Index of drugs

Rheumatoid arthritis (RA) (in combination with methotrexate): to reduce the signs and symptoms and improve physical fitness in adult patients with an active form of disease inadequately responding to treatment with antirheumatic disease-modifying drugs (DMARDs), including Methotrexate or in adult patients with severe, an active and progressive form of the disease who had not previously been treated with methotrexate or other disease-modifying drugs (DMARDs). In these groups of patients, radiological studies showed a reduction in the progression of joint damage.Crohn's disease in adults: treatment of moderate to severe active form of Crohn's disease in adult patients who did not respond to a full and appropriate corticosteroid and / or immunosuppressive regimen or treatment was poorly tolerated or contraindicated; treatment of the active form of Crohn's disease with fistulas in adult patients who have not responded to properly conducted standard treatment (including antibiotics, drainage and immunosuppressive therapy).Crohn's disease in children: treatment of severe active form of Crohn's disease in children and adolescents aged 6 to 17 who have not responded to conventional treatment, including treatment with corticosteroids, immunomodulatory treatment and basic dietary treatment or who have had intolerance or contraindications to such treatments . The drug has been studied only in combination with standard immunosuppressive therapy.Ulcerative colitis: treatment of moderate or severe active ulcerative colitis in adult patients who have not responded adequately to standard therapy, including treatment with corticosteroids and 6-mercaptopurine (6-MP) or azathioprine (AZA), or have been tolerated or contraindicated treatment.Ulcerative colitis in children and adolescents: treatment of severe active ulcerative colitis in children and adolescents aged 6 to 17 years who have not responded adequately to standard therapy, including treatment with corticosteroids and 6-MP or AZA, or treatment was poorly tolerated or contraindicated.Ankylosing spondylitis: treatment of severe, active forms of ankylosing spondylitis in adult patients who have not responded adequately to conventional treatment.Psoriatic arthritis: treatment of active and progressive psoriatic arthritis in adults when the response to previous treatment with disease-modifying antirheumatic drugs (DMARDs) was insufficient. Infliximab should be given in combination with methotrexate alone or in patients who have been poorly tolerated or contraindicated in methotrexate therapy. In radiological studies, patients with polyarticular symmetrical forms of psoriatic arthritis have demonstrated that treatment with infliximab improves physical activity and reduces the rate of progression of peripheral joint damage.Psoriasis: treatment of moderate to severe plaque psoriasis in adult patients who have stopped responding to treatment, have contraindications or do not tolerate other general treatment regimens, including treatment with cyclosporine, methotrexate or PUVA.

1 vial contains 100 mg of infliximab.

Infliximab is a chimeric human-mouse monoclonal antibody that binds with high affinity to both soluble and transmembrane forms of human tumor necrosis factor alpha (TNF_α), but not binding to lymphotoxin (TNF_β). It inhibits the functional activity of TNF_α in various biological testsin vitro. In vivo, infliximab rapidly forms stable complexes with human TNF_α, which is synonymous with the loss of biological activity by TNF_α. In RA, infliximab treatment reduced infiltration of inflammatory cells to inflamed joints, as well as the expression of molecules responsible for cell adhesion, chemotacticity and tissue degradation.After treatment with infliximab, there was a decrease in interleukin-6 (IL-6) and serum c-reactive protein (CRP) in serum, and increased hemoglobin in RA patients with initially reduced hemoglobin levels, compared to baseline results. In patients with psoriasis, treatment with infliximab resulted in decreased epidermal inflammation and normalization of keratinocyte differentiation in psoriasis plaques. In psoriatic arthritis, short-term treatment with infliximab reduces the number of T-cells and blood vessels in the synovium and cutaneous psoriatic lesions. Treatment with infliximab for patients with Crohn's disease was associated with a significant reduction in the usually elevated levels of the inflammatory indicator - C-reactive protein (CRP) in the serum. One-time intravenous infusion at a dose of 1, 5, 10 or 20 mg / kg infliximab caused a dose-proportional increase in C_max in blood and AUC. The volume of distribution at equilibrium does not depend on the dose administered and indicates that infliximab is predominantly distributed in the vascular compartment. There was no drug accumulation in the blood that would be clinically relevant. The routes for elimination of the drug have not been determined. Infliximab was not detected unchanged in urine. Medium T_0,5 is 8-9.5 days.

Hypersensitivity to infliximab, other mouse proteins or other components of the preparation. Tuberculosis or other severe infections such as sepsis, abscesses and opportunistic infections. Moderate or severe heart failure (NYHA class III / IV).

