Drug Interaction Report

MONITOR: Coadministration with inhibitors of CYP450 2D6 may increase the plasma concentrations of fesoterodine's active metabolite, 5-hydroxymethyl tolterodine, which is partially metabolized by the isoenzyme. The interaction has not been examined in pharmacokinetic studies. In poor metabolizers of CYP450 2D6, representing maximum CYP450 2D6 inhibition, 5-hydroxymethyl tolterodine peak plasma concentration (Cmax) and systemic exposure (AUC) are increased 1.7- and 2-fold, respectively, relative to extensive metabolizers.

MANAGEMENT: No initial dosing adjustments are recommended when fesoterodine is used in combination with CYP450 2D6 inhibitors. 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.

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.