Most of the safety data for Copaxone 40 have been accumulated on the basis of the use of Copaxone-Teva 20 mg / ml in the form of daily injections.This section presents data accumulated during the time of 4 placebo-controlled clinical trials on the use of Copaxone-Teva in the form of injections in the dose of 20 mg / ml once a day and 1 placebo-controlled study of the use of Copaxon 40 in the form of SC injections in a dose of 40 mg / ml 3 times a week.
Copaxone-Teva 20 mg / ml (applied daily)
Most often, during clinical trials of the Copaxone-Teva drug, reactions at the injection site were noted. A placebo-controlled study showed that the proportion of patients reporting these adverse events was at least 70% for Copaxone-Teva and 37% for placebo at least once. Most often, redness was observed. pain. Sealing, itching, swelling, inflammation and hypersensitivity.
A reaction associated with at least one or more symptoms (vasodilation, chest pain, dyspnoea, heart palpitations or tachycardia), which manifests itself a few minutes after the injection, is called an immediate post-injection reaction. At least one of the symptoms of this reaction was observed at least once in 31% of patients treated with Copaxone-Teva, compared with 13% of patients with placebo.
All the undesirable reactions most frequently observed in the Nazis who received the Copaxone-Teva drug compared to the placebo group are presented below. These data were obtained from four registration, double-blind, placebo-controlled trials involving 512 patients who received Copaxon-Teva daily and 509 patients who received a placebo for 36 months. Three studies involved 269 patients with a diagnosis of relapsing-remitting multiple sclerosis who received Copaxone-Teva daily for 35 months and 271 patients from the placebo group. In the fourth study, 243 patients (the Kopakson-Teva group) participated in the first clinical withdrawal of the disease, who had a high risk of developing clinically confirmed multiple sclerosis and 238 patients receiving placebo. The duration of the study was 36 months.
The frequency of unwanted reactions is classified as follows: very often (≥1 / 10); often (≥1 / 100, but <1/10): infrequently (≥1 / 1000, but <1/100): rarely (≥1 / 10000, but <1/11000).
Infections and infestations: very often - infections, influenza; often - bronchitis, gastroenteritis, otitis media, Herpes simplex, rhinitis, periodontal abscess, vaginal candidiasis *; infrequently - abscess, inflammation of subcutaneous fat, furunculosis, pyelonephritis, Herpes zoster.
Neoplasms, including polyps and cysts: often benign neoplasms of the skin, neoplasms: infrequently - skin cancer.
From the hematopoietic and lymphatic systems: often - lymphadenopathy *; infrequently - leukocytosis, leukopenia, splenomegaly, thrombocytopenia, a change in the morphology of lymphocytes.
From the immune system: often - hypersensitivity reactions.
From the endocrine system: infrequently - goitre, hyperthyroidism.
From the side of metabolism and nutrition: often - anorexia, weight gain *; infrequent alcohol intolerance, gout, hyperlipidemia, hypernatremia, decreased ferritin concentration in serum.
Mental disturbance: very often - anxiety *, depression; often - nervousness; infrequent - unusual dreams, psychosis, euphoria, hallucinations, aggressiveness, mania, personality disorders, suicidal attempts.
From the nervous system: very often - headache; often - perversion of taste, hypertonic muscle, migraine, speech disorders, fainting,tremor*; infrequently, carpal tunnel syndrome, cognitive disorders, convulsions, dysgraphia, dyslexia, dystonia, motor function disorders, myoclonus, neuritis, neuromuscular blockade, nystagmus, paralysis, peroneal nerve palsy, stupor, visual field defect.
On the part of the organs of vision: often - diplopia, impaired vision *; infrequently - cataract, corneal damage, dryness of sclera and cornea, hemorrhage in the eye, ptosis of the eyelids, mydriasis, atrophy of the optic nerve.
From the side of the organs of hearing and balance: often - hearing impairment.
From the cardiovascular system: very often - vasodilation *; often - a feeling of palpitations *, tachycardia *; infrequently - extrasystole, sinus bradycardia, paroxysmal tachycardia, varicose veins.
From the respiratory system: very often - shortness of breath *; often - cough, seasonal rhyitis; infrequently - apnea, sensation of suffocation, epistaxis, hyperventilation of the lungs, laryngospasm, pulmonary disorders.
