Flammegis® (FLAMMEGIS®)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceInfliximabInfliximab
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  • Infliximab
    lyophilizate d / infusion 
    BIOCAD, CJSC     Russia
  • Remicade®
    lyophilizate d / infusion 
    MSD FARMASYUTIKALS, LLC     Russia
  • Flammegis®
    lyophilizate d / infusion 
    Selltrion Halcocea Co., Ltd.     The Republic of Korea
    • Dosage form: & nbsplyophilizate for the preparation of concentrate for the preparation of a solution for infusions
    Composition:

    1 bottle contains:

    active substance: infliximab 100 mg (1 ml reconstituted solution contains 10 mg infliximab);

    Excipients: sucrose 500 mg, polysorbate-80 0.5 mg, sodium dihydrogen phosphate monohydrate 2.2 mg, disodium hydrogen phosphate dihydrate 6.1 mg.

    Description:

    Powder or mass of white or almost white color.

    Pharmacotherapeutic group:immunosuppressive - antibodies monoclonal
    ATX: & nbsp

    L.04.A.B.02   Infliximab

    L.04.A.B   Inhibitors of tumor necrosis factor-α (TNF-α)

    Pharmacodynamics:

    Infliximab is a chimeric mouse-human monoclonal aMr.titelo, which binds with high affinity to soluble and transmembrane forms of TNFα, but does not bind to lymphotoxin alpha (LTα).

    Infliximab inhibits the functional activity of TNFα in various test samples in vitro. The use of infliximab in transgenic mice prevented the development of polyarthritis associated with the constitutional expression of human TNFα.The introduction of infliximab after the onset of the disease led to the healing of structural damage to the joints. In vivo infliximab rapidly forms stable complexes with human TNFα, which is accompanied by a decrease in the biological activity of TNFα.

    Elevated concentrations of TNFα were determined in the joints of patients with rheumatoid arthritis and correlated with disease activity. In patients with rheumatoid arthritis, infliximab therapy resulted in a reduction in infiltration of inflammatory cells into the inflamed joints, as well as a decrease in the expression of molecules mediating cellular adhesion, chemoattraction, and tissue destruction. After treatment with infliximab, there was a decrease in serum concentrations of interleukin-6 (IL-6) and C-reactive protein (CRP), as well as an increase in hemoglobin concentration in patients with rheumatoid arthritis with a lower hemoglobin concentration than baseline. Significant reduction in the number of lymphocytes in peripheral blood or their proliferative response to mitogenic stimulation compared with the response of cells of untreated patients in vitro was not detected.

    In patients with psoriasis, infliximab therapy reduced inflammation in the epidermal layer and normalized keratinocyte differentiation in psoriatic plaques. In patients with psoriatic arthritis, short-term therapy with infliximab was accompanied by a decrease in the number of T cells and blood vessels in the synovium and skin areas affected by the psoriatic process.

    Histological examination of colon biopsy specimens taken before and 4 weeks after the administration of infliximab revealed a significant decrease in the concentration of TNFα. Therapy with infliximab in patients with Crohn's disease was accompanied by a significant decrease in the concentration of the nonspecific serum inflammatory marker - SRV. The total number of peripheral blood leukocytes during treatment with infliximab changed to a minimal extent, although for lymphocytes, monocytes and neutrophils, there was a tendency to normalize their number. In patients who received infliximab, the proliferative response of peripheral blood mononuclear cells to stimulation did not decrease compared to that of untreated patients.No significant changes in the secretion of cytokines by stimulated mononuclear cells of peripheral blood after treatment with infliximab have been detected. The study of mononuclear cells of biopsy specimens of the intestinal plate of the intestinal mucosa showed that therapy with infliximab causes a decrease in the number of cells expressing TNF-α and interferon-γ. Additional histological studies confirmed that infliximab reduces the infiltration of inflammation cells and the content of markers of inflammation in the affected areas of the intestine. Endoscopic studies demonstrated healing of the intestinal mucosa in patients who received infliximab.

    Pharmacokinetics:

    A single intravenous infusion of infliximab at doses of 1, 3, 5, 10 or 20 mg / kg was accompanied by a dose-proportional increase in the maximum serum concentration (CmOh) and the area under the curve "concentration-time" (AUC). The volume of distribution in the equilibrium state (median 3.0-4.1 L) was independent of the dose and indicated the circulation of infliximab predominantly in the vascular bed. Pharmacokinetics did not depend on time.The ways to remove infliximab are not defined. Unchanged infliximab in the urine was not detected. In patients with rheumatoid arthritis, the clearance and volume of distribution did not vary with age or body weight. The pharmacokinetics of infliximab in elderly patients have not been studied. Studies in patents with liver or kidney disease have not been conducted.

    After a single dose of 3, 5 or 10 mg / kg, the median CmOh was 77, 118 and 277 μg / ml, respectively. The median of the terminal half-life period was from 8 to 9.5 days. Infliximab was detected in serum for at least 8 weeks in most patients with Crohn's disease (after a single dose of 5 mg / kg) or rheumatoid arthritis (with maintenance therapy of 3 mg / kg every 8 weeks).

    Repeated use of infliximab (5 mg / kg at 0, 2 and 6 weeks in patients with fistula form of Crohn's disease, and 3 or 10 mg / kg every 4 or 8 weeks in patients with rheumatoid arthritis) was accompanied by a small the accumulation of infliximab in the serum after the second dose. In the future, clinically significant accumulation was not observed. Most patients with frontal form of Crohn's disease infliximab was detected in serum for 12 weeks (ranging from 4 to 28 weeks) after administration in this regimen.

    Children

    Population analysis of pharmacokinetic data of patients with ulcerative colitis (n=60), Crohn's disease (n= 112), juvenile rheumatoid arthritis (n= 117) and Kawasaki's disease (n= 16) at the age of 2 months to 17 years showed that the effect of infliximab nonlinearly depends on the body weight. When taking 5 mg / kg infliximab every 8 weeks, the expected median of the equilibrium state (area under the concentration-time curve (AUCss)) in patients aged 6 to 17 years was approximately 20% less than the estimated median equilibrium exposure in adults. It is assumed that the median AUCss in patients aged 2 to less than 6 years, 40% lower than in adult patients, although the number of patients whose data support this assumption is limited.

    Indications:

    Rheumatoid arthritis. Therapy of patients with rheumatoid arthritis in active form, who had previous therapy with baseline antirheumatic drugs (CPAP), including methotrexate, was ineffective, as well as therapy of patients with severe progressive rheumatoid arthritis in active form,who have not previously been treated with methotrexate or other DMARD. Therapy is performed in combination with methotrexate. Combination therapy with infliximab and methotrexate allows to reduce the symptoms of the disease, improve the functional state and slow the progression of joint damage.

