The Food and Drug Administration’s evaluation of postmarketing adverse event reports for the multiple sclerosis drug dalfampridine indicate that the risk of seizures is highest soon after starting treatment with the recommended dose.
Seizures are a known risk of the drug, and the majority of them occurred within days to weeks of starting treatment. Seizures also occurred in patients without any history of them, according to the FDA statement issued on July 23.
The risk of seizures increases with higher blood levels of the drug, and because it is eliminated through the kidneys, the risk of seizures is higher in patients with kidney impairment, the agency said.
The sustained-release formulation of the potassium channel blocker dalfampridine, marketed as Ampyra by Acorda Therapeutics, was approved in January 2010 to improve walking in people with multiple sclerosis, at a dose of 10 mg twice a day. For more than 20 years before approval, a compounded formulation of the drug, called fampridine, was used off label to improve walking ability in people with different neurologic conditions. However, it was difficult to regulate blood levels of fampridine, which has a narrow therapeutic range, and the sustained formulation, dalfampridine, was developed to overcome this limitation.
The FDA statement provided the following recommendations aimed at clinicians, which includes information in the original label (now updated):
• Dalfampridine is contraindicated in patients with a history of seizures or who have moderate to severe renal impairment (a creatine clearance below 50 mL/min).
• The potential benefits of treatment with dalfampridine "should be carefully considered against the risk of seizures" before prescribing the drug to patients with mild renal impairment (creatine clearance 51 mL/min to 80 mL/min).
• Before starting treatment, a patient’s creatinine clearance level should be known (using the Cockroft-Gault equation), and should be checked annually during treatment, "even when serum creatinine levels appear to be normal."
• Patients should be advised not to take double or extra doses of dalfampridine if they miss a dose; and they should take the tablets whole, and not divide, crush, chew, or dissolve the tablets.
• Dalfampridine should be discontinued permanently if a patient has a seizure.
Seizures and other adverse events associated with dalfampridine should be reported to the FDA’s MedWatch program or at 800-332-1088.