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 clinical practice.
A total of 1,038 patients on FYCOMPA (2, 4, 8, or 12 mg once daily) constituted the safety population in the pooled analysis of Phase 3 placebo controlled studies (Studies 1, 2, and 3) in patients with partial onset seizures. Approximately 51% of patients were female and the mean age was 35 years.
Adverse Reactions Leading to Discontinuation: In controlled Phase 3 clinical trials (Studies 1, 2, and 3), the rate of discontinuation as a result of an adverse reaction was 3%, 8% and 19% in patients randomized to receive at the recommended doses of 4 mg, 8 mg and 12 mg/day, respectively, and 5% in patients randomized to receive placebo [see Pharmacology: Pharmacodynamics: Clinical Efficacy & Safety under Actions]. The adverse events most commonly leading to discontinuation (≥1% in the 8 mg or 12 mg group and greater than placebo) were dizziness, somnolence, vertigo, aggression, anger, ataxia, blurred vision, irritability, and dysarthria.
Most Common Adverse Reactions: Table 1 gives the incidence in the Phase 3 controlled trials (Studies 1, 2, and 3) of the adverse reactions that occurred in ≥2% of patients with partial-onset seizures in any FYCOMPA dose group. Overall, the most frequently reported dose-related adverse reactions in patients receiving at doses of 8 mg or 12 mg (≥4% and occurring at least 1% higher than the placebo group) included dizziness (36%), somnolence (16%), fatigue (10%), irritability (9%), falls (7%), nausea (7%), ataxia (5%), balance disorder (4%), gait disturbance (4%), vertigo (4%), and weight gain (4%). For almost every adverse reaction, rates were higher on 12 mg and more often led to dose reduction or discontinuation. (See Table 1.)
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Weight Gain: Weight gain has been observed with FYCOMPA use in adults.
In the controlled Phase 3 epilepsy clinical trials, FYCOMPA-treated adults gained an average of 1.1 kg (2.5 lbs) compared to an average of 0.3 kg (0.7 lbs) in placebo-treated adults with a median exposure of 19 weeks. The percentages of adults who gained at least 7% and 15% of their baseline body weight in FYCOMPA-treated patients were 9.1% and 0.9%, respectively, as compared to 4.5% and 0.2% of placebo-treated patients, respectively.
Clinical monitoring of weight is recommended.
Comparison of Sex and Race: No significant sex differences were noted in the incidence of adverse reactions.
Although there were few non-Caucasian patients, no differences in the incidences of adverse reactions compared to Caucasian patients were observed.
Postmarketing Experience: The following adverse reactions have been identified during post approval use of FYCOMPA. 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.
Dermatologic: Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) and Stevens-Johnson Syndrome (SJS) (see Precautions).