Prolonged-release fampridine improves walking in a proportion of patients with multiple sclerosis

Abstract

Fampridine is indicated to improve walking in adult multiple sclerosis (MS) patients. Indications vary between countries and the prescribing neurologist should be aware of the labeling and indication in his own country. The prolonged-release formulation of 4-aminopyridine has reduced the risk of seizure to a level near the intrinsic MS risk, and the risk can be further minimized if it emphasized that patients should not exceed the recommended dose of 10 mg twice a day, should not catch up on missed doses and should not divide, crush or chew tablets. It is imperative to check the renal function before and during treatment and make sure the patient does not get concomitant medications affecting the renal elimination. The use of fampridine is considered safe, and the side effects are often mild and acceptable. Approximately one-third of MS patients treated with fampridine will experience an improvement of their walking speed above 20% on the timed 25-foot walk test (T25FW), which is considered to be clinically relevant.

Keywords::

• Ampyra
• dalfampridine
• fampridine
• Fampyra
• immediate-release 4-aminopyridine
• MSWS-12
• prolonged-release 4-aminopyridine
• T25FW

Financial & competing interests disclosure

HK Mathiesen has received funding for congress participation from TEVA, Merck Serono, Bayer Schering and Biogen Idec. PS Sorensen has served on scientific advisory boards for Biogen Idec, Merck Serono, Novartis, Genmab, TEVA, Elan and GlaxoSmithKline (GSK); has served on steering committees or independent data monitoring boards in clinical trials sponsored by Merck Serono, Genmab, TEVA, GSK, Bayer Schering, and has received funding of travel for these activities; and has received speaker honoraria from Biogen Idec, Merck Serono, TEVA, Bayer Schering, Sanofi-Aventis, Genzyme and Novartis. His department has received research support from Biogen Idec, Bayer Schering, Merck Serono, TEVA, Baxter, Sanofi-Aventis, BioMS, Novartis, Bayer, RoFAR, Roche, Genzyme, the Danish Multiple Sclerosis Society, the Danish Medical Research Council and the European Union Sixth Framework Programme: Life Sciences, Genomics and Biotechnology for Health. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• • 4-aminopyridine (4-AP) is a potassium channel blocker improving nerve transmission in demyelinated axons.

• • Fampridine is indicated for improvement of walking in multiple sclerosis (MS) patients older than 18 years of age with walking disability. Different restrictions concerning expanded disability status scale (EDSS) exist in different countries. Prescribing physician should be aware of labeling and indications according to their own country.

• • Fampridine can be used in all subtypes of MS (relapsing-remitting, primary progressive, secondary progressive) regardless the use of immunomodulatory drugs. However, data concerning concomitant treatment with immunosuppressive treatments are wanted.

• • The patient should not be in relapse and should be on stable medication at the time of initiation of fampridine treatment.

• • Prolonged-release formula of 4-AP (fampridine, Ampyra^©, Fampyra^©) 10 mg twice a day has reduced the risk of seizures, is safe and side effects are often mild.

• • Patients should be carefully instructed not to increase the dose, catch up on missed doses or chew, crush or divide tablets. It will only increase the risk of side effects.

• • Treatment of fampridine should be initiated and continued by neurologist with special experience in MS and the efficacy of fampridine should be evaluated after a period of 2 weeks using timed 25-foot walk test (T25FW), 12-question multiple sclerosis walking scale (MSWS-12) and the patient’s evaluation of the effects on walking as well as other aspects of MS and quality of life (QoL).

• • Improvement in the T25FW of 20% and a 4-point reduction in the MSWS-12 are considered clinically relevant.

• • Fampridine is contraindicated in patients with a history of seizures or with moderate to severe renal impairment (creatinine clearance [CrCl] <50 ml/min) and the potential benefits of fampridine should be carefully considered against the risk of seizures in patients with mild renal impairment (50 ml/min < CrCl < 80 ml/min). CrCl should be known before initiation of the treatment and should be monitored at least once a year.

• • Fampridine is contraindicated in case of allergy against 4-AP.

• • Fampridine is contraindicated in patients using organic cation transporter 2 [OCT2] inhibitors such as cimetidine due to the risk of increased serum levels of medication, leading to seizures.

• • Fampridine is not recommended for children and during pregnancy and breastfeeding until safety data exist.

• • Evaluation of the effect should be performed at least once a year. If there are doubts about the effect, a new T25FW and MSWS-12 should be performed followed by 2 weeks without medication. If the repeated T25FW and MSWS-12 is unchanged or even better, the treatment should be discontinued permanently. If there was a clear worsening in the T25FW and/or the MSWS-12 after the 2 untreated weeks, the patient should resume the fampridine treatment.