    Crohn's disease in adults. Therapy of patients aged 18 years with Crohn's disease in active form, medium or severe degree, including fistula formation, with inefficiency, intolerance or contraindication to standard therapy including glucocorticosteroids and / or immunosuppressants (in the fistula form - antibiotics, immunosuppressants and drainage). The therapy with infliximab helps to reduce the symptoms of the disease, to achieve and maintain remission, to mucosal healing and fistula closure, to reducing the number ca decrease in the dose or elimination of glucocorticosteroids, an improvement in the quality of life of patients.

    Crohn's disease the children and adolescents. Therapy of children and adolescents aged 6 to 17 years inclusive, with Crohn's disease in active form,moderate or severe with ineffectiveness, intolerance or the presence of contraindications to standard therapy, including glucocorticosteroids and / or immunosuppressants. The therapy with infliximab helps reduce symptoms of the disease, achieve and maintain remission, reduce the dose or eliminate glucocorticosteroids, improve the quality of life of patients.

    Ulcerative colitis the of adults. Therapy of patients with ulcerative colitis, in whom conventional therapy was not effective enough, including the use of glucocorticosteroids, 6-mercaptopurine or azathioprine. Infliximab therapy promotes healing of the intestinal mucosa, reducing symptoms of the disease, reducing the dose or eliminating glucocorticosteroids, reducing the need for inpatient treatment, establishing and maintaining remission, and improving the quality of life of patients.

    Ulcerative colitis the children and teenagers. Therapy of children and teenagers aged from 6 before 17 years inclusive from ulcerative colitis of moderate or severe severity with an insufficient response to standard therapy with the use of glucocorticosteroids, 6thercaptopurine or azathioprine, or in the presence of intolerance or contraindications to standard therapy.

    Ankylosing spondylitis. Therapy of patients with ankylosing spondylitis with severe axial symptoms and laboratory indices of inflammatory activity that did not respond to standard therapy. Therapy with infliximab helps to reduce the symptoms of the disease and improve the functional activity of the joints.

    Psoloriatic arthritis. Therapy of patients with progressive psoriatic arthritis in active form with an inadequate response to BPH. Infliximab is used in combination with methotrexate or in the form of monotherapy in cases of intolerance or the presence of contraindications to methotrexate. Therapy with infliximab allows to achieve a reduction in the symptoms of arthritis and improve the functional activity of patients, as well as a reduction in the degree of radiologic progression in peripheral psoriatic polyarthritis.

    Psoriasis. Therapy of patients with severe psoriasis subject to systemic therapy, as well as patients with moderate psoriasis with inefficiency, intolerance or contraindications to PUVA therapy.Therapy leads to a reduction in inflammatory phenomena in the skin and normalization of the process of keratinocyte differentiation.

    Contraindications:

    - Hypersensitivity to infliximab and other mouse proteins, as well as to any of the excipients of the drug;

    - severe infectious process, for example, sepsis, abscess, tuberculosis, opportunistic infections;

    - chronic heart failure III-IV functional class by classification NYON;

    - Pregnancy and breastfeeding;

    - age less than 18 years (with Crohn's disease and ulcerative colitis - less than 6 years).

    Carefully:

    - Chronic or recurrent infections in the anamnesis, including with concomitant therapy with immunosuppressants;

    - intensive therapy with immunosuppressive drugs or long-term PUVA therapy in history;

    - carriage of the hepatitis B virus;

    - demyelinating diseases;

    - increased risk of developing malignant tumors due to smoking;

    - malignant neoplasms in the anamnesis, continuation of therapy in patients with developed malignant neoplasms;

    - chronic heart failure I-II functional class by classification NYHA.

    Pregnancy and lactation:

    Women of childbearing age who are receiving treatment with infliximab and for at least 6 months after graduation should use reliable contraceptive methods.

    Pregnancy

    Data from approximately 450 patients who received infliximab during pregnancy (including about 230 in the first trimester), do not indicate the possibility of the development of unforeseen effects on the outcome of pregnancy.

    As a result of inhibition of TNFα, the use of infliximab during pregnancy can affect the normal immune response of the newborn. According to toxicity studies in mice, no evidence of toxicity for pregnant females, embryotoxicity, or teratogenicity was found with a similar antibody (selectively inhibiting mouse TNF-α activity).

    The available clinical experience is limited, and to avoid possible risks, the use of infliximab is not recommended during pregnancy.

    Infliximab penetrates the placenta and is found in the serum of newborn infants within 6 months after the infusion of infliximab in a pregnant patient.Consequently, such children may be at increased risk of developing infection, and the use of live vaccines is not recommended for them within 6 months after the last infusion of maternal infliximab during pregnancy.

    Breastfeeding period

    It is not known whether infliximab with milk from people and whether it is absorbed after ingestion. Since human immunoglobulins are excreted in breast milk, a woman should not be breast-fed for at least 6 months after the administration of infliximab.

    Impact on fertility

    The research data are insufficient to conclude that infliximab influences fertility and reproductive function.

    Dosing and Administration:

    The administration of infliximab should be carried out under the supervision of physicians with experience in the diagnosis and therapy of rheumatoid arthritis, inflammatory bowel disease, ankylosing spondylitis, psoriatic arthritis or psoriasis. Infusion of the drug should be carried out under the supervision of a physician trained to detect infusion reactions.

    When taking infliximab, concomitant therapy (glucocorticosteroids or immunosuppressants) should be optimized.

    The drug is administered intravenously drip for at least 2 hours. All patients should remain under medical supervision for 1-2 hours after the infusion to prevent acute infusion reactions. When carrying out the infusion, emergency means should be available (such as epinephrine, antihistamines, glucocorticosteroids and artificial ventilation). Pre-introduction of antihistamines, hydrocortisone and / or paracetamol, as well as a reduction in the rate of infusion to reduce the risk of infusion reactions, especially in patients who developed infusion reactions with the previous administration of the drug, are allowed.

    In the treatment of adult patients who have tolerated at least the first three 2-hour infusions (the phase of induction of infliximab) and are on maintenance therapy, it is possible to shorten the duration of subsequent infusions to a minimum of 1 hour. If in the future with an accelerated introduction of the drug there will be an infusion reaction, then in the case of continued therapy, a return to slower infusions is recommended.

    The possibility of reducing the time of infusion with the administration of the drug in a dose of more than 6 mg / kg has not been studied.

    Therapy of rheumatoid arthritis

    The initial single dose of infliximab is 3 mg / kg intravenously. Then, the drug is administered at the same dose 2 weeks and 6 weeks after the first administration (induction phase), and every 8 weeks thereafter (maintenance phase of therapy).

