Copaxone 40teva solution of subcutaneous injection vv40mg ml 1ml N12
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Description
Slightly opalescent solution from colorless to light yellow.
Active ingredients
Release form
Pharmacological effect
Pharmacological action - immunomodulatory.
The mechanism of action of Glatiramer acetate in patients with multiple sclerosis is not fully understood. Glatiramer acetate is thought to alter the immune processes that are thought to play a major role in the pathogenesis of multiple sclerosis. This hypothesis is confirmed by the results of studies conducted to study the pathogenesis of experimental allergic encephalomyelitis (EAE). EAE is often used as an experimental model of multiple sclerosis. Studies in animals and in patients with multiple sclerosis have shown that administration of Glatiramer Acetate causes peripheral induction and activation of Glatiramer acetate-specific suppressor T-lymphocytes.
Relapsing-remitting multiple sclerosis. The results of a 12-month, placebo-controlled study confirmed the efficacy of Copaxone® 40 at a dosage of 40 mg / ml for sc administration 3 times a week in reducing the frequency of exacerbations.
When conducting a registration clinical trial, the criterion for inclusion of patients with relapsing-remitting multiple sclerosis was at least one documented clinical exacerbation in the last 12 months or 2 exacerbations in the last 24 months, or one exacerbation in the last 12-24 months with at least one foci accumulating contrast (Gd +) and rendered on T1-weighted MRI images for the last 12 months.
The primary goal of the study was to determine the total number of confirmed exacerbations. The secondary goal is to determine the cumulative number of new / increased foci detected on T2-weighted MRI images, and the cumulative number of foci accumulating contrast and visualized on T1-weighted images on the 6th and 12th months of the study.
The study was randomized to 1404 patients in a 2: 1 ratio to the group treated with Copaxone® 40 at a dose of 40 mg / ml (n = 943), or to the placebo group (n = 461), respectively. Both groups were comparable in terms of baseline demographic indicators, characteristics of the course of multiple sclerosis, and MRI parameters.Patients had an average of 2 exacerbations during the 2 years prior to screening.
Compared with the placebo group, patients treated with Copaxone® 40 at a dose of 40 mg / ml 3 times a week, there was a statistically significant decrease in the frequency of exacerbations and the total number of foci on T2-weighted images and foci that accumulate contrast on T1-weighted images that corresponds to the therapeutic effect of the drug Copaxone®-Teva 20 mg / ml with its daily administration.
A direct comparative analysis of the efficacy and safety of the drug at a dose of 20 mg / ml (with daily administration) and 40 mg / ml (with 3 times weekly administration) was not carried out in the framework of this study.
During this 12-month study, there was no evidence of the effect of the drug on the progression of disability or the duration of exacerbations. Currently there are no data regarding the use of the drug in patients with primary or secondary progressive multiple sclerosis.
Pharmacokinetics
Patient pharmacokinetics studies have not been conducted.
Datain vitro, as well as limited data obtained with the participation of healthy volunteers show that with sc injection, the active substance is rapidly absorbed, with most of it breaking up into small fragments in the subcutaneous tissue.
Pre-Clinical Data
Preclinical data based on studies of pharmacological safety, repeated administration toxicity, reproductive toxicity, genotoxicity, or carcinogenicity do not indicate the presence of specific harmful factors for a person other than the data already included in the sections of this preparation. Due to the lack of data on pharmacokinetics, it is impossible to determine the permissible concentration limits in humans compared with animals. In a small number of rats and monkeys that were injected with the drug for at least 6 months, there was a deposition of immune complexes in the glomeruli. In a 2-year study in rats, there was no deposition of immune complexes in the glomeruli.
In sensitized animals (guinea pigs and mice), anaphylaxis was observed after administration of the drug. The relevance of this data is unknown to humans.Toxic effects at the injection site after repeated administration of the drug to animals refers to common reactions.
Indications
Relapsing-remitting multiple sclerosis.
Contraindications
hypersensitivity to Glatiramer acetate or mannitol;
pregnancy;
children's age up to 18 years (efficiency and safety are not studied).
Carefully: predisposition to the development of allergic reactions; cardiovascular diseases; impaired renal function.
Use during pregnancy and lactation
There is no data on the use of Copaxone® 40 during pregnancy, the possible risk of use during pregnancy has not been established.
Studies on animals are insufficient to establish the effect of the drug on pregnancy, embryo / fetus development, childbirth and postnatal development. The drug Copaxone 40 is contraindicated during pregnancy. During treatment, you must use reliable methods of contraception.
