Drug Interactions between dalfampridine and givinostat

MONITOR CLOSELY: Coadministration with inhibitors 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. Elevated plasma levels of dalfampridine may increase the risk of adverse effects, particularly seizures.

MANAGEMENT: Caution and assessment of the potential benefits against the risk of seizures should be considered if dalfampridine is used concurrently with OCT2 inhibitors. Some international product labeling considers concomitant use to be contraindicated. Individual product labeling should be consulted for both dalfampridine and the coadministered OCT2 inhibitor for more specific guidance.