    Therapy with infliximab should be carried out simultaneously with the use of methotrexate.

    In most patients, a clinical response is achieved within 12 weeks. If there is insufficient response, or if the effect of therapy is lost in the subsequent period, an increase in the dose of infliximab in increments of 1, 5 mg / kg, up to 7.5 mg / kg every 8 weeks, or a reduction in the intervals between administrations infliximab in a dose of 3 mg / kg to 4 weeks. At achievement of the clinical answer therapy should be continued in a corresponding dose and a mode of infusions.

    In the absence of the effect of therapy during the first 12 weeks, and also in response to an increase in the dose of infliximab or a reduction in the intervals between infusions, consideration should be given to the advisability of continuing therapy.

    Therapy of severe or moderate severity of active forms Crohn's disease in adults

    The initial dose of infliximab is 5 mg / kg intravenously, the second infusion at the same dose 2 weeks after the first. If there is no response after two injections, further use of infliximab is not advisable. For responding patients, infliximab therapy can be continued, with one of two possible options: the drug is administered at a dose of 5 mg / kg at 6 weeks after the first administration and then every 8 weeks; in the supporting phase of therapy, some patients may need to increase the dose to 10 mg / kg to achieve the effect; the drug is administered again at a dose of 5 mg / kg for a relapse of the disease (see Sections "Reassignment" and "Side effect").

    Despite the inadequacy of the comparative data, limited data indicate that some patients who initially responded to a 5 mg / kg dose but subsequently lost the response may regain their response when the dose is increased. Care should be taken to evaluate the possibility of continuing therapy for patients who did not show signs of therapeutic improvement after changing the dose of the drug.

    The total duration of therapy with infliximab is determined by the attending physician.

    Therapy of severe or moderate severity of active form of Crohn's disease in children and adolescents aged 6 to 17 years inclusive

    The initial dose of infliximab is 5 mg / kg intravenously. Then the drug is administered in the same dose 2 weeks and 6 weeks after the first injection, and then every 8 weeks. In the absence of effect during the first 10 weeks, further use of infliximab is not recommended.

    In some patients, a shorter interval between infusions may be required to maintain a clinical effect, while for some patients a longer interval may be sufficient. In patients who have an interval between infusions reduced to less than 8 weeks, the risk of developing adverse events may be increased. It is necessary to carefully evaluate the need to continue therapy in the absence of additional effect from therapy with a change in the dosing interval.

    Therapy with infliximab should be carried out simultaneously with the use of immunomodulators: 6-mercaptopurine, azathioprine or methotrexate.

    If there is a response to therapy with infliximab, the total duration of therapy is determined by the attending physician.

    The efficacy and safety of infliximab in patients younger than 6 years of age have not been studied.

    Crohn's disease with fistula the of adults

    A drug Infliximab administered in a single dose of 5 mg / kg intravenously, then the drug is administered in the same dose 2 weeks and 6 weeks after the first administration. In the absence of an answer after the administration of these three doses, continued treatment with infliximab is impractical. If there is a response, therapy can be continued, and one of two possible strategies should be selected:

    - The drug is administered at a dose of 5 mg / kg at 2 weeks and 6 weeks after the first administration and then every 8 weeks; some patients may need to increase the dose to 10 mg / kg to achieve the effect of therapy;

    - the drug is administered repeatedly at the same dose for relapse of the disease (see Sections "Re-appointment" and "Side-effect").

    Despite the inadequacy of the comparative data, limited data indicate that some patients who initially responded to a 5 mg / kg dose but subsequently lost the response may regain their response when the dose is increased.Care should be taken to evaluate the possibility of continuing therapy for patients who did not show signs of therapeutic improvement after a dose change. The total duration of therapy with infliximab is determined by the attending physician.

    Comparative studies of these two variants of Crohn's disease therapy were not carried out. The available data on the use of the drug in the second variant of therapy (repeated administration in case of relapse) are limited.

    Therapy of ulcerative colitis in adults

    The initial dose of infliximab is 5 mg / kg intravenously. Then the drug is administered in the same dose 2 weeks and 6 weeks after the first injection, and then every 8 weeks. Some patients may need to increase the dose to 10 mg / kg to achieve the effect. The available data indicate the onset of the effect of therapy in the period up to 14 weeks (after the administration of 3 doses). If the effect did not occur during this time, the question of whether to continue therapy should be decided. If there is a response to therapy, the total duration of therapy with infliximab is determined by the attending physician.

    Therapy of ulcerative colitis the children and adolescents from 6 to 17 years inclusive

    The initial dose of infliximab is 5 mg / kg intravenously. Then the drug is administered in the same dose 2 weeks and 6 weeks after the first injection, and then every 8 weeks. The available data do not support the continued use of infliximab in the absence of effect within 8 weeks after the first infusion.

    If there is a response to therapy with infliximab, the total duration of therapy is determined by the attending physician.

    The efficacy and safety of infliximab in patients younger than 6 years of age has not been studied.

    Therapy of ankylosing spondylitis

    The initial dose of infliximab is 5 mg / kg intravenously. Then the drug is administered in the same dose 2 weeks and 6 weeks after the first injection, and then every 6-8 weeks. In the absence of effect for 6 weeks (after the introduction of two doses) continue therapy is not appropriate.

    Therapy of psoriatic arthritis

    The initial dose of infliximab is 5 mg / kg intravenously. Then the drug is administered in the same dose 2 weeks and 6 weeks after the first injection, and then every 8 weeks.

    Therapy of psoriasis

    The initial dose of infliximab is 5 mg / kg intravenously.Then the drug is administered in the same dose 2 weeks and 6 weeks after the first injection, and then every 8 weeks. If there is no effect for 14 weeks (after the administration of four doses), it is not advisable to continue therapy with infliximab. The total duration of therapy with infliximab is determined by the attending physician.

    Repeated administration of rheumatoid arthritis and Crohn's disease

    In case of relapse of the disease infliximab can be re-appointed within 16 weeks after the last dose. In clinical studies, hypersensitivity reactions were infrequent and were observed if the interval without infliximab before reintroduction was less than 1 year. The efficacy and safety of repeated administration of the drug more than 16 weeks without the use of the drug have not been studied.

    Repeated administration for ulcerative colitis

    The effectiveness and safety of the drug when it is used repeatedly under a different scheme (not every 8 weeks) have not been studied.

    Re-appointment with ankylosing spondylitis

    The efficacy and safety of the drug when it is re-applied in a different way (not every 6-8 weeks) has not been studied.

