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4-Aminopyradine

 

What is Ampyra?

Formerly known as fampridine SR, Ampyra is a tablet containing a sustained-release formula of 4-aminopyridine, which blocks tiny pores, or potassium channels, on the surface of nerve fibers. This blocking ability may improve the conduction of nerve signals in nerve fibers whose insulating myelin coating has been damaged by MS. Until the emergence of this symptomatic therapy there was no pharmacologic treatment available for MS-related difficulty with walking.

Clinical Trials

Clinical trials of Ampyra have reported that a significantly greater proportion of people on the therapy had a consistent improvement in walking speed, motor function and sensation
compared to those who took placebo. Among those taking Ampyra who improved in walking speed there was a statistically significant improvement in leg strength. 2 3 4

A randomized, double-blind, placebo-controlled, crossover trial of oral 4-aminopyridine also indicated that it had a significant impact on fatigue 1.

Further study and clinical practice may help determine the extent to which the drug may impact other functions not measured in these clinical trials, and provide hints as to which individuals are most likely to respond.

Potential Side Effects

In the first phase III study, common adverse events (side effects) experienced more often by those on active treatment included back pain, dizziness, insomnia, fatigue, nausea and balance disorder. Two serious adverse events led participants to discontinue taking the drug (one case of anxiety and one seizure in a person who developed sepsis from a urinary tract infection). In the second phase III study, additional common adverse events in those on therapy included urinary tract infection, falls, and headache.

Adverse events (side effects) were experienced during the trials including back pain, insomnia, fatigue, nausea, paresthesias, dizziness, and light-headedness 4 5.
Seizures can occur as a result of excess dosing.

Ampyra was approved for persons with any type of multiple sclerosis. However, the drug should NOT be taken by individuals with a history of seizures, or by those with moderate to severe renal impairment. If a person has moderate to severe kidney impairment, then there is a danger that the concentration of the drug will increase in the blood beyond the amount considered safe, potentially resulting in seizures.

Some people in the clinical trials of Ampyra experienced a worsening of their MS symptoms when they stopped taking the medication. It was unclear whether this reflected a return to their pre-trial state or an actual relapse, but the FDA did not make a distinction between the two when listing possible side effects. The FDA did, however, determine that the risk-benefit ratio for Ampyra is satisfactory.

Availability

While Ampyra has been approved by the FDA in January of this year and is available on prescription in the U.S., it is unavailable in New Zealand as it is currently being reviewed by Medsafe.

However 4-aminopyridine or fampridine, a compounding version of Ampyra, can be obtained from compounding pharmacies in New Zealand.

One potential risk to weigh up in taking the compounding drug is the increased risk of inconsistent dosing and the subsequent potential for seizures.

The main difference between Ampyra and 4-AP is that Ampyra has been formulated to give a slow, sustained release. 

However, 4-AP can be obtained from compounding pharmacies as a slow release formulation by compounding it with Methocel. But there is still a risk of inconsistent and excess dosing so it is recommended that the dosage is ramped starting on a lower dose and that you are careful to be aware of any side effects that you may  experience.

4-Aminopyradine (slow release) can be obtained from a compounding pharmacy in Auckland:

Pharmaceutical Compounding Auckland

info@pharmaceutical.co.nz

09 442 1727

Prescribing Information

The maximum recommended dose of AMPYRA is one 10 mg tablet twice daily, taken with or without food, and should not be exceeded. Doses should be taken approximately 12 hours apart. Patients should not take double or extra doses if a dose is missed.

No additional benefit was demonstrated at doses greater than 10 mg twice daily and adverse reactions and discontinuations because of adverse reactions were more frequent at higher doses. Tablets should only be taken whole; do not divide, crush, chew, or dissolve.

Due to the risk of excess dosing and the potential inconsistency of the release of 4-AP it is recommended that you ramp the dosage, beginning with 5mg once a day

Ensure that you obtain professional medical advice

It is important to consult your doctor before pursuing any treatment path.

References

1 Fatigue in progressive multiple sclerosis: results of a randomized, double-blind, placebo-controlled, crossover trial of oral 4-aminopyridine 

Rossini PM, Pasqualetti P, Pozzilli C, Grasso MG, Millefiorini E, Graceffa A, Carlesimo GA, Zibellini G, Caltagirone C.

2 Sustained-release oral fampridine in multiple sclerosis: a randomised, double-blind, controlled trial

The Lancet, Volume 373, Issue 9665,

3 Efficacy and safety of 4-aminopyridine in patients with long-term spinal cord injury: a randomized, double-blind, placebo-controlled trial

Grijalva I, Guízar-Sahagún G, Castañeda-Hernández G, Mino D, Maldonado-Julián H, Vidal-Cantú G, Ibarra A, Serra O, Salgado-Ceballos H, Arenas-Hernández R.

4 The effect of 4-aminopyridine on clinical signs in multiple sclerosis: a randomized, placebo-controlled, double-blind, cross-over study

van Diemen HA, Polman CH, van Dongen TM, van Loenen AC, Nauta JJ, Taphoorn MJ, van Walbeek HK, Koetsier JC.

5  4-Aminopyridine in patients with multiple sclerosis: dosage and serum level related to efficacy and safety

Clin Neuropharmacol. 1993 Jun;16(3):195-204.