Hepatic impairment

Gilenya must not be used in patients with severe hepatic impairment (Child-Pugh class C) (see section 4.3). Although no dose adjustments are needed in patients with mild or moderate hepatic impairment, caution should be exercised when initiating treatment in these patients (see sections 4.4 and 5.2).

Diabetic patients

Gilenya has not been studied in multiple sclerosis patients with concomitant diabetes mellitus. Gilenya should be used with caution in these patients due to a potential increase in the risk of macular oedema (see sections 4.4 and 4.8). Regular ophthalmological examinations should be conducted in these patients to detect macular oedema.

Paediatric population

The safety and efficacy of Gilenya in children aged 0 to 18 years have not yet been established. Currently available data are described in section 5.2 but no recommendation on a posology can be made.

4.3 Contraindications

 Known immunodeficiency syndrome.

Patients with increased risk for opportunistic infections, including immunocompromised patients (including those currently receiving immunosuppressive therapies or those immunocompromised by prior therapies).

Severe active infections, active chronic infections (hepatitis, tuberculosis).

Known active malignancies, except for patients with cutaneous basal cell carcinoma.

Severe liver impairment (Child-Pugh class C).

Hypersensitivity to the active substance or to any of the excipients.

4.4 Special warnings and precautions for use

 Bradyarrhythmia

Initiation of Gilenya treatment results in a transient decrease in heart rate and may also be associated with atrioventricular conduction delays (see sections 4.8 and 5.1). Therefore, all patients should be observed for a period of 6 hours for signs and symptoms of bradycardia. Should post-dose bradyarrhythmia-related symptoms occur, appropriate clinical management should be initiated and observation should be continued until the symptoms have resolved.

After the first dose, the decline in heart rate starts within one hour and is maximal at approximately 4-5 hours. With continued administration, heart rate returns to baseline within one month. Conduction abnormalities were typically transient and asymptomatic. They usually did not require treatment and resolved within the first 24 hours on treatment.

Gilenya has not been studied in patients with sitting heart rate less than 55 beats per minute, patients receiving concurrent therapy with beta blockers or in those with a history of syncope.

Gilenya has also not been studied in patients with second degree or higher AV block, sick-sinus syndrome, ischaemic cardiac disease, congestive heart failure or significant cardiovascular disease. Use of Gilenya in such patients should be based on overall benefit-risk assessment and careful observation during initiation of therapy is recommended due to the potential for serious rhythm disturbances. Before initiation of treatment in these patients, advice from a cardiologist is recommended.

Gilenya has not been studied in patients with arrhythmias requiring treatment with class Ia (e.g. quinidine, disopyramide) or class III (e.g. amiodarone, sotalol) antiarrhythmic medicinal pr