Drug Interaction Report

MONITOR: Coadministration with inhibitors and/or substrates of organic cation transporter 2 (OCT2) may increase the plasma concentrations of dalfampridine. In vitro studies have shown that OCT2 is the primary transporter responsible for the active tubular secretion of dalfampridine, which accounts for approximately 60% of its renal elimination - the major route of clearance for dalfampridine. When a single 10 mg dose of dalfampridine was administered to 23 healthy volunteers with the OCT2 inhibitor cimetidine (400 mg every 6 hours), dalfampridine systemic exposure (AUC) was 25% higher relative to the reference value. The interaction has not been studied with OCT2 substrates, but competitive inhibition for active tubular secretion is possible. Elevated plasma levels of dalfampridine may increase the risk of adverse effects, particularly seizures.

MANAGEMENT: Caution is advised when dalfampridine is used with OCT2 inhibitors and/or substrates. The potential benefits of concomitant use should be considered against the risk of seizures.

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.