    Repeated administration of psoriatic arthritis

    The effectiveness and safety of the drug when it is used repeatedly under a different scheme (not every 8 weeks) have not been studied.

    Repeated an appointment with psoriasis

    The limited experience of repeated administration of a single dose of infliximab after a 20-week interval suggests that therapy may be less effective and may be accompanied by a higher incidence of infusion reactions (mild and moderate severity) compared with the initial induction regimen. The limited experience of re-appointment of infliximab in the induction mode after exacerbation of the disease suggests that the therapy may be accompanied by a higher incidence of infusion reactions (including severe) compared with the administration regimen every 8 weeks.

    Re-appointment regardless of the indications

    In the case of a breakthrough in maintenance therapy and the need for renewal of therapy, re-administration of infliximab in induction is not recommended. Renewal of therapy should be carried out in the regime of one infusion with the subsequent administration of infusions in the regime of maintenance therapy.

    Patients over 65 years of age

    Efficacy and safety of the drug in elderly patients have not been studied. No significant age-related differences in the distribution and excretion of the drug in clinical studies were observed. Correction of the dose is not required.

    Patients with impaired function Pschech and liver

    The efficacy and safety of the drug in this category of patients have not been studied.

    INSTRUCTION FOR PREPARATION OF INFUSION SOLUTION

    1) Calculate the dose and the required number of vials of infliximab (each vial contains 100 mg of infliximab) and the required volume of the finished drug solution.

    2) In aseptic conditions, dissolve the contents of each vial and 10 ml of water for injection using a syringe with a needle 21 (0.8 mm) or a smaller caliber. Before the introduction of the solvent, remove the plastic lid from the vial and wipe the cork with a 70% solution of ethyl alcohol. Insert the needle of the syringe into the vial through the center of the rubber stopper, and direct the water jet along the wall of the bottle.

    Gently stir the solution by rotating the vial until the freeze-dried powder is completely dissolved. Avoid prolonged and vibrational mixing.

    DO NOT BURST.When dissolving, the formation of foam is possible, in this case allow the solution to stand for 5 minutes.

    The resulting solution should be colorless or slightly yellow in color and opalescent. There may be a small amount of fine semitransparent particles in it, since infliximab is a protein. In the case of opaque particles, foreign inclusions and a discolored color, the solution can not be used.

    3) Bring the total volume of the prepared dose of the solution infliximab to 250 ml 0.9% solution of sodium chloride for injection. To do this, remove the volume from the glass vial or infusion bag containing 250 ml of 0.9% sodium chloride solution, equal to the volume of the prepared solution of infliximab in water for injection. Then slowly add the previously prepared infliximab solution and a bottle or infusion bag with 0.9% sodium chloride solution and gently mix. DO NOT INDUCE THE UNINTENDED PREPARATION!

    4) Carry out infusion for at least the recommended time. Use only an infusion system with a built-in sterile, pyrogen-free filter with low protein-binding activity (pore size not more than 1.2 μm).In connection with the lack of a preservative in the preparation, begin the introduction of the infusion solution as soon as possible, but not later than 3 hours after its preparation. Dissolution and dilution should be carried out in aseptic conditions.

    5) Do not enter infliximab together with any other medicinal products through one infusion system.

    6) Visually check the infusion solution before starting the injection. In the case of opaque particles, foreign inclusions and a discolored color, the solution can not be used.

    7) The unused portion of the infusion solution is not subject to further use and must be destroyed.

    Side effects:

    Upper respiratory tract infections were the most frequent adverse reactions reported in clinical trials, their incidence was 25.3% in patients who received infliximab, compared with 16.5% in the control group. The most serious adverse reactions associated with the use of TNF inhibitors that were reported with infliximab included reactivation of hepatitis B virus, chronic heart failure, serious infections (including sepsis,opportunistic infections and tuberculosis), serum sickness (delayed-type hypersensitivity reactions), hematologic reactions, systemic lupus erythematosus / lupus-like syndrome, demyelinating syndrome, hepatobiliary disorders, lymphoma, hepatolienne T-cell lymphoma, intestinal or perianal abscess (with Crohn's disease) and serious infusion reactions.

    Table of unwanted reactions

    Table 1 lists the undesirable reactions (including fatal) observed in clinical trials and reported during the post-registration period. Adverse reactions in the body systems are distributed in frequency into the following categories: very frequent (≥1 / 10), frequent (≥1 / 100 and <1/10), infrequent (≥1 / 1000 and <1/100), rare (≥ 1/10000 and <1/1000) and very rare (<1/10000), is unknown (the frequency can not be estimated based on the available data). In each column, unwanted reactions are in order of decreasing severity.

    Table 1. Adverse events detected during clinical trials and post-marketing period

    Class system / organ

    Frequency

    reactions

    The nature of the reaction

    Infectious and parasitic diseases

    highly

    frequent

    viral infections (eg, influenza, herpes)

    frequent

    bacterial infections (eg, sepsis, cellulitis, abscess)

    infrequent

    tuberculosis, fungal infections (eg, candidiasis)

    rare

    meningitis, opportunistic infections (such as invasive fungal infections (pneumocystis, histoplasmosis, aspergillosis, coccidiomycosis, cryptococcosis, blastomycosis), bacterial infections (atypical mycobacterial infection, listeriosis salmonellosis) and viral infections (cytomegalovirus infection)), parasitic infections, hepatitis B reactivation

    Benign, malignant and

    rare

    lymphoma, non-Hodgkin's lymphoma, Hodgkin's disease, leukemia, melanoma

    unspecified

    neoplasms (including cysts and polyps)

    unknown

    hepatolienne T-cell lymphoma (adolescents and young people with Crohn's disease and ulcerative colitis), Merkel's carcinoma

    Violations of the blood and lymphatic system

    frequent

    neutropenia, leukopenia, anemia, lymphadenopathy

    infrequent

    thrombocytopenia, lymphopenia, lymphocytosis

    rare

    agranulocytosis, thrombotic thrombocytopenic purpura, pancytopenia,hemolytic anemia, idiopathic thrombocytopenic purpura

    Infringements from

    immune system

    frequent

    respiratory allergic reactions

    infrequent

    anaphylactic reactions, lupus-like syndrome, serum sickness or serum-type reactions

    rare

    anaphylactic shock, vasculitis, reactions of the type of sarcoidosis

    Disorders of the psyche

    frequent

    depression, insomnia

    infrequent

    amnesia, anxiety, confusion, drowsiness, nervousness

    rare

    apathy

    Disturbances from the nervous system

    highly

    frequent

    headache

    frequent

    vertigo, dizziness, hyposthenia, paresthesia

    infrequent

    epileptic seizure, neuropathy

    rare

    transverse myelitis, demyelinating disorders of the central nervous system (by type of multiple sclerosis, neuritis visuallyth nerve), demyelinatingsoupe violations of the peripheral nervous system (Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy and multifocal motor neuropathy)

