Suspension of Gilenya should be considered if a patient develops a serious infection and consideration of benefit-risk should be undertaken prior to re-initiation of therapy.

Elimination of fingolimod following discontinuation of therapy may take up to two months and vigilance for infection should therefore be continued throughout this period. Patients should be instructed to report symptoms of infection up to 2 months after discontinuation of fingolimod.

Macular oedema

Macular oedema with or without visual symptoms has been reported in 0.4% of patients treated with fingolimod 0.5 mg, occurring predominantly in the first 3-4 months of therapy (see section 4.8). An ophthalmological eva luation is therefore recommended at 3-4 months after treatment initiation. If patients report visual disturbances at any time while on therapy, eva luation of the fundus, including the macula, should be carried out.

Patients with history of uveitis and patients with diabetes mellitus are at increased risk of macular oedema (see section 4.8). Gilenya has not been studied in multiple sclerosis patients with concomitant diabetes mellitus. It is recommended that multiple sclerosis patients with diabetes mellitus or a history of uveitis undergo an ophthalmological eva luation prior to initiating therapy and have follow-up eva luations while receiving therapy.

Continuation of Gilenya in patients with macular oedema has not been eva luated. It is recommended that Gilenya be discontinued if a patient develops macular oedema. A decision on whether or not Gilenya therapy should be re-initiated after resolution of macular oedema needs to take into account the potential benefits and risks for the individual patient.

Liver function

During clinical trials, elevations 3-fold the upper limit of normal (ULN) or greater in liver transaminases occurred in 8% of patients treated with fingolimod 0.5 mg compared to 2% of placebo patients. Elevations 5-fold the ULN occurred in 2% of patients on fingolimod and 1% of patients on placebo. In clinical trials, fingolimod 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 fingolimod. The majority of elevations occurred within 3-4 months. Serum transaminase levels returned to normal within approximately 2 months after discontinuation of fingolimod.

Gilenya has not been studied in patients with severe pre-existing hepatic injury (Child-Pugh class C) and should not be used in these patients (see section 4.3).

Due to the immunosuppressive properties of fingolimod, initiation of treatment should be delayed in patients with active viral hepatitis until resolution.

Recent (i.e. within last 6 months) transaminase and bilirubin levels should be available before initiation of treatment with Gilenya. In the absence of clinical symptoms, liver transaminases should be monitored at Months 1, 3 and 6 on therapy and periodically thereafter. If liver transaminases rise above 5 times the ULN, more frequent monitoring should be instituted, including serum bilirubin and alkaline phosphatase (ALP) measurement. With repeated confirmation of liver transaminases above 5 times the ULN, treatment with Gilenya should be interrupted and only re-commenced once liver transaminase values have normalised.

Patients who develop symptoms suggestive of hepatic dysfu