Patients should be carefully monitored for signs of infection before, during and after treatment with infliximab (elimination of infliximab may take up to 6 months, which is why it is very important to observe patients during this period). An increased risk of infection occurs in elderly patients and in children, therefore these groups of patients should be treated with extreme caution. Caution should be used when considering infliximab for patients with a history of chronic infection or recurring infections, as well as immunosuppressive therapy. Patients should be advised to avoid exposure to factors potentially increasing the risk of infection if possible. If a new infection occurs in a patient treated with infliximab, it should be closely monitored and the overall diagnostic process should be performed. If severe infection or sepsis occurs, infliximab should be discontinued and appropriate treatment for infection should be started. In the event of a severe systemic disease, an invasive fungal infection should be considered, for example aspergillosis, candidiasis, pneumocystosis, histoplasmosis, coccidioidomycosis or blastomycosis. Appropriate antifungal empiric therapy should be implemented while conducting diagnostic tests, taking into account both the risk of severe fungal infection and the risk of antifungal treatment. In patients who have lived or traveled in endemic areas with invasive fungal infections, such as histoplasmosis, coccidioidomycosis or blastomycosis, the benefit-risk ratio should be carefully evaluated before commencing treatment with infliximab. All patients should be examined for active or latent tuberculosis before starting infliximab. This study should include a detailed history of tuberculosis or any possible contact with people with tuberculosis and prior and / or current immunosuppressive therapy. It should also be performed in all patients (local recommendations may be used) appropriate screening (chest X-ray, tuberculin test). If you are diagnosed with active tuberculosis, you can not start infliximab treatment. When latent tuberculosis is diagnosed, as well as in patients with several risk factors for tuberculosis or a serious risk factor for tuberculosis and a negative test for latent tuberculosis and for patients with history of latent or active tuberculosis in the past when it can not be confirmed whether they have received appropriate treatment , the benefits and risks of treatment with infliximab should be carefully weighed down and preventive tuberculosis treatment should be started before starting treatment with the preparation. In patients with Crohn's disease with fistulas with acute purulent fistulas, infliximab treatment must not be started until the possible source of infection is ruled out, in particular the abscess.Before starting treatment with infliximab, tests for HBV infection should be performed. HBV carriers who require treatment with infliximab, during treatment with the preparation and a few months after the end of therapy should be closely monitored in order to detect symptoms of active HBV infection. In patients who have recovered from hepatitis B, treatment with infliximab should be discontinued and antiviral and supportive therapy initiated. Patients with liver dysfunction should be examined for liver damage. If jaundice and / or ALT are ≥5 higher than the upper limit of normal (ULN), treatment with infliximab should be discontinued and a thorough examination of existing disorders should be performed. In patients with pre-existing or recent symptoms of demyelinating disorders, the benefit-risk ratio should be carefully evaluated before commencing treatment with infliximab. If these disorders develop, discontinue treatment with the preparation. Due to the risk of developing malignancies in patients treated with TNF antagonists, special care should be taken when administering infliximab to patients with a history of malignancy, patients at an increased risk of malignant tumors due to heavy smoking, and considering continuing treatment in patients who have malignant tumor. Caution should also be exercised in patients with psoriasis who have received extensive immunosuppressive therapy or long-term PUVA therapy. Periodic skin examinations are recommended, especially in patients with risk factors for developing skin cancer. Due to the risk of developing liver and spleen T-cell lymphoma, the potential risk of combination therapy with azathioprine or 6-mercaptopurine with infliximab should be considered (this applies especially to adolescents and young adult males). All patients with ulcerative colitis who have an increased risk of dysplasia or colorectal cancer (eg patients with long-standing ulcerative colitis or primary sclerosing cholangitis) and patients who previously had dysplasia or colon cancer should be treated before starting during treatment and during the course of the disease, examine at regular intervals for dysplasia. The test should include a colonoscopy and biopsies in accordance with local recommendations. Because the probability of an increased risk of developing cancer in patients with newly diagnosed dysplasia is not determined, the risk and benefit for each patient must be carefully assessed and cessation of treatment should be considered. Patients with moderate heart failure (NYHA class I / II) treated with infliximab should be monitored closely, and if new symptoms of heart failure or worsening of existing symptoms persist, do not continue treatment with the