Rheumatoid arthritis. The preparation in combination with Methotrexate (MTX) is indicated in adult patients to treat moderate to severe active rheumatoid arthritis (RA), if the response to disease-modifying anti-rheumatic drugs (LMPCh) (DMARDs), including Methotrexate, it is insufficient. The drug can be used alone if methotrexate is poorly tolerated or if further treatment with methotrexate is not recommended. It has been shown that the preparation administered in combination with methotrexate reduces the rate of progression of joint damage measured radiologically and improves the functional status.Axial spondyloarthritis. The drug is indicated in adult patients for the treatment of active axial severe spondyloarthritis, which includes: ankylosing spondylitis (ATA) - adults with active rigid spondylitis who have shown insufficient response to NSAIDs or their non-steroidal anti-inflammatory drugs they do not tolerate; Axial spondyloarthritis without radiographic changes characteristic of AS - adults with severe form of axial spondyloarthritis without radiographic changes characteristic of AS, but with objective signs of inflammation manifested by increased concentration of C-reactive protein (CRP) or demonstrated by magnetic resonance imaging, who showed insufficient response on NSAIDs or not tolerate them.Psoriatic arthritis. The preparation in combination with MTX is indicated in adult patients for the treatment of active psoriatic arthritis, if the response to previous LMPCh treatment is insufficient. The drug can be used alone if methotrexate is poorly tolerated or if further treatment with methotrexate is not recommended.
Composition:
1 pre-filled syringe contains 200 mg of certolizumab pegol in 1 ml.
Action:
Certolizumab selectively neutralizes the action of TNFα (proinflammatory cytokine), both membrane and soluble. Incubation of monocytes with certolizumab caused a dose-dependent inhibition, induced by lipopolysaccharide (LPS), production of TNFα and IL1β in human monocytes. Certolizumab does not contain a crystallizing fragment (Fc) that is normally found in complete antibodies, which is whyin vitro does not bind complement and does not cause antibody-dependent cellular cytotoxicity. It does not induce apoptosisin vitro in human monocytes or lymphocytes derived from peripheral blood, it also does not cause neutrophil degranulation. After subcutaneous administration of Cmax between 54 and 171 h after the injection. The bioavailability after subcutaneous administration compared to intravenous administration is about 80%. Certolizumab pegol is a fragment of the Fab 'antibody conjugated to PEG (polyethylene glycol) to extend the elimination half-life of Fab' (which is 14 days) to values comparable to the half-life of the complete antibody molecule. The Fab 'fragment breaks down into peptides and amino acids in the proteolytic process. The detached PEG molecule is rapidly removed from the plasma and excreted through the kidneys.
Contraindications:
Hypersensitivity to the active substance or to any of the excipients. Active tuberculosis or other severe infections, such as sepsis or opportunistic infections. Moderate or severe heart failure (NYHA class III / IV).
Precautions:
Treatment must not be initiated in patients with active infection, including chronic or localized infections, until the infection is controlled. If a patient develops a new severe infection, discontinue the preparation until the infection is controlled. Caution should be exercised when considering the use of the preparation in patients with a history of recurring infections or in cases that may predispose to infections, including concomitant administration of immunosuppressive drugs. All patients should be screened for both active and latent tuberculosis infection prior to treatment initiation. Appropriate screening (i.e.skin tuberculin test and chest X-ray examination). Treatment should be discontinued if active tuberculosis is diagnosed. In all situations, the expected benefits and possible risks associated with treatment should be carefully considered. If latent tuberculosis is diagnosed, appropriate anti-tuberculosis therapy should be initiated before starting treatment. The initiation of anti-tuberculosis therapy should also be considered for patients who have had active or latent tuberculosis in the past who can not be confirmed for appropriate treatment and in patients at high risk of tuberculosis despite a negative test for latent tuberculosis. If there is any suspicion of occult tuberculosis, regardless of BCG vaccination, biological screening for tuberculosis should be considered before commencing treatment with certolizumab. Due to the risk of reactivation of hepatitis B before treatment of patients at increased risk of HBV infection, it should be evaluated for signs of previous HBV infection. In patients who develop HBV reactivation, discontinue treatment and appropriate treatment. Caution should be exercised (due to