction Report

Coadministration with inhibitors of CYP450 3A4 may increase the plasma concentrations of mirabegron, which has been shown in vitro to be a substrate of the isoenzyme. However, in vivo results indicate that CYP450 3A4 may play a limited role in the overall elimination. In a study consisting of 23 healthy male and female subjects, mirabegron peak plasma concentration (Cmax) increased by 45% and systemic exposure (AUC) increased by 80% when a single 100 mg dose of mirabegron was administered following multiple dosing of ketoconazole 400 mg daily for 9 days. No dosage adjustment is recommended when mirabegron is administered in combination with ketoconazole and probably other CYP450 3A4 inhibitors.

Food reduces the oral absorption and bioavailability of mirabegron. According to the product labeling, administration of a 50 mg tablet with a high-fat meal decreased mirabegron peak plasma concentration (Cmax) and systemic exposure (AUC) by 45% and 17%, respectively, whereas administration with a low-fat meal decreased mirabegron Cmax and AUC by 75% and 51%, respectively. In phase 3 clinical studies demonstrating both safety and efficacy, mirabegron was administered without regards to food content and intake. Therefore, mirabegron can be taken with or without food at the recommended dosage.