It is not known whether Glatiramer acetate is excreted in breast milk, so if you need to use Copaxone® 40 during lactation, you should evaluate the expected benefits of therapy for the mother and the potential risk to the child.
Dosage and administration
PC, 40 mg of drug Copaxone® 40 (one syringe filled with a solution for injection) 3 times a week, the minimum interval between injections is 48 hours. The drug is not intended for intravenous or intramuscular administration.
Currently, data on the duration of treatment is not available. The decision on the appointment of a long course of treatment should be made by the attending physician in each case.
Patients are recommended to be trained in self-injection technology. The first injection (as well as 30 minutes after it) should be supervised by a qualified specialist. To reduce the risk of irritation or pain in the injection area, it is necessary to change the area for injection each time.
Each syringe with the drug Copaxone® 40 is intended for single use only.
Recommendations for patients on the use of the drug
1. Make sure that the patient has everything needed for the injection: a disposable syringe filled with a solution of Copaxone® 40, a container for used syringes, a cotton swab moistened with alcohol.
2Before injection, remove the disposable syringe from the blister strip packaging, removing the protective paper strip.
3. Hold the syringe with the solution at room temperature for at least 20 minutes.
4. Before administering Copaxone® 40, wash hands thoroughly with soap and water.
5. Carefully inspect the solution in the syringe. In the presence of suspended particles or solution color changes, it should not be used.
6. Choose an injection site.
Possible zones for independent injections are marked on fig. 1: arms, thighs, buttocks, stomach (approximately 5 cm around the navel). Do not inject into sore spots, discolored, reddened skin or areas with seals and nodules. Inside each injection zone there is enough space for multiple injections. It is recommended to make a scheme of injection sites and have it with you. For injections on the buttocks and arms, the patient may need the help of another person.
Figure 1. Location of injection sites
7. Remove the protective cap from the needle.
8. Pretreat the injection site with a cotton swab moistened with an alcohol solution and slightly fold the skin into the fold with your thumb and forefinger (Fig. 2).
Figure 2.
9. Positioning the needle of the syringe perpendicular to the injection site (Fig. 3), pierce the skin and evenly pressing on the plunger of the syringe, inject its contents into the injection site.
Figure 3.
10. Remove the needle by moving the syringe perpendicular to the injection site.
11. Place the syringe in a container for used syringes.
If the patient forgot to inject Copaxone® 40, an injection should be given immediately, as soon as the patient remembers it. You can not enter a double dose of the drug.
Special patient groups
Children. The drug is not recommended for use in patients under 18 years of age, since no clinical studies have been conducted in these age groups.
Elderly age. The efficacy and safety of the drug in the elderly have not been studied.
Impaired renal function. The efficacy and safety of the drug in patients with renal insufficiency have not been studied.
Side effects
Most of the safety data on the use of Copaxone® 40 have been accumulated on the basis of using Copaxone®-Teva 20 mg / ml in the form of daily injections. This section presents data accumulated during 4 placebo-controlled clinical studies on the use of Copaxone®-Teva as a sc injection in a dose of 20 mg / ml 1 time per day and 1 placebo-controlled study of the use of Copaxone® 40 in the form of s / c injections in a dose of 40 mg / ml 3 times a week.Copaxone®-Teva 20 mg / ml (used daily).
Most often during clinical studies of the drug Copaxone®-Teva, reactions at the injection site were observed. A placebo-controlled study showed that the proportion of patients reporting these adverse events was at least 1 time 70% for Copaxone®-Teva and 37% for placebo. Redness, pain, induration, itching, swelling, inflammation and hypersensitivity were most commonly observed.
A reaction associated with at least one or more symptoms (vasodilation, chest pain, shortness of breath, heart palpitations or tachycardia) that occurs 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 receiving Copaxone®-Teva, compared with 13% of patients from the placebo group.
All adverse reactions most frequently observed in patients receiving Copaxone®-Teva compared with the placebo group are presented below. These data were obtained in the course of 4 registration double-blind, placebo-controlled studies involving 512 patients who received Copaxone®-Teva daily and 509 patients who received placebo for 36 months. In 3 studies, 269 patients were diagnosed with relapsing-remitting multiple sclerosis who received Copaxone®-Teva daily for 35 months and 271 patients from the placebo group. In the 4th study, 243 patients participated (Kopakson®-Teva group) with the first clinical episode 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 incidence of adverse 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 <1/1000).
