Ureleve Drug Interactions

Moderate and Strong CYP3A4 Inhibitors: In a clinical metabolic inhibition study, a 3.8-fold increase in silodosin maximum plasma concentrations and 3.2-fold increase in Silodosin exposure were observed with concurrent administration of a strong CYP3A4 inhibitor, 400 mg ketoconazole. Use of strong CYP3A4 inhibitors such as itraconazole or ritonavir may cause plasma concentrations of Silodosin to increase. Concomitant administration of strong CYP3A4 inhibitors and Silodosin is contraindicated.
The effect of moderate CYP3A4 inhibitors on the pharmacokinetics of silodosin has not been evaluated. Concomitant administration with moderate CYP3A4 inhibitors (e.g., diltiazem, erythromycin, verapamil) may increase concentration of Silodosin. Exercise caution and monitor patients for adverse events when co-administering Silodosin with moderate CYP3A4 inhibitors.
Strong P-glycoprotein (P-gp) Inhibitors: In vitro studies indicated that Silodosin is a P-gp substrate. Ketoconazole, a CYP3A4 inhibitor that also inhibits P-gp, caused significant increase in exposure to Silodosin. Inhibition of P-gp may lead to increased Silodosin concentration. Silodosin is therefore not recommended in patients taking strong P-gp inhibitors such as cyclosporine.
Alpha-Blockers: The pharmacodynamic interactions between Silodosin and other alpha-blockers have not been determined. However, interactions may be expected, and Silodosin should not be used in combination with other alpha-blockers.
Digoxin: The effect of co-administration of Silodosin and digoxin 0.25 mg/day for 7 days was evaluated in a clinical trial in 16 healthy males, aged 18 to 45 years. Concomitant administration of Silodosin and digoxin did not significantly alter the steady state pharmacokinetics of digoxin. No dose adjustment is required.
PDE5 Inhibitors: Co-administration of Silodosin with a single dose of 100 mg sildenafil or 20 mg tadalafil was evaluated in a placebo-controlled clinical study that included 24 healthy male subjects, 45 to 78 years of age. Orthostatic vital signs were monitored in the 12-hour period following concomitant dosing. During this period, the total number of positive orthostatic test results was greater in the group receiving Silodosin plus a PDE5 inhibitor compared with Silodosin alone. No events of symptomatic orthostasis or dizziness were reported in subjects receiving Silodosin with a PDE5 inhibitor.
Other Concomitant Drug Therapy: Antihypertensive: The pharmacodynamic interactions between Silodosin and antihypertensive have not been rigorously investigated in a clinical study. However, approximately one-third of the patients in clinical studies used concomitant antihypertensive medications with Silodosin. The incidence of dizziness and orthostatic hypotension in these patients was higher than in the general Silodosin population (4.6% versus 3.8% and 3.4% versus 3.2%, respectively). Exercise caution during concomitant use with antihypertensive and monitor patients for possible adverse events.
Metabolic Interactions: In vitro data indicate that Silodosin does not have the potential to inhibit or induce cytochrome P450 enzyme systems.
Food Interactions: The effect of a moderate fat, moderate calorie meal on Silodosin pharmacokinetics was variable and decreased Silodosin maximum plasma concentration (C_max) by approximately 18 to 43% and exposure (AUC) by 4 to 49% across three different studies. Safety and efficacy clinical trials for Silodosin were always conducted in the presence of food intake. Patients should be instructed to take Silodosin with a meal to reduce risk of adverse events.