Orencia
Orencia: instructions for use and reviews
- 1. Release form and composition
- 2. Pharmacological properties
- 3. Indications for use
- 4. Contraindications
- 5. Method of application and dosage
- 6. Side effects
- 7. Overdose
- 8. Special instructions
- 9. Application during pregnancy and lactation
- 10. Use in childhood
- 11. Drug interactions
- 12. Analogs
- 13. Terms and conditions of storage
- 14. Terms of dispensing from pharmacies
- 15. Reviews
- 16. Price in pharmacies
Latin name: Orensia
ATX code: L04AA24
Active ingredient: abatacept (Abatacept)
Manufacturer: Bristol-Myers Squibb Holdings Pharma, Ltd. Liability Company (Bristol-Myers Squibb Holdings Pharma, Ltd. Liability Company) (Puerto Rico / USA); Bristol-Myers Squibb S. R. L. (Bristol-Myers Squibb SrL) (Italy)
Description and photo update: 2019-23-10
Prices in pharmacies: from 14300 rubles.
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Orencia is an immunosuppressive drug. Basic antirheumatic drug.
Release form and composition
Orencia is available in the following dosage forms:
- solution for subcutaneous administration 125 mg / ml: colorless or light yellow, slightly opalescent or transparent (1.007 ml each in colorless glass syringes with an automatically retractable needle or in ordinary transparent glass syringes; in a cardboard box 1 regular syringe or 1 or 4 syringes with an automatically retractable needle, as well as instructions for the preparation and instructions for using the syringe);
- lyophilisate for preparing a solution for infusion 250 mg: white or almost white powder or porous mass (262.5 mg each in glass vials sealed with a rubber stopper and an aluminum cap with a protective plastic lid; in a cardboard box 1 bottle, 1 silicone-free sterile syringe and instructions on the use of Orencia).
Composition for 1 syringe with solution for subcutaneous administration:
- active substance: abatacept - 125.875 mg;
- auxiliary components: sodium hydrogen phosphate anhydrous, poloxamer, sodium dihydrogen phosphate monohydrate, sucrose, water for injection.
Packing is carried out taking into account the overload of 0.7% (or 0.007 ml). This is necessary to ensure that the declared dose has been fully withdrawn from the syringe. The extracted amount of the drug corresponds to 125 mg.
Composition for 1 bottle with lyophilisate:
- active substance: abatacept - 262.5 mg;
- auxiliary components: sodium dihydrogen phosphate monohydrate, sodium hydroxide (until pH 7.5 is reached), hydrochloric acid (until pH 7.5 is reached), maltose monohydrate, sodium chloride.
Packing is carried out taking into account the re-packing of 5% (or 12.5 mg). This is necessary to ensure that the declared dose is completely removed from the vial. The extractable amount of active ingredient from one bottle corresponds to 250 mg.
Pharmacological properties
Pharmacodynamics
Abatacept is a soluble protein that consists of the extracellular domain of antigen-4-cytotoxic T-lymphocytes associated with a modified Fc-fragment of IgG1 (immunoglobulin G1) of a person. The molecular weight of abatacept is about 92 kDa (kilodalton). It is a recombinant protein produced by genetic engineering on an isolated mammalian cell culture. The drug selectively modulates a key co-stimulatory signal required for the complete activation of T-lymphocytes, which in turn express CD 28 (differentiation cluster 28). In patients with RA (rheumatoid arthritis), activated T-lymphocytes are present in the synovial fluid. They play an important role in the pathogenesis of autoimmune diseases, including rheumatoid arthritis. Full activation of T-lymphocytes occurs if two signals are received from antigen-presenting cells:signal 1 - for recognition of a specific antigen by T-cell receptors; signal 2 (nonspecific) - involves the binding of CD86 and CD80 molecules located on the surface of antigen-presenting cells with CD28 receptors, which are located on the surface of T-lymphocytes. Abatacept inhibits the second pathway by specifically binding to CD80 and CD86. Orensia influences the response of naive (non-activated) T lymphocytes to a greater extent than memory T cells. Orensia influences the response of naive (non-activated) T lymphocytes to a greater extent than memory T cells. Orensia influences the response of naive (non-activated) T-lymphocytes to a greater extent than memory T-cells.