    Vision disorders

    frequent

    conjunctivitis

    infrequent

    keratitis, periorbital edema, meiobite

    rare

    endophthalmitis

    unknown

    transient loss of vision during or within 2 hours after infusion

    Heart Disease

    frequent

    tachycardia, palpitations

    infrequent

    heart failure (occurrence and deterioration), arrhythmia, syncope, bradycardia

    rare

    cyanosis, pericardial effusion

    unknown

    Myocardial ischemia / myocardial infarction during or within 2 hours after infusion

    Vascular disorders

    frequent

    lowering blood pressure, increasing blood pressure, ecchymosis, strong "hot flashes", "hot flashes"

    infrequent

    violation of peripheral blood circulation, thrombophlebitis, hematoma

    rare

    circulatory insufficiency, petechia, vasospasm

    Disturbances from the respiratory system of the chest and mediastinal organs

    highly

    frequent

    upper respiratory tract infection, sinusitis

    frequent

    infections of the lower respiratory tract (eg, bronchitis, pneumonia), shortness of breath, nosebleeds

    infrequent

    pulmonary edema, bronchospasm, pleurisy, pleural effusion

    highly

    rare

    interstitial lung disease (including rapid disease progression, pulmonary fibrosis and pneumonitis)

    Disorders from the gastrointestinal tract

    highly

    frequent

    abdominal pain, nausea

    frequent

    Gastrointestinal bleeding, diarrhea, dyspepsia, gastroesophageal reflux, constipation

    infrequent

    Intestinal perforation, intestinal stenosis, diverticulitis, pancreatitis, cheilitis

    Disturbances from the liver of the bile excretory Putuey

    frequent

    impaired liver function, increased "hepatic" transaminases

    infrequent

    hepatitis, hepatocyte damage, cholecystitis

    rare

    autoimmune hepatitis, jaundice

    highly

    rare

    liver failure

    Disturbances from the skin and subcutaneous tissues

    frequent

    the appearance or deterioration of psoriasis, including pustular psoriasis (mainly palmar-plantar form), urticaria, rash, itching, excessive sweating, dry skin, fungal dermatitis, eczema, alopecia

    infrequent

    bullous rash, onychomycosis, seborrhea, furunculosis, rosacea, skin papilloma, hyperkeratosis, skin pigmentation disorder

    highly

    rare

    toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, furunculosis

    Disturbances from musculoskeletal and connective tissue

    frequent

    arthralgia, myalgia, back pain

    Disorders from the kidneys and urinary tract

    frequent

    urinary tract infection

    infrequent

    pyelonephritis

    Violations of the genitals and mammary gland

    infrequent

    vaginitis

    General disorders and disorders at the site of administration

    highly

    frequent

    infusion reactions, pain

    frequent

    pain in the chest, fatigue, fever, reactions at the injection site, chills, swelling

    infrequent

    delayed wound healing

    rare

    formation of granulomatous foci

    Laboratory and instrumental data

    infrequent

    formation of autoantibodies

    rare

    violation of the development of complement factors

    Infusion reactions

    In the post-marketing period, when infliximab was used, there were cases of development of seizures and anaphylactoid reactions, including pharyngeal / laryngeal edema and severe bronchospasm. Very rarely reported cases of transient loss of vision, myocardial ischemia or myocardial infarction during infusion or within 2 hours after infusion.

    Infusion reactions after repeated infliximab injection

    Most serious infusion reactions were noted during 2 infusions (Week 2). The interval between the last maintenance dose and the first repeated induction dose was from 35 to 231 days.Symptoms included (but were not limited to) dyspnoea, urticaria, edema of the face and lowering blood pressure. In all cases, after stopping therapy with infliximab and / or at the beginning of another therapy, signs and symptoms were completely passed.

    Hypersensitivity reactions of delayed type (HRT)

    In clinical studies, HRT reactions were infrequent and occurred during the interval without taking infliximab for less than 1 year. In studies of psoriasis, HRT reactions occurred at the beginning of the course of therapy. Symptoms and symptoms included myalgia and / or arthralgia accompanied by fever and / or rash, some patients experienced itching, swelling of the face, lips or hands, dysphagia, urticaria, sore throat and headache.

    Data on the incidence of HRT reactions after the interval without the use of infliximab is not enough, but limited data from clinical studies suggest an increased risk of HRT reactions with an increase in the interval without taking infliximab.

    Immunogenicity

    In patients who developed antibodies to infliximab, infusion reactions developed more likely (approximately 2-3 times).Concomitant use of immunosuppressants decreased the likelihood of developing infusion reactions.

    Infections

    Tuberculosis, bacterial infections, including sepsis and pneumonia, invasive fungal, viral or other opportunistic infections have been observed in patients receiving infliximab. Some of these infections were lethal, the most frequently reported opportunistic infections with a mortality rate of more than 3% included pneumocystis, candidiasis, listeriosis and aspergillosis.

    Malignant neoplasms and lymphoproliferative diseases

    In clinical studies of infliximab, in which 5780 patients (5,494 patient-years of age) received therapy, 5 cases of lymphoma and 26 cases of malignancy (other than lymphoma) were diagnosed compared with the absence of lymphoma and 1 case of cancer (in addition to lymphoma) in 1,600 patients , who received a placebo (941 patient-years).

    Long-term follow-up (up to 5 years) of 3,210 patients (6234 patient-years) after clinical trials of infliximab reported 5 cases of lymphoma and 38 cases of malignancy (in addition to lymphoma).

    In the post-marketing period, rare cases of hepatolienne T-cell lymphoma were reported in patients with Crohn's disease and ulcerative colitis who received infliximab, most patients were adolescents or young adult males.

    Cardiovascular failure

    In the post-marketing period, cases of heart failure increased with infliximab in the presence or absence of additional factors. In addition, there were rare reports of a newly diagnosed heart failure, including in patients who had no previous cardiovascular disease. Some of these patients were under the age of 50 years.

    Changes in the liver and bile ducts

    In clinical studies in patients on the background of therapy with infliximab, there was a slight or moderate increase in ALT activity and ACT without the development of severe liver damage. In the post-marketing period, there were very few reports of jaundice and hepatitis, in some cases showing signs of autoimmune hepatitis, in patients who received infliximab.

