Drug Interactions between aprepitant and silodosin

MONITOR: Coadministration with inhibitors of CYP450 3A4 may increase the plasma concentrations of silodosin, which is primarily metabolized by the isoenzyme. In a pharmacokinetic study, administration of a single 8 mg dose of silodosin with the potent CYP450 3A4 inhibitor ketoconazole (400 mg) resulted in a 3.8-fold increase in silodosin peak plasma concentration (Cmax) and a 3.2-fold increase in systemic exposure (AUC). The interaction has not been studied with moderate CYP450 3A4 inhibitors such as diltiazem, erythromycin, and verapamil.

MANAGEMENT: Caution is advised if silodosin is prescribed in combination with inhibitors of CYP450 3A4. Pharmacologic response to silodosin should be monitored more closely whenever a CYP450 3A4 inhibitor is added to or withdrawn from therapy, and the silodosin dosage adjusted as necessary. Patients should be advised to avoid rising abruptly from a sitting or recumbent position and to notify their physician if they experience dizziness, lightheadedness, syncope, orthostasis, or tachycardia. Taking silodosin at bedtime may minimize the occurrence of orthostatic effects. Patients should also avoid driving or operating hazardous machinery until they know how the medication affects them.