New FDA communication, label change for MS drug

July 31, 2012

FDA has announced a safety communication regarding the risk of seizures in patients with multiple sclerosis starting dalfampridine (Ampyra, Acorda Therapeutics). The safety communication stemmed from a review of post-marketing adverse event reports.

On July 23, FDA announced a safety communication regarding the risk of seizures in patients with multiple sclerosis (MS) starting dalfampridine (Ampyra, Acorda Therapeutics). The drug was approved by FDA in 2010 to improve walking in patients with MS. The safety communication stemmed from a review of post-marketing adverse event reports.

Seizures are a known risk of dalfampridine therapy at the approved dose of 10 mg twice daily. According to FDA, most post-marketing cases occurred days to weeks after starting therapy and in patients with no known history of seizures. The risk of seizures increases with increasing drug concentrations, and given that dalfampridine is cleared renally, patients with even mild renal impairment (creatinine clearance [CrCl] of 51-80 mL/min) can accumulate the drug to levels that may precipitate a seizure. FDA reminds clinicians that mild renal impairment in patients over the age of 50 is common due to an age-associated decline in kidney function. For this reason, patients with a CrCl of 51-80mL/min are considered to be at an increased risk of seizures and FDA warns clinicians to weight the risks versus benefits of therapy carefully in the patient population.

FDA has required a label change to recommend baseline calculation of CrCl repeated at least annually and clarification that if a dose is missed patients should not double their dose. The tablets should be administered whole and not crushed, dissolved, or chewed. Dalfampridine is contraindicated in patients with a history of seizures or with a CrCl≤50mL/min. Clinicians should discontinue dalfampridine in their patients who experience a seizure on therapy and are urged to report the adverse event to FDA.

“The risk of seizures on Ampyra is not a new finding; however, this safety communication highlights the important of appropriate patient selection for the use of Ampyra, as well as proper monitoring,” Diana Sobieraj, PharmD, assistant professor at the University of Connecticut School of Pharmacy, Storrs, Conn., told Drug Topics. “Patient education is also paramount since this is an extended-release formulation-patients should be aware that taking the tablet whole and not trying to 'catch up' if they miss a dose will help to assure proper drug concentrations.”