Drug Interaction Report

MONITOR: Coadministration with ledipasvir may increase the plasma concentrations of orally administered drugs that are substrates of the P-glycoprotein (P-gp) and/or breast cancer resistance protein (BCRP) transporters. The proposed mechanism is decreased clearance in the intestine due to inhibition of P-gp or BCRP-mediated drug efflux by ledipasvir.

MANAGEMENT: Caution is advised if ledipasvir must be used concurrently with medications that are substrates of the P-gp and/or BCRP transporters, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever ledipasvir is added to or withdrawn from therapy.

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.