In vitro animal studies have shown that abatacept attenuates inflammation and reduces T-lymphocyte-dependent antibody production. It inhibits the activation of T-lymphocytes, which is confirmed by a decrease in the proliferation and production of cytokines in lymphocytes (interleukin-2, interferon-γ and F110-alpha). In experiments on rats with collagen-induced arthritis, the drug suppressed inflammation, reduced antigen-specific production of interferon-γ and the synthesis of anti-collagen antibodies.
Pharmacokinetics
The pharmacokinetics of abatacept after subcutaneous administration is linear. The minimum and maximum equilibrium plasma concentrations of the drug were reached approximately 85 days after the start of therapy and were 6.6-113.8 μg / ml and 9.8-132.4 μg / ml, respectively. When administered subcutaneously, the bioavailability of abatacept is lower than with intravenous infusion (about 79% of the bioavailability of Orencia when administered intravenously). Systemic clearance averages 0.28 ml / h / kg, and the volume of distribution is about 0.11 l / kg. Regardless of the route of administration (subcutaneous or intravenous), the terminal half-life was 14.3 days.
With repeated intravenous administration of abatacept (on the 1st, 15th and 30th days, and then once every 4 weeks), the maximum plasma concentration and AUC (area under the concentration-time curve) increased proportionally in the dose interval 2– 10 mg / kg. After the introduction of 10 mg / kg, the half-life of the drug was 13.1 days (it varies in the range of 8-25 days), the volume of distribution was 0.071 l / kg (it varies in the range of 0.02-0.13 l / kg), systemic clearance - 0.22 ml / h / kg, equilibrium plasma concentration - 25 μg / ml, maximum plasma concentration - 290 μg / ml.
It was found that in patients with high body weight, the clearance of abatacept is higher. The patient's age and gender (taking into account the correction for body weight) did not affect the drug clearance. The clearance of Orencia does not change with the simultaneous use of anti-inflammatory drugs, methotrexate and tumor necrosis factor blockers.
Abatacept is a hydrophilic compound and has a peculiar spatial structure, therefore it does not undergo hepatic metabolism with the participation of enzymes of the cytochrome P 450 system. Due to the high molecular weight of the drug, its excretion in the urine is unlikely.
There are no data on the effect of impaired renal and / or liver function on the pharmacokinetic parameters of abatacept.
In children and adolescents aged 6–17 years with a diagnosis of juvenile idiopathic arthritis, after Orencia administration at a dose of 10 mg / kg, the clearance of abatacept was higher than in adults (0.44 ml / h / kg versus 0.3 ml / h / kg). The volume of distribution was 0.12 l / kg, and the half-life was 11.2 days. Average serum drug concentrations were lower than in adult patients (due to higher clearance).
Indications for use
Orencia is used in adult patients with moderate to severe rheumatoid arthritis in order to reduce symptoms of the disease, improve functional activity, suppress the progression of structural damage, and enhance clinical response. The drug is used both as monotherapy and in combination with basic anti-inflammatory drugs.
In children and adolescents over the age of 6 years, Orensia is used in the form of a lyophilisate for the preparation of a solution for infusion for moderate or severe active juvenile idiopathic arthritis with multiple joint damage.
Contraindications
Absolute:
- severe uncontrolled infectious diseases (for example, opportunistic infections and sepsis) before control is established;
- infections in the active phase (including tuberculosis) before they stop or become chronic;
- simultaneous use with tumor necrosis factor blockers;
- joint reception with anakinra, gold preparations and azathioprine;
- children under 6 years of age (for intravenous administration);
- children and adolescents up to 18 years of age (for subcutaneous administration);
- the period of pregnancy and breastfeeding;
- increased individual sensitivity to the main or auxiliary components of the drug.
Relative (Orencia is used with caution): the presence of recurrent infectious lesions; conditions that predispose to infections (for example, diabetes mellitus); hepatitis; elderly age.
