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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References
- Bradley's Neurology in Clinical Practice. 6th ed. WB Saunders, Elsevier, Philadelphia, Pa2012: 92-116
- Adopted Names page.(Accessed October 2, 2012)
- Guidelines and best practices for appropriate use of dalfampridine in managed care populations.Am J Manag Care. 2011; 17: S154-S160
- Acorda Therapeutics.(Accessed August 10, 2012)
- Effects of 4-aminopyridine in patients with multiple sclerosis.J Neurol Sci. 1983; 60: 353-362
- Ampyra [package insert].Acorda Therapeutics Inc, Hawthorne, NY2012
- Effects of 4-aminopyridine on demyelinated axons, synapses and muscle tension.Brain. 2000; 123: 171-184
- Aminopyridines potentiate synaptic and neuromuscular transmission by targeting the voltage-activated calcium channel beta subunit.J Biol Chem. 2009; 284: 36453-36461
- Pharmacokinetics and tolerability of single escalating doses of fampridine sustained-release tablets in patients with multiple sclerosis: a Phase I-II, open-label trial.Clin Ther. 2009; 31: 2206-2214
- Steady-state pharmacokinetics and tolerability of orally administered fampridine sustained-release 10-mg tablets in patients with multiple sclerosis: a 2-week, open-label, follow-up study.Clin Ther. 2009; 31: 2215-2223
- Single-dose pharmacokinetics of sustained-release fampridine (Fampridine-SR) in healthy volunteers and adults with renal impairment.J Clin Pharmacol. 2010; 50: 151-159
- Absorption characteristics of sustained-release 4-aminopyridine (fampridine SR) in patients with chronic spinal cord injury.J Clin Pharmacol. 2000; 40: 402-409
- Intravenous infusion of 4-AP in chronic spinal cord injured subjects.Spinal Cord. 2000; 38: 7-15
- Dalfampridine sustained-release for symptomatic improvement of walking speed in patients with multiple sclerosis.Core Evid. 2010; 5: 107-112
Kieseier B, Goodman A. Impact of combined dalfampridine extended release and interferon-a on patient reported outcomes in placebo-controlled clinical trials. Poster presented at: 63rd Annual Meeting of the American Academy of Neurology; April 9–16, 2011; Honolulu, Hawaii
- Clinical overview of the seizure risk of dalfampridine.Expert Opin Drug Saf. 2012; 11: 651-657
- Assessment of the cardiac safety of fampridine-SR sustained-release tablets in a thorough QT/QTc evaluation at therapeutic and supratherapeutic doses in healthy individuals.Expert Opin Investig Drugs. 2009; 18: 1807-1815
- Effects of 4-aminopyridine on cardiac repolarization, PR interval, and heart rate in patients with spinal cord injury.Pharmacotherapy. 2003; 23: 133-136
- Different effects of 4-aminopyridine on sensory and motor fibers: pathogenesis of paresthesias.Neurology. 1986; 36: 117-120
- 4-Aminopyridine toxicity mimics autoimmune-mediated limbic encephalitis.Neurology. 2009; 72: 1100-1101
- Severe accidental overdose of 4-aminopyridine due to a compounding pharmacy error.J Emerg Med. 2011; 41: 51-54
- Sustained-release oral fampridine in multiple sclerosis: a randomised, double-blind, controlled trial.Lancet. 2009; 373: 732-738
- A phase 3 trial of extended release oral dalfampridine in multiple sclerosis.Ann Neurol. 2010; 68: 494-502
- Dalfampridine extended-release tablets: one year of post-marketing safety experience in the United States [abstract].Mult Scler. 2011; 17: S216
- Dalfampridine: a medication to improve walking in patients with multiple sclerosis.Ann Pharmacother. 2012; 46: 1010-1015
- Contribution of impaired mobility and general symptoms to the burden of multiple sclerosis.Adv Ther. 2009; 26: 1043-1057
- Acorda Therapeutics®, Financial Assistance - Ampyra® (dalfampridine extended release tablet).(Accessed August 13, 2012)
- Ampyra (Dalfampridine) Extended Release Tablets.(Accessed August 11, 2012)
Article Info
Publication History
Published online: November 05, 2012
Accepted:
October 5,
2012
Identification
Copyright
© 2012 Elsevier HS Journals, Inc. Published by Elsevier Inc. All rights reserved.
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- CorrectionsClinical TherapeuticsVol. 35Issue 6
- PreviewIn 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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