Research: Safety of Fampridine

Epub ahead of printCornblath CR et al. The Safety Profile of Dalfampridine Extended Release in Multiple Sclerosis Clinical Trials.Clin Ther. 2012 Apr 11.

BACKGROUND: Dalfampridine (fampridine outside the United States) is a broad-spectrum potassium channel blocker. This means it works by manipulating the flow of potassium ions into and out of nerve cells. Dalfampridine extended-release tablets have been approved by the FDA and EMA to improve walking speed in MSers.

OBJECTIVE: The objective is to review the safety profile of dalfampridine extended-release tablets with respect to its expected use in MSers.

METHODS: The authors reviewed published data relevant to MSer safety profiles based on searches of articles in PubMed published up to December 31, 2010, using the search terms fampridine OR dalfampridine OR 4-aminopyridine AND (multiple sclerosis) in combination with toxicity, safety, clinical trial, pharmacokinetics, and seizures. These searches were supplemented with data derived from the approved package insert and relevant sections of the New Drug Application (22-250) as submitted to the FDA.

RESULTS:  The literature searches returned 58 unique citations, of which 26 were considered relevant for characterizing the safety profile of dalfampridine; excluded citations were as follows: reviews (19), evaluation of 3,4-diaminopyridine (4), intravenous dosing (2), inadequate information on patient doses (2), preclinical models (2), and “other” (3). Dalfampridine is nearly completely (approximately 96%) eliminated unchanged in urine, with limited transformation to 2 inactive metabolites and low risk for interaction with drugs metabolized by hepatic P450 cytochromes. 

“This means it is unlikely to interact with other drugs in the liver.” 

However, in MSers with renal impairment mean peak plasma concentrations were 68%-101% higher and apparent clearance was 43%-73% lower relative to those without impairment, precluding dalfampridine use in MSers with moderate or severe renal impairment. 

Dalfampridine has a narrow therapeutic range. At the therapeutic dose of 10 mg twice daily, adverse events were generally mild to moderate and, consistent with the mechanism of action of dalfampridine, were primarily related to stimulatory effects on the nervous system. 

A thorough study suggested a low risk of induction of QT prolongation and associated cardiac arrhythmias in healthy individuals at therapeutic (10 mg, twice daily) or supratherapeutic (30 mg, twice daily) doses. 

“The QT interval refers to effects on the electrical conduction system in the heart.”

Although the incidence of seizures was dose related, data from the clinical trials of dalfampridine extended-release tablets suggest that the risk of seizure at the therapeutic dose, in MSers with no history of seizure, is not likely to be higher than background rates in MS.

“This is good news as this has always been a concern of using this drug.”

CONCLUSION: In MSers, dalfampridine has a narrow therapeutic range but an acceptable safety profile when used at the therapeutic dose of 10 mg twice daily.

“We are still having problems getting this drug funded under the NHS. The PCTs or Commissioner are unconvinced whether or not this drug impacts on the quality of life of MSers with walking difficulties. One PCT asked us if the drug prevents falls and hence fractures. A good questions as this may be construed to be a positive in relation to impact on QoL. The harsh facts are that until NICE reviews fampridine and we get a green light, i.e. it is deemed cost-effective to be used in the NHS, PCTs and Commissioners will always have a reason to say no. It is a pity as a minority of MSers respond very well to this drug.”

Other posts of interest on this blog in relation to fampridine:

12 Mar 2012
On 21 October 2009, there was a suggestion on this blog that fampridine might have a negative effect due to the additional strain put on damaged nerves, which obviously put me right off. “There is now good evidence that 
21 Jan 2011
“The Committee adopted a negative opinion recommending that fampridine, from Biogen-Idec Ltd, should not be granted a marketing authorisation. Fampyra was intended to be used to improve the walking ability of adult 
21 May 2011
Following the re-examination of its previous negative opinion, the European Medicines Agency has granted fampridine a conditional marketing authorisation; i.e. it has been licensed in Europe to improve the walking of PwMS 
21 Oct 2009
For these reasons I am wary about the long-term use of Fampridine in MS-related motor fatigue. I am worried that Fampridine may speed up the rate of disability progression. I stand to be proved incorrect on this; we will only 

01 Feb 2010
The drug was previously known as fampridine sustained release. Given at doses greater than the recommended 10 mg twice a day, dalfampridine can cause seizures. The most common adverse events reported in clinical 
15 Feb 2012
Re: “Fampyra or Fampridine” and “There is nothing to support the idea that MS symptoms can be pharmaceutically treated.” There is a very good scientific rationale for why fampridine works in MS and the trial results are 
28 Jul 2011
More recently the drug Fampridine has been licensed to improve walking speed in MS’ers; I suspect that MS’ers with heat sensitivity or fatigue-related conduction block will be more likely to be fampridine responders (see 
11 Nov 2011
Drugs like Fampridine and Nerispridine are said to improve walking in MS’ers with walking difficulties yet I have not seen MS welfare advocates, including this blog, champion the rights of MS’ers to gain access to these 

