FYCOMPA SIDE EFFECTS
- Generic Name: perampanel tablets, for oral use
- Brand Name: Fycompa
- Drug Class: Anticonvulsants AMPA Glutamate Antagonists
SIDE EFFECTS
The following serious adverse reactions are described below and elsewhere in the labeling:
- Serious Psychiatric and Behavioral Reactions
- Suicidal Behavior and Ideation
- Neurologic Effects
- Falls
- Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan Hypersensitivity
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 clinical practice.
Partial-Onset Seizures
Adult and Adolescent Patients (12 years of age and older)
A total of 1,038 patients receiving FYCOMPA (2, 4, 8, or 12 mg once daily) constituted the safety population in the pooled analysis of the placebo-controlled trials (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 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 FYCOMPA at the recommended doses of 4 mg, 8 mg, and 12 mg per day, respectively, and 5% in patients randomized to receive placebo. The adverse reactions most commonly leading to discontinuation (≥1% in the 8 mg or 12 mg FYCOMPA group and greater than placebo) were dizziness, somnolence, vertigo, aggression, anger, ataxia, blurred vision, irritability, and dysarthria.
Most Common Adverse Reactions
Table 2 gives the incidence in the controlled clinical trials (Studies 1, 2, and 3) of the adverse reactions that occurred in ≥2% of patients with partial-onset seizures in the FYCOMPA 12 mg dose group and more frequent than placebo (in order of decreasing frequency for the 12 mg dose group).
The most common dose-related adverse reactions in patients receiving FYCOMPA 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.
Table 1. Adverse Reactions in Pooled Placebo-Controlled Trials in Adult and Adolescent Patients with Partial-Onset Seizures (Studies 1, 2, and 3) (Reactions ≥ 2% of Patients in Highest FYCOMPA Dose (12 mg) Group and More Frequent than Placebo)
| Placebo n=442 % |
FYCOMPA | |||
| 4 mg n=172 % |
8 mg n=431 % |
12 mg n=255 % |
||
| Dizziness | 9 | 16 | 32 | 43 |
| Somnolence | 7 | 9 | 16 | 18 |
| Headache | 11 | 11 | 11 | 13 |
| Irritability | 3 | 4 | 7 | 12 |
| Fatigue | 5 | 8 | 8 | 12 |
| Falls | 3 | 2 | 5 | 10 |
| Ataxia | 0 | 1 | 3 | 8 |
| Nausea | 5 | 3 | 6 | 8 |
| Vertigo | 1 | 4 | 3 | 5 |
| Back pain | 2 | 2 | 2 | 5 |
| Dysarthria | 0 | 1 | 3 | 4 |
| Anxiety | 1 | 2 | 3 | 4 |
| Blurred vision | 1 | 1 | 3 | 4 |
| Gait disturbance | 1 | 1 | 4 | 4 |
| Weight gain | 1 | 4 | 4 | 4 |
| Cough | 3 | 1 | 1 | 4 |
| Upper respiratory tract infection | 3 | 3 | 3 | 4 |
| Vomiting | 3 | 2 | 3 | 4 |
| Hypersomnia | 0 | 1 | 2 | 3 |
| Anger | <1 | 0 | 1 | 3 |
| Aggression | 1 | 1 | 2 | 3 |
| Balance disorder | 1 | 0 | 5 | 3 |
| Diplopia | 1 | 1 | 1 | 3 |
| Head injury | 1 | 1 | 1 | 3 |
| Hypoaesthesia | 1 | 0 | 0 | 3 |
| Pain in extremity | 1 | 0 | 2 | 3 |
| Constipation | 2 | 2 | 2 | 3 |
| Myalgia | 2 | 1 | 1 | 3 |
| Coordination abnormal | 0 | 1 | <1 | 2 |
| Euphoric mood | 0 | 0 | <1 | 2 |
| Confusional state | <1 | 1 | 1 | 2 |
| Hyponatremia | <1 | 0 | 0 | 2 |
| Limb injury | <1 | 1 | 1 | 2 |
| Mood altered | <1 | 1 | <1 | 2 |
| Arthralgia | 1 | 0 | 3 | 2 |
| Asthenia | 1 | 1 | 2 | 2 |
| Contusion | 1 | 0 | 2 | 2 |
| Memory impairment | 1 | 0 | 1 | 2 |
| Musculoskeletal pain | 1 | 1 | 1 | 2 |
| Oropharyngeal pain | 1 | 2 | 2 | 2 |
| Paraesthesia | 1 | 0 | 1 | 2 |
| Peripheral edema | 1 | 1 | 1 | 2 |
| Skin laceration | 1 | 0 | 2 | 2 |
Pediatric Patients (4 to <12 years of age)
In two studies in pediatric patients 4 to <12 years of age with epilepsy, a total of 225 patients received FYCOMPA, with 110 patients exposed for at least 6 months, and 21 patients for at least 1 year. Adverse reactions in pediatric patients 4 to <12 years of age were similar to those seen in patients 12 years of age and older.
Primary Generalized Tonic-Clonic Seizures
A total of 81 patients receiving FYCOMPA 8 mg once daily constituted the safety population in the placebo-controlled trial in patients with primary generalized tonic-clonic seizures (Study 4). Approximately 57% of patients were female, and the mean age was 27 years.
In the controlled primary generalized tonic-clonic seizure clinical trial (Study 4), the adverse reaction profile was similar to that noted for the controlled partial-onset seizure clinical trials (Studies 1, 2, and 3).
Table 3 gives the incidence of adverse reactions in patients receiving FYCOMPA 8 mg (≥4% and higher than in the placebo group) in Study 2. The most common adverse reactions in patients receiving FYCOMP A (≥10% and greater than placebo) were dizziness (32%), fatigue (15%), headache (12%), somnolence (11%), and irritability (11%).
The adverse reactions most commonly leading to discontinuation in patients receiving FYCOMPA 8 mg (≥2% and greater than placebo) were vomiting (2%) and dizziness (2%).
Table 2. Adverse Reactions in a Placebo-Controlled Trial in Patients with Primary Generalized Tonic-Clonic Seizures (Study 4) (Reactions ≥ 4% of Patients in FYCOMPA Group and More Frequent than Placebo)
| Placebo n=82 % |
FYCOMPA 8 mg n=81 % |
|
| Dizziness | 6 | 32 |
| Fatigue | 6 | 15 |
| Headache | 10 | 12 |
| Somnolence | 4 | 11 |
| Irritability | 2 | 11 |
| Vertigo | 2 | 9 |
| Vomiting | 2 | 9 |
| Weight gain | 4 | 7 |
| Contusion | 4 | 6 |
| Nausea | 5 | 6 |
| Abdominal pain | 1 | 5 |
| Anxiety | 4 | 5 |
| Urinary tract infection | 1 | 4 |
| Ligament sprain | 0 | 4 |
| Balance disorder | 1 | 4 |
| Rash | 1 | 4 |
Weight Gain
Weight gain has occurred with FYCOMPA.
In controlled partial-onset seizure 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.
Similar increases in weight were also observed in adult and adolescent patients treated with FYCOMPA in the primary generalized tonic-clonic seizure clinical trial.
Elevated Triglycerides
Increases in triglycerides have occurred with FYCOMPA use.
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 incidence 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)
Psychiatric: Acute psychosis, hallucinations, delusions, paranoia, delirium, confusional state, disorientation, memory impairment.
SRC: NLM .