Safinamide Tablets

The following serious adverse reactions are discussed in greater detail in other sections of labeling:

• Hypertension [see WARNINGS AND PRECAUTIONS]
• Serotonin Syndrome [see WARNINGS AND PRECAUTIONS]
• Falling Asleep During Activities of Daily Living [see WARNINGS AND PRECAUTIONS]
• Dyskinesia [see WARNINGS AND PRECAUTIONS]
• Hallucinations / Psychotic Behavior [see WARNINGS AND PRECAUTIONS]
• Impulse Control / Compulsive Behaviors [see WARNINGS AND PRECAUTIONS]
• Withdrawal-Emergent Hyperpyrexia and Confusion [see WARNINGS AND PRECAUTIONS]
• Retinal Pathology [see WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Clinical trials are conducted under widely varying conditions; therefore, adverse reactions observed in the clinical trials of a drug cannot be directly compared to the incidence in the clinical trials of another drug and may not reflect the incidence observed in clinical practice.

Table 1 shows the incidence of adverse reactions with an incidence of at least 2% on XADAGO 100 mg/day and greater than placebo in controlled studies in Parkinson's disease (Study 1 and Study 2). The most common adverse reactions associated with XADAGO treatment in which the incidence for XADAGO 100 mg/day was at least 2% greater than the incidence for placebo were dyskinesia, fall, nausea, and insomnia.

In pooled placebo-controlled studies (Study 1 and Study 2) in patients with Parkinson's disease taking a stable dose of carbidopa/levodopa with or without other PD medications, there was an increase in the incidence of XADAGO-treated patients who discontinued from the study because of adverse reactions. The incidence of patients discontinuing from Study 1 and Study 2 for any adverse reaction was 5% for XADAGO 50 mg/day, 6% for XADAGO 100 mg/day, and 4% for placebo. The most frequently reported adverse reaction causing study discontinuation was dyskinesia (1% of patients treated with XADAGO 50 mg/day or XADAGO 100 mg/day vs. 0% for placebo).

Table 1: Percentage of Patients with Adverse Reactions with an Incidence ≥ 2% in the XADAGO 100 mg/day Group and Greater than Placebo in Studies 1 and 2.

In Study 1 and Study 2, the proportion of patients who experienced a shift from normal to above the upper limit of normal for serum alanine aminotransferase (ALT) was 5% for XADAGO 50 mg, 7% for XADAGO 100 mg, and 3% for placebo. No patient treated with XADAGO experienced an increase in ALT that was 3 times the upper limit of normal or higher.

The proportion of patients with a shift from normal to above the upper limit of normal for serum aspartate aminotransferase (AST) was 7% for XADAGO 50 mg, 6% for XADAGO 100 mg, and 3% for placebo. The incidence of patients with an increase in AST to at least 3 times the upper limit of normal was similar for XADAGO and placebo.

Postmarketing Experience

The following adverse reactions have been identified during post-approval of use of safinamide outside of the United States. 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.

A postmarketing report describes a patient who developed a hypersensitivity reaction consisting of swelling of the tongue and gingiva, dyspnea and skin rash. The symptoms resolved shortly after XADAGO was discontinued, but reappeared following rechallenge a month later.