Fingolimod

Contraindications

4 CONTRAINDICATIONS Fingolimod capsules are 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 [see Warnings and Precautions (5.1) ] • 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 fingolimod capsules. Observed reactions include rash, urticaria and angioedema upon treatment initiation [see Warnings and Precautions (5.14) ] . • Recent myocardial infarction, unstable angina, stroke, transient ischemic attack (TIA), decompensated heart failure with hospitalization, or Class III/IV heart failure. (4) • History of Mobitz Type II 2 nd degree or 3 rd degree AV block or sick sinus syndrome, unless patient has a pacemaker. (4) • Baseline QTc interval ≥500 msec. (4) • Cardiac arrhythmias requiring anti-arrhythmic treatment with Class Ia or Class III anti-arrhythmic drugs. (4) • Hypersensitivity to fingolimod or its excipients. (4)

Pregnancy & Breastfeeding

8.1 Pregnancy Risk Summary Available observational pregnancy registry data suggest that use of fingolimod is associated with an increased prevalence of major birth defects in comparison to the general population. However, limitations in the number of exposed pregnant women and in the study design preclude definitive conclusions (see Data) . Data from prospective reports to the pregnancy registry are currently not sufficient to allow for an adequate assessment of the drug-associated risk for miscarriage. Based on findings from animal studies, fingolimod may cause fetal harm when administered to a pregnant woman. In oral studies conducted in rats and rabbits, fingolimod demonstrated developmental toxicity, including an increase in malformations (rats) and embryolethality, when given to pregnant animals. In rats, the highest no-effect dose was less than the recommended human dose of 0.5 mg/day on a body surface area (mg/m 2 ) basis. The most common fetal visceral malformations in rats were persistent truncus arteriosus and ventricular septal defect. The receptor affected by fingolimod (sphingosine 1-phosphate receptor) is known to be involved in vascular formation during embryogenesis ( see Data ) . Advise pregnant women of the potential risk to a fetus. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown. Clinical Considerations In females planning to become pregnant, fingolimod should be stopped 2 months before planned conception. The possibility of severe increase in disability should be considered in women who discontinue or are considering discontinuation of fingolimod because of pregnancy or planned pregnancy. In many of the cases in which increase in disability was reported after stopping fingolimod, patients had stopped fingolimod because o