GILENYA 0.5 mg hard capsules

Each capsule contains 0.5 mg fingolimod (as hydrochloride).

For a full list of excipients, see section 6.1.

Hard capsule

Capsule of 16 mm with bright yellow opaque cap and white opaque body; imprint with black ink, “FTY0.5 mg” on cap and two radial bands imprinted on the body with yellow ink.

Gilenya is indicated as single disease modifying therapy in highly active relapsing remitting multiple sclerosis for the following adult patient groups:

- Patients with high disease activity despite treatment with a beta-interferon.

These patients may be defined as those who have failed to respond to a full and adequate course (normally at least one year of treatment) of beta-interferon. Patients should have had at least 1 relapse in the previous year while on therapy, and have at least 9 T2-hyperintense lesions in cranial MRI or at least 1 Gadolinium-enhancing lesion. A “non-responder” could also be defined as a patient with an unchanged or increased relapse rate or ongoing severe relapses, as compared to the previous year.

or

- Patients with rapidly evolving severe relapsing remitting multiple sclerosis defined by 2 or more disabling relapses in one year, and with 1 or more Gadolinium enhancing lesions on brain MRI or a significant increase in T2 lesion load as compared to a previous recent MRI.

The treatment should be initiated and supervised by a physician experienced in multiple sclerosis.

Posology

The recommended dose of Gilenya is one 0.5 mg capsule taken orally once daily. Gilenya can be taken with or without food.

If a dose is missed treatment should be continued with the next dose as planned.

Patients can switch directly from beta interferon or glatiramer acetate to Gilenya provided there are no signs of relevant treatment-related abnormalities, e.g. neutropenia.

Special populations

Elderly population

Gilenya should be used with caution in patients aged 65 years and over due to insufficient data on safety and efficacy (see section 5.2).

Renal impairment

Gilenya was not studied in patients with renal impairment in the multiple sclerosis pivotal studies. Based on clinical pharmacology studies, no dose adjustments are needed in patients with mild to severe renal impairment.

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.

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.

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 products. class Ia and class III antiarrhythmic medicinal products have been associated with cases of torsades de pointes in patients with bradycardia. Since initiation of Gilenya treatment results in decreased heart rate, Gilenya should not be co-administered with these medicinal products.

At treatment initiation in patients receiving beta blockers, or other substances which may decrease heart rate (e.g. verapamil, digoxin, anticholinesteratic agents or pilocarpine), caution should be exercised because o