preparation. Patients should be monitored for evidence of dyscrasia. In patients with confirmed significant haematological disorders, discontinuation of infliximab should be considered. The use of the preparation should be discontinued if the activation of autoimmune phenomena is observed, e.g. symptoms suggestive of lupus-like syndrome and the detection of antibodies against double-stranded DNA. There is limited safety experience in patients after surgery, including arthroplasty. When planning surgery, the long half-life of infliximab should be taken into account. Patients requiring surgery during treatment with infliximab must be carefully monitored for infection. In the case of Crohn's disease, a lack of response to treatment may indicate the presence of a fixed intestinal stenosis that may require surgical treatment. Available data suggest that infliximab does not worsen or cause bowel obstruction. If you experience acute infusion-related reactions, stop the infusion immediately. Antibodies against infliximab may be associated with an increase in the frequency of infusion-related reactions. There was a relationship between the development of antibodies to infliximab and the shortened duration of response to treatment. Concomitant administration of immunomodulators was associated with a reduction in the incidence of antibodies to infliximab and the incidence of infusion-related reactions. Patients who discontinue immunosuppressive therapy before or during treatment with infliximab have an increased risk of developing these antibodies.If severe reactions occur, symptomatic treatment should be initiated and no further infusions of infliximab should be given. The risk of late type hypersensitivity reactions increases with prolonged intervals between consecutive administrations. Patients being treated again after a long break must be closely watched due to the possibility of late type hypersensitivity symptoms. The use of infliximab in combination with anakinra, abatacept or other biological medicines is not recommended. The simultaneous use of infliximab and live vaccines is not recommended. It is recommended that children receive all vaccines, if possible, at any given age according to current guidelines before infliximab is started. The safety and efficacy of infliximab in children and adolescents <18 years of age have not been established in the treatment of psoriasis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, juvenile rheumatoid arthritis; no recommendation on a dosage. The safety and efficacy of infliximab in children <6 years of age have not been established in the treatment of Crohn's disease, ulcerative colitis.

Limited data on the use of infliximab during pregnancy does not indicate an unexpected effect on the outcome of pregnancy. Due to inhibition of TNF_α, infliximab given during pregnancy may impair normal immune response in newborns. The available clinical experience is too limited to exclude the risk and therefore the preparation is not recommended during pregnancy. Women of childbearing potential should use effective contraception both over time and for at least 6 months after discontinuing treatment with infliximab. Infliximab crosses the placenta and is detected up to 6 months in the serum of infants born to women treated with the preparation during pregnancy. As a consequence, these babies may be at greater risk of infection. It is not recommended to give vaccines containing live microbes to infants if less than 6 months have passed since the last infusion of infliximab in pregnant mother. It is not known whether infliximab is excreted in human milk or absorbed by the oral route. Human immunoglobulins are excreted in breast milk, so women should not breast-feed during and for at least 6 months after stopping infliximab treatment.

Very common: viral infections (eg influenza, virus infectionherpes), headache, upper respiratory tract infections, sinusitis, abdominal pain, nausea, infusion-related reactions, pain. Common: bacterial infections (eg sepsis, cellulitis, abscess), neutropenia, leukopenia, anemia, generalized enlargement of the lymph nodes, allergic reactions from the respiratory system, depression, insomnia, diarrheal and extralorative vertigo, hypoesthesia, paresthesia, inflammation conjunctivitis, tachycardia, palpitations, hypotension, hypertension, bruising, flushing, facial flushing, lower respiratory tract infections (eg bronchitis, pneumonia), dyspnoea, epistaxis, gastrointestinal haemorrhage, diarrhea, dyspepsia, reflux gastro-oesophageal, constipation, liver dysfunction, increased transaminases, new onset or exacerbation of psoriasis, including pustular psoriasis (primarily hand and feet), urticaria, rash, pruritus, excessive sweating, dry skin, skin mycosis, eczema, alopecia, joint pain, muscle pain, b back pain, urinary tract infection, chest pain, fatigue, fever, injection site reactions, chills, swelling. Uncommon: tuberculosis, fungal infections (eg candidiasis), thrombocytopenia, lymphopenia, lymphocytosis, anaphylactic reactions, lupus-like syndrome, serum sickness, serum sickness-like symptoms, amnesia, agitation, confusion, drowsiness, nervousness, epileptic seizure, neuropathy, keratitis , periorbital edema, barley, heart failure (new onset or worsening), arrhythmia, syncope, bradycardia, peripheral ischemia, thrombophlebitis, hematoma, pulmonary edema, bronchospasm, pleurisy, pleural effusion, intestinal perforation, intestinal stricture, diverticulitis pancreatitis, inflammation