4-Aminopyridine (4-AP) (also known as aminopyridine, fampridine, dalfampridine and Fampyra) is known as a “potassium channel blocker”. This means that it can block the flow of potassium ions in nerve cells, which results in a more effective nerve impulse traveling down toward the muscles. It has been used for many years to treat symptoms associated with MS. The poor nerve impulses in patients with MS is the cause of most of the symptoms of the disease. The improved nerve conduction provided by the 4-AP means that the muscles receive the messages better to tell them when to work and the stronger muscle contractions improve strength and fatigue in many patients. Probably the most common problems people who suffer from Multiple Sclerosis (MS) face on a daily basis are weakness and fatigue. Also many patients are faced with visual problems and with cognitive or concentration effects. Very few of the standard treatments have much effect on these situations. However, clinical research has shown that many patients can benefit from this little-known medication, 4-Aminopyridine (4AP).
Why has my doctor not told me of this option?
4-AP is not a patentable medication, since it was discovered many years before its effects on MS were known. Some doctors may be aware of its existence, but are not aware that it is available. The medication is available through our laboratory on prescription as either slow release or immediate release capsules. Some doctors prefer to use an immediate release capsule exclusively, while others will change their patients to a sustained release form after a person’s correct dosage is determined.
A commercial version of 4AP is soon to be available called Fampyra which is very expensive. It is a 10mg, slow release tablet taken every 12 hours. It is expected to release its contents uniformly over a specific number of hours. Real life situations consist of differing diets and health conditions that make it unrealistic to expect that a swallowed dose will dissolve precisely as expected, time after time. While the slow release filler could help ease stomach distress for some medications, it is not likely an effective method for achieving consistent, clinically effective blood levels for drugs with narrow clinical windows.
From our experience, we conclude that the new commercial drug is likely to be less efficient and potentially more harmful than the compounded capsules. A single dose every 12 hours may be fine for some people, but the wide variation in the MS population can make it ineffective – and possibly dangerous – for others. For doctors who choose to dose more carefully, we suggest that 5mg immediate release capsules are a superior choice.
What kind of side effects can occur?
Patients report that side effects are usually minor, and include parenthesis (usually tingling sensations around the face) and occasional stomach problems. The most serious side effect is seizures, which is a dose-related problem. For this reason the dosage is tailored to each individual and the person’s maximum dose should never be exceeded.
Dosing with Aminopyridine
There’s a “trick” to using 4AP correctly which is a ramping schedule shown below. Begin at 5mg per day and increases per the schedule to a level of 30 to 40mg per day – 0.23mg/pound. It is profoundly unwise to use more than that. It typically takes two weeks to achieve the maximum effective, safe dose. Doses are spaced four to five hours apart. Here is one suggested ramping schedule:
・ 5mg per day – in the morning – for 2 days
・ Then, 5mg BID (twice daily; breakfast and late afternoon) for 3 days.
・ Then, 5mg TID (3 times a day; every 5-6 hours while awake) for 4 days = 15 mg/day
・ Then, 5mg QID (4 times a day; every 4-5 hours while awake) for 5 days = 20 mg/day
・ Then, IF TOLERATED and if needed may go up gradually to 10mg QID (4 times a day; every 4-5 hours while awake) = 40 mg/day maximum