10 thoughts on “Research: Safety of Fampridine”

  1. Then why on earth is NICE not reviewing Fampradine?I have PPMS. As you know, there is no medication that can benefit me or modify my disease course. My walking is getting bad. I am very much struggling.I have asked my neurologist to submit an IFR for Famridine and he (my neurologist) and the physiotherapist who was sitting in on the meeting began to tell me that it will be unwise to do such a thing because there's no way to prove that I am an exceptional case who qualifies for Fampridine.I insisted they do the paperwork and issue an IFR. I told them to do their jobs and start taking an initiative. I argued that the actuality I am 27 years of age and basically neglected by the NHS is reason enough to suggest I am an exceptional case for Fampridine. They looked annoyed with me but said they will do as I requested. (I agree, I could have been more tactful but I get frustrated.)I honestly think that neurologists are reluctant to go the extra mile for us MSers, especially those with progressive MS. I also think PCTs are evil bastards who need to be sacked and forced into real jobs.Fampradine should be an option for people like me, no argument. If it doesn't work then I'll come off it and you can save some shrapnel, but at least let my try some.

  2. Re: "Fampradine should be an option for people like me, no argument. If it doesn't work then I'll come off it and you can save some shrapnel, but at least let my try some."I agree, but the average IFR takes up to about 2 hours of admin time. Your MS team may have already had one rejected. NICE has it own rules, which I disagree with. Let's fight!

  3. I am currently taking fampridine the last eight weeks with the help of my neurologist and MS nurse who have been extremely helpful. They are currently approaching the PCT with their findings and pursuing an IFR.I can only say this medication has been extremely helpful up-to-date as I also suffer from ppms.

  4. Glad to see the comments re-walking disaster.I have also replied and had a four week trial from Biogen. This is basically an assessment period using the 25 foot walk. At baseline. The walk is measured without medication and two weeks later again. If you are a responder medication is supplied for four weeks free of charge. You can discuss this approach with your neurologist, but at present. The drug is not funded by the NHS and, depending on the results an IFR is made independently to the PCT by the neurologist.hopefully, this information will be of use to others placed in my situation.

    1. Bottom line; the drug is too expensive! An 80% reduction in price would be appropriate. This is a repurposed drug therefore too much profit will be viewed as greed.

  5. As you state, in the bottom line. The drug is expensive but so is the condition. The overall benefits to health is significant and this is the argument being put forward to the PCT. Only one can really state the real benefits from a personal perspective when one is actually living with the condition themselves. Hopefully Nice will take this into consideration in their next appraisal.

  6. Gavin Giovannoni,have read this blog with mounting interest. I am aware that fampridine or fampyra administered in the USA to over 62,000 people with MS. I have now been taking fampridine for eight weeks now and can directly see the benefits, namely: clearer cognition, clearer speech, reduced salivation, partial strength restored-left hemiplegia. Reduction in spasticity, being able to stand to dry myself after a shower. Sensitivity to heat, now being able to stand up with more confidence. This drug provides a more sensible approach to the management of MS.

  7. A further consideration is when fampridine is combined with a FES (functional electronic stimulation). I presently score 6.5 on the EDSS and have worn a FES for approximately 5 years, from getting up to going to bed. This combination therapy. Hopefully we'll keep me relatively mobile for some years to come. I am mobile driving an automatic car and feel included in family dynamics. This I realise is not a cure, but a remedial therapy, which will maintain my independent status.I realise that this is a good medium to air. My views.

  8. a further improvement has been in my breathing. I can now inhale and exhale far better than previously. As my breathing was noted to be shallow and weak at times. In the mornings. My lungs were somewhat congested and I had to expectorate a somewhat frothy sputum, which was clear.I know this sounds rather dramatic, but my breathing is far more normal as a consequence of taking fampridine for approximately 9 weeks. The consequence of which is being disabled but more content. As you may realise this dictation has been generated by an ex-nurse with this condition.

  9. having taken fampridine for approximating 11 weeks now. I can definitely state the benefits that the drug is having upon my total well-being. I realise that this is remedial treatment for a progressive condition. I only hope that others placed in my position have the willpower to assert themselves with the relevant authorities. My neurologist and MS nurse are testament to this as they have seen actual results with the four responders taking this medication. Hopefully, it will be appraised and funded on the NHS.

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