of the lips, hepatitis, hepatocellular damage, cholecystitis, bullous rash, onychomycosis, seborrhea, rosacea, dermal papilloma, hyperkeratosis, abnormal pigmentation of the skin, pyelonephritis, vaginitis, impaired healing processes, dated autoantibodies.Rarely: meningitis, opportunistic infections (pneumocystosis, histoplasmosis, aspergillosis, coccidioidomycosis, cryptococcosis, blastomycosis, atypical mycobacteria, listeriosis, salmonellosis and cytomegalovirus infection), parasitic infections, reactivation of hepatitis B virus, lymphoma, lymphoma non-Hodgkin's disease, leukemia, agranulocytosis, thrombocytopenic purpura, pancytopenia, hemolytic anemia, idiopathic thrombocytopenic purpura, anaphylactic shock, vasculitis, sarcoid-like reaction, apathy, transverse myelitis, demyelinating diseases of the central nervous system (a disease similar to multiple sclerosis and optic neuritis), demyelinating diseases of the peripheral nervous system (such as: Guillain-Barré syndrome, chronic demyelinating inflammatory polyneuropathy and multifocal motor neuropathy), internal inflammation of the eye, cyanosis, pericardial effusion, cardiovascular failure, vasospasm, interstitial lung disease (including rapidly progressing disease, pulmonary fibrosis and pneumonia), autoimmune hepatitis, jaundice, toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, furunculosis, granulomatous lesions, abnormal complement system. Not known: melanoma, hepato-splenic T-cell lymphoma (especially in adolescents and young adult patients with Crohn's disease and ulcerative colitis), Merkel cell carcinoma, transient loss of vision during infusion or within 2 hours after infusion, myocardial ischaemia (myocardial infarction occurring during infusion or within 2 hours after infusion), hepatic failure, worsening of symptoms of dermatomyositis.

Intravenously. Treatment with the preparation should be initiated and supervised by a physician experienced in the diagnosis and treatment of rheumatoid arthritis or inflammatory bowel disease, ankylosing spondylitis, psoriatic arthritis or psoriasis. During the treatment with the preparation, the doses of other medicines used simultaneously, eg corticosteroids or immunosuppressive drugs should be optimized.
Adults (≥ 18 years old). Rheumatoid arthritis: 3 mg / kg in intravenous infusion, subsequent infusions at a dose of 3 mg / kg they are given 2 and 6 weeks after the first infusion and then every 8 weeks. Treatment with infliximab requires the simultaneous administration of methotrexate. Clinical response is achieved within 12 weeks of treatment. If the patient's response is not adequate or the response disappears after this period, a gradual dose increase of about 1.5 mg / kg should be considered, up to a maximum dose of 7.5 mg / kg every 8 weeks. Alternatively, 3 mg / kg may be considered. , every 4 weeks if appropriate response is obtained in patients, the treatment should be continued with the selected dose or with the chosen frequency of administration. Continuation of treatment should be considered carefully in patients who have not had any therapeutic benefit during the first 12 weeks of treatment or after adjusting the dose.Moderate to severe, active form of Crohn's disease: 5 mg / kg in intravenous infusion, followed by an additional 5 mg / kg 2 weeks after the first administration of the drug. If the patient does not respond to treatment after 2 doses, no additional treatment with infliximab should be used. The available data do not justify continuing treatment with infliximab for patients who did not respond within 6 weeks to the first infusion. For patients responding to treatment, the following alternative treatments are recommended:a. support - further infusions at a dose of 5 mg / kg after 6 weeks after the first dose, followed by infusion every 8 weeks orb. re-submission - infusion at a dose of 5 mg / kg if the disease symptoms recur. Despite the lack of comparative reports, there are limited data showing that patients who initially responded to treatment at a dose of 5 mg / kg but who subsequently lost their response can be restored by increasing the dose. Careful consideration should be given to continuing treatment in patients who have not received any therapeutic benefit after adjusting the dose.The active form of Crohn's disease with fistulas: 5 mg / kg Intravenous infusion, followed by 2 and 6 weeks after the first administration, should be given additional infusions of 5 mg / kg. If the patient does not respond to treatment after 3 doses, infliximab should not be continued.For patients responding to treatment, the following alternative treatments are recommended:a. support - further infusions at a dose of 5 mg / kg every 8 weeks orb. re-submission - infusion at a dose of 5 mg / kg if the symptoms of the disease recur, followed by infusions of 5 mg / kg. every 8 weeks. Despite the lack of comparative reports, there are limited data showing that patients who initially responded to treatment at a dose of 5 mg / kg but who subsequently lost their response can be restored by increasing the dose the drug. Careful consideration should be given to continuing treatment in patients who have not received any therapeutic benefit after adjusting the dose. Experience with re-administration in case of relapse of signs or symptoms of Crohn's disease is limited. There are no comparative results on the benefit-risk balance with other alternative methods of continuous treatment.Re-administration in Crohn's disease