Orensi, instructions for use: method and dosage
Solution for subcutaneous administration
The drug is administered subcutaneously, once a week. A single dose is 125 mg (one filled syringe) and does not depend on the patient's body weight. Orencia is administered with or without a loading dose. There are two options:
- Orensya is prescribed for the first time: with a loading dose - before subcutaneous administration, the patient is injected with abatacept intravenously (in the form of a lyophilisate for preparing a solution for infusion, the procedure is performed according to the instructions for this dosage form); then the first subcutaneous injection is carried out during the day; without loading dose - the drug is administered at a dose of 125 mg subcutaneously, once a week;
- The patient is transferred from the intravenous form of Orencia to a solution for subcutaneous administration: instead of the next scheduled intravenous infusion, the drug is administered subcutaneously.
A solution for subcutaneous administration should not be administered intravenously (neither in the form of injections, nor in the form of infusions). Orencia can be administered by both a healthcare professional and the patient independently, but in the second case, the healthcare professional must make sure that the patient is doing everything correctly and clearly follows the instructions.
Before the introduction, it is necessary to examine the solution in the syringe: it should be transparent or with a slight opalescence, from colorless to light yellow. If the color of the solution is changed and / or particles are found in it, such a solution cannot be injected.
The entire volume of the solution in the syringe is injected once. It is recommended to change the injection site with each injection. Orencia should not be injected into areas with rough or too delicate skin, as well as into damaged or reddened areas of the skin.
If the next injection is missed for a period of less than three days, it should be carried out as soon as the patient remembers about the missed time. Next, you need to adhere to the weekly plan for the introduction of Orencia. If more than three days have passed after missing the next injection, the patient should consult a doctor, who, after clarifying the stage of the disease and the patient's condition, will give instructions on the further schedule of drug injections.
In elderly patients, Orencia is used in usual doses.
Lyophilisate for preparation of solution for infusion
Orencia is administered intravenously over 30 minutes.
Recommended single doses for adults:
- patients weighing less than 60 kg - 500 mg (2 bottles);
- patients weighing 60–100 kg - 750 mg (3 bottles);
- patients weighing more than 100 kg - 1000 mg (4 vials).
After the first administration of abatacept, subsequent doses are administered after 2 and 4 weeks, and then once every 4 weeks.
Orencia is not used in children under 6 years of age. Recommended doses for children and adolescents aged 6-17 years:
- children and adolescents weighing up to 75 kg - 10 mg / kg of body weight per injection (the dose is calculated individually before each infusion);
- children and adolescents weighing more than 75 kg - use the dosage regimen for adults (but not more than 1000 mg of the drug per injection).
The prepared solution should not be used with equipment containing silicone.
To prepare a solution, the contents of one vial with a lyophilisate are diluted in 10 ml of water for injection. To inject the solvent, you must use a disposable silicone-free syringe with a needle size 18–21 (the needle is inserted directly into the rubber stopper without opening the bottle). In order to reduce foaming, water is added to the bottle slowly, holding the syringe plunger with your fingers. In this case, the jet of solvent should be directed to the wall of the vial, and not to the lyophilisate itself. Then you must carefully mix the contents (the bottle cannot be shaken, you can only make careful circular movements). The resulting concentrate is colorless or pale yellow. It is forbidden to use a solution if it has a different color, foreign particles are visible in it or it is cloudy.
After preparation, the concentrate is immediately diluted with 0.9% sodium chloride solution to obtain a 100 ml infusion solution. Dilution is carried out as follows: first, 10 ml is taken from a 100 ml vial with sodium chloride for each Orencia vial; then the resulting concentrate is added to the remaining solution with sodium chloride (for this, a disposable non-silicone syringe is used, which is included in the kit). The concentration of the resulting solution is 5, 7.5 or 10 mg / ml (depending on the number of vials used - 2, 3 or 4).
The prepared solution is administered to the patient. The shelf life of the infusion solution is 24 hours. It can be stored at room temperature no more than 25 ° С or in a refrigerator at + 2 … + 8 ° С. Immediately before administration, the solution is inspected again for foreign particles or discoloration.
The duration of the infusion is 30 minutes. For administration, it is necessary to use an infusion system with a sterile pyrogen-free filter that has a low ability to bind proteins (acceptable pore size range is 0.2–1.2 µm). Orencia should not be administered through one infusion system at the same time as other drugs.
