A total of 1703 patients on GILENYA (0.5 or 1.25 mg once daily) constituted the safety population in the 2 controlled studies in patients with relapsing remitting MS (RRMS) [see Clinical S tudies (14)].

Study 1 was a 2-year placebo-controlled clinical study in 1272 MS patients treated with GILENYA 0.5 mg (n=425), GILENYA 1.25 mg (n=429) or placebo (n= 418).

Adverse reactions in Study 2, a 1-year active-controlled (vs. interferon beta-1a, n=431) study including 849 patients with MS treated with fingolimod, were generally similar to those in Study 1.

Vascular Events

Vascular events, including ischemic and hemorrhagic strokes, peripheral arterial occlusive disease and posterior reversible encephalopathy syndrome were reported in premarketing clinical trials in patients who received GILENYA doses (1.25-5 mg) higher than recommended for use in MS. No vascular events were observed with GILENYA 0.5 mg in the premarketing database.

Lymphomas

Cases of lymphoma (cutaneous T-cell lymphoproliferative disorders or diffuse B-cell lymphoma) were reported in premarketing clinical trials in MS patients receiving GILENYA at, or above, the recommended dose of 0.5 mg. Based on the small number of cases and short duration of exposure, the relationship to GILENYA remains uncertain.

Table 1 Adverse Reactions in Study 1 (occurring in ≥1% of patients, and reported for GILENYA 0.5 mg at ≥1% higher rate than for placebo)  Primary System Organ C lass
Preferred Term

 GILENYA 0.5   mg
N=425
%
 Placebo
N=418
% 
Infections   
     Influenza viral infections 13 10
     Herpes viral infections 9 8
     Bronchitis 8 4
     Sinusitis  7 5
     Gastroenteritis 5 3
      Tinea infections 4 1
Cardiac Disorders   
     Bradycardia 4 1
Nervous system disorders   
     Headache 25 23
     Dizziness 7 6
     Paresthesia 5 4
     Migraine 5 1
Gastrointestinal disorders   
     Diarrhea 12 7
General disorders and administration site conditions   
     Asthenia 3 1
Musculoskeletal and connective tissue disorders   
     Back pain 12 7
Skin and subcutaneous tissue disorders   
     Alopecia 4 2
     Eczema 3 2
     Pruritus 3 1
Investigations   
     ALT/AST increased 14 5
     GGT increased 5 1
     Weight decreased 5 3
     Blood triglycerides increased 3 1
Respiratory, thoracic and mediastinal disorders   
     Cough 10 8
     Dyspnea 8 5
Psychiatric disorders   
     Depression 8 7
Eye disorders   
     Vision blurred 4 1