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Clinical Overview of Dalfampridine: An Agent With a Novel Mechanism of Action to Help With Gait Disturbances

  • Author Footnotes
    ⁎ Current affiliation: Kaiser Permanente, Denver, Colorado.
    Michael D. Egeberg
    Footnotes
    ⁎ Current affiliation: Kaiser Permanente, Denver, Colorado.
    Affiliations
    Department of Clinical Pharmacy, University of Colorado, Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, Colorado
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  • Caleb Y. Oh
    Affiliations
    Department of Clinical Pharmacy, University of Colorado, Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, Colorado
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  • Jacquelyn L. Bainbridge
    Correspondence
    Address correspondence to: Jacquelyn L. Bainbridge, PharmD, FCCP, University of Colorado, Skaggs School of Pharmacy and Pharmaceutical Sciences, Department of Clinical Pharmacy and Department of Neurology, 12850 E. Montview Blvd, C238, Aurora, CO 80045
    Affiliations
    Department of Clinical Pharmacy and Department of Neurology, University of Colorado, Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, Colorado
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  • Author Footnotes
    ⁎ Current affiliation: Kaiser Permanente, Denver, Colorado.

      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 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.

      Key words

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      Linked Article

      • Corrections
        Clinical TherapeuticsVol. 35Issue 6
        • Preview
          In the article by Michael D. Egeberg, Caleb Y. Oh, and Jacquelyn L. Bainbridge, titled “Clinical Overview of Dalfampridine: An Agent With a Novel Mechanism of Action to Help With Gait Disturbances” (Clin Ther. 2012;34:2185-2194), the authors overstated the statistical significance of the increased risk of seizures with dalfampridine in the following places and regret the error. Statements in the manuscript referring to a statistical significance of the seizure risk associated with dalfampridine should be modified to read as follows:
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