Spirometric eva luation of respiratory function and eva luation of DLCO should be performed during therapy with GILENYA if clinically indicated.

Elevations of liver enzymes may occur in patients receiving GILENYA. Recent (i.e. within last 6 months) transaminase and bilirubin levels should be available before initiation of GILENYA therapy.

During clinical trials, 3-fold the upper limit of normal (ULN) or greater elevation in liver transaminases occurred in 8% of patients treated with GILENYA 0.5 mg, as compared to 2% of patients on placebo. Elevations 5-fold the ULN occurred in 2% of patients on GILENYA and 1% of patients on placebo. In clinical trials, GILENYA was discontinued if the elevation exceeded 5 times the ULN. Recurrence of liver transaminase elevations occurred with rechallenge in some patients, supporting a relationship to drug. The majority of elevations occurred within 3-4 months. Serum transaminase levels returned to normal within approximately 2 months after discontinuation of GILENYA.

Liver enzymes should be monitored in patients who develop symptoms suggestive of hepatic dysfunction, such as unexplained nausea, vomiting, abdominal pain, fatigue, anorexia, or jaundice and/or dark urine.  GILENYA should be discontinued if significant liver injury is confirmed. Patients with pre-existing liver disease may be at increased risk of developing elevated liver enzymes when taking GILENYA.

Because GILENYA exposure is doubled in patients with severe hepatic impairment, these patients should be closely monitored, as the risk of adverse reactions is greater [see Use in Spec ific Populations (8.5) and Clinical Pharmacology (12.3)]. 

Based on animal studies, GILENYA may cause fetal harm. Because it takes approximately 2 months to eliminate GILENYA from the body, women of childbearing potential should use effective contraception to avoid pregnancy during and for 2 months after stopping GILENYA treatment.

In MS clinical trials, patients treated with GILENYA 0.5 mg had an average increase of approximately 2 mmHg in systolic pressure, and approximately 1 mmHg in diastolic pressure, first detected after approximately 2 months of treatment initiation, and persisting with continued treatment. In controlled studies involving 854 MS patients on GILENYA 0.5 mg and 511 MS patients on placebo, hypertension was reported as an adverse reaction in 5% of patients on GILENYA 0.5 mg and in 3% of patients on placebo. Blood pressure should be monitored during treatment with GILENYA.

Fingolimod remains in the blood and has pharmacodynamic effects, including decreased lymphocyte counts, for up to 2 months following the last dose of GILENYA. Lymphocyte counts generally return to the normal range within 1-2 months of stopping therapy [see Clinical Pharmacology (12.2)]. Because of the continuing pharmacodynamic effects of fingolimod, initiating other drugs during this period warrants the same considerations needed for concomitant administration (e.g., risk of additive immunosuppressant effects) [see Drug Interactions (7)].

The following serious adverse reactions are described elsewhere in labeling:

The most frequent adverse reactions (incidence ≥10% and > placebo) for GILENYA 0.5 mg were headache, influenza, diarrhea, back pain, liver enzyme elevations, and cough. The only adverse event leading to treatment interruption reported at an incidence