Drug Interaction Report

CONTRAINDICATED: Coadministration with potent inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of silodosin, which is primarily metabolized by the isoenzyme. Severe hypotension and priapism may occur. In pharmacokinetic studies, administration of a single 8 mg dose of silodosin with the potent CYP450 3A4 inhibitor ketoconazole 400 mg/day for 4 days resulted in a 3.8-fold increase in silodosin peak plasma concentration (Cmax) and 3.2-fold increase in systemic exposure (AUC). Coadministration of a single 4 mg dose of silodosin with ketoconazole 200 mg/day for 4 days resulted in 3.7- and 2.9-fold increases in silodosin Cmax and AUC, respectively.

MANAGEMENT: Concomitant use of silodosin with potent CYP450 3A4 inhibitors is considered contraindicated. Some authorities recommend avoiding concomitant use of silodosin during and for 2 weeks after treatment with itraconazole.

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.

Food enhances the oral absorption and bioavailability of tenofovir, the active entity of tenofovir disoproxil fumarate. According to the product labeling, administration of the drug following a high-fat meal increased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of tenofovir by approximately 14% and 40%, respectively, compared to administration in the fasting state. However, administration with a light meal did not significantly affect the pharmacokinetics of tenofovir compared to administration in the fasting state. Food delays the time to reach tenofovir Cmax by approximately 1 hour. Tenofovir disoproxil fumarate may be administered without regard to meals.