Antineoplastic, immunosuppressive or immune modulating therapies are expected to increase the risk of immunosuppression.Use caution when switching patients from long-acting therapies with immune effects such as natalizumab or mitoxantrone.

Heart rate-lowering drugs (e.g., beta blockers or diltiazem)

Experience with GILENYA in patients receiving concurrent therapy with beta blockers is limited. These patients should be carefully monitored during initiation of therapy. When GILENYA is used with atenolol, there is an additional 15% reduction of heart rate upon GILENYA initiation, an effect not seen with diltiazem[see Warnings and Precautions(5.1)].

Laboratory test interaction

BecauseGILENYA reduces blood lymphocyte counts via redistribution in secondary lymphoid organs, peripheral blood lymphocyte counts cannot be utilized to eva luate the lymphocyte subset status of a patient treated with GILENYA. A recent CBC should be available before initiating treatment with GILENYA.

8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Pregnancy Category C

There are no adequate and well-controlled studies in pregnant women. In oral studies conducted in rats and rabbits, fingolimod demonstrated developmental toxicity, including teratogenicity (rats) and embryolethality, when given to pregnant animals. In rats, the highest no-effect dose was less than the recommended human dose (RHD) of 0.5 mg/day on a body surface area (mg/m2) basis. The most common fetal visceral malformations in rats included persistent truncus arteriosus and ventricular septal defect. The receptor affected by fingolimod (sphingosine1-phosphate receptor) is known to be involved in vascular formation during embryogenesis. Because it takes approximately 2 months to eliminate fingolimod from the body, potential risks to the fetus may persist after treatment ends [see Warnings and Precautions (5.7, 5.8)]. GILENYA should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Pregnancy Registry

A pregnancy registry has been established to collect information about the effect of GILENYA use during pregnancy. Physicians are encouraged to enroll pregnant patients, or pregnant women may enroll themselves in the GILENYA pregnancy registry by calling 1-877-598-7237.

Animal Data
When fingolimod was orally administered to pregnant rats during the period of organogenesis (0, 0.03, 0.1, and 0.3 mg/kg/day or 0, 1, 3, and 10 mg/kg/day), increased incidences of fetal malformations and embryo-fetal deaths were observed at all but the lowest dose tested (0.03 mg/kg/day), which is less than the RHD on a mg/m2 basis. Oral administration to pregnant rabbits during organogenesis (0, 0.5, 1.5, and 5 mg/kg/day) resulted in increased incidences of embryo-fetal mortality and fetal growth retardation at the mid and high doses. The no-effect dose for these effects in rabbits (0.5 mg/kg/day) is approximately 20 times the RHD on a mg/m2 basis.

When fingolimod was orally administered to female rats during pregnancy and lactation (0, 0.05, 0.15, and 0.5 mg/kg/day), pup survival was decreased at all doses and a neurobehavioral (learning) deficit was seen in offspring at the high dose. The low-effect dose of 0.05 mg/kg/day is similar to the RHD on a mg/m2 basis.

8.2 Labor and Deli