Index of drugs

Rheumatoid arthritis. The preparation, in combination with Methotrexate, is indicated for the treatment of moderate to severe active rheumatoid arthritis in adult patients who have an inadequate response to their previous treatment with at least one disease-modifying anti-rheumatic drug (DMARDs), including Methotrexate (MTX) or tumor necrosis factor TNF. During treatment with abatacept in combination with methotrexate, reduction in the progression of joint damage and improvement in physical function was demonstrated.A polyarticular form of juvenile idiopathic arthritis. The preparation, in combination with methotrexate, is indicated for the treatment of moderate to severe active polyarticular juvenile idiopathic arthritis (JIA) in pediatric patients 6 years of age and older who have an inadequate response to other disease-modifying anti-rheumatic drugs (DMARDs), in at least one TNF inhibitor. The use of the preparation in children under the age of 6 has not been studied.

1 vial (10 ml) contains 250 mg of abatacept. The preparation contains sodium.

Abatacept is a fusion protein consisting of the extracellular domain of human CLTA-4 antigen combined with a modified Fc fragment of human G1 immunoglobulin (IgG1). Abatacept is produced in recombinant DNA technology in Chinese hamster ovary cells. It selectively modulates the key costimulatory signal necessary for full activation of CD28 expressing T lymphocytes. Two signals flowing from antigen presenting cells are necessary for full activation of T lymphocytes: recognition of a specific antigen by the T cell receptor (signal 1) and a second co-stimulatory signal. The main route of costimulation involves the combination of CD80 and CD86 molecules on the surface of antigen presenting cells with CD28 receptor on T lymphocytes (signal 2). Abatacept selectively inhibits this costimulatory route by specifically binding to CD80 and CD86. The results of the study indicate that abatacept has a stronger effect on the response of T lymphocytes, previously not found in any stimulus, than on the response of memory T lymphocytes. Under the influence of abatacept, a dose-dependent decrease in the plasma concentration of the soluble interleukin-2 receptor, which is a marker of T-cell activation, was observed; plasma interleukin-6, which is the product of activated synovial macrophages and fibroblast synoviocytes in rheumatoid arthritis; rheumatoid factor, autoantibodies produced by blood cells; and C-reactive protein, an acute phase substrate of the inflammatory process. In addition, there was a decrease in the content of matrix metalloproteinase-3 in the serum, which induces cartilage destruction and tissue remodeling. There was also a decrease in serum TNFα. After repeated intravenous infusions (days 1, 15, 30 and then every 4 weeks), the pharmacokinetics of abatacept in RA patients showed a dose-proportional increase in C_max and AUC, in the dose range of 2 mg / kg up to 10 mg / kg After administration of the 10 mg / kg dose, the mean final T_0,5 was 13.1 days (range 8-25 days). There was no systemic accumulation of abatacept during treatment with repeated doses of 10 mg / kg, at 1-month intervals. In population pharmacokinetic analyzes, abatacept clearance was increased with increasing body weight.

Hypersensitivity to the active substance or any of the excipients. Severe and uncontrolled infections, such as sepsis and opportunistic infections.