Side effects
Side effects identified during clinical trials and post-marketing use of the drug Orencia:
- digestive system: often - nausea, dyspeptic disorders, diarrhea, aphthous stomatitis, abdominal pain, ulceration of the oral mucosa; infrequently - gastritis;
- cardiovascular system: often - rush of blood to the skin, increased blood pressure; infrequently - bradycardia, decreased blood pressure, vasculitis, tachycardia, palpitations, feeling of heat;
- respiratory system: often - exacerbation of chronic obstructive pulmonary disease, cough; infrequently - shortness of breath, shortness of breath, bronchospasm; rarely - a spasm in the throat;
- mental and neurological disorders: often - dizziness, headache, burning and tingling sensations; infrequently - anxiety, migraine, sleep disturbances (including insomnia), depression;
- sense organs: often - conjunctivitis; infrequently - decreased visual acuity, dry eyes;
- musculoskeletal system: often - pain in the arms and legs; infrequently - joint pain;
- skin and subcutaneous fat: often - skin rash (including dermatitis), pruritus, pathological hair loss; infrequently - dry skin, erythema, a tendency to bruise, psoriasis, excessive sweating;
- genitals and mammary gland: infrequently - heavy menstruation, absence of menstruation;
- hematopoietic system: often - leukopenia; infrequently - thrombocytopenia;
- immune system: infrequently - hypersensitivity reactions;
- benign and malignant neoplasms: infrequently - squamous cell keratinizing skin cancer, basal cell skin cancer, skin papillomas; rarely - malignant lung tumors, lymphoma;
- infections and invasions: very often - infections of the upper respiratory tract (nasopharyngitis and tracheitis); often - pneumonia, rhinitis, lower respiratory tract infections (including bronchitis), influenza, herpes infections (including oral herpes, herpes simplex and shingles), urinary tract infections; infrequently - musculoskeletal infections, onychomycosis, skin abscesses, dental infections, inflammation of the pelvic organs, pyelonephritis, sepsis; rarely - infections of the gastrointestinal tract, tuberculosis, bacteremia;
- laboratory tests: often - increased activity of liver enzymes;
- other reactions: often - asthenia, increased fatigue, reactions at the injection site; infrequently - weight gain, flu-like syndrome.
Overdose
Orencia doses up to 50 mg / kg (with intravenous infusion) did not cause any obvious toxic reactions. In case of overdose, specialist supervision is recommended. If necessary, symptomatic treatment is prescribed.
Specific signs of abatacept overdose have not been described.
special instructions
Hypersensitivity reactions
The likelihood of hypersensitivity reactions occurs when treating with any protein preparations for injection. Such reactions have been reported in clinical studies in Orencia. After the first injection of the drug, there is a risk of developing anaphylactoid or anaphylactic reactions, including life-threatening ones. In post-marketing studies, a single case of fatal anaphylaxis was noted after the first intravenous infusion of the drug.
If serious allergic reactions occur, the administration of Orensia should be discontinued (regardless of the route of administration) and appropriate antiallergic treatment should be initiated. Further use of abatacept is not recommended.
Infectious lesions
During therapy with the drug, cases of the development of infections, including serious ones (pneumonia and sepsis), have been reported. In some patients, especially those taking immunosuppressants concurrently with abatacept, such infections were fatal. If a new infectious disease is detected in the course of treatment with Orencia, it is necessary to establish careful monitoring of the patient, and if another new serious infection develops, abatacept should be completely canceled.
Before the appointment of Orencia, patients with latent tuberculosis should receive standard anti-tuberculosis treatment.
During the use of antirheumatic drugs, the reactivation of the hepatitis B virus is possible, therefore, before starting therapy, it is necessary to exclude the presence of this infection. The use of abatacept in patients with viral hepatitis has not been studied.
Malignant tumors
The potential role of Orencia in the development of malignant tumors has not been established. The incidence of neoplasms when using the infusion form of abatacept was approximately the same for patients who received the drug and for the control group who received placebo.
Impact on the immune system
Medicines that affect the immune response, including the drug Orencia, can change the effectiveness of vaccination, reduce the body's resistance to infectious agents and the ability to resist the development of malignant tumors.