Infections and invasions: very often - infections, flu; often - bronchitis, gastroenteritis, otitis media,Herpes simplex, rhinitis, periodontal abscess, vaginal candidiasis *; infrequently - abscess, inflammation of the subcutaneous fat, furunculosis, pyelonephritis,Herpes zoster.
Neoplasms, including polyps and cysts: often - benign skin neoplasms, neoplasms; infrequently - skin cancer.
From the hematopoietic and lymphatic systems: often - lymphadenopathy *; infrequently - leukocytosis, leukopenia, splenomegaly, thrombocytopenia, changes in the morphology of lymphocytes.
On the part of the immune system: often - hypersensitivity reactions.
On the part of the endocrine system: infrequently - goiter, hyperthyroidism.
Metabolism and nutrition: often - anorexia, weight gain *; infrequently - alcohol intolerance, gout, hyperlipidemia, hypernatremia, a decrease in the concentration of ferritin in the blood serum.
Mental Disruption: very often - anxiety *, depression; often - nervousness; infrequently - unusual dreams, psychosis, euphoria, hallucinations, aggressiveness, mania, personality disorders, suicidal attempts.
From the nervous system: very often - a headache; often - taste perversion, hypertonicity of muscles, migraine, speech disorders, fainting, tremor *; infrequently - carpal tunnel syndrome, cognitive disorders, convulsions, dysgraphia, dyslexia, dystonia, impaired motor functions, myoclonus, neuritis, neuromuscular blockade, nystagmus, paralysis, including peroneal nerve, stupor, visual field defect.
From the organs of vision: often - diplopia, visual impairment *; infrequently - cataract, corneal damage, dry sclera and cornea, hemorrhage in the eye, eyelid ptosis, mydriasis, optic nerve atrophy.
From the side of hearing and balance: often - hearing impairment.
From the CCC: very often - vasodilation *; often - palpitations *, tachycardia *; infrequently - extrasystole, sinus bradycardia, paroxysmal tachycardia, varicose veins.
On the part of the respiratory system: very often - shortness of breath *; often - cough, seasonal rhinitis; infrequently - apnea, choking sensation, epistaxis, hyperventilation, laryngism, pulmonary disorders.
From the digestive tract: very often - nausea *; often - anorectal disorders, constipation, caries, dyspepsia, dysphagia, fecal incontinence, vomiting *; infrequently - colitis, enterocolitis, colon polyposis, belching, esophageal peptic ulcer, periodontitis, rectal bleeding, enlarged salivary glands.
Liver and biliary tract: often - deviation of liver function tests; infrequently - cholelithiasis, hepatomegaly.
On the part of the skin and subcutaneous fat: very often - skin rash *; often - ecchymosis, hyperhidrosis, pruritus, skin diseases *, urticaria; infrequently - angioedema, contact dermatitis, erythema nodosum, skin nodules.
From the musculoskeletal system and connective tissue: very often - arthralgia, back pain *; often - neck pain; infrequently - arthritis, bursitis, pain in the side, muscular atrophy, osteoarthritis.
On the part of the kidneys and urinary system: often - imperative urges, pollakiuria, urinary retention; infrequently - hematuria, nephrolithiasis, urinary tract diseases, deviations from the urine test.
Pregnancy, postpartum and perinatal conditions: infrequently - spontaneous abortion.
From the genital and breast organs: infrequently - breast engorgement, erectile dysfunction, pelvic organ prolapse, priapism, prostate diseases, abnormalities in smears from the cervical canal, testicular dysfunction, vaginal bleeding, vulvovaginal disorders.
Other: very often - asthenia, chest pain *, reactions at the injection site *, **, pain *; often - chills *, face *, atrophy at the injection site ***, local reactions *, peripheral edema, edema, fever; infrequently - hypothermia, immediate post-injection reaction, inflammation, cyst, hangover, mucosal diseases, post-vaccination 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 undesirable reaction without the “*” sign indicates a difference less than or equal to 2%.
** “Reactions at the injection site (RMI)” (various types) include any adverse events that occur at the injection site, with the exception of atrophy and necrosis, which are listed separately.
*** Refers to localized lipoatrophy at the injection site.
During the 4th clinical study indicated above, an open phase of the study followed the placebo-controlled phase, which lasted 5 years. During this study, no changes in the previously established safety profile of Copaxone®-Teva were detected.
In patients with multiple sclerosis who received Copaxone®-Teva when conducting uncontrolled clinical trials, as well as during the period of post-marketing use, there were rare (≥1 / 10000, but <1/1000) cases of anaphylactoid reactions.
Copaxone® 40 at a dosage of 40 mg / ml (used 3 times a week).In 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 the placebo group, which included 461 patients.
