Adverse reactions : תופעות לוואי

4.8.        Undesirable effects
In all clinical trials, injection-site reactions were seen to be the most frequent adverse reactions and were reported by the majority of patients receiving Copaxone. In controlled studies, the proportion of patients reporting these reactions, at least once, was higher following treatment with Copaxone (70%) than placebo injections (37%). The most commonly reported injection-site reactions, in clinical trials and in post marketing experience, were erythema, pain, mass, pruritus, oedema, inflammation, hypersensitivity, and rare occurrences of lipoatrophy and skin necrosis.
A reaction, associated with at least one or more of the following symptoms, has been described as the Immediate Post-Injection Reaction: vasodilatation (flushing), chest pain, dyspnoea, palpitation or tachycardia. This reaction may occur within minutes of a Copaxone injection. At least one component of this Immediate Post-Injection Reaction was reported at least once by 31% of patients receiving Copaxone compared to 13% of patients receiving placebo.
All adverse reactions, which were more frequently reported in Copaxone vs. placebo-treated patients, are presented in the table below. This data was derived from four pivotal, double-blind, placebo-controlled clinical trials with a total of 512 patients treated with Copaxone and 509 patients treated with placebo for up to 36 months. Three trials in relapsing-remitting MS (RRMS) included a total of 269 patients treated with Copaxone and 271 patients treated with placebo for up to 35 months. The fourth trial in patients who have experienced a first clinical episode and were determined to be at high risk of developing clinically definite MS included 243 patients treated with Copaxone and 238 patients treated with placebo for up to 36 months.
System Organ Class (SOC)         Very Common (≥1/10)    Common (≥1/100 to <1/10)         Uncommon (≥1/1,000 to <1/100)
Infections and infestations   Infection, Influenza      Bronchitis, Gastroenteritis,   Abscess, Cellulitis, Furuncle, Herpes Simplex, Otitis         Herpes Zoster, Pyelonephritis
Media, Rhinitis, Tooth
Abscess, Vaginal
Candidiasis*
Neoplasms benign, malignant                             Benign Neoplasm of Skin,       Skin Cancer and unspecified (incl cysts                             Neoplasm and polyps)
Blood and lymphatic system                              Lymphadenopathy*               Leukocytosis, Leukopenia, disorders                                                                              Splenomegaly Thrombocytopenia,
Lymphocyte Morphology
Abnormal
Immune system disorders                                 Hypersensitivity Endocrine disorders                                                                    Goitre, Hyperthyroidism Metabolism and nutrition                                Anorexia, Weight               Alcohol Intolerance, Gout, disorders                                               Increased*                     Hyperlipidaemia, Blood Sodium Increased, Serum
Ferritin Decreased
Psychiatric disorders         Anxiety*, Depression      Nervousness                    Abnormal Dreams, Confusional State, Euphoric
Mood, Hallucination,
Hostility, Mania, Personality
Disorder, Suicide Attempt
Nervous system disorders      Headache,                 Dysgeusia, Hypertonia,         Carpal Tunnel Syndrome, Migraine, Speech Disorder,     Cognitive Disorder,
Syncope, Tremor*               Convulsion, Dysgraphia,
Dyslexia, Dystonia, Motor
Dysfunction, Myoclonus,
Neuritis, Neuromuscular
Blockade, Nystagmus,
Paralysis, Peroneal Nerve
Palsy, Stupor, Visual Field
Defect
Eye disorders                                           Diplopia, Eye Disorder*        Cataract, Corneal Lesion, Dry Eye, Eye Haemorrhage,
Eyelid Ptosis, Mydriasis,
Optic Atrophy
Ear and labyrinth disorders                             Ear Disorder
Cardiac disorders                                       Palpitations*, Tachycardia*    Extrasystoles, Sinus Bradycardia, Tachycardia
Paroxysmal
Vascular disorders            Vasodilatation*                                          Varicose Vein Respiratory, thoracic and     Dyspnoea*                 Cough, Rhinitis Seasonal       Apnoea, Epistaxis, mediastinal disorders                                                                  Hyperventilation, Laryngospasm, Lung
Disorder, Choking Sensation

System Organ Class (SOC)                 Very Common (≥1/10)                 Common (≥1/100 to <1/10)               Uncommon (≥1/1,000 to <1/100)
Gastrointestinal disorders            Nausea*                               Anorectal Disorder,                  Colitis, Colonic Polyp, Constipation, Dental Caries,         Enterocolitis, Eructation,
Dyspepsia, Dysphagia,                Oesophageal Ulcer,
Faecal Incontinence,                 Periodontitis, Rectal
Vomiting*                            Haemorrhage, Salivary Gland
Enlargement
Hepatobiliary disorders                                                     Liver Function Test                  Cholelithiasis, Hepatomegaly Abnormal
Skin and subcutaneous tissue          Rash*                                 Ecchymosis, Hyperhidrosis,           Angioedema, Dermatitis disorders                                                                   Pruritus, Skin Disorder*,            Contact, Erythema Nodosum, Urticaria                            Skin Nodule
Musculoskeletal and                   Arthralgia, Back Pain*                Neck Pain                            Arthritis, Bursitis, Flank Pain, connective tissue disorders                                                                                      Muscle Atrophy, Osteoarthritis
Renal and urinary disorders                                                 Micturition Urgency,                 Haematuria, Nephrolithiasis, Pollakiuria, Urinary                 Urinary Tract Disorder, Urine
Retention                            Abnormality
Pregnancy, puerperium and                                                                                        Abortion perinatal Conditions
Reproductive system and                                                                                          Breast Engorgement, Erectile breast disorders                                                                                                 Dysfunction, Pelvic Prolapse, Priapism, Prostatic Disorder,
Smear Cervix Abnormal,
Testicular Disorder, Vaginal
Haemorrhage, Vulvovaginal
Disorder
General disorders and                 Asthenia, Chest Pain*,                Chills*, Face Oedema*,               Cyst, Hangover, Hypothermia, administration site conditions        Injection Site Reactions*§,           Injection Site Atrophy♣,             Immediate Post-Injection Pain*                                 Local Reaction*, Oedema              Reaction, Inflammation, Peripheral, Oedema, Pyrexia          Injection Site Necrosis,
Mucous Membrane Disorder
Injury, poisoning and                                                                                            Post Vaccination Syndrome procedural complications

* More than 2% (>2/100) higher incidence in the Copaxone treatment group than in the placebo group. Adverse reaction without the * symbol represents a difference of less than or equal to 2%.

§ The term ‘Injection site reactions’ (various kinds) comprises all adverse events occurring at the injection site excluding injection site atrophy and injection site necrosis, which are presented separately within the table.

♣ Includes terms which relate to localized lipoatrophy at the injection sites.

In the fourth trial noted above, an open-label treatment phase followed the placebo-controlled period (see section 5.1). No change in the known risk profile of Copaxone was observed during the open-label follow-up period of up to 5 years.
The following adverse reaction reports were collected from MS patients treated with Copaxone in uncontrolled clinical trials and from post-marketing experience with Copaxone: hypersensitivity reactions (including rare occurrence of anaphylaxis, >1/10000, < 1/1000).

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