Drug Interaction Report

GENERALLY AVOID: Coadministration with inhibitors of the hepatic influx transporters organic anion transporting polypeptides (OATP) 1B1 and 1B3 may increase the plasma concentrations and adverse effects of brincidofovir. In clinical studies, coadministration with a single 600 mg oral dose of the OATP1B1 and 1B3 inhibitor cyclosporine increased the mean systemic exposure (AUC) and peak plasma concentration (Cmax) of brincidofovir by 374% and 269%, respectively.

MANAGEMENT: The manufacturer advises that, where possible, coadministration of brincidofovir with OATP1B1 or 1B3 inhibitors should be avoided and alternative medicines considered. However, if concomitant use is necessary, administration of the OATP1B1 or 1B3 inhibitor should be postponed by at least 3 hours after the administration of brincidofovir. Patients should also be closely monitored for brincidofovir-related adverse reactions such as elevations in hepatic transaminases and bilirubin, diarrhea, nausea, vomiting, and abdominal pain.

ADJUST DOSING INTERVAL: Food may reduce as well as delay the absorption of dabrafenib. In study subjects, administration of dabrafenib with a high-fat meal decreased peak plasma concentration (Cmax) and systemic exposure (AUC) by 51% and 31%, respectively, and delayed median Tmax by approximately 3.6 hours compared to administration in the fasted state.

MANAGEMENT: Dabrafenib should be taken at least 1 hour before or 2 hours after a meal.

ADJUST DOSING INTERVAL: Administration with food decreases the oral bioavailability of brincidofovir. According to the product labeling, administration of brincidofovir tablets with a low-fat meal (approximately 400 calories, 25% of calories from fat) was associated with a reduction in the systemic exposure (AUC) and peak plasma concentration (Cmax) of brincidofovir by 31% and 49%, respectively, compared to administration under fasting. However, no clinically meaningful changes in intracellular concentrations of cidofovir diphosphate were observed. The effect of food on the oral suspension formulation has not been evaluated.

MANAGEMENT: Brincidofovir oral tablets and suspension should be taken on an empty stomach. If necessary, the oral tablets may be taken with a low-fat meal.