Оренсия®
Producer: Bristol-Myers Squibb Comp. (Bristol-Myers Skvibb Komp.) USA
Code of automatic telephone exchange: L04AA24
Release form: Liquid dosage forms. Lyophilisate for preparation of solution for infusions.
General characteristics. Structure:
Active ingredient: 250 mg of an abatatsept.
Excipients: maltoses monohydrate, dihydrophosphate sodium monohydrate, sodium chloride, Acidum hydrochloricum, sodium hydroxide.
* - packing is made taking into account a rebookmark in 5% - 262.5 mg.
Pharmacological properties:
Pharmacodynamics. Immunosuppressant. Абатацепт represents the soluble protein consisting of the extracellular domain of antigen of 4 cytotoxic T lymphocytes (CTLA-4) connected with the fragment of G1 immunoglobulin (IgG1) of the person modified by Fc. Абатацепт is rekombinatny protein which is produced by method of genetic engineering on system of cells of mammals.
Абатацепт selectively modulates key to - the stimulating signal necessary for full activation of the T lymphocytes expressing a cluster-differintsirovki 28 (CD28). With a pseudorheumatism T lymphocytes are found in patients in synovial fluid. The activated T lymphocytes play an important role in a pathogeny of a pseudorheumatism and other autoimmune diseases. Full activation of T lymphocytes requires 2 signals from antigenprezentiruyushchy cells: the first for recognition of a specific antigen receptors of T-cells (a signal 1); the second (the main, nonspecific) to - the stimulating signal includes binding of the molecules CD80 and CD86 on a surface of antigenprezentiruyushchy cells with CD28 receptor on a surface of T lymphocytes (a signal 2). Абатацепт specifically contacts CD80 and CD86, selectively inhibiting this way. It is established what абатацепт more influences the answer of not activated (naive) T lymphocytes, than memory T lymphocytes.
In the researches in vitro and on models at animals it is shown what абатацепт reduces antibody formation, dependent on T lymphocytes, and an inflammation. In vitro абатацепт reduces activation of T lymphocytes what decrease in proliferation and production of cytokines in lymphocytes of the person testifies to (ФНОα, interferon scale and interleykina-2). At rats with kollagenindutsirovanny arthritis абатацепт suppresses an inflammation, scale reduces formation of anti-collagenic antibodies and antigenspetsifichny products of interferon.
Table 1. Pharmacokinetic parameters (average value and confidence intervals) at healthy people and sick RA at intravenous administration of an abatatsept in a dose of 10 mg/kg.
* were carried out to infusions for 1, 15, 30 days, and then monthly.
The pharmacokinetics of an abatatsept at patients with a pseudorheumatism and healthy volunteers was comparable.
Distribution. At repeated in introduction, proportional increase in Cmax and AUC values in the range of doses from 2 mg/kg to 10 mg/kg was observed. At introduction in a dose of 10 mg/kg of Css in plasma it is reached by 60th day, at the same time average value (interval) Cmax is equal to 24 (from 1 to 66) mkg/ml. System cumulation of an abatatsept in an organism was not observed at patients with a pseudorheumatism at long repeated administration of drug in a dose of 10 bucketed mg/kg in 1 month.
Metabolism and removal. Researches for assessment of metabolism and elimination of an abatatsept at people were not conducted. Due to the space structure and hydrophily абатацепт it is not metabolized in a liver by isoenzymes of system of P450 cytochrome. Considering the big molecular mass of an abatatsept, it is supposed what абатацепт is not removed with urine
Pharmacokinetics in special clinical cases. It was revealed that higher clearance of an abatatsept is observed at patients with high body weight.
The age and sex of patients (at correction on body weight) did not influence clearance of an abatatsept.
Co-administration of a methotrexate, antiinflammatory drugs, corticosteroids and blockers of a factor of a necrosis of a tumor did not influence clearance of an abatatsept.
