Drug Interaction Report

MONITOR: Coadministration with danicopan may increase the plasma concentrations of drugs that are substrates of the efflux transporters breast cancer resistance protein (BCRP) and/or P-glycoprotein (P-gp). The proposed mechanism involves decreased clearance due to inhibition of BCRP and P-gp by danicopan. In clinical drug interaction studies, when subjects were coadministered the BCRP substrate rosuvastatin (single 20 mg dose) with danicopan at steady state (200 mg three times daily for 4 days), the peak plasma concentration (Cmax) and systemic exposure (AUC) of rosuvastatin increased by 3.3-fold and 2.2-fold, respectively. In addition, when the P-gp substrate fexofenadine (single 180 mg dose) was coadministered with danicopan (150 mg three times daily for 4 days), the peak plasma concentration (Cmax) and systemic exposure (AUC) of fexofenadine increased by 1.4-fold and 1.6-fold, respectively. Similarly, when subjects were coadministered the P-gp substrate tacrolimus (single 2 mg dose) with danicopan (200 mg three times daily for 5 days), the Cmax and AUC of tacrolimus increased by 1.1-fold and 1.5-fold, respectively.

MANAGEMENT: Caution and clinical monitoring are recommended if danicopan is coadministered with drugs that are substrates of the transporters BCRP and/or P-gp, particularly sensitive substrates, or those with a narrow therapeutic range. Dosage adjustments as well as closer clinical and laboratory monitoring for the development of adverse effects may be appropriate for some drugs whenever danicopan is added to or withdrawn from therapy. Individual product labeling should be consulted for further guidance.

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.