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.

H2 antagonists may reduce the clearance of nicotine. Cimetidine, 600 mg given twice a day for two days, reduced clearance of an intravenous nicotine dose by 30%. Ranitidine, 300 mg given twice a day for two days, reduced clearance by 10%. The clinical significance of this interaction is not known. Patients should be monitored for increased nicotine effects when using the patches or gum for smoking cessation and dosage adjustments should be made as appropriate.