During treatment with the drug, as well as within 3 months after the termination of therapy, vaccination with live vaccines should not be carried out (the use of inactivated vaccines is permissible). In children, it is recommended to complete the routine vaccination before starting abatacept treatment.
It was found that Orensia does not significantly affect the effectiveness of immunization with the 23-valent pneumococcal vaccine and the trivalent (three-component) seasonal influenza virus vaccine. After these vaccines, the majority of patients showed an increase in antibody titer, that is, the immune response was adequate.
Determination of blood glucose
Blood glucose tests performed on the day of abatacept administration may turn out to be false positives (due to a reaction with maltose, which is part of Orencia). For reliable determination of glucose levels, it is recommended to use methods that exclude a reaction with maltose.
Influence on the ability to drive vehicles and complex mechanisms
Side effects such as dizziness and visual impairment can affect the speed of psychomotor reactions and the ability to concentrate, therefore, during treatment with Orencia, you should refrain from potentially dangerous and difficult work until an individual reaction is determined.
Application during pregnancy and lactation
Abatacept should not be used during pregnancy, as there are no relevant clinical studies of the drug.
During breastfeeding, the use of Orencia is prohibited, since it is not known whether abatacept passes into breast milk.
Pediatric use
The solution for subcutaneous administration is contraindicated in children and adolescents under 18 years of age (there is no data on the safety and efficacy of the drug in childhood and adolescence).
Intravenous administration of Orencia is possible according to indications in children over 6 years of age.
Drug interactions
Orensia is not recommended to be used concomitantly with tumor necrosis factor blockers, as the risk of serious infections increases. If a patient is transferred from tumor necrosis factor blocker therapy to abatacept treatment, his condition should be monitored because of the increased risk of infection. Orencia is not recommended for use in conjunction with other biological drugs intended for the treatment of RA (for example, anakinra), as well as azathioprine and gold preparations.
Abatacept is allowed to be combined with basic anti-inflammatory drugs (salicylates, glucocorticosteroids, methotrexate) and other anti-inflammatory drugs that are used less frequently (sulfasalazine, leflunomide, chloroquine / hydroxychloroquine). When combined with methotrexate, glucocorticosteroids, tumor necrosis factor-alpha inhibitors and non-steroidal anti-inflammatory drugs, the clearance of abatacept did not change.
In the case of the simultaneous use of Orencia with drugs that cause a decrease in the number of lymphocytes, it is possible to potentiate the effect of abatacept on the immune system.
Analogs
Orencia's analogs are Sulfasalazine, Azulfidine, Methotrexat-Ebeve, Methotrexat-RONC, Methotrexat-Teva, Kineret, Arresto, Arava, Acellbia, Leflunomid, Mabtera, Ralef, Redditux, Elafra, etc.
Terms and conditions of storage
Keep out of the reach of children, in a dark place at a temperature of + 2 … + 8 ° C. The solution must not be frozen.
Shelf life: solution for subcutaneous administration - 2.5 years; lyophilisate for preparation of solution for infusion - 3 years.
Terms of dispensing from pharmacies
Dispensed by prescription.
Reviews about Orencia
Since the drug is quite expensive and not everyone can buy it even according to indications, there are very few reviews about Orencia. Patients who have used this drug for the treatment of rheumatoid arthritis respond very well to it. It is really effective, does not cause deterioration, and adverse reactions are extremely rare. Orencia's intravenous form is suitable even for children. The main disadvantage is the high cost.
Price for Orencia in pharmacies
The drug in the form of a lyophilisate for the preparation of a solution for infusion of 250 mg (1 bottle in a set with a syringe) can be bought for 17,700-18,200 rubles. The price for Orensia in the form of a solution for subcutaneous administration of 125 mg / ml (in packs of 4 syringes with a volume of 1.007 ml) is 71,200-73,700 rubles.
Orencia: prices in online pharmacies
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Drug name Price Pharmacy |
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Orencia 250 mg lyophilisate for the preparation of solution for infusion 1 pc. RUB 14,300 Buy |
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Orensia 125 mg / ml solution for subcutaneous administration 1.007 ml 4 pcs. RUB 53,900 Buy |
Anna Kozlova Medical journalist About the author
Education: Rostov State Medical University, specialty "General Medicine".
Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!