    Antinuclear antibodies (ANA) / antibodies to double-stranded DNA (dsDNA)

    Antibodies to double-helical native DNA (anti-dsDNA) began to be detected in approximately 17% of patients. Nevertheless, reports of the development of lupus or lupus-like syndrome remained infrequent.

    Patients of childhood

    Patients of childhood with Crohn's disease

    Adverse events that were more common in children than in adults with Crohn's disease: anemia, blood in the stool, leukopenia, hot flashes, viral infections, neutropenia, bone fractures, bacterial infections, allergic reactions from the respiratory tract.

    Yingfusion reactions

    In 17.5% of patients, one or more infusion reactions may occur. Serious infusion reactions were absent, in very rare cases, patients had serious anaphylactic reactions.

    Immunogenicity

    Very rarely antibodies to infliximab were found in children

    Infections

    The most frequent infectious complications were upper respiratory tract infections and pharyngitis, the most frequent serious infectious complication was abscess, pneumonia, virus activation Herpes zoster.

    Post-registration period data

    In the post-registration period, spontaneous serious adverse events in childhood patients included cases of malignant neoplasms (including hepatolenal T-cell lymphoma), transient disorders of "hepatic" enzymes, lupus-like syndrome and the appearance of autoantibodies.

    Special Populations

    Elderly patients (≥65 years of age)

    In patients with a diagnosis of rheumatoid arthritis who received methotrexate and infliximab, the incidence of serious infections was higher than in patients younger than 65 years of age.

    Overdose:

    A single injection of infliximab in a dose of 20 mg / kg did not cause a toxic effect. Clinical data on overdose is not available. If necessary, symptomatic therapy should be given.

    Interaction:

    Special studies of interaction were not conducted.

    In patients with rheumatoid arthritis, psoriatic arthritis and Crohn's disease, simultaneous use with methotrexate or other immunomodulators reduces the formation of antibodies to infliximab and increases the concentration of the latter in plasma. However, due to the limitations of the method used to determine the concentration of infliximab and antibodies to infliximab in the blood serum, the results are not unambiguous.

    Glucocorticosteroids do not have a clinically significant effect on the pharmacokinetics of infliximab.

    It is not recommended simultaneous application of infliximab and other biological agents used for the same indications, including anakinra and abatacept.

    It is not recommended simultaneous use of the drug infliximab and live vaccines.

    It is not recommended simultaneous use of the drug infliximab and therapeutic drugs containing infectious agents.

    Special instructions:

    In order to improve the traceability of the use of biological medicinal products, it is recommended to record the name and series of the drug in the patient's medical record.

    It was demonstrated that the dissolved drug retained chemical and physical stability for 48 hours at a temperature of 2-8 ° C and 30 ± 2 ° C / relative humidity of 65 ± 5%. From a microbiological point of view, the drug should be used as soon as possible within 3 hours after dissolution and dilution.

    Infusion reactions and hypersensitivity reactions

    The use of infliximab may be associated with the development of acute infusion reactions, including anaphylactic shock and HRT reactions.

    Acute infusion reactions, including anaphylactic, may develop during (within seconds) or within a few hours after infusion. If an acute reaction occurs, the infusion should be stopped immediately. When carrying out the infusion, emergency means should be available (such as epinephrine, antihistamines, hydrocortisone and / or artificial ventilation). Preliminary administration of antihistamines, hydrocortisone and / or paracetamol is possible to prevent mild and transient effects.

    Perhaps the formation of antibodies to infliximab, which may be associated with an increase in the frequency of infusion reactions. A small part of the infusion reactions were severe allergic reactions. There was a correlation between the formation of antibodies to infliximab and a decrease in the duration of response to therapy. Joint use with immunomodulators was associated with a decrease in the incidence of antibodies to infliximab and a decrease in the frequency of infusion reactions. The effect of joint therapy with immunomodulators was more pronounced in patients receiving episodic therapy than in patients on maintenance therapy.In patients who stopped using immunosuppressants before or during treatment with infliximab, the risk of antibody formation is increased. Antibodies to infliximab may not always be detected in serum samples. With the development of a serious reaction, symptomatic therapy should be prescribed, subsequent infusions of infliximab should not be given.

    In clinical trials, cases of development of HRT reactions were reported. The available data suggest that an increase in the interval without taking infliximab increases the risk of HRT reactions. Patients should immediately seek medical attention for any adverse event. When resumption of therapy in patients after a long break should be carefully monitored signs and symptoms of HRT reactions.

    Infections

    Before and during and after therapy, the patient should be closely monitored for signs of possible infection, including tuberculosis. Since the withdrawal of infliximab occurs within 6 months, the patient should be monitored during this period.Therapy with infliximab should be discontinued if the patient develops a serious infection or sepsis.

    Caution should be exercised in the use of infliximab in patients with chronic infections or a recurrent history of infection, including those receiving concomitant therapy with immunosuppressants. Patients should avoid exposure to possible risk factors for infection.

    TNFα is a mediator of inflammation and a modulator of cellular immunity. Experimental data have shown that TNFα is necessary for purification from intracellular infections. Clinical experience shows that immunological protection against infections can be compromised in some patients receiving infliximab therapy.

    It should be borne in mind that inhibition of TNFα activity may mask such symptoms of infection as fever. Early recognition of atypical clinical manifestations of serious infections and typical clinical manifestations of rare and atypical infections is critical for reducing the delay in diagnosis and therapy.

    Patients receiving therapy with TNFα inhibitors are at greater risk of developing serious infections.

    Tuberculosis, bacterial infections, including sepsis and pneumonia, invasive fungal, viral or other opportunistic infections have been observed in patients receiving infliximab. Some of these infections were fatal, the most frequently reported opportunistic infections with a mortality rate of more than 5% included pneumocystis, candidiasis, listeriosis and aspergillosis.

    Patients who developed an infection during treatment with infliximab should be closely monitored and fully diagnosed. The use of infliximab should be discontinued if developed the patient of a new serious infection or sepsis, prescribe antibacterial or antifungal therapy before the control of the infectious process.

    Tuberculosis

    Cases of development of active tuberculosis were reported in patients who received infliximab. Most cases of tuberculosis were extrapulmonary local or disseminated.

    Before the start of therapy with infliximab, the patient should be closely monitored for the identification of both active and latent tuberculosis.The examination should include a careful history, including whether the patient had tuberculosis in the past, whether they had contacts with patients with tuberculosis, and whether immunosuppressant therapy has been or is being conducted. It is necessary to conduct the necessary screening tests (chest x-ray, tuberculin test). It should be noted that in seriously ill patients and in patients with immunosuppression, there may be floora false-negative tuberculin test is conducted.

    When diagnosing active tuberculosis, infliximab therapy can not be started.

