Drug Interactions between fesoterodine and mirabegron

MONITOR: Coadministration with moderate inhibitors of CYP450 3A4 such as grapefruit juice may increase the plasma concentrations of fesoterodine's active metabolite, 5-hydroxymethyl tolterodine, which is partially metabolized by the isoenzyme. The possibility of prolonged and/or increased pharmacologic effects of fesoterodine should be considered. Because 5-hydroxymethyl tolterodine is also metabolized by CYP450 2D6, the clinical significance of the interaction may be greater in patients who are CYP450 2D6-deficient, or so-called poor metabolizers of CYP450 2D6 (approximately 7% of Caucasians and less than 2% of Asians and individuals of African descent) who may rely more on the 3A4 metabolic pathway for clearance of the drug.

MANAGEMENT: Caution is advised if fesoterodine is administered with grapefruit or grapefruit juice. Patients should be advised to notify their physician if they experience potential adverse effects of fesoterodine such as irregular heartbeat, blurry vision, difficulty urinating, dry mouth, headache, drowsiness, dizziness, gastrointestinal upset, or constipation.

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.