In general, in patients who took Copaxone® 40 3 times a week, undesirable reactions at the injection site coincided with those observed with daily administration of Copaxone®-Teva 20 mg / ml.
In particular, RMI and immediate post-injection reactions (NPIR) with the administration of 3 times a week of drug Copaxone® 40 were observed less frequently than with daily injections of Copaxone®-Teva (35.5 compared to 70% for PMI and 7.8%). compared with 31% - for NPIR, respectively).
In 36% of patients when using the drug Copaxone® 40, compared with 5% of patients while receiving a placebo, RMI was observed. In 8% of patients treated with Copaxone®40 compared with 2% of patients taking placebo, NPIR was detected.
However, several specific adverse reactions were noted:
- in patients with multiple sclerosis who received the drug Copaxone®-Teva 20 mg / ml when conducting uncontrolled clinical studies, as well as based on the results of post-marketing experience in rare cases (≥1 / 10000, but <1/1000), an anaphylactic reaction was observed. In patients taking the drug Copaxone® 40, such cases were 0.3% (infrequently: ≥1 / 1000, but <1/100);
- not a single case of necrosis at the injection site was detected;
- in 2.1% of patients who received the drug Kopakson® 40 (often: ≥1 / 100, but <1/10), there were cases of redness of the skin and pain in the extremities, which were not detected when using the drug Kopakson®-Teva 20 mg / ml:
- in one patient (0.1%) who received the drug Copaxone® 40 (infrequently: ≥1 / 1000, but <1/100), drug-induced liver damage and toxic hepatitis were observed, which were also rare in patients with multiple sclerosis who took the drug Copaxone®-Teva 20 mg / ml during post-marketing surveillance.
Overdose
Received several reports of overdose (up to 300 mg of Glatiramer acetate). No adverse reactions, other than those listed in the “Side Effects” section, were observed.
In case of overdose, careful observation, symptomatic and supportive treatment is indicated.
Interaction with other drugs
The interaction between Copaxone® 40 and other drugs has not been separately evaluated. No data on the interaction with interferon beta.
An increase in cases of reactions at the injection site with simultaneous administration of the drug Copaxone® 40 with corticosteroids.
In a studyin vitro It has been suggested that Glatiramer acetate has a high level of association with plasma proteins and is not displaced from the association with plasma proteins alone, as well as phenytoin or carbamazepine. Nevertheless, since the drug Copaxone® 40 has a potential effect on protein-binding substances, it is necessary to control its simultaneous use with other drugs.
special instructions
Initiation of treatment with Copaxone® 40 should be carried out under the supervision of a neurologist and a physician experienced in the treatment of multiple sclerosis. The drug is not indicated for the treatment of primary or secondary progressive multiple sclerosis.
Patients should be informed about the possibility of adverse reactions, including arising immediately after the injection of the drug Copaxone® 40. Most of these symptoms are short-lived, spontaneously resolved without consequences. With the development of serious adverse reactions should immediately discontinue therapy and contact your doctor or call an ambulance. The decision on the use of symptomatic therapy is taken by the doctor.
There is no evidence that certain groups of patients are more at risk of such reactions. However, patients with cardiovascular diseases should be monitored by a physician throughout the entire treatment period.
Several cases of seizures and / or anaphylactoid or allergic reactions have been identified. Severe hypersensitivity reactions (bronchospasm, anaphylactic reaction, or urticaria) can also be rare. In case of severe reactions, it is necessary to prescribe the appropriate treatment and stop taking the drug. Antibodies to Glatiramer acetate were detected in the serum of patients. After a course of treatment with an average duration of 3-4 months, their maximal concentration was recorded, which subsequently decreased and stabilized at a level just above the baseline.
There is no evidence that antibodies to Glatiramer acetate have a neutralizing effect or affect the clinical efficacy of the drug.
In patients with renal insufficiency, renal function should be monitored, although there is no convincing evidence that the deposition of immune complexes has an effect on glomerular filtration.
If a patient does not have the ability to store syringes with the drug Copaxone® 40 in a refrigerator, then storage is allowed at a temperature of 15–25 ° C, but not more than 1 month. If during the month syringes with the drug were not used and the blister cell packaging was not opened, these syringes should be further stored in a refrigerator (2–8 ° C).
Influence on ability to drive vehicles and mechanisms.Studies on the impact on the ability to drive vehicles and mechanisms was not conducted.
Storage conditions
In the dark place at a temperature of 2-8 ° C (not freezing).
Keep out of the reach of children.