BETHESDA, MD 23 July 2012—The seizures that can occur during dalfampridine therapy in patients with multiple sclerosis most often happen within weeks, even days, of starting the recommended dosage, FDA said today in a drug safety communication.
The "vast majority" of these seizures, the agency also said, happened in patients who had not before had a seizure.
New labeling (PDF) for the potassium-channel blocker recommends that clinicians monitor patients' estimated creatinine clearance at least once a year during therapy. For those patients whose estimated creatinine clearance is 51–80 mL/min at any time, the labeling now recommends the clinicians carefully consider the potential benefits of dalfampridine therapy against the risk of seizure.
The drug's labeling has always recommended that clinicians know their patients' creatinine clearance or estimate it before starting dalfampridine therapy. Moderate or severe renal impairment is a contraindication to the use of the drug, which is marketed only as 10-mg extended-release tablets.
During some of the trials of dalfampridine in patients with multiple sclerosis, the incidence of seizures with the dosage of 15 mg twice daily was more than four times higher than the incidence with the dosage of 10 mg twice daily. The labeling states that patients with a creatinine clearance of 51–80 mL/min who take dalfampridine 10 mg twice daily—the only recommended dosage—may accumulate enough drug in their bloodstream to have plasma levels nearly as high as those in people who took 15 mg twice daily.
FDA originally approved the marketing of dalfampridine, or Ampyra, in January 2010.
This approval included a risk evaluation and mitigation strategy, with a medication guide and communications to prescribers and pharmacists.
Ampyra's FDA-approved medication guide (PDF) tells patients the drug can cause seizures. The medication guide also tells patients that their chance of having a seizure is higher if they take too much of the drug or have kidney problems.
The letter to pharmacists, according to information at FDA's website, tells them about the potential risk of seizures in patients who receive a compounded formulation of dalfampridine, previously known as fampridine, instead of the extended-release tablets. This letter also tells pharmacists to contact the prescriber to verify the dosage and "reinforce the dosage administration recommendation" if the dosage is other than 10 mg twice daily.
Ampyra is marketed by Acorda Therapeutics Inc.