Prescribing 4-aminopyridine for Multiple Sclerosis

4-aminopyridine (4-AP) is indicated for symptomatic treatment in patient with a decreased walking capacity due to multiple sclerosis. A potassium channel blocker, 4-AP, is considered a muscle strengthener. The Food and Drug Administration (FDA) approved of the compounding on 4-AP in 2010 along with a commercially available form, dalfampridine (Ampyra), which is an extended-release form. In clinical trials, a significantly greater proportion of patients improved walking speed (feet per second) when taking 10mg twice a day compared to placebo (34.8% vs. 8.3% in one clinical trial). Doses greater than 20mg per day were associated with an increased incidence of seizure activity.

Prescribing 4-AP should carefully be done because increased doses correlate with increased risk of seizures and other toxicities. Every patient will respond to 4-AP differently, some patients may experience side effects at doses lower than 20mg daily. This is where compounding of 4-AP helps patients get the right dose that is safe and effective. Commercially available dalfampridine is only available in 10mg capsules, while 4-AP can be compounded as low as 5mg capsules. Starting with lower doses can help monitor tolerance in patients and assist in helping them get to a dose that will improve their walking capacity with minimal risk of toxicity.

References:

  1. Mayo Clinic. Multiple sclerosis [Internet]. Rochester (MN): Mayo Foundation for Medical Education and Research. Available from: http://www.mayoclinic.org/diseases-conditions/multiple-sclerosis/home/ovc-20131882
  2. Ampyra (dalfampridine) prescribing information. Ardsley (NY): Acorda Therapeutics Inc; 2010 Jan. Revised 2016 Oct.
  3. Stenager E, Dalgas U, Ravnborg M and Jensen HB. 4-aminopyridine for symptomatic treatment of multiple sclerosis: a systematic review. Therapeutic Advances in Neurological Disorders. 2014; 7(2):97-113.
  4. Bever CT et al. The effects of 4-aminopyridine in multiple sclerosis patients. Journal of American Academy of Neurology. 1994 Jun; 44(6).