GILENYA® 0.5 mg hard capsules
Each capsule contains 0.5 mg fingolimod (as hydrochloride).
For the 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 at least one disease modifying therapy (for exceptions and information about washout periods see sections 4.4 and 5.1).
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 at least one disease modifying therapy. 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.
The same first dose monitoring as for treatment initiation is recommended when treatment is interrupted for:
• 1 day or more during the first 2 weeks of treatment.
• more than 7 days during weeks 3 and 4 of treatment.
• more than 2 weeks after one month of treatment.
If the treatment interruption is of shorter duration than the above, the treatment should be continued with the next dose as planned (see section 4.4).
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 listed in section 6.1.
Bradyarrhythmia
Initiation of Gilenya treatment results in a transient decrease in heart rate and may also be associated with atrioventricular conduction delays, including the occurrence of isolated reports of transient, spontaneously resolving complete AV block (see sections 4.8 and 5.1).
After the first dose, the decline in heart rate starts within one hour, and is maximal within 6 hours. This post-dose effect persists over the following days, although usually to a milder extent, and usually abates over the next weeks. With continued administration, the average heart rate returns towards baseline within one month. However individual patients may not return to baseline heart rate by the end of the first month. Conduction abnormalities were typically transient and asymptomatic. They usually did not require treatment and resolved within the first 24 hours on treatment. If necessary, the decrease in heart rate induced by fingolimod can be reversed by parenteral doses of atropine or isoprenaline.
All patients should have an ECG and blood pressure measurement performed prior to and 6 hours after the first dose of Gilenya. All patients should be monitored for a period of 6 hours for signs and symptoms of bradycardia with hourly heart rate and blood pressure measurement. Continuous (real time) ECG monitoring during this 6 hour period is recommended.
Should post-dose bradyarrhythmia-related symptoms occur, appropriate clinical management should be initiated and monitoring should be continued until the symptoms have resolved. Should a patient require pharmacological intervention during the first-dose monitoring, overnight monitoring in a medical facility should be instituted and the first-dose monitoring should be repeated after the second dose of Gilenya.
If the heart rate at 6 hours is the lowest since the first dose was administered (suggesting that the maximum pharmacodynamic effect on the heart may not yet be manifest), monitoring should be extended by at least 2 hours and until heart rate increases again. Additionally, if after 6 hours, the heart rate is <45 bpm, or the ECG shows new onset second degree or higher grade AV block or a QTc interval ≥500 msec, extended monitoring (at least overnight monitoring), should be performed, and until the findings have resolved. The occurrence at any time of third degree AV block should also lead to extended monitoring (at least overnight monitoring).
Due to the risk of serious rhythm disturbances, Gilenya should not be used in patients with second degree Mobitz type II or higher AV block, sick-sinus syndrome, or sino-atrial heart block, a history of symptomatic bradycardia or recurrent syncope, or in patients with significant QT prolongation (QTc>470msec (female) or >450msec (male)). Since significant bradycardia may be poorly tolerated in patients with known ischaemic heart disease (including angina pectoris), cerebrovascular disease, history of myocardial infarction, congestive heart failure, history of cardiac arrest, uncontrolled hypertension or severe sleep apnoea, Gilenya should not be used in these patients. In such patients, treatment with Gilenya should be considered only if the anticipated benefits outweigh the potential risks. If treatment is considered, advice from a cardiologist should be sought prior to initiation of treatment in order to determine the most appropriate monitoring, at least overnight extended monitoring is recommended for treatment initiation (see also section 4.5).
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 p
