Indication and Important Safety Information
- GILENYA is a sphingosine 1-phosphate receptor modulator indicated for the treatment of adult patients with relapsing forms of multiple sclerosis (MS) to reduce the frequency of clinical exacerbations and to delay the accumulation of physical disability.
Important Safety Information
- GILENYA is contraindicated in patients with recent myocardial infarction (MI), unstable angina, stroke, transient ischemic attack, decompensated heart failure (HF) requiring hospitalization or Class III/IV HF, and in patients with a history or presence of Mobitz Type II 2nd or 3rd degree atrioventricular (AV) block or sick sinus syndrome, unless patient has a pacemaker, baseline QTc interval ≥500 ms, and treatment with Class Ia or Class III anti-arrhythmics.
- Patients should be monitored during GILENYA initiation because of the risk for bradyarrhythmia and AV blocks. Observe all patients for signs and symptoms of bradycardia for at least 6 hours after first dose with hourly pulse and blood pressure (BP) measurement. Obtain an electrocardiogram (ECG) prior to dosing and at the end of the observation period. Patients who develop a heart rate (HR) <45 bpm or new onset 2nd degree or higher AV block should be monitored until resolution. Patients at lowest post-dose HR at end of observation period should be monitored until HR increases. Begin continuous ECG monitoring in patients with symptomatic bradycardia, and if pharmacological intervention is needed, continue ECG monitoring overnight in a medical facility and repeat first-dose monitoring for 2nd dose. Some patients may experience a 2nd decrease in HR within 24 hours after the first dose.
- Patients with pre-existing ischemic heart disease, history of MI or cardiac arrest, CHF, cerebrovascular disease, uncontrolled hypertension, history of symptomatic bradycardia or recurrent syncope, severe untreated sleep apnea, AV block, sinoatrial heart block, and patients on concomitant drugs that slow HR or AV conduction should be evaluated by a physician and, if treated with GILENYA, should be monitored overnight with continuous ECG in a medical facility after the first dose due to higher risk of symptomatic bradycardia or heart block. Patients with or at risk for QT prolongation or on concomitant QT-prolonging drugs with a known risk of torsades de pointes should also be monitored overnight with continuous ECG. If GILENYA is discontinued for >14 days after the first month of treatment, the effects on HR and AV conduction may recur on reintroduction of treatment and the same precautions for initial dosing should apply. Take same precautions if treatment is interrupted ≥1 day within the first 2 weeks or for >7 days during weeks 3 and 4.
- GILENYA may increase the risk of infections. A recent complete blood count should be available before initiating GILENYA. Suspension of GILENYA should be considered if a patient develops a serious infection. Monitor for signs and symptoms of infection during treatment and up to 2 months after discontinuation. Do not start GILENYA in patients with active acute or chronic infections. Two patients receiving a higher dose of GILENYA (1.25 mg) in conjunction with high-dose corticosteroid therapy died of herpetic infections. Concomitant use with antineoplastic, immunosuppressive, or immune modulating therapies would be expected to increase the risk of immunosuppression. To avoid additive immunosuppressive effects, consider the duration and mode of action of such substances.
- Before initiating GILENYA, patients without a history of chickenpox or without vaccination against varicella zoster virus (VZV) should be tested for antibodies to VZV. VZV vaccination of antibody-negative patients should be considered prior to commencing GILENYA treatment, following which GILENYA initiation should be postponed for 1 month.
- Macular edema can occur, with or without visual symptoms. An ophthalmologic evaluation should be performed before starting GILENYA and at 3 to 4 months after initiation. Monitor visual acuity at baseline and during routine patient evaluations. Patients with diabetes mellitus or history of uveitis are at increased risk and should have regular ophthalmologic evaluations.
- Rare cases of posterior reversible encephalopathy syndrome (PRES) were reported in patients receiving GILENYA. Symptoms reported included sudden onset of severe headache, altered mental status, visual disturbances, and seizure. Symptoms of PRES are usually reversible but may evolve into ischemic stroke or cerebral hemorrhage. Delay in diagnosis and treatment may lead to permanent neurological sequelae. If PRES is suspected, GILENYA should be discontinued.
- Decreases in pulmonary function tests can occur. Dose-dependent reductions in forced expiratory volume over 1 second (FEV1) and diffusion lung capacity for carbon monoxide (DLCO) were observed in GILENYA patients as early as 1 month after initiation. The changes in FEV1 appear to be reversible after discontinuing GILENYA; however, there is insufficient information to determine the reversibility of DLCO. Obtain spirometry and DLCO when clinically indicated.
- Liver transaminases may increase. Recent liver transaminase and bilirubin levels should be available before initiating GILENYA. Elevations 3- and 5-fold the upper limit of normal occurred with GILENYA. Recurrence of liver transaminase elevations occurred with rechallenge in some patients. The majority of elevations occurred within 6 to 9 months and returned to normal within 2 months after discontinuing GILENYA. Assess liver enzymes if symptoms suggestive of hepatic injury develop. Discontinue GILENYA if significant liver injury is confirmed.
- GILENYA may cause fetal harm. Women of childbearing potential should use effective contraception during and for 2 months after stopping GILENYA. A registry for women who become pregnant during GILENYA treatment is available. For information, contact the GILENYA Pregnancy Registry by calling OUTCOME at 1-877-598-7237, sending an e-mail to email@example.com, or accessing gilenyapregnancyregistry.com.
- BP should be monitored during treatment with GILENYA. An average increase of 3 mm Hg in systolic and 2 mm Hg in diastolic BP was observed.
- GILENYA remains in the blood, and has pharmacodynamic effects, including decreased lymphocyte counts, for up to 2 months following the last dose. Lymphocyte counts generally return to normal range within 1 to 2 months of stopping therapy. Initiating other drugs during this period warrants the same considerations needed for concomitant administration.
- Closely monitor patients receiving systemic ketoconazole. The use of live attenuated vaccines should be avoided during and for 2 months after stopping GILENYA.
- The most common adverse reactions with GILENYA (incidence ≥10% and >placebo) compared with placebo were headache (25% vs 23%), influenza (13% vs 10%), diarrhea (12% vs 7%), back pain (12% vs 7%), liver transaminase elevations (14% vs 5%), and cough (10% vs 8%).