"The U.S. Food and Drug Administration today approved Aptiom (eslicarbazepine acetate) as an add-on medication to treat seizures associated with epilepsy.
Epilepsy is a brain disorder caused by abnormal or excessive activity in the brain"...
The following serious adverse reactions are described below and elsewhere in the labeling:
- Serious Psychiatric and Behavioral Reactions [see WARNINGS AND PRECAUTIONS]
- Suicidal Behavior and Ideation [see WARNINGS AND PRECAUTIONS]
- Dizziness and Gait Disturbance [see WARNINGS AND PRECAUTIONS]
- Somnolence and Fatigue [see WARNINGS AND PRECAUTIONS]
- Falls [see WARNINGS AND PRECAUTIONS]
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.
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 [see Clinical Studies]. 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 [see WARNINGS AND PRECAUTIONS].
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 2: Adverse Reactions
in Pooled Placebo-Controlled Trials in 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)
|Upper respiratory tract infection||3||3||3||4|
|Pain in extremity||1||0||2||3|
|Coordination abnormal||0||1||< 1||2|
|Euphoric mood||0||0||< 1||2|
|Confusional state||< 1||1||1||2|
|Limb injury||< 1||1||1||2|
|Mood altered||< 1||1||< 1||2|
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 4. The most common adverse reactions in patients receiving FYCOMPA ( ≥ 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 3: 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)
|FYCOMPA 8 mg
|Urinary tract infection||1||4|
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 pediatric patients treated with FYCOMPA in the primary generalized tonic-clonic seizure clinical trial.
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.
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).
Read the Fycompa (perampanel tablets, for oral use) Side Effects Center for a complete guide to possible side effects
With concomitant use, FYCOMPA at a dose of 12 mg per day reduced levonorgestrel exposure by approximately 40% [see CLINICAL PHARMACOLOGY]. Use of FYCOMPA with oral or implant contraceptives containing levonorgestrel may render them less effective. Additional non-hormonal forms of contraception are recommended.
Cytochrome P450 Inducers
The concomitant use of known cytochrome P450 (CYP) enzyme inducers including carbamazepine, phenytoin, or oxcarbazepine with FYCOMPA decreased the plasma levels of perampanel by approximately 50-67% [see CLINICAL PHARMACOLOGY]. The starting doses for FYCOMPA should be increased in the presence of enzyme-inducing AEDs [see DOSAGE AND ADMINISTRATION].
When these enzyme-inducing AEDs are introduced or withdrawn from a patient's treatment regimen, the patient should be closely monitored for clinical response and tolerability. Dose adjustment of FYCOMPA may be necessary [see DOSAGE AND ADMINISTRATION].
Concomitant use of FYCOMPA with other strong CYP3A inducers (e.g., rifampin, St. John's wort) is not recommended.
Alcohol And Other CNS Depressants
The concomitant use of FYCOMPA and CNS depressants including alcohol may increase CNS depression. A pharmacodynamic interaction study in healthy subjects found that the effects of FYCOMPA on complex tasks such as driving ability were additive or supra-additive to the impairment effects of alcohol [see CLINICAL PHARMACOLOGY]. Multiple dosing of FYCOMPA 12 mg per day also enhanced the effects of alcohol to interfere with vigilance and alertness, and increased levels of anger, confusion, and depression. These effects may also be seen when FYCOMPA is used in combination with other CNS depressants. Care should be taken when administering FYCOMPA with these agents. Patients should limit activity until they have experience with concomitant use of CNS depressants (e.g., benzodiazepines, narcotics, barbiturates, sedating antihistamines). Advise patients not to drive or operate machinery until they have gained sufficient experience on FYCOMPA to gauge whether it adversely affects these activities.
Drug Abuse And Dependence
FYCOMPA contains perampanel and is listed as a Schedule III controlled substance.
Prescription drug abuse is the intentional non-therapeutic use of a drug, even once, for its rewarding psychological or physiological effects. Drug addiction, which develops after repeated drug abuse, is characterized by a strong desire to take a drug despite harmful consequences, difficulty in controlling its use, giving a higher priority to drug use than to obligations, increased tolerance, and sometimes physical withdrawal. Drug abuse and drug addiction are separate and distinct from physical dependence (for example, abuse may not be accompanied by physical dependence) [see Dependence].
Studies of human abuse potential were performed to evaluate the abuse potential of FYCOMPA (8 mg, 24 mg, and 36 mg) as compared to alprazolam C-IV (1.5 mg and 3 mg), and oral ketamine C-III (100 mg) in recreational polydrug users. Supra-therapeutic doses of FYCOMPA 24 and 36 mg produced responses for “Euphoria” that were similar to ketamine 100 mg and alprazolam 3 mg. For “High,” FYCOMPA 24 mg and 36 mg produced responses comparable to ketamine 100 mg and significantly higher than both doses of alprazolam on a visual analog scale (VAS). “Drug Liking,” “Overall Drug Liking,” and “Take Drug Again” for FYCOMPA were each statistically lower than ketamine 100 mg. In addition, for “Bad Drug Effects,” FYCOMPA 24 mg and 36 mg produced responses significantly higher than ketamine 100 mg. For “Sedation,” FYCOMPA 24 and 36 mg produced responses similar to alprazolam 3 mg and higher than ketamine 100 mg.
Additionally, on VAS measures related to dissociative phenomena such as “Floating,” “Spaced Out,” and “Detached,” FYCOMPA at supra-therapeutic doses produced responses similar to ketamine 100 mg and greater than both doses of alprazolam tested. Of note, due to somnolence a number of subjects had missing data around Tmax of FYCOMPA. The above described data might represent an underestimate of FYCOMPA's effects. The duration of effects of higher doses of FYCOMPA on the majority of measures was much greater than alprazolam 3 mg and ketamine 100 mg.
In this study, the incidence of euphoria following FYCOMPA administration 8 mg, 24 mg, and 36 mg was 37%, 46%, 46%, respectively, which was higher than alprazolam 3 mg (13%) but lower than ketamine 100 mg (89%).
Physical dependence is characterized by withdrawal symptoms after abrupt discontinuation or a significant dose reduction of a drug.
The potential for FYCOMPA to produce withdrawal symptoms has not been adequately evaluated.This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 7/14/2015
Additional Fycompa Information
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