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Fampyra: New safety information

New safety information indicates that Ampyra (dalfampridine), which is used to improve walking in people with multiple sclerosis (MS), is associated with a relatively low risk of seizures (Jara and colleagues. Neuropsychiatr Dis Treat 2013;9:365-370). However, the seizure risk is higher than previously reported.

Dalfampridine (also known as fampridine or 4-aminopyridine [4-AP]) was approved (as Ampyra; Fampyra in other countries) by the U.S. Food and Drug Administration in 2010. But a risk management program was required due to concerns about the risk of seizures and other side effects with the drug.

Dalfampridine blocks potassium channels which are involved in nerve transmission and early studies indicated it had the potential to improve nerve conduction in demyelinated neurons (Stefoski and colleagues. Ann Neurol 1987;21:71-77). Altering nerve conduction has been shown to improve vision in people with optic neuritis (Jones and colleagues. J Neurol Sci 1983;60:353-362; Horton and colleagues. Neurology 2013; epublished April 24, 2013), and improves leg strength and walking ability in MS (Bever and colleagues. Neurology 1996;47:1457-1462). However, some people found that the drug also worsened sensory symptoms (such as tingling or numbness), and toxicities limited the use of the drug (Bever and colleagues. Ann Neurol 1990;27:421-427). Higher doses were associated with a risk of epilepsy-like seizures (Bever and colleagues. Neurology 1994;44:1054-1059).

To reduce these risks, dalfampridine was reformulated as an extended-release (ER) drug a decade ago (Darlington C. Curr Opin Investig Drugs 2000;1:375-379). Two phase III trials examined the safety and effectiveness of dalfampridine ER in MS (Goodman and colleagues. Lancet 2009;373:732-738; Goodman and colleagues. Ann Neurol 2010;68:494-502). Overall, only 35-43% of people show some benefit with the drug. Responders to the drug said it substantially improved their mobility although the gain in walking speed was quite small – about 1 second faster when walking 25 feet.

To date, about 46,000 people in the U.S. have now tried the drug. The drug is generally well tolerated. The safety analysis found that the most common side effects are dizziness, insomnia, balance disorder, headache, nausea and urinary tract infections (Jara 2013). A label revision in 2013 now includes a warning about a risk of severe allergic reactions.

A total of 85 seizures were reported for the 1-year period ending March 2011, for an incidence of about 5 per 1000 patient-years (i.e. 0.5% per year). The seizure risk was previously estimated to be 0.3% (FDA review 2010). Many of these seizures occurred in people at higher risk with the drug, including those with a history of convulsions, kidney disease, and people who used an incorrect dose. (The correct dose is 10 mg twice a day.) A separate study of the FDA database reported 160 seizures during the period January 2010 to March 2012, but a similar incidence (0.46%) (Fernandez and colleagues. Expert Rev Clin Pharmacol 2012;5:649-665).

Seizure risk will continue to be assessed as part of the risk management plan. In addition, the Canadian Interventional Extension Trial and the LIBERATE observational study are expected to provide safety updates later this year.

It’s important not to exceed the prescribed dose of Fampyra/Ampyra. The researchers added that caution is needed when taking other drugs. Talk to your doctor and pharmacist about other medications you are taking to ensure that they don’t lower the seizure threshold. This list includes some antibiotics, some psychiatric drugs, and street drugs such as cocaine and methamphetamine.

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