Drug Interaction Report

GENERALLY AVOID: Coadministration with potent inhibitors of the P-glycoprotein (P-gp) efflux transporter may significantly increase the oral bioavailability of silodosin, which has been shown in vitro to be a substrate of P-gp. In a pharmacokinetic study, administration of a single 8 mg dose of silodosin with the potent CYP450 3A4/P-gp 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). However, the extent to which P-gp inhibition actually contributes to the overall interaction is unknown.

MANAGEMENT: Concomitant use of silodosin with potent P-gp inhibitors such as cyclosporine is not recommended.

ADJUST DOSING INTERVAL: Food may reduce the oral bioavailability of silodosin. The effect of a moderate-fat, moderate-calorie meal on silodosin pharmacokinetics was variable and decreased silodosin maximum plasma concentration (Cmax) by approximately 18% to 43% and systemic exposure (AUC) by 4% to 49% across three different studies. The maximum effect of food (i.e., coadministration with a high-fat, high-calorie meal) on the pharmacokinetics of silodosin was not evaluated. Safety and efficacy clinical trials for silodosin were always conducted in the presence of food intake.

MANAGEMENT: Patients should be instructed to take silodosin with a meal to reduce the risk of adverse events.