Drug Interaction Report

MONITOR: Coadministration with tucatinib may increase the plasma concentrations of drugs that are substrates of the P-glycoprotein (P-gp) transporter. The mechanism likely involves tucatinib-mediated inhibition of P-gp. When a single 0.5 mg dose of digoxin, a P-gp substrate, was administered with tucatinib (300 mg twice daily), digoxin peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 2.4-fold and 1.5-fold, respectively. Increased exposure to the P-gp substrate may increase the risk of toxicity.

MANAGEMENT: Caution is advised if tucatinib is used concomitantly with P-gp substrates, particularly those with a narrow therapeutic index. A dose reduction of the P-gp substrates as well as clinical and laboratory monitoring may be appropriate.

Food prolongs the gastrointestinal absorption of selexipag. When taken with food, the time to peak concentration (Tmax) was delayed and peak plasma concentration (Cmax) was approximately 30% lower. Selexipag systemic exposure (AUC) and that of its active metabolite did not significantly change, however. Selexipag may be taken with or without food. Tolerability may be improved when taken with food.