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         Very Common            Common (≥1/100 to         Uncommon (≥1/1,000 to           Rare       not known (SOC)                   (≥1/10)                 <1/10)                      <1/100)                (≥1/10,000    (cannot be to <1/1,000    estimated from the available data)
Infections and            Infection, Influenza   Bronchitis,                Abscess, Cellulitis, infestations                                     Gastroenteritis, Herpes    Furuncle, Herpes Zoster, Simplex, Otitis Media,     Pyelonephritis
Rhinitis, Tooth Abscess,
Vaginal Candidiasis*
Neoplasms benign,                                Benign Neoplasm of Skin,   Skin Cancer malignant and                                    Neoplasm unspecified (incl cysts and polyps)
Blood and lymphatic                              Lymphadenopathy*           Leukocytosis, Leukopenia, system disorders                                                            Splenomegaly Thrombocytopenia,
Lymphocyte Morphology
Abnormal
Immune system                                    Hypersensitivity disorders
Endocrine disorders                                                         Goitre, Hyperthyroidism Metabolism and                                   Anorexia, Weight           Alcohol Intolerance, Gout, nutrition disorders                              Increased*                 Hyperlipidaemia, Blood Sodium Increased, Serum
Ferritin Decreased
Psychiatric disorders     Anxiety*,              Nervousness                Abnormal Dreams, Depression                                        Confusional State, Euphoric Mood, Hallucination,
Hostility, Mania,
Personality Disorder,
Suicide Attempt
Nervous system            Headache,              Dysgeusia, Hypertonia,     Carpal Tunnel Syndrome, disorders                                        Migraine, Speech           Cognitive Disorder, Disorder, Syncope,         Convulsion, Dysgraphia,
Tremor*                    Dyslexia, Dystonia, Motor
Dysfunction, Myoclonus,
Neuritis, Neuromuscular
Blockade, Nystagmus,
Paralysis, Peroneal Nerve
Palsy, Stupor, Visual Field
Defect



System Organ Class         Very Common        Common (≥1/100 to          Uncommon (≥1/1,000 to            Rare        not known (SOC)                   (≥1/10)             <1/10)                       <1/100)                 (≥1/10,000     (cannot be to <1/1,000     estimated from the available data)
Eye disorders                                Diplopia, Eye Disorder*     Cataract, Corneal Lesion, Dry Eye, Eye Haemorrhage,
Eyelid Ptosis, Mydriasis,
Optic Atrophy
Ear and labyrinth                            Ear Disorder disorders
Cardiac disorders                            Palpitations*,              Extrasystoles, Sinus Tachycardia*                Bradycardia, Tachycardia
Paroxysmal
Vascular disorders        Vasodilatation*                                Varicose Vein Respiratory, thoracic     Dyspnoea*          Cough, Rhinitis Seasonal    Apnoea, Epistaxis, and mediastinal                                                          Hyperventilation, disorders                                                                Laryngospasm, Lung Disorder, Choking
Sensation
Gastrointestinal          Nausea*            Anorectal Disorder,         Colitis, Colonic Polyp, disorders                                    Constipation, Dental        Enterocolitis, Eructation, Caries, Dyspepsia,          Oesophageal Ulcer,
Dysphagia, Faecal           Periodontitis, Rectal
Incontinence, Vomiting*     Haemorrhage, Salivary
Gland Enlargement
Hepatobiliary disorders                      Liver Function Test         Cholelithiasis,                Toxic          Hepatic Abnormal                    Hepatomegaly                   hepatitis,     failure# Liver injury
Skin and subcutaneous     Rash*              Ecchymosis,                 Angioedema, Dermatitis tissue disorders                             Hyperhidrosis, Pruritus,    Contact, Erythema Skin Disorder*, Urticaria   Nodosum, Skin Nodule
Musculoskeletal and       Arthralgia, Back   Neck Pain                   Arthritis, Bursitis, Flank connective tissue         Pain*                                          Pain, Muscle Atrophy, disorders                                                                Osteoarthritis Renal and urinary                            Micturition Urgency,        Haematuria, disorders                                    Pollakiuria, Urinary        Nephrolithiasis, Urinary Retention                   Tract Disorder, Urine
Abnormality
Pregnancy, puerperium                                                    Abortion and perinatal
Conditions
Reproductive system                                                      Breast Engorgement, and breast disorders                                                     Erectile Dysfunction, Pelvic Prolapse, Priapism,
Prostatic Disorder, Smear
Cervix Abnormal,
Testicular Disorder,
Vaginal Haemorrhage,
Vulvovaginal Disorder


System Organ Class               Very Common                 Common (≥1/100 to               Uncommon (≥1/1,000 to                  Rare             not known (SOC)                         (≥1/10)                      <1/10)                            <1/100)                       (≥1/10,000          (cannot be to <1/1,000          estimated from the available data)
General disorders and          Asthenia, Chest             Chills*, Face Oedema*,           Cyst, Hangover, administration site            Pain*, Injection Site       Injection Site Atrophy♣,         Hypothermia, Immediate conditions                     Reactions*§, Pain*          Local Reaction*, Oedema          Post-Injection Reaction, Peripheral, Oedema,              Inflammation, Injection Site
Pyrexia                          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.

# Few cases were reported with liver transplantation.
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