    If suspicion of latent tuberculosis should be consulted phthisiatrician. In all cases described below, the risk / benefit of infliximab therapy should be carefully evaluated.

    When diagnosing latent tuberculosis, appropriate therapy should be started before infliximab therapy begins.

    In patients with several or significant risk factors for developing tuberculosis, but whose latent tuberculosis is not confirmed by the test, the need for antituberculous therapy should be considered before initiating therapy with infliximab.

    Consideration should be given to the need for the use of antituberculosis therapy before initiating therapy with infliximab in patients with active or latent tuberculosis in history, for which an adequate course of therapy can not be confirmed.

    Patients should consult a doctor if signs or symptoms of tuberculosis appear (persistent cough, weight loss / weight loss, subfebrile fever) during or after therapy with infliximab.

    Invasive fungal infections

    In the group of patients who received infliximab, suspicion of invasive fungal infections such as aspergillosis, candidiasis, pneumocystosis, histoplasmosis, coccidiomycosis or blastomycosis should always occur when the patient develops a serious systemic disease, at an early stage should consult a specialist in the diagnosis and therapy of invasive fungal diseases in the examination of such patients . Invasive fungal infections can be represented by disseminated, not localized lesions, and the result of the analysis on antigens and antibodies in some patients with active infection may be negative.The need to initiate empirical antifungal therapy before the end of laboratory studies should be assessed, considering both the risk of developing a serious fungal infection and the effects of antifungal therapy.

    For patients who have lived or visited regions endemic for invasive fungal infections, such as histoplasmosis, coccidiomycosis or blastomycosis, the benefits and risks of therapy with infliximab should be carefully evaluated before therapy begins.

    Fistula of the Crohn's disease

    Patients with Crohn's disease with acute purulent fistulas should not be started with infliximab before detecting and eliminating another possible foci of infection, especially an abscess.

    Reactivation of the hepatitis B virus

    Reactivation of the hepatitis B virus was observed in patients, chronic carriers of the virus, who received TNF antagonists, including infliximab, in some cases with a fatal outcome. Hepatitis B virus carriers who require infliximab therapy should carefully monitor signs and symptoms of infection during the course of therapy and for several months after graduation.Sufficient data on the effectiveness of the combined use of antiviral therapy (to prevent the reactivation of the virus) and TNF-α inhibitors in patients - chronic virus carriers are absent.

    When hepatitis B is reactivated, therapy with infliximab should be discontinued and appropriate antiviral therapy is prescribed.

    Dysfunction of the liver and biliary tract

    In the post-marketing period of infliximab use, cases of jaundice and non-infectious hepatitis were rarely observed, sometimes with signs of autoimmune hepatitis. There have been reports of isolated cases of liver failure leading to death or requiring a liver transplant. Patients with signs or symptoms of liver dysfunction should be examined for liver damage. In the case of jaundice or increased ALT activity to a level exceeding 5-fold upper the value of the norm, it is necessary to cancel infliximab and conduct a thorough investigation of the violation.

    Simultaneous use of the TNFα inhibitor and anakin

    Simultaneous use of anakinra and other TNFα (etanercept) inhibitor in clinical trialswas accompanied by the development of serious infections and neutropenia and did not lead to an additional clinical effect compared to etanercept monotherapy. Due to the nature of the side effects observed with simultaneous therapy with anakinra and etanercept, similar types of toxicity can occur with combined therapy with anakinro and other TNFα inhibitors. In this regard, the simultaneous use of infliximab and anakinra is not recommended.

    Simultaneous use of the inhibitor of TNF-α and abatacept

    In clinical studies, the combined use of TNF inhibitors and abatacept was associated with an increased risk of infections, including serious infections, compared with the use of only single TNF inhibitors, without increasing clinical benefit. The simultaneous use of infliximab and abatacept is not recommended.

    Simultaneous application with other biological preparations

    There is insufficient data on the joint use of infliximab and other biological agents intended for use for the same indications. The simultaneous use of infliximab with these drugs is not recommended due to a possible increase in the risk of infection and other possible pharmacological interactions.

    Transfer from another biological preparation

    Care should be taken when transferring from one biological product to another, as cross-biological activity may increase the risk of developing adverse events, including infections.

    Live vaccines and medications containing infectious agents

    Data on the response to vaccination or the possibility of secondary transmission of infection when using live vaccines in patients are insufficient. The use of live vaccines can lead to a clinical manifestation of infections, including disseminated infection. The simultaneous use of infliximab and live vaccines is not recommended.

    Use of drugs containing infectious agents, such as live attenuated bacteria (eg, BCG instillation for cancer therapy), can lead to a clinical manifestation of infections, including disseminated infection. It is not recommended simultaneous use of infliximab and medications containing infectious agents.

    Autoimmune processes

    In rare cases, the relative deficiency of TNFα caused by anti-TNF therapy can initiate the development of an autoimmune process.When symptoms of lupus-like syndrome occur with infliximab and positive tests for antibodies to double-stranded DNA, infliximab therapy should be discontinued.

    Neurological disorders

    The use of TNF inhibitors, including infliximab, in rare cases was accompanied by the appearance or growth of clinical and / or radiographic signs of demyelinating diseases of the central nervous system (including multiple sclerosis) and the peripheral nervous system, including Guillain-Barre syndrome. Patients with existing or newly emerging demyelinating diseases should carefully weigh the benefit and risk of anti-TNF therapy before prescribing infliximab. In the case of the development of such diseases, therapy with infliximab should be discontinued.

    Malignant tumors and lymphoproliferative disorders

    When conducting clinical trials using anti-TNF agents, a more frequent development of lymphoma was observed in patients receiving an anti-TNF agent than in patients in the control group. In clinical studies of infliximab, according to all approved indications, the appearance of lymphoma was rare, although more often than expected in general among the population.In the post-registration period, the development of leukemia in patients receiving TNF antagonists was reported. Since the risk of developing lymphoma and leukemia is elevated in patients with rheumatoid arthritis with a prolonged highly active inflammatory disease, risk assessment is difficult.

    In clinical studies on the use of infliximab with a possible new indication, chronic obstructive pulmonary disease (COPD) (severe and moderate severity), the incidence of neoplasms in smokers (or former smokers) was higher in the group receiving infliximab, than in the control group. Caution should be exercised in prescribing anti-TNF therapy to patients who are at increased risk of developing malignant tumors due to smoking.

    According to available data, the risk of developing lymphomas or other malignant neoplasms in patients receiving TNF inhibitors can not be ruled out. Caution should be exercised in prescribing TNF inhibitors to patients with malignant neoplasms in history or continuing therapy in patients with advanced malignancy.

