title: Clinical overview of dalfampridine: an agent with a novel mechanism of action to help with gait disturbances.
abstract: 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 shown an increased risk of seizures with dalfampridine use that appears to be dose related [corrected].
  
  
  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 safety concern and will require health care providers to be diligent in monitoring patients and to ensure adequate patient education [corrected]. The addition of dalfampridine as symptomatic therapy for MS may lead to additional novel products in the future.
authors.affiliation: Department of Clinical Pharmacy, University of Colorado, Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, Colorado 80045, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Egeberg
authors.forename: Caleb Y
authors.initials: CY
authors.lastname: Oh
authors.forename: Jacquelyn L
authors.initials: JL
authors.lastname: Bainbridge
mesh_terms: D015761:4-Aminopyridine / Q000008:administration & dosage / Q000009:adverse effects / Q000191:economics / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000818:Animals; D016527:Drug Costs; D004347:Drug Interactions; D005684:Gait / Q000187:drug effects*; D020233:Gait Disorders, Neurologic / Q000175:diagnosis / Q000188:drug therapy* / Q000191:economics / Q000503:physiopathology; D006801:Humans; D009103:Multiple Sclerosis / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D018579:Patient Selection; D026902:Potassium Channel Blockers / Q000008:administration & dosage / Q000009:adverse effects / Q000191:economics / Q000493:pharmacokinetics / Q000627:therapeutic use*; D020127:Recovery of Function; D012307:Risk Factors; D012640:Seizures / Q000139:chemically induced; D016896:Treatment Outcome; D016138:Walking
chemical_list: D026902:Potassium Channel Blockers; D015761:4-Aminopyridine