Researches on impact assessment of renal failures and liver on a pharmakokiknetika of an abatatsept were not conducted.
Indications to use:
— for reduction of symptoms, strengthening of the clinical answer, suppression of progressing of structural damages and improvement of functional activity at adult patients with moderately expressed or heavy active pseudorheumatism at the insufficient answer on one or several basic antiinflammatory (such as methotrexate) or biological antirheumatic drugs;
— for reduction of manifestations and symptoms at children at the age of 6 years is also more senior with moderately expressed or heavy course of active juvenile idiopathic arthritis with multiple damage of joints.
Route of administration and doses:
Абатацепт it is possible to apply in the form of monotherapy or in combination with basic antiinflammatory drugs (for example, with a methotrexate).
The drug Orensiya® is administered in/in in the form of infusion within 30 min. in the doses specified in the table. Adults after the first introduction are recommended to enter the following doses in 2 and 4 weeks, and then each 4 weeks.
To children aged from 6 up to 17 years with body weight less than 75 kg the dose of drug makes 10 mg/kg of body weight. The dose should be calculated individually just before each administration of drug. For children with the body weight of 75 kg and more mode of a drug dosing same, as for adults. The maximum dose makes 1000 mg.
Rules of preparation of infusion solution and administration of drug. Solution of an abatatsept cannot be used with the equipment incorporating silicone.
After removal of a protective plastic cover, the stopper is wiped with the sterile cotton wool moistened in alcohol. Contents of one bottle are dissolved in 10 ml of water for injections, using the one-time bessilikonovy syringe which is available complete with drug (the water stream at dissolution of drug should be directed to a bottle wall). To reduce foaming, the bottle should be turned carefully before full dissolution of powder. Not to stir up! After dissolution of powder from a bottle it is necessary to let out the air through a needle to remove all bubbles which could be formed. The received concentrate has to be colourless or pale yellow. It is impossible to use muddy solution, solution of other color or containing foreign debris.
The received concentrate immediately dilute to 100 ml 0.9% with chloride sodium solution for injections for receiving infusion solution as follows: from 100 ml of a bottle from sodium chloride select 10 ml of solution on each added bottle of an abatatsept. Then slowly add the concentrate received earlier by means of the one-time bessilikonovy syringe which is included in the drug package to the remained solution. Concentration of an abatatsept in the received solution makes respectively about 5, 7.5 or 10 mg/ml when using 2, 3 or 4 bottles of drug.
It is possible to store ready solution during 24 h the refrigerator at a temperature from 2 ° to 8 °C. If before introduction in solution foreign particles or discoloration are observed, solution needs to be poured out. The prepared solution it is necessary to enter a current of 24 h after opening of a bottle.
The prepared infusion solution is entered within 30 min. through infusional system with the sterile depyrogenized filter with low ability to connect proteins (the size of a time from 0.2 to 1.2 microns). Абатацепт it is impossible to enter along with other drugs through one infusional system.
Features of use:
Use at pregnancy and feeding by a breast. Use at pregnancy and in the period of a lactation (breastfeeding) is contraindicated.
Use for children. Use for children under 6 years is contraindicated.
At purpose of immunomodulatory drugs it is necessary to carry out tuberkulinovy skin test for identification of existence of a tuberculosis infection. Абатацепт it was not applied at patients with positive tuberkulinovy test therefore safety of drug at patients with latent tuberculosis is unknown. At positive reaction before purpose of an abatatsept it is necessary to carry out standard antitubercular therapy.
During treatment abatatsepty and within 3 months after its cancellation live vaccines should not be used. The drugs influencing immune system including абатацепт, can reduce efficiency of vaccination.
Obtaining false positive results when determining level of glucose of blood in day of administration of drug by tests on a basis глюкозодегидрогеназы-пирролохинолинхинона due to reaction with the maltose which is contained in drug is possible. If determination of level of glucose is required, it is necessary to use the methods excluding reaction with a maltose.
Side effects:
Side reactions which were observed in clinical trials at use of an abatatsept or placebo with other types of therapy of a pseudorheumatism. Determination of frequency of side reactions: very often (> 10%), it is frequent (> 1% and <10%), sometimes (> 0.1% and <1%), is rare (> 0.01% and <0.1%).
Infections and invasions: often - lower respiratory tract infections (including bronchitis), infections of urinary tract, the simple and surrounding herpes, upper respiratory tract infections (including tracheitises, nasopharyngites), rhinitis; sometimes - the infections of teeth infected skin ulcers, an onychomycosis.
Benign and malignant tumors: seldom - a skin basal cell carcinoma, lung cancer, a lymphoma, a miyelodisplastichesky syndrome.
From system of a hemopoiesis: sometimes - thrombocytopenia, a leukopenia.
From TsNS and peripheral nervous system: very often - a headache; often - вертиго; sometimes - a depression, alarm, paresthesias.
From an organ of sight: sometimes - conjunctivitis, decrease in visual acuity, dryness of an eye.
From cardiovascular system: often - arterial hypertension, inflows; sometimes - tachycardia, bradycardia, heartbeat, feeling of heat, decrease in the ABP.
From respiratory system: often - cough, HOBL aggravation, an asthma; sometimes - a bronchospasm, a pharyngalgia.
From the alimentary system: often - abdominal pains, diarrhea, nausea, dyspepsia, deviations of laboratory indicators of function of a liver (including increase in activity of transaminases); sometimes - gastritis, an ulceration of a mucous membrane of an oral cavity, aphthous stomatitis.
Dermatological reactions: often - rash (including dermatitis); sometimes - formation of bruises, an alopecia, a xeroderma, psoriasis.
From a musculoskeletal system: sometimes - an arthralgia, extremity pains.
From a reproductive system: sometimes - an amenorrhea.
Others: often - fatigue, an adynamy; sometimes - a grippopodobny syndrome, increase in body weight.
In clinical placebos - controlled researches at 0.05% of patients the following serious infections which communication with drug, at least, was possible were observed: bronchitis, pneumonia, acute pyelonephritis, diverticulitis, intestinal abscess, local infections, abscess of skin, infection of muscles and bones, sepsis, bacteremia, empyema, hepatitis E, tuberculosis.
Interaction with other medicines:
At the patients getting абатацепт with FNO blockers serious infections arose more often than at FNO receiving only blockers. The combination of an abatatsept with blockers of FNO is not recommended.
Data on safety and efficiency of a combination of an abatatsept with anakinry or rituksimaby are not enough therefore such combinations are not recommended.
Абатацепт it was not studied in a combination with the drugs causing decrease in number of lymphocytes. At such combination potentiation of action of an abatatsept on immune system is possible.
Contraindications:
— combined use with FNO blockers;
— heavy uncontrollable infections (sepsis, opportunistic infections), active infections (including tuberculosis) before establishment of control over it;
— pregnancy;
— period of a lactation (breastfeeding);
— children's age up to 6 years;
— hypersensitivity to drug components.
With care it is necessary to apply at patients with recurrent infections; the states contributing to infections (diabetes mellitus), hepatitises; at patients of advanced age. Introduction of an abatatsept should be stopped in case of development of an infectious disease.
Overdose:
The drug Orensiya® is administered in a look in/in infusion under medical observation. At doses to 50 mg/kg overt toxic effects were not observed. Symptoms of overdose are not described.
Treatment: at overdose observation of the doctor and, if necessary, performing symptomatic therapy is recommended.
Storage conditions:
Drug should be stored in the unavailable to children, protected from light place at a temperature from 2 °C to 8 °C. A period of validity - 3 years.
Issue conditions:
According to the recipe
Packaging:
250 mg - bottles glass (1) complete with the syringe bessilikonovy sterile (1 piece) - trays plastic (1) - boxes cardboard.