From the gastrointestinal tract: very often - nausea *; often - anorectal disorders, constipation, caries, dyspepsia, dysphagia, incontinence, vomiting *; infrequently - colitis, enterocolitis, polyposis of the large intestine, belching, peptic ulcer disease, periodontitis, rectal bleeding, enlargement of the salivary glands.
From the liver and bile ducts: often - deviation of liver function tests; infrequently - cholelithiasis, hepatomegaly.
From the skin and subcutaneous fat: very often - skin rash *; often - ecchymosis, hyperhidrosis, skin itching, skin diseases *, urticaria; infrequently - angioedema, contact dermatitis, nodal erythema, cutaneous nodules.
From the musculoskeletal system and connective tissue: very often - arthralgia, back pain *; often - pain in the neck; infrequently - arthritis, bursitis, pain in the side, muscle atrophy, osteoarthritis.
From the side of the kidneys and the urinary system: often imperative urges, pollakiuria. retention of urine; infrequently - hematuria, nephrolithiasis. diseases of the urinary tract, deviations from the laboratory norms of urinalysis.
Pregnancy, postpartum and perinatal conditions: infrequent - spontaneous abortion.
From the genitals and the breast: infrequent breast engorgement, erectile dysfunction, prolapse of pelvic organs, priapism, prostate diseases, deviation of laboratory parameters in smears from the cervical canal, dysfunction of the testicles, vaginal bleeding, vulvovaginal disorders.
Other: very often - asthenia, chest pain *, reactions at the injection site * and **, pain *; often - chills *, face swelling *, atrophy at the injection site ***, local reactions *, peripheral edema, edema, fever; infrequently - hypothermia, immediate postinjection reaction, inflammation, cyst, hangover syndrome, mucosal diseases, post-drinking syndrome, necrosis at the injection site.
* The probability of occurrence of such cases in patients taking Copaxone-Teva is more than 2% (> 2/100) compared with the placebo group. An undesired reaction without a "*" sign indicates a difference of less than or equal to 2%.
** "Reactions at the injection site" (various types) includes any undesirable events occurring at the injection site, with the exception of atrophy and necrosis, which are given separately.
*** Refers to localized lipoatrophy at the injection site.
In the fourth clinical study described above, after the placebo-controlled phase, an "open" phase of the study followed, which lasted 5 years. During this study, no changes were detected in the previously established safety profile of Copaxon-Teva.
In patients with multiple sclerosis who received Copaxone-Teva in uncontrolled clinical trials,as well as during the postmarketing period, rare cases of anaphylactoid reactions were recorded (≥1 / 10,000, but <1/1000).
Copaxone 40 at a dosage of 40 mg / ml (applied three times a week)
In the course of a double-blind, placebo-controlled study that lasted 12 months, the safety of Copaxone 40 was evaluated in 943 patients with a diagnosis of relapsing-remitting multiple sclerosis compared with a placebo group of 461 patients.
In Overall, in patients who took Copaxone 40 three times a week, adverse reactions at the injection site were consistent with the rates that were observed with the daily administration of Copaxon-Teva 20 mg / ml.
In particular, reactions at the injection site (PMI) and immediate post-injection reactions (NPIR) with the administration of Copaxone 40 three times a week were less frequent than with the daily injections of Copaxone-Toeva (35.5% compared to 70% for RMI and 7.8% compared with 31% for IRPI respectively).
In 36% of patients with COPA 40, compared to 5% of patients, RMI was observed with placebo. In 8% of patients who received Copaxone 40 but compared with 2% of patients taking placebo, HNDP.
In this case, several specific undesirable reactions were noted:
in patients with multiple sclerosis who received the drug Kopakson-Teva 20 mg / ml pr], uncontrolled clinical trials, as well as the results of postmarketing experience in rare cases (≥1 / 10,000, but <1/1000), anaphylactic reaction was observed. In patients taking Copakson 40. Such cases were 0.3% (infrequently: ≥1 / 1000, but <1/100);
nor one case of necrosis at the injection site was not found:
in 2.1% of patients treated with Copaxone 40 (often: ≥1 / 100, but <1/10). cases of redness of the skin and pain in the limbs that were not detected in the case of using Copaxone-Teva 20 mg / ml were observed:
in one patient (0.1%). who received the drug Copaxon 40 (infrequently: ≥1 / 1000, but <1/100). observed drug-induced liver damage and toxic hepatitis, which were also rare in patients with multiple sclerosis who took the drug Kopakson-Teva 20 mg / ml during post-marketing surveillance.