Drug Interaction Report

MONITOR: Coadministration with vandetanib may increase the plasma concentrations of drugs that are substrates of organic cation transporter 2 (OCT2). The mechanism is inhibition of OCT2-mediated renal tubular secretion by vandetanib. In healthy study subjects, single-dose coadministration of metformin and vandetanib increased metformin peak plasma concentration (Cmax) by 50% and systemic exposure (AUC) by 74%.

MANAGEMENT: Caution is advised when vandetanib is used with drugs that are substrates of OCT2, particularly those with a narrow therapeutic range such as metformin. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever vandetanib is added to or withdrawn from therapy.

GENERALLY AVOID: Varenicline may enhance the effects of alcohol as well as alter the way an individual reacts to alcohol. During postmarketing use, some patients have reported experiencing increased intoxicating effects of alcohol while taking varenicline. In addition, some reported cases of neuropsychiatric events, including unusual and sometimes aggressive behavior directed toward oneself or others, may have been worsened by concomitant use of alcohol. These events were often accompanied by amnesia.

MANAGEMENT: Patients should be advised to limit their consumption of alcohol until they know whether varenicline affects their tolerance for alcohol, and to exercise caution driving or operating machinery until they know how quitting smoking and/or varenicline may affect them. Patients should immediately stop taking varenicline and contact their physician if they develop agitation, hostility, aggressive behavior, depressed mood, or changes in behavior or thinking that are not typical for them, or if they develop suicidal ideation or behavior.