Amifampridine

The concomitant use of amifampridine and medicinal products with non-depolarising muscle relaxant effects (e.g. mivacurium, pipercurium) may lead to a decreased effect of both products and should be taken into consideration.

Amifampridine should be used with caution in patients with renal or hepatic impairment. A starting dose of 5 mg amifampridine (half tablet) once per day is recommended in patients with moderate or severe impairment of renal or hepatic function. For patients with mild impairment of renal or hepatic function, a starting dose of 10 mg amifampridine (5 mg twice a day) per day is recommended. Patients should be titrated more slowly than those without renal or hepatic impairment with doses increased in 5 mg increments every 7 days. If any adverse reaction occurs, upward dose titration should be discontinued.

The concomitant use of amifampridine and substances known to lower the epileptic threshold may lead to an increased risk of seizures. The decision to administer proconvulsant or epileptic-threshold lowering substances concomitantly should be carefully considered in the light of the severity of the associated risks. These substances include most anti-depressants (tricyclic antidepressants, selective serotonin uptake inhibitors), neuroleptics (phenothiazines and butyrophenones), mefloquine, bupropion and tramadol. In the event of a seizure, treatment should be discontinued.

The concomitant use of amifampridine and medicinal products with atropinic effects may reduce the effect of both active substances and should be taken into consideration. Medicinal products with atropinic effects include tricyclic anti-depressants, most H₁ atropinic anti-histamines, anticholinergic, anti-Parkinson medicinal products, atropinic antispasmodics, disopyramide, phenothiazine neuroleptics and clozapine.

The concomitant use of amifampridine and medicinal products with cholinergic effects (e.g. direct or indirect cholinesterase inhibitors) may lead to an increased effect of both products and should be taken into consideration.

The concomitant use of amifampridine and medicinal products with depolarising muscle relaxant effects (e.g. suxamethonium) may lead to a decreased effect of both products and should be taken into consideration.

Amifampridine should not be used during pregnancy. Women of childbearing potential must use effective contraception during amifampridine treatment. No adequate clinical data on exposed pregnancies are available for amifampridine. Amifampridine has shown no effect on embryo-foetal viability and development in rabbits; however, in rats, an increase in the number of mothers delivering still-born offspring was observed.

It is unknown whether amifampridine is excreted in human breast milk. Available reproductive data in animals have shown presence of amifampridine in milk of breast-feeding mothers. Assessment of breast-feeding neo-natal animals showed no indication of adverse reactions when exposed to amifampridine through breast-milk. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from amifampridine therapy taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman.

Fertility

Non-clinical safety data are available regarding the effects of amifampridine on reproductive function. No impairment of fertility has been observed in non-clinical studies with amifampridine.

Due to adverse reactions such as drowsiness, dizziness, seizures and blurred vision, amifampridine may have minor or moderate influence on the ability to drive or use machines.

Summary of the safety profile

The most commonly reported adverse reactions are paraesthesias (such as peripheral and peribucal paraesthesias) and gastro-intestinal disorders (such as epigastralgia, diarrhoea, nausea and abdominal pain). The intensity and incidence of most adverse reactions is dose-dependent.

The table below lists the adverse reactions reported with amifampridine.

Tabulated list of adverse reactions

Frequencies are defined as: Very common (≥1/10), Common (≥1/100 to <1/10), Uncommon (≥1/1000 to <1/100), Rare (≥1/10,000 to <1/1,000), Very rare (<1/10,000) and Unknown (cannot be estimated from available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

Frequencies were estimated based on a clinical study to evaluate the effects of amifampridine on cardiac repolarization at a single dose of 30 mg or 60 mg in healthy volunteers.

Adverse Reactions Reported with Amifampridine:

¹ Adverse reactions reported in a clinical study to evaluate the effects of amifampridine on cardiac repolarization at a single dose of 30 mg or 60 mg in healthy volunteers.