llowing convention: very common (1/10); common (1/100 to <1/10); uncommon (1/1,000 to <1/100); rare ( 1/10,000 to < 1/1,000); very rare (< 1/10,000); not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are ranked in order of decreasing seriousness.
Tabulated list of adverse reactions
Infections and infestations
Very common:
Influenza viral infections
Common:
Herpes viral infections
Bronchitis
Sinusitis
Gastroenteritis
Tinea infections
Uncommon:
Pneumonia
Blood and lymphatic system disorders
Common:
Lymphopenia
Leucopenia
Psychiatric disorders
Common:
Depression
Uncommon:
Depressed mood
Nervous system disorders
Very common:
Headache
Common:
Dizziness
Paraesthesia
Migraine
Eye disorders
Common:
Vision blurred
Eye pain
Uncommon:
Macular oedema*
Cardiac disorders
Common:
Bradycardia
Atrioventricular block
Vascular disorders
Common:
Hypertension
Respiratory, thoracic and mediastinal disorders
Very common:
Cough
Common:
Dyspnoea
Gastrointestinal disorders
Very common:
Diarrhoea
Skin and subcutaneous tissue disorders
Common:
Eczema
Alopecia
Pruritus
Musculoskeletal and connective tissue disorders
Very common:
Back pain
General disorders and administration site conditions
Common:
Asthenia
Investigations
Very common:
Alanine transaminase (ALT) increased
Common:
Gamma-glutamyl transferase (GGT) increased
Hepatic enzyme increased
Liver function test abnormal
Blood triglycerides increased
Weight decreased
Uncommon:
Neutrophil count decreased
* Not reported in Study D2301 (FREEDOMS) with Gilenya 0.5 mg. Frequency category is based on the incidence with Gilenya 0.5 mg (0.5% vs. 0.2% in the interferon beta-1a group) in Study D2302 (TRANSFORMS).
Description of selected adverse reactions
Infections
In multiple sclerosis clinical studies the overall rate of infections (72%) and serious infections (2%) at the 0.5 mg dose was similar to placebo. However, lower respiratory tract infections, primarily bronchitis and, to a lesser extent, pneumonia were more common in Gilenya-treated patients.
Two fatal cases of herpes infection occurred at the higher 1.25 mg dose: A case of herpes simplex encephalitis in a patient in whom initiation of acyclovir therapy was delayed by one week, and a case of primary disseminated varicella zoster infection in a patient not previously exposed to varicella receiving concomitant high-dose steroid therapy for a multiple sclerosis relapse.
Macular oedema
In multiple sclerosis clinical studies macular oedema occurred in 0.4% of patients treated with the recommended dose of 0.5 mg and 1.1% of patients treated with the high