and rheumatoid arthritis: if the symptoms of the disease come back, the medicine may be given again within 16 weeks of the last infusion. Late type hypersensitivity reactions have been observed uncommonly. They occurred when the interruption in the use of the drug was shorter than 1 year. The efficacy and safety of re-use after an interval longer than 16 weeks have not been evaluated.Ulcerative colitis: 5 mg / kg in intravenous infusion, then at 2 and 6 weeks after the first administration, additional infusions should be given at a dose of 5 mg / kg, and then every 8 weeks. Available data indicate that clinical response is achieved within 14 weeks of treatment, i.e. after administration of 3 doses. The continuation of treatment should be carefully considered in patients who have not had any therapeutic benefit during this period. The safety and efficacy of re-administration were not established differently than every 8 weeks.Ankylosing spondylitis: 5 mg / kg intravenous infusion, then 2 and 6 weeks after the first administration, additional infusions should be given at a dose of 5 mg / kg, and then every 6 to 8 weeks. If the patient does not respond to treatment until 6 weeks (i.e. 2 doses), no further doses of infliximab should be given. The safety and efficacy of re-administration were not established differently than every 6 to 8 weeks.Psoriatic arthritis: 5 mg / kg intravenous infusion, followed by 2 and 6 weeks after the first administration should be given additional infusions of 5 mg / kg, and then every 8 weeks. The safety and efficacy of re-administration was not determined differently than every 8 weeks.Psoriasis: 5 mg / kg in intravenous infusion, then after 2 and 6 weeks from the first administration should be given additional infusions of 5 mg / kg and then every 8 weeks. If the patient does not respond to treatment after 14 weeks (ie after administration of 4 doses ) no further doses of infliximab should be given. Limited experience with repeated administration of one dose of psoriasis after 20 weeks. the interval indicates a reduction in efficacy and an increase in cases of mild or moderate infusion-related reactions compared to the first course of treatment. The limited experience of re-treatment after the Next rejection of the disease by means of reinduction patterns suggests a higher rate of infusion reactions, including severe infusion reactions, compared to 8 weeks. maintenance treatment.Re-administration of the drug in individual indications: in the case of discontinuation of maintenance therapy and the need for re-inclusion of the drug, it is not recommended to use a reinduction regimen. In this situation, infliximab should be re-administered in a single dose followed by a maintenance dose in accordance with the above recommendations.Children and youth. Crohn's disease (6 to 17 years): 5 mg / kg in intravenous infusion, followed by infusions of 5 mg / kg 2 and 6 weeks after the first infusion and then every 8 weeks. Available data do not justify continuing treatment with infliximab for children and adolescents who have not responded to the first 10 weeks of treatment. Some patients may require shorter intervals between individual doses to maintain clinical benefit, while others may have to take longer breaks. In patients who have been shortened to less than 8 weeks between dosages, the risk of side effects may be greater. In the case of people who have not shown any signs of additional therapeutic benefits after changing the interval between doses, the possibility of continuing the therapy according to the schedule with a shortened interval should be carefully considered.The safety and efficacy of infliximab has not been established in children with Crohn's disease <6 years of age; no recommendation on a dosage.Ulcerative colitis (6 to 17 years): 5 mg / kg in intravenous infusion, followed by infusions of 5 mg / kg 2 and 6 weeks after the first infusion and then every 8 weeks. Available data do not justify continuing treatment with infliximab in children and adolescents who have not responded during the first 8 weeks of treatment. The safety and efficacy of infliximab has not been established in children with ulcerative colitis aged <6 years; no recommendation on a dosage.Special groups of patients. No dose adjustment is necessary in elderly patients. The drug has not been studied in patients with impaired renal or (or) hepatic function; no dose recommendation can be given.Way of giving: The drug should be administered as an intravenous infusion lasting 2 hours. All patients should be observed for at least 1-2 hours after the infusion to notice the acute reactions associated with the infusion of the drug. An emergency kit must be available while administering infliximab. To prevent moderate and transient infusion reactions, premedication with an antihistamine, Hydrocortisone and / or Paracetamol is recommended. You can also reduce the rate of infusion to reduce the risk of infusion-related reactions, especially in cases where infusion-related reactions have occurred in the past. In carefully selected adult patients who tolerated at least the initial 3-hour infusions of infliximab (induction phase) and receive maintenance treatment, subsequent infusions may be included in not less than 1 hour. If a patient develops a shorter infusion, an infusion reaction occurs, and treatment is to be continued, a slower rate of infusion may be considered. No studies on shorter infusion times at doses> 6 mg / kg have been performed.