Label Changes for:
Changes have been made to the WARNINGS and PRECAUTIONS sections of the safety label.
Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER)
WARNINGS AND PRECAUTIONS
5.4 Posterior Reversible Encephalopathy Syndrome
- new section added
- Patients who in the last 6 months experienced myocardial infarction, unstable angina, stroke, TIA, decompensated heart failure requiring hospitalization or Class III/IV heart failure
- 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 ms
- Treatment with Class Ia or Class III anti-arrhythmic drugs
5 WARNINGS AND PRECAUTIONS
5.1 Bradyarrhythmia and Atrioventricular Blocks
- Because of a risk for bradyarrhythmia and atrioventricular (AV) blocks, patients should be monitored during GILENYA treatment initiation [see Dosage and Administration (2)].
Reduction in heart rate
- After the first dose of GILENYA, the heart rate decrease starts within an hour. On Day 1, the maximal decline in heart rate generally occurs within 6 hours .....
- In the post-marketing setting, third degree AV block and AV block with junctional escape have been observed during the first-dose six-hour observation period .....
7 DRUG INTERACTIONS
QT prolonging drugs
- GILENYA has not been studied in patients treated with drugs that prolong the QT interval. Drugs that prolong the QT interval have been associated with cases of torsades de pointes in patients with bradycardia. Since initiation of GILENYA treatment results in decreased heart rate and may prolong the QT interval, patients on QT prolonging drugs with a known risk of torsades de pointes (e.g., citalopram, chlorpromazine, haloperidol, methadone, erythromycin) should be monitored overnight with continuous ECG in a medical facility [see Dosage and Administration (2) and Warnings and Precautions (5.1)].
- The blood levels of fingolimod and fingolimod-phosphate are increased by 1.7-fold when used concomitantly with ketoconazole.
Drugs that slow heart rate or atrioventricular conduction (e.g., beta blockers or diltiazem)
- Experience with GILENYA in patients receiving concurrent therapy with drugs that slow the heart rate or atrioventricular conduction (e.g., beta blockers, digoxin, or heart-rate slowing calcium channel blockers such as diltiazem or verapamil) is limited. Because initiation of GILENYA treatment may result in .....
17 PATIENT COUNSELING INFORMATION
17.2 Cardiac Effects
- Advise patients that initiation of GILENYA treatment results in a transient decrease in heart rate. Inform patients that they will need to be observed in the doctor's office or other facility for at least 6 hours after the first dose. Advise patients that if GILENYA is discontinued for more than 14 days, effects similar to those observed on treatment initiation may be seen and observation for at least 6 hours will be needed on treatment re-initiation, and that the same precautions will be taken if treatment is interrupted for more than one day within the first 2 weeks of treatment, or for more than 7 days during week 3 and 4 of treatment
Extensive changes to:
- What is the most important information I should know about GILENYA?
- Who should not take GILENYA?
- What should I tell my doctor before taking GILENYA?
- How should I take GILENYA?
5 WARNINGS AND PRECAUTIONS
5.5 Hepatic Effects
- "...the majority of elevations...within 3-4 months" is changed to "...occurred within 6-9 months."