Adverse reactions : תופעות לוואי

4.8   Undesirable effects

Summary of the safety profile
The clinical development program has included over 1,900 patients, with different types of epilepsy, exposed to rufinamide. The most commonly reported adverse reactions overall were headache, dizziness, fatigue, and somnolence. The most common adverse reactions observed at a higher incidence than placebo in patients with Lennox-Gastaut syndrome were somnolence and vomiting. Adverse reactions were usually mild to moderate in severity. The discontinuation rate in Lennox-Gastaut syndrome due to adverse reactions was 8.2% for patients receiving Inovelon tablets and 0% for patients receiving placebo. The most common adverse reactions resulting in discontinuation from the Inovelon tablets treatment group were rash and vomiting.

Tabulated list of adverse reactions
Adverse reactions reported with an incidence greater than placebo, during the Lennox-Gastaut syndrome double-blind studies or in the overall rufinamide- exposed population, are listed in the table below by MedDRA preferred term, system organ class and by frequency.

Frequencies are defined as: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000).


System
Organ Class       Very Common Common                              Uncommon           Rare Infections and                Pneumonia infestations                  Influenza
Nasopharyngitis
Ear infection
Sinusitis
Rhinitis
Immune system                                                        Hypersensitivity* disorders
Metabolism and                    Anorexia nutrition                         Eating disorder disorders                         Decreased appetite
Psychiatric                       Anxiety disorders                         Insomnia

Nervous system Somnolence*        Status epilepticus* disorder       Headache           Convulsion
Dizziness*         Coordination Abnormal*
Nystagmus
Psychomotor hyperactivity
Tremor
Eye Disorders                     Diplopia
Vision blurred

Ear and                           Vertigo
Labyrinth disorders
Respiratory,                      Epistaxis thoracic and mediastinal disorders
Gastrointestinal Nausea           Abdominal pain upper disorders        Vomiting         Constipation
Dyspepsia
Diarrhoea

Hepato-biliary                                                Hepatic enzyme disorders                                                     increase Skin and                          Rash* subcutaneous tissue disorders                  Acne
Musculoskeletal                   Back pain and connective tissue and bone disorders
Reproductive                      Oligomenorrhoea system and breast disorders
General           Fatigue         Gait disturbance* disorders and administration site conditions
Investigations                    Weight decrease
Injury, poisoning                 Head injury and procedural                    Contusion complications
*Cross reference to section 4.4.

Additional information on special populations
Paediatric Population (age 1 to less than 4 years)
In a multicentre, open-label study comparing the addition of rufinamide to any other AED of the investigator’s choice to the existing regimen of 1 to 3 AEDs in paediatric patients, 1 to less than 4 years of age with inadequately controlled LGS, 25 patients, of which 10 subjects were aged 1 to 2 years, were exposed to rufinamide as adjunctive therapy for 24 weeks at a dose of up to 45 mg/kg/day, in 2 divided doses. The most frequently reported TEAEs in the rufinamide treatment group (occurring in ≥10% of subjects) were upper respiratory tract infection and vomiting (28.0% each), pneumonia and somnolence (20.0% each), sinusitis, otitis media, diarrhoea, cough and pyrexia (16.0% each), and bronchitis, constipation, nasal congestion, rash, irritability and decreased appetite (12.0% each). The frequency, type and severity of these adverse reactions were similar to that in children 4 years of age and older, adolescents and adults. Age characterisation in patients less than 4 years was not identified in the limited safety database due to small number of patients in the study.


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.