• Patients who in the last 6 months experienced myocardial infarction, unstable angina, stroke, TIA, decompensated heart failure (HF) requiring hospitalization or Class III/IV HF
• History or presence of Mobitz Type II second-degree or third-degree atrioventricular (AV) block or sick sinus syndrome, unless patient has a functioning pacemaker
• Baseline QTc interval ≥500 msec
• Treatment with Class Ia or Class III anti-arrhythmic drugs
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, 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 the same precautions if treatment is interrupted ≥1 day within the first 2 weeks or for >7 days during weeks 3 and 4.
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 is recommended prior to commencing GILENYA treatment, following which GILENYA initiation should be postponed for 1 month.
Typical symptoms associated with PML are diverse, progress over days to weeks, and include progressive weakness on one side of the body or clumsiness of limbs, disturbance of vision, and changes in thinking, memory, and orientation leading to confusion and personality changes. MRI signs may be apparent before clinical symptoms.
At the first sign or symptom suggestive of PML, withhold GILENYA and perform an appropriate diagnostic evaluation.