lack of research) when deciding to resume treatment with TNF antagonists after controlling the reactivation of HBV infection and to closely monitor the patient's condition. Caution should be used when deciding to treat patients with a history of malignancy or continuing treatment of patients who have developed a cancerous process. The risk of malignant tumors (including leukemia) can not be excluded in patients using the product. The risk of developing malignancies in children and adolescents treated with TNF antagonists can not be excluded. Caution should be exercised when using any TNF antagonist in patients with COPD and in patients - heavy smokers. Use with caution in patients with mild heart failure (NYHA class I / II). Treatment should be discontinued if new symptoms of congestive heart failure appear or there is a worsening of existing symptoms. In the event of signs and symptoms indicative of haemorrhagic diathesis (eg persistent fever, subcutaneous haemorrhage, bleeding, paleness), the patient should immediately consult a doctor. Discontinuation of treatment should be considered in patients with confirmed significant haematological disorders. Due to the risk of exacerbation or exacerbation of demyelinating disease, including multiple sclerosis, the expected benefits and possible risks of treatment with a TNF-antagonist should be considered in patients with demyelinating disorders o. That previously or recently appeared. If an anaphylactic reaction occurs, the preparation should be discontinued immediately. Particular care should be taken in patients who have previously experienced severe hypersensitivity reactions to another TNF-blocking agent. Due to the immunosuppressive action of TNF antagonists, the drug may affect the body's defenses against infections and malignant neoplastic processes. The preparation may cause the formation of antinuclear antibodies. If symptoms suggestive of a lupus-like syndrome occur as a result of the use of the preparation, treatment must be discontinued. Due to the lack of data, live or attenuated vaccines should not be used. The use of certolizamab in combination with anakinra or abatacept is not recommended. When planning a surgical procedure, the 14-day half-life of certolizumab pegol should be considered. A patient who requires surgery during the treatment with the product should be carefully monitored to rule out the presence of an infection. Caution should be used in the elderly and special attention should be paid to the possibility of infections. Due to the lack of data, the efficacy and safety of the preparation in children and adolescents <18 years of age have not been established.
Pregnancy and lactation:
Due to the inhibitory effect on TNFα, the administration of the drug during pregnancy may interfere with the normal immune response in the newborn, therefore, no certolizumab should be administered during pregnancy.It is not known whether certolizumab is excreted in human milk, however, because human immunoglobulins are excreted in breast milk, a decision should be made to continue or discontinue treatment after considering the benefits of breastfeeding for the child and the benefits of treatment for the mother. Women of childbearing potential should use adequate contraception during treatment and for at least 5 months after the last dose. In animals, effects on sperm motility assessment parameters and a tendency to reduce the sperm count with no apparent effect on fertility were observed.
Side effects:
Common: bacterial infections (including gastrointestinal abscess), viral infections (including herpes virus infection, papilloma virus, influenza virus); diseases with eosinophilia, leukopenia (including neutropenia, lymphopenia); headaches (including migraine), sensory disturbances; hypertension; hepatitis (including increased liver enzymes); rash; fever, pain, weakness, pruritus, reactions at the injection site. Uncommon: sepsis (including multiorgan failure, septic shock), tuberculosis, fungal infections (including opportunistic infections); tumors of the blood and lymphatic system (including lymphomas and leukemia), parenchymal tumors, non-melanoma skin cancer, precancerous lesions (including oral leukoplakia, pigment staining), benign tumors and cysts (including cutaneous papillomas); anemia, lymphadenopathy, thrombocytopenia, thrombocytosis; vasculitis, lupus erythematosus, hypersensitivity to drugs (including anaphylactic shock), allergic reactions, positive results of autoantibody determinations; electrolyte imbalance, dyslipidemia, appetite disorders; changes in body weight; anxiety and mood disorders (including associated symptoms); peripheral neuropathies, dizziness, muscular tremor; visual impairment (including decreased vision), eye and eyelid inflammation, lacrimation; dizziness of peripheral origin; cardiomyopathies (including heart failure), ischaemia associated with coronary artery disease, arrhythmia (including atrial