Amifampridine SERB

Treatment should be initiated under supervision of a physician experienced in the treatment of the disease. Posology Amifampridine SERB should be given in divided doses, three or four times a day. The recommended starting dose is 15 mg amifampridine a day, which can be increased in 5 mg increments every 4 to 5 days, to a maximum of 60 mg per day.

No single dose should exceed 20 mg. Tablets are to be taken with food. 2 for further information about bioavailability of amifampridine in the fed and fasted state. If treatment is discontinued, patients may experience some of the symptoms of LEMS.

Renal or hepatic impairment Amifampridine SERB 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.

2). Paediatric population The safety and efficacy of Amifampridine SERB in children aged 0 to 17 years has not been established. No data are available. 3 Method of administration For oral use only.

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. 6 Table 1 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.

Table 1:

Adverse reactions reported with amifampridine MedDRA System organ class MedDRA Preferred term Frequency Psychiatric disorders Sleep disorders, anxiety Unknown Nervous system disorders Convulsions, chorea, myoclonia drowsiness, weakness, fatigue, headache Unknown Dizziness1, hypoaesthesia1, paraesthesia1 Very common Eye disorders Blurred vision Unknown Cardiac disorders Cardiac rhythm disorders, palpitations Unknown Vascular disorders Raynaud's syndrome Unknown Cold extremities1 Common Respiratory, thoracic and mediastinal disorders Bronchial hypersecretion, asthma attack in asthmatic patients or patients with a history of asthma, cough Unknown Gastrointestinal disorders Hypoaesthasia oral1, paraesthesia oral1, peripheral and peribucal paraesthesias, nausea1 Very common Abdominal pain Common Diarrhoea, epigastralgia Unknown Hepatobiliary disorders Elevated liver enzyme levels (transaminases) Unknown Skin and subcutaneous disorders Hyperhidrosis1, cold sweat1 Very common 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.

2). No studies have been conducted in patients with hepatic impairment. In view of the risk of markedly increased exposure to medicinal product, patients with renal or hepatic impairment must be carefully monitored. The dose of amifampridine should be titrated more slowly in patients with renal and hepatic impairment than those with normal renal and hepatic function.

2). Seizures Exposure to amifampridine is associated with an increased risk for epileptic seizures. 5). In the event of a seizure, treatment should be discontinued. 3). Amifampridine was not genotoxic in a standard battery of in vitro and in vivo tests.

The correlation between the use of amifampridine and the development of tumours in humans is unknown at this time. Most Schwannomas are benign and asymptomatic. They can present in many locations, therefore the clinical presentation can be varied.

A diagnosis of Schwannoma should be considered for patients who present with symptoms such as a mass that is painful on palpation or symptoms similar to a compressive neuropathy. Schwannomas are generally slow-growing and can exist for months to years without producing symptoms.

The benefit of continuing treatment with amifampridine should be reviewed for any patient who develops a Schwannoma. Amifampridine should be used with caution in patients with an increased risk of Schwannomas, such as patients with past medical history of such tumours, neurofibromatosis Type 2 or schwannomatosis.

Cardiac effects Clinical and electrocardiogram (ECG) monitoring are indicated at the initiation of the treatment and yearly thereafter. In case of signs and symptoms indicative of cardiac arrhythmias, ECG should be performed immediately.

4 Concomitant diseases Patients must be told to inform any physician they consult that they are taking this medicinal product, since close monitoring of a concomitant disease, particularly asthma, may be necessary.

1. 4)