Adverse reactions : תופעות לוואי

4.8   Undesirable effects

Summary of the safety profile
In all controlled and uncontrolled trials in patients with partial-onset seizures, 1,639 patients have received perampanel of whom 1,147 have been treated for 6 months and 703 for longer than 12 months.

In the controlled and uncontrolled study in patients with primary generalised tonic-clonic seizures, 114 patients have received perampanel of whom 68 have been treated for 6 months and 36 for longer than 12 months.

Adverse reactions leading to discontinuation:
In the controlled Phase 3 partial-onset seizures clinical trials, the rate of discontinuation as a result of an adverse reaction was 1.7% (3/172), 4.2% (18/431) and 13.7% (35/255) in patients randomised to receive perampanel at the recommended doses of 4 mg, 8 mg and 12 mg/day, respectively, and 1.4% (6/442) in patients randomised to receive placebo. The adverse reactions most commonly (≥1% in the total perampanel group and greater than placebo) leading to discontinuation were dizziness and somnolence.

In the controlled Phase 3 primary generalised tonic-clonic seizures clinical trial, the rate of discontinuation as a result of an adverse reaction was 4.9% (4/81) in patients randomized to receive perampanel 8 mg, and 1.2% (1/82) in patients randomized to receive placebo. The adverse reaction most commonly leading to discontinuation (≥2% in the perampanel group and greater than placebo) was dizziness.

Post-marketing use
Severe cutaneous adverse reactions (SCARs) including drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported in association with perampanel treatment (see section 4.4).


Tabulated list of adverse reactions
In the table below, adverse reactions, which were identified based on review of the full Fycompa clinical studies safety database, are listed by System Organ Class and frequency.
The following convention has been used for the classification of adverse reactions: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), not known (cannot be estimated from the available data).

Within each frequency category, adverse reactions are presented in order of decreasing seriousness.

System Organ             Very common        Common           Uncommon          Not known Class
Metabolism and                              Decreased

System Organ            Very common        Common           Uncommon         Not known Class nutrition disorders                        appetite
Increased appetite
Psychiatric                                Aggression       Suicidal disorders                                  Anger            ideation
Anxiety          Suicide
Confusional      attempt state            Hallucinations
Psychotic disorder
Nervous system          Dizziness          Ataxia disorders               Somnolence         Dysarthria
Balance disorder
Irritability

Eye disorders                              Diplopia
Vision blurred
Ear and labyrinth                          Vertigo disorders
Gastrointestinal                           Nausea disorders
Skin and                                                                     Drug Reaction subcutaneous                                                                 with Eosinophilia tissue disorders                                                             and Systemic Symptoms
(DRESS)*
Stevens - Johnson
Syndrome (SJS)*
Musculoskeletal                            Back pain and connective tissue disorders
General disorders                          Gait disturbance
Fatigue
Investigations                             Weight increased
Injury, poisoning                          Fall and procedural complications
* See section 4.4

Paediatric population
Based on the clinical trial database of 196 adolescents exposed to perampanel from double- blind studies for partial onset seizures and primary generalized tonic-clonic seizures, the overall safety profile in adolescents was similar to that of adults, except for aggression, which was observed more frequently in adolescents than in adults.
Based on the clinical trial database of 180 paediatric patients exposed to perampanel from a multicentre, open label study, the overall safety profile in children was similar to that established for adolescents and adults, except for somnolence, irritability, aggression, and agitation, which were observed more frequently in the paediatric study compared to studies in adolescents and adults.


Available data in children did not suggest any clinically significant effects of perampanel on growth and development parameters including body weight, height, thyroid function, insulin-like growth factor-1 (IGF-1) level, cognition (as assessed by Aldenkamp-Baker neuropsychological assessment schedule [ABNAS]), behaviour (as assessed by Child Behavior Checklist [CBCL]), and dexterity (as assessed by Lafayette Grooved Pegboard Test [LGPT]). However, long term effects [greater than 1 year] on learning, intelligence, growth, endocrine function, and puberty in children remain unknown.


Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.
Any suspected adverse events should be reported to the Ministry of Health according to the National Regulation by using an online form: https://sideeffects.health.gov.il