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.