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1501352 
Journal Article 
Clinical overview of dalfampridine: an agent with a novel mechanism of action to help with gait disturbances 
Egeberg, MD; Oh, CY; Bainbridge, JL 
2012 
Yes 
Clinical Therapeutics
ISSN: 0149-2918 
34 
11 
2185-2194 
English 
23123001 
WOS:000312114900001 
BACKGROUND: Medication used to treat multiple sclerosis (MS) can be categorized as disease-modifying therapies, symptomatic therapies, or treatment of acute exacerbations. Dalfampridine is the first symptomatic therapy approved by the Food and Drug Administration to improve walking in patients with MS.

OBJECTIVE: This article reviews the pharmacology, pharmacodynamic properties, and pharmacokinetic properties of dalfampridine, as well as its clinical efficacy, safety profile, pharmacoeconomic considerations, and place in therapy.

METHODS: Three PubMed searches were conducted for original articles published in English between 1966 and August 2012 with human study participants. Articles concerning the pharmacology, pharmacokinetic properties, pharmacodynamic properties, efficacy, and safety profile of dalfampridine were evaluated.

RESULTS: Dalfampridine theoretically works to improve conduction and enhance walking by inhibiting potassium channels in the axonal membrane and by prolonging action potentials in demyelinated neurons. The efficacy of dalfampridine has been reported in 2 Phase III clinical trials in patients with MS. When comparing dalfampridine 10 mg twice daily with placebo, these studies found a statistically significant improvement in walking (42.9% vs 9.3% and 35% vs 8%; P < 0.001). However, clinical trials and postmarketing surveillance have found a statistically significant increased risk of seizures with dalfampridine.

CONCLUSIONS: Dalfampridine has a unique mechanism of action, leading to its approval as the first symptomatic therapy for MS to improve walking speed. The increased risk of seizures can be a significant safety concern and will require health care providers to be diligent in monitoring patients and to ensure adequate patient education. The addition of dalfampridine as symptomatic therapy for MS may lead to additional novel products in the future. 
4-aminopyridine; Ampyra; dalfampridine; fampridine; multiple sclerosis; walking