    Caution should also be exercised in patients with psoriasis or intensive therapy with immunosuppressants or long-term PUVA therapy in history.

    Post-registration studies reported cases of the formation of malignant tumors, some fatal, among children, adolescents and adult young people (under 22 years of age) who received inhibitors of TNF (initiation of therapy at <18 years of age), including infliximab. Approximately half of the cases reported lymphomas. Other cases are represented by a number of different malignant tumors, including malignant tumors usually associated with immunosuppression. The risk of developing malignant neoplasms in patients receiving TNF inhibitors can not be ruled out.

    In the post-marketing period, reports were received of rare cases of hepatolyenal T-cell lymphoma in the treatment of TNF inhibitors, including infliximab. This rare type of T-cell lymphoma is characterized by a very aggressive course of the disease and usually ends in a lethal outcome. All cases of infliximab therapy have been reported in patients with a diseaseCrohn's or ulcerative colitis, most of them were reported in adolescents or young adult males. All reported cases of hepatolienne T-cell lymphoma have been reported in patients who simultaneously received azathioprine or 6-mercaptopurine. The possible risk of simultaneous use of azathioprine or 6-mercaptopurine and infliximab should be carefully evaluated. The risk of developing hepatolienneal lymphoma in patients receiving infliximab, can not be ruled out.

    There have been reports of the development of Merkel's carcinoma and melanoma in patients receiving TNFα blockers, including infliximab. It is recommended to periodically inspect the skin in patients, especially in patients with risk factors for malignant skin tumors.

    All patients with ulcerative colitis who are at increased risk of developing dysplasia or colon carcinoma (eg, patients with prolonged ulcerative colitis or primary sclerosing cholangitis), or who have previously diagnosed these diseases, should be monitored regularly for dysplasia before and after therapy.Observation should include a colonoscopy and biopsy, depending on the recommendations adopted. It is not known whether treatment with infliximab affects the risk of developing dysplasia or colorectal cancer.

    Since the possibility of increasing the risk of developing malignant neoplasms in patients with newly diagnosed dysplasia receiving infliximab therapy has not been established, the risks and benefits of infliximab therapy should be carefully evaluated and a decision to continue or discontinue therapy should be made.

    Heart failure

    Infliximab should be used with caution in patients with chronic heart failure I-II functional class by classification NYHA. Patients should be monitored, and in the event of new or worsening of existing signs of heart failure, therapy with infliximab should be discontinued.

    Hematologic reactions

    There have been reports of pancytopenia, leukopenia, neutropenia, and thrombocytopenia in patients receiving TNF inhibitors, including infliximab. All patients with development of signs and symptoms of blood dyscrasia (persistent fever, bruising, bleeding, pallor) should be immediately examined.In the case of severe hematologic abnormalities, infliximab therapy should be discontinued.

    Other

    Data on the safety of infliximab in patients who underwent surgery, including arthroplasty, are limited. When planning operations, it is necessary to take into account the long half-life of infliximab. When performing operations, patients receiving treatment with infliximab require close monitoring of infections and timely treatment of infections in the event of occurrence.

    The lack of response to Crohn's disease therapy may indicate the presence of a fixed fibrotic stricture, which may require surgical therapy. The available data suggest that infliximab does not contribute to deterioration or the formation of stricture.

    Special patient groups

    Elderly patients (≥65 years of age)

    The incidence of serious infections in elderly patients (≥65 years) was higher than in patients younger than 65 years of age. Some of these infections led to death. When treating elderly patients, one should be especially attentive to the risk of developing infections.

    Patients of childhood

    Infections

    In clinical studies, infections in children were reported more often than in adults.

    Vaccination

    Patients are advised to undergo a full vaccination as far as possible according to the current calendar of preventive vaccinations before initiating therapy with infliximab.

    Malignant neoplasms and lymphoproliferative disorders

    Post-registration studies reported cases of the formation of malignant tumors, some fatal, among children, adolescents and adult young people (under the age of 22 years) who received inhibitors of TNF (initiation of therapy aged <18 years), including infliximab. Approximately half of the cases reported lymphomas. Other cases are represented by a number of different malignant tumors, including malignant tumors usually associated with immunosuppression. The risk of developing malignant neoplasms in patients receiving TNF inhibitors can not be ruled out.

    In the post-marketing period, reports were received of rare cases of hepatolyenal T-cell lymphoma in the treatment with TNF inhibitors, including infliximab. This rare type of T-cell lymphoma is characterized by a very aggressive course of the disease and usually ends in a lethal outcome. All cases of treatment with infliximab have been reported in patients with Crohn's disease or ulcerative colitis, most of them have been reported in adolescents or young adult males. All reported cases of hepatolienne T-cell lymphoma have been reported in patients who simultaneously received azathioprine or 6-mercaptopurine. The possible risk of simultaneous use of azathioprine or 6-mercaptopurine and infliximab should be carefully evaluated. The risk of developing hepatolienneal lymphoma in patients receiving infliximab, can not be ruled out.

    Infliximab therapy for children and adolescents under the age of 17 years with rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis or psoriasis, as well as therapy for children under the age of 6 with Crohn's disease or ulcerative colitis has not been studied. Prior to receiving data on the safety and efficacy of infliximab, the drug should not be used for these indications in the appropriate age groups.

    Effect on the ability to drive transp. cf. and fur:

    Care should be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions, as the drug may cause dizziness and other side effects that may affect these abilities.

    Form release / dosage:Liofilizate for the preparation of concentrate for the preparation of a solution for infusions, 100 mg.
    Packaging:

    For 100 mg infliximab in bottles of colorless glass hydrolytic class I, sealed with stoppers from butyl rubber, closed by crimping aluminum caps and detachable plastic caps.

    On 1 bottle together with the instruction on medical application place in a pack a cardboard.

    Storage conditions:

    At a temperature of 2 to 8 ° C. Do not freeze.

    Keep out of the reach of children.

    Shelf life:

    3 years. Do not use after the expiration date printed on the package.

    If the drug is not used immediately, its storage time and condition prior to administration are the responsibility of the person using it; The drug should not be stored for longer than 24 hours at a temperature of 2-8 ° C.

    Terms of leave from pharmacies:On prescription
    Registration number:LP-003075
    Date of registration:06.07.2015
    Date of cancellation:2020-07-06
    The owner of the registration certificate:Selltrion Halcocea Co., Ltd.Selltrion Halcocea Co., Ltd. The Republic of Korea
    Manufacturer: & nbsp
    Representation: & nbspEGIS ZAO Pharmaceutical Plant EGIS ZAO Pharmaceutical Plant Hungary
    Information update date: & nbsp01.11.2015
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