Pharmacology Update

Dalfampridine Extended Release Tables (Ampyra™ )

By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD. Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; and Assistant Professor of Medicine, University of California, San Francisco. Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Drs. Elliott and Chan report no financial relationship to this field of study.

The FDA has approved a potassium channel blocker to improve walking in adults with multiple sclerosis. Dalfampridine was originally used as a bird poison and was previously known as fampridine. It has been used in a compounded formulation since the 1980s. It is marketed by Acorda Therapeutics as Ampyra™ .

Indications

Dalfampridine is indicated for improving the walking ability (increase in walking speed) in patients with multiple sclerosis.1

Dosage

The recommended dose is 10 mg twice daily (roughly 12 hours apart). It may be taken with or without food.1

Dalfampridine is available as 10 mg tablets.

Potential Advantages

Dalfampridine produced a 25% improvement in walking speed compared to 5% for placebo.1,2

Potential Disadvantages

Dalfampridine can cause seizures and this effect is dose-dependent.1 The drug is contraindicated in patients with moderate-to-severe renal impairment. The most common adverse events are urinary tract infection, insomnia, dizziness, headache, nausea, back pain, and balance disorder.

Comments

Dalfampridine is a potassium channel blocker and is reported to restore conduction of action potential in some demyelinated nerve fibers.3 Its effectiveness was evaluated in two randomized, placebo-controlled trials in multiple sclerosis patients with a mean duration of disease of 13 years and a mean Kurtzke Expanded Disability Status Scale (EDSS) score of 6.1 Potential subjects with a history of seizures or EEG evidence of epileptiform activity were excluded. The study designs differed slightly. Study 1 (n = 296) was a 14-week, double-blind protocol with a 4-week no-treatment follow-up after single-blind placebo run-in.2 Study 2 (n = 237) had 9 weeks of double-blind treatment and 2 weeks of no-treatment follow-up. Study participants were randomized to dalfampridine (10 mg twice daily) or placebo. The primary endpoint was walking speed as measured by the Timed 25-foot Walk (T25W). A responder was defined as a patient with a faster walking speed for at least 3 of the 4 visits during the double-blind treatment period than the maximum speed for any of the first 5 off-drug visits (4 before the treatment and one 2 weeks into the follow-up period). Response rates were 34.8% for dalfampridine vs 3% for placebo in study 1 and 42.9% vs 9.3% in study 2. The average improvement in walking speed was about 25% vs 4.7% (or 0.51 feet/sec vs 0.1 feet/sec) and was maintained during the 14-week treatment period.2 Timed walk responders showed a reduced self-assessed ambulation-related disability compared to non-responders independent of whether they were randomized to dalfampridine or placebo.2 The most frequent adverse events were insomnia, fatigue, back pain, and balance disorders. The discontinuation rate was 5% for dalfampridine and 4% for placebo.2

Clinical Implications

Dalfampridine is the first drug of its kind for patients with multiple sclerosis. A large proportion of patients with multiple sclerosis has difficulty walking. However, the benefit of the drug is modest (additional 0.4 feet/sec over a 25-foot walk compared to placebo) and only about one-third of patients are considered responders. There is no evidence that dalfampridine affects the progression of multiple sclerosis. Only some MS patients would be expected to benefit from the mechanism of dalfampridine.2

References

1. Ampyra Product Labeling. Hawthorne, NY: Acorda Therapeutics, Inc.; January 2010.

2. Goodman AD, et al. Sustained-release oral fampridine in multiple sclerosis: A randomised, double-blind, controlled trial. Lancet 2009;373:732-738.

3. Kachuck NJ. Sustained release oral fampridine in the treatment of multiple sclerosis. Expert Opin Pharmacother 2009;10:2025-2035.