Fingolimod

GILENYA is indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in patients 10 years of age and older. GILENYA is a sphingosine 1-phosphate receptor modulator indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in patients 10 years of age and older.

Fingolimod is metabolized by sphingosine kinase to the active metabolite, fingolimod-phosphate. Fingolimod-phosphate is a sphingosine 1-phosphate receptor modulator, and binds with high affinity to sphingosine 1-phosphate receptors 1, 3, 4, and 5. Fingolimod-phosphate blocks the capacity of lymphocytes to egress from lymph nodes, reducing the number of lymphocytes in peripheral blood. The mechanism by which fingolimod exerts therapeutic effects in multiple sclerosis is unknown, but may involve reduction of lymphocyte migration into the central nervous system.

Assessments are required prior to initiating GILENYA. Recommended dosage for adults and pediatric patients (10 years of age and older) weighing more than 40 kg: 0.5 mg orally once daily, with or without food. Recommended dosage for pediatric patients (10 years of age and above) weighing less than or equal to 40 kg: 0.25 mg orally once daily, with or without food. First-Dose Monitoring (including reinitiation after discontinuation greater than 14 days and dose increases): Observe all patients for bradycardia for at least 6 hours, monitor pulse and blood pressure hourly. Electrocardiograms (ECGs) prior to dosing and at end of observation period required.

GILENYA is contraindicated in patients who have: in the last 6 months experienced myocardial infarction, unstable angina, stroke, transient ischemic attack (TIA), decompensated heart failure requiring hospitalization or Class III/IV heart failure a history or presence of Mobitz Type II second-degree or third-degree AV block or sick sinus syndrome, unless patient has a functioning pacemaker a baseline QTc interval ≥ 500 msec cardiac arrhythmias requiring anti-arrhythmic treatment with Class Ia or Class III anti-arrhythmic drugs had a hypersensitivity reaction to fingolimod or any of the excipients in GILENYA. Observed reactions include rash, urticaria and angioedema upon treatment initiation.

Infections: GILENYA may increase the risk. Obtain a complete blood count (CBC) before initiating treatment. Monitor for infection during treatment and for 2 months after discontinuation. Do not start in patients with active infections. Progressive Multifocal Leukoencephalopathy (PML): Withhold GILENYA at the first sign or symptom suggestive of PML. Macular Edema: Increases the risk of macular edema. Obtain a baseline evaluation of the fundus, including the macula, near the start of treatment with GILENYA. Conduct an evaluation of the fundus, including the macula, 3 to 4 months after treatment start, periodically while on therapy and any time there is a change in vision. Consider discontinuing GILENYA if macular edema develops. Diabetes mellitus and uveitis increase the risk. Liver Injury: Obtain liver enzyme results before initiation and periodically during treatment.

The following serious adverse reactions are described elsewhere in labeling: Bradyarrhythmia and Atrioventricular Blocks Infections Progressive Multifocal Leukoencephalopathy Macular Edema Liver Injury Posterior Reversible Encephalopathy Syndrome Respiratory Effects Fetal Risk Severe Increase in Disability After Stopping GILENYA Tumefactive Multiple Sclerosis Increased Blood Pressure Malignancies Immune System Effects Following GILENYA Discontinuation Hypersensitivity Reactions Most common adverse reactions (incidence ≥ 10% and greater than placebo): Headache, liver transaminase elevation, diarrhea, cough, influenza, sinusitis, back pain, abdominal pain, and pain in extremity.

Systemic Ketoconazole: Monitor during concomitant use. Vaccines: Avoid live attenuated vaccines during, and for 2 months after stopping GILENYA treatment.

GILENYA capsules should be stored at 20ºC to 25ºC (68ºF to 77ºF), excursions permitted to 15ºC to 30ºC (59ºF to 86ºF). Protect from moisture.