fibrillation), palpitations; haemorrhage or bleeding (at any location), hypercoagulability (including thrombophlebitis, pulmonary embolism), fainting, edema (including peripheral, facial), bruises (including haematomas, ecchymosis); asthma and related symptoms, pleural effusion and associated symptoms, congestion and inflammation of the airways, cough; ascites, ulceration and perforation of the gastrointestinal tract, gastroenteritis (at any location), stomatitis, indigestion, abdominal distension, dry mouth and throat; hepatopathy (including cirrhosis of the liver), cholestasis, increased bilirubin in the blood; alopecia, onset of psoriasis or worsening of psoriasis symptoms (including pustular psoriasis of the hands), dermatitis and eczema, abnormal perspiration, skin ulcers, hypersensitivity to light, acne, hyperpigmentation and dry skin, nail diseases and nail bed; muscle diseases, increased levels of creatine phosphokinase in the blood; impaired renal function, the presence of blood in the urine, bladder and urethral diseases; menstrual disorders and abnormal uterine bleeding (including amenorrhea), breast diseases; chills, flu-like conditions, changed sensations of ambient temperature, night sweats, flushing of the face with a feeling of heat; increased alkaline phosphatase in the blood, longer coagulation time; skin damage, impaired healing. Rare: stomach and intestinal tumors, malignant melanoma; pancytopenia, splenomegaly, erythrocytosis, abnormal white blood cell morphology; angioneurotic edema, sarcoidosis, serum sickness, inflammation of the subcutaneous tissue (including erythema nodosum); thyroid disease; hemosiderosis; suicide attempt, delirium, weakening of intellectual performance; convulsions, cranial nerve inflammation, coordination or balance disorder; tinnitus; pericarditis, atrioventricular block; stroke, arteriosclerosis, Raynaud's, cyanobacteria, telangiectasias; interstitial pneumonia, pneumonia; odynophagia, increased motor skills; cholelithiasis; exfoliation, bladder diseases, changes in hair structure; nephropathy (including nephritis); sexual dysfunctions; fistula; increase in uric acid in the blood. Frequency unknown: multiple sclerosis, Guillain-Barré syndrome.During the use of certolizumab in other indications uncommon was observed: narrowing and obstruction of the gastrointestinal tract, deterioration of the general physical condition, spontaneous abortion and azoospermia. The onset of multiple sclerosis has been associated with a group of TNF inhibitors, but the incidence of cases of people using Cimzia is unknown. Seizures may occur.
Dosage:
Treatment should be initiated and supervised by specialist doctors experienced in the diagnosis and treatment of the diseases in which the drug is indicated. Patients should receive a Patient Warning Card.The loading dose. Adults: the recommended starting dose is 400 mg (given as 2 subcutaneous injections of 200 mg each) at weeks 0, 2 and 4. When used in RA and in psoriatic arthritis, methotrexate should be continued, if appropriate.Maintenance dose. Rheumatoid arthritis: adults:200 mg every 2 weeks. Once the clinical response has been confirmed, an alternative maintenance dose of 400 mg every 4 weeks may be considered. During treatment with the preparation, methotrexate should be continued, if appropriate.Axial spondyloarthritis:Adults: 200 mg every 2 weeks or 400 mg every 4 weeksPsoriatic arthritis: adults:200 mg every 2 weeks. After confirmation of clinical response, an alternative maintenance dose of 400 mg every 4 weeks may be considered. Methotrexate should be continued during treatment, if indicated. In the above indications, available data indicate that clinical response usually occurs within 12 weeks of treatment. Continuation of treatment should be carefully considered in patients who have not received therapeutic benefit during the first 12 weeks of treatment.Skip the dose. Patients who skipped the dose should take the Next dose as soon as they remember and then continue to use the medicine according to the dosage schedule recommended by the doctor.Special groups of patients. The efficacy and safety of the medicine has not yet been established in children and adolescents under 18 years of age. In older patients (≥ 65 years), no dose adjustment is necessary. The drug has not been studied in patients with renal or hepatic impairment in the above-mentioned groups of patients, therefore no recommendation on a posology can be made.Method of administration. It should only be given by subcutaneous injection, injecting the entire contents of the pre-filled syringe (1 ml). Places suitable for injection are thigh or abdomen. After proper training to familiarize yourself with the injection technique using the pre-filled syringe, patients can inject themselves into their own hands if the doctor deems it desirable and will request a follow-up visit if necessary. The pre-filled syringe with a needle shield should only be used by healthcare professionals.