FINGOLIMOD SIDE EFFECTS

SIDE EFFECTS

The following serious adverse reactions are described elsewhere in labeling:

• Bradyarrhythmia and Atrioventricular Blocks
• Infections
• Progressive Multifocal Leukoencephalopathy
• Macular Edema
• Liver Injury
• Posterior Reversible Encephalopathy Syndrome
• Respiratory Effects
• Fetal Risk
• Severe Increase in Disability After Stopping GILENYA
• Increased Blood Pressure
• Malignancies
• Immune System Effects Following GILENYA Discontinuation
• Hypersensitivity Reactions

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Adults

In clinical trials (Studies 1, 2, and 3), a total of 1212 patients with relapsing forms of multiple sclerosis received GILENYA 0.5 mg. This included 783 patients who received GILENYA 0.5 mg in the 2-year placebo-controlled trials (Studies 1 and 3) and 429 patients who received GILENYA 0.5 mg in the 1-year active-controlled trial (Study 2). The overall exposure in the controlled trials was equivalent to 1716 person-years. Approximately 1000 patients received at least 2 years of treatment with GILENYA 0.5 mg. In all clinical studies, including uncontrolled extension studies, the exposure to GILENYA 0.5 mg was approximately 4119 person-years.

In placebo-controlled trials, the most frequent adverse reactions (incidence ≥ 10% and greater than placebo) for GILENYA 0.5 mg were headache, liver transaminase elevation, diarrhea, cough, influenza, sinusitis, back pain, abdominal pain, and pain in extremity. Adverse events that led to treatment discontinuation and occurred in more than 1% of patients taking GILENYA 0.5 mg were serum transaminase elevations (4.7% compared to 1% on placebo) and basal cell carcinoma (1% compared to 0.5% on placebo).

Table 1 lists adverse reactions in clinical studies in adults that occurred in ≥ 1% of GILENYA-treated patients and ≥ 1% higher rate than for placebo.

Table 1: Adverse Reactions Reported in Adult Studies 1 and 3 (Occurring in ≥ 1% of Patients and Reported for GILENYA 0.5 mg at ≥ 1% Higher Rate than for Placebo)

Adverse reactions of seizure, dizziness, pneumonia, eczema, and pruritus were also reported in Studies 1 and 3, but did not meet the reporting rate criteria for inclusion in Table 1 (difference was less than 1%).

Adverse reactions with GILENYA 0.5 mg in Study 2, the 1-year active-controlled (versus interferon beta-1a) study were generally similar to those in Studies 1 and 3.

Vascular Events

Vascular events, including ischemic and hemorrhagic strokes, and peripheral arterial occlusive disease were reported in premarketing clinical trials in patients who received GILENYA doses (1.25-5 mg) higher than recommended for use in MS. Similar events have been reported with GILENYA in the postmarketing setting although a causal relationship has not been established.

Seizure

Cases of seizures, including status epilepticus, have been reported with the use of GILENYA in clinical trials and in the postmarketing setting in adults. In adult clinical trials, the rate of seizures was 0.9% in GILENYA-treated patients and 0.3% in placebo-treated patients. It is unknown whether these events were related to the effects of multiple sclerosis alone, to GILENYA, or to a combination of both.

Pediatric Patients 10 Years Of Age And Older

In the controlled pediatric trial (Study 4), the safety profile in pediatric patients receiving GILENYA 0.25 mg or 0.5 mg daily was similar to that seen in adult patients.

In the pediatric study, cases of seizures were reported in 5.6% of GILENYA-treated patients and 0.9% of interferon beta-1a-treated patients.

Postmarketing Experience

The following adverse reactions have been identified during postapproval use of GILENYA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Hepatobiliary Disorders: Liver injury

Infections: infections including cryptococcal infections, progressive multifocal leukoencephalopathy.

Musculoskeletal and connective tissue disorders: arthralgia, myalgia

Nervous system disorders: posterior reversible encephalopathy syndrome , seizures, including status epilepticus

Neoplasms, benign, malignant, and unspecified (incl cysts and polyps): melanoma, Merkel cell carcinoma, and cutaneous T cell lymphoma (including mycosis fungoides)

Skin and subcutaneous tissue disorders: hypersensitivity