Special Warning : אזהרת שימוש

4.4     Special warnings and precautions for use

Renal and hepatic impairment
The pharmacokinetics of amifampridine has been assessed in a single dose Phase I study in patients with renal impairment (see section 5.2).

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. Upward dose titration should be discontinued if any adverse reaction occurs (see section 4.2).

Seizures

Exposure to amifampridine is associated with an increased risk for epileptic seizures. The risk of seizures is dose-dependent and is increased in patients with risk factors which lower the epileptic threshold; including use in combination with other medicinal products known to lower the epileptic threshold (see section 4.5). In the event of a seizure, treatment should be discontinued.

Carcinogenicity risk

The use of amifampridine in patients with the non-paraneoplastic form of LEMS should only be commenced following a thorough assessment of the risk-benefit to the patient.

In a 2-year dietary carcinogenicity study, benign and malignant Schwannomas have been observed in rats treated with amifampridine (see section 5.3). 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.

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.

Effects on Driving

4.7    Effects on ability to drive and use machines

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 (see section 4.8).

Important information about some ingredients of the medicine
FIRDAPSE is gluten-free medicinal product. Do not use if you are allergic to any of the other ingredients of this medicine (see Section 6.1).