Drug Interaction Report

MONITOR: Coadministration with vandetanib may increase the plasma concentrations of drugs that are substrates of the P-glycoprotein transporter, such as digoxin and dabigatran. The mechanism involves increased absorption and/or decreased clearance due to inhibition of drug efflux mediated by intestinal and renal/hepatic P-glycoprotein, respectively. Vandetanib is a weak P-glycoprotein inhibitor. The clinical significance is unknown. In healthy subjects, coadministration of a single 0.25 mg dose of digoxin with a 300 mg dose of vandetanib increased the mean digoxin Cmax by 29% and the mean AUC by 23%.

MANAGEMENT: Caution is advised if vandetanib must be used concomitantly with medications that are substrates of P-glycoprotein, particularly those with a narrow therapeutic range such as digoxin. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever vandetanib is added to or withdrawn from therapy.