It is not recommended to associate abatacept with TNF antagonists. When changing treatment with TNF blockers to abatacept, patients should be monitored for signs of infection. Special care should be taken when treating patients with a history of allergic reactions to abatacept or any of the excipients. In the event of a severe allergic or anaphylactic reaction, treatment should be discontinued immediately and appropriate treatment instituted.The preparation may affect the body's defenses against infections and malignant tumors and may affect the response to vaccination. Simultaneous use of the preparation with biological immunosuppressants or immunomodulators may increase the effect of the drug on the immune system. No data available to assess the safety and efficacy of the drug in combination with anakinra or rituximab. The treatment should not be initiated in patients with active infections until control of the infection is obtained. Special care should be taken when considering the use of the preparation in patients with recurrent infections or conditions that may predispose them to a history of infection. Patients who have had a new infection during treatment should be closely monitored. If a patient develops a serious infection, discontinue the preparation. Before starting treatment, patients should be tested for latent tuberculosis. Antirheumatic treatment is associated with the activation of hepatitis B - before the start of treatment, tests for viral hepatitis should be performed. Immunosuppressive therapy with abatacept may be associated with progressive multifocal leukoencephalopathy (PML). If neurological symptoms suggestive of PML occur during treatment, the drug should be discontinued and appropriate therapy should be given. Live vaccines should not be used during abatacept or within 3 months of discontinuation. There are no data on the secondary transmission of infection from subjects receiving vaccines with attenuated microorganisms to patients treated with the preparation. Available data on the effects of vaccination in patients using the drug are inadequate. The drug may impair the effectiveness of some vaccinations. Before applying the preparation, it is recommended that patients with juvenile idiopathic arthritis should have all vaccinations in accordance with the current guidelines. Due to the generally higher prevalence of infections and malignant tumors in the elderly, caution should be used when treating patients in this age group. Theoretically, it is possible that the treatment with the preparation may increase the risk of autoimmune processes in adults and children, for example exacerbation of multiple sclerosis; in clinical trials, abatacept therapy did not lead to increased production of autoantibodies. The product has not been studied in patients with renal or hepatic impairment. The preparation contains maltose, it can interfere with blood Glucose reading by devices that use strip test with glucose dehydrogenase pyrroloquinolinequinone (GDH-PQQ), causing falsely increased blood glucose reading on the day of infusion. Patients who need to control the glucose levels in which the formulation is used should be advised to consider using non-maltose-based methods, such as methods using nicotinamide adenine dinucleotide dehydrogenase (GDH-NAD) glucose oxidase, glucose oxidase or glucose hexokinase.

Due to the lack of sufficient data, the preparation should not be used during pregnancy unless clearly necessary. Women of childbearing potential should use effective contraception during treatment and up to 14 weeks after the last dose of abatacept. During treatment with the preparation and up to 14 weeks after the last dose of abatacept, women should not breast-feed.

Very common: headache. Common: high blood pressure, abnormal liver function test (including transaminase elevation), nausea, cough, abdominal pain, diarrhea, nausea, dyspepsia, rash (including dermatitis), lower respiratory tract infection (including bronchitis) ), urinary tract infection, herpes, upper respiratory tract infection (including tracheitis, rhinitis), runny nose, hypertension, sudden redness of the face, tiredness, weakness. Uncommon: hypotension, weight gain, tachycardia, bradycardia, palpitations, thrombocytopenia, leukopenia, paraesthesia, conjunctivitis, reduced visual acuity, dizziness, gastritis, mouth ulcers, aphthous stomatitis, increased tendency to bruises, baldness, dry skin, joint pain, pain in the limbs, infection of teeth, infected skin ulcers, onychomycosis, basal cell carcinoma, hypotension, sudden feeling of heat, lack of menstruation, flu-like symptoms, depression, anxiety.The side effects reported in abatacept-treated patients that did not occur at a higher rate than in the placebo group (i.e., the difference was> 0.2%), but considered medically important were: often: shingles; uncommon: pneumonia, hypersensitivity, pyelonephritis, bronchospasm, urticaria, psoriasis, cystitis, migraine, feeling of compressed throat, dry eyes; rarely: sepsis, bacteremia.

Treatment should be initiated and supervised by specialist doctors experienced in the diagnosis and treatment of rheumatoid arthritis.Adults. Intravenous infusion lasting 30 minutes. Patients with a <60 kg - 500 mg (2 vials), mc.≥ 60 kg to ≤ 100 kg - 750 mg (3 vials),> 100 kg - 1000 mg (4 vials). The recommended dose is about 10 mg / kg. After the initial dose, subsequent doses should be administered 2 and 4 weeks after the first infusion, and then every 4 weeks. When used in combination with other disease-modifying anti-rheumatic drugs (DMARDs), corticosteroids, salicylates, NSAIDs or painkillers, no dose adjustment is required. No dose adjustment is required in elderly patients.Children and youth. Juvenile idiopathic arthritis: patients from 6 to 17 years of age less than 75 kg, the recommended dose is 10 mg / kg based on the patient's weight during each administration. Pediatric patients weighing 75 kg or more should take the drug according to the dosing schedule established for adults, but without exceeding the maximum permitted dose of 1000 mg. The preparation should be administered in the form of 30-minute intravenous infusions. After the initial treatment, the preparation should be administered from 2 to 4 weeks after the first infusion and the Next doses in the 4-week period. intervals. The product has not been studied in patients with renal or hepatic impairment - it is not possible to determine the recommended doses.