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| Primary information |
|---|
| ID | 16379 |
| Therapeutic ID | Th1889 |
| Protein Name | Abatacept |
| Sequence | >Th1889_Abatacept
MDPQCTMGLSNILFVMAFLLSGAAPLKIQAYFNETADLPCQFANSQNQSLSELVVFWQDQENLVLNEVYLGKEKFDSVHSKYMGRTSFDSDSWTLRLHNLQIKDKGLYQCIIHHKKPTGMIRIHQMNSELSVLANFSQPEIVPISNITENVYINLTCSSIHGYPEPKKMSVLLRTKNSTIEYDGVMQKSQDNVTELYDVSISLSVSFPDVTSNMTIFCILETDKTRLLSSPFSIELEDPQPPPDHIPWITAVLPTVIICVMVFCLILWKWKKKKRPRNSYKCGTNTMEREESEQTKKREKIHIPERSDEAQRVFKSSKTSSCDKSDTCF |
| Molecular Weight | 92300.0 Da |
| Chemical Formula | C3498H5458N922O1090S32 |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting point | NA |
| Half-life | 16.7 (12-23) days in healthy subjects; 13.1 (8-25) days in RA subjects; 14.3 days when subcutaneously administered to adult RA patients. |
| Description | Abatacept is a disease-modifying antirheumatic drug (DMARD) used in the management of rheumatic conditions, such as rheumatoid or psoriatic arthritis, and for the prophylaxis of acute graft-versus-host disease. |
| Indication/Disease | Abatacept is indicated in adult patients for the treatment of moderately-to-severely active rheumatoid arthritis and for the treatment of active psoriatic arthritis.In patients two years of age and older, abatacept is also indicated for the treatment of moderately-to-severely active juvenile idiopathic arthritis. Abatacept is also indicated for the prophylaxis of acute graft-versus-host disease, in combination with methotrexate and a calcineurin inhibitor such as tacrolimus, in patients two years of age and older who are undergoing hematopoietic stem cell transplantation from a matched or 1 allele-mismatched unrelated donor. |
| Pharmacodynamics | Abatacept is the first in a new class of drugs known as Selective Co-stimulation Modulators. Known as a recombinant fusion protein, the drug consists of the extracellular domain of human cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) linked to a modified Fc portion of human immunoglobulin G1 (IgG1. The Fc portion of the drug consists of the hinge region, the CH2 domain, and the CH3 domain of IgG1. Although there are multiple pathways and cell types involved in the pathogenesis of rheumatoid arthritis, evidence suggests that T-cell activation may play an important role in the immunopathology of the disease. |
| Mechanism of Action | Abatacept is a selective costimulation modulator - like CTLA-4, the drug has shown to inhibit T-cell (T lymphocyte) activation by binding to CD80 and CD86, thereby blocking interaction with CD28. Blockade of this interaction has been shown to inhibit the delivery of the second co-stimulatory signal required for optimal activation of T-cells. This results in the inhibition of autoimmune T-Cell activation that has been implcated in the pathogenesis of rheumatoid arthritis. |
| Toxicity | Most common adverse events (≥10%) are headache, upper respiratory tract infection, nasopharyngitis, and nausea. Doses up to 50 mg/kg have been administered without apparent toxic effect. |
| Metabolism | NA |
| Absorption | When a single 10 mg/kg intravenous infusion of abatacept is administered in healthy subjects, the peak plasma concentration (Cmax) was 292 mcg/mL. When multiple doses of 10 mg/kg was given to rheumatoid arthritis (RA) patients, the Cmax was 295 mcg/mL. The bioavailability of abatacept following subcutaneous administration relative to intravenous administration is 78.6%. |
| 0.07 L/kg [RA Patients, IV administration] 0.09 L/kg [Healthy Subjects, IV administration] 0.11 L/kg [RA patients, subcutaneous administration] |
| Clearance | 0.23 mL/h/kg [Healthy Subjects after 10 mg/kg Intravenous Infusion] 0.22 mL/h/kg [RA Patients after multiple 10 mg/kg Intravenous Infusions] 0.4 mL/h/kg [juvenile idiopathic arthritis patients]. The mean systemic clearance is 0.28 mL/h/kg when a subcutaneously administered to adult RA patients. The clearance of abatacept increases with increasing body weight. |
| Categories | Agents reducing cytokine levels,Amino Acids, Peptides, and Proteins,Antibodies,Antineoplastic Agents, Immunological,Antineoplastic and Immunomodulating Agents,Antirheumatic Agents,Biologics for Rheumatoid Arthritis Treatment,Blood Proteins,CD80-directed Antibody Interactions,CD86-directed Antibody Interactions,Decreased Cytokine Activity,Disease-modifying Antirheumatic Agents,Globulins,Immune Checkpoint Inhibitors,Immunoconjugates,Immunologic Factors,Immunosuppressive Agents,Proteins,Selective Immunosuppressants,Selective T Cell Costimulation Modulator,Serum Globulins |
| Patents Number | CA2110518 |
| Date of Issue | 2007-05-22 |
| Date of Expiry | 2012-06-16 |
| Drug Interaction | NA |
| Target | T-lymphocyte activation antigen CD80, T-lymphocyte activation antigen CD86, Cytotoxic T-lymphocyte protein 4 |
| Brand Name | Orencia |
| Company | Bristol Myers Squibb Pharma Eeig |
| Brand Description | Bristol Myers Squibb Pharma Eeig |
| Prescribed For | Intravenous |
| Chemical Name | 250 mg |
| Formulation | None |
| Physical Appearance | fever, chills, night sweats, flu symptoms, weight loss, feeling very tired, dry cough, sore throat, warmth, pain or redness of your skin trouble breathing, stabbing chest pain, wheezing, cough with yellow or green mucus, pain or burning when you urinate, and signs of skin infection such as itching, swelling, warmth, redness, or oozing |
| Route of Administration | Orencia belongs to a class of drugs called DMARDs, Immunomodulators; Immunosuppressants. |
| Recommended Dosage | Orencia is a prescription medicine used to treat the symptoms of Moderate-to-Severe Rheumatoid Arthritis and Psoriatic Arthritis. |
| Contraindication | NA |
| Side Effects | ORENCIA for Injection is a lyophilized powder for intravenous infusion. ORENCIA for Injection is supplied as a sterile, white, preservative-free, lyophilized powder for reconstitution and dilution prior to intravenous administration. Following reconstitution of the lyophilized powder with 10 mL of Sterile Water for Injection, USP, the solution of ORENCIA is clear, colorless to pale yellow, with a pH range of 7.2 to 7.8. Each single-use vial of ORENCIA for Injection provides 250 mg abatacept, maltose (500 mg), monobasic sodium phosphate (17.2 mg), and sodium chloride (14.6 mg) for administration. |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |