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| Primary information |
|---|
| ID | 10578 |
| Therapeutic ID | Th1119 |
| Protein Name | Tocilizumab |
| Sequence | >Th1119_Tocilizumab
QVQLQESGPGLVRPSQTLSLTCTVSGYSITSDHAWSWVRQPPGRGLEWIGYISYSGITTYNPSLKSRVTMLRDTSKNQFSLRLSSVTAADTAVYYCARSLARTTAMDYWGQGSLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
|
| Molecular Weight | 148000 |
| Chemical Formula | C6428H9976N1720O2018S42 |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting point | NA |
| Half-life | 11 days for 4 mg/kg and up to 13 days for 8 mg/kg |
| Description | Recombinant, humanized, anti-human interleukin 6 receptor (IL-6R) monoclonal antibody. The light chain is made up of 214 amino acids and the heavy chain is made up of 448 amino acids. |
| Indication/Disease | Indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response to one or more Disease-Modifying Anti-Rheumatic Drugs (DMARDs). It is also indicated for the treatment of active polyarticular juvenile idiopathic arthritis (PJIA) and active systemic juvenile idiopathic arthritis (SJIA) in patients 2 years of age and older. |
| Pharmacodynamics | A decrease in C-reactive protein (CRP) was noted as early as week 2. Changes in pharmacodynamic parameters were observed (i.e., decreases in rheumatoid factor, erythrocyte sedimentation rate (ESR), serum amyloid A and increases in hemoglobin) with both doses, however the greatest improvements were observed with 8 mg per kg tocilizumab. Similar pharmacodynamic changes were also observed in active polyarticular juvenile idiopathic arthritis and active systemic juvenile idiopathic arthritis patients. |
| Mechanism of Action | Interleukin (IL)-6 plays essential roles not only in the immune response, but also in haematopoiesis and the central nervous system. Deregulated production of IL-6 has been found in chronic inflammatory autoimmune diseases, such as rheumatoid arthritis (RA), systemic onset juvenile idiopathic arthritis (soJIA), Crohn's disease (CD) and systemic lupus erythematosus (SLE). Furthermore, IL-6 activities can explain many symptoms of these diseases. More importantly, serum levels of IL-6 are correlated with disease activity. Tocilizumab binds specifically to both soluble and membrane-bound IL-6 receptors (sIL-6R and mIL-6R), and has been shown to inhibit IL-6-mediated signaling through these receptors. |
| Toxicity | Data regarding overdoses of tocilizumab are not readily available.[L12789] Patients experiencing an overdose may develop neutropenia.[L12789] In case of overdose, monitor patients for signs of adverse reactions and provide symptomatic and supportive treatment.[L12789] |
| Metabolism | Tocilizumab, like other monoclonal antibodies, is expected to be metabolized to smaller proteins and amino acids by proteolytic enzymes.[A19126] |
| Absorption | A 162mg subcutaneous dose given weekly has a Cmax of 51.3±23.2µg/mL and an AUC of 8254±3833µg |
| In rheumatoid arthritis patients, the central volume of distribution is 3.5L, the peripheral volume of distribution is 2.9L, and the volume of distribution at steady state is 6.4L.[L12789] In giant cell arteritis patients, the central volume of distribution is 4.09L, the peripheral volume of distribution if 3.37L, and the volume of distribution at steady state is 7.46L.[L12789] In pediatric patients with polyarticular juvenile arthritis, the central volume of distribution is 1.98L, the peripheral volume of distribution is 2.1L, and the volume of distribution at steady state is 4.08L.[L12789] In pediatric patients with systemic juvenile idiopathic arthritis, the central volume of distribution is 1.87L, the peripheral volume of distribution is 2.14L, and the volume of distribution at steady state is 4.01L.[L12789] |
| Clearance | The linear clearance in rheumatoid arthritis patients is 12.5mL/h, in giant cell arteritis patients is 6.7mL/h, in polyarticular juvenile idiopathic arthritis patients is 5.8mL/h, and in systemic juvenile idiopathic arthritis is 5.7mL/h.[L12789] Clearance is dose dependent and changes from non linear at low doses to linear at higher doses.[L12789] |
| Categories | NA |
| Patents Number | CA2201781 |
| Date of Issue | 1-Dec-2010 |
| Date of Expiry | 6-Jul-2015 |
| Drug Interaction | NA |
| Target | Interleukin-6 receptor subunit alpha |
| Brand Name | ACTEMRA |
| Company | Genentech |
| Brand Description | Genentech |
| Prescribed For | ACTEMRA (tocilizumab) is indicated for the treatment ofRheumatoid Arthritis, Polyarticular Juvenile Idiopathic Arthritis (PJIA), Juvenile Idiopathic Arthritis (SJIA). |
| Chemical Name | NA |
| Formulation | Single-use vials are available for intravenous administration containing 80 mg per 4 mL, 200 mg per 10 mL, or 400 mg per 20 mL of ACTEMRA. Injectable solutions of ACTEMRA are formulated in an aqueous solution containing disodium phosphate dodecahydrate and sodium dihydrogen phosphate dehydrate (as a 15 mmol per L phosphate buffer), polysorbate 80 (0.5 mg per mL), and sucrose (50 mg per mL). |
| Physical Appearance | Sterile, preservative-free solution, colorless to pale yellow liquid, with a pH of about 6.5 |
| Route of Administration | Intravenous infusion, Subcutaneous |
| Recommended Dosage | Rheumatoid Arthritis: The recommended dosage of ACTEMRA for adult patients given as a 60-minute single intravenous drip infusion is 4 mg per kg every 4 weeks followed by an increase to 8 mg per kg every 4 weeks based on clinical response. For SC dosage: Patients less than 100 kg weight = 162 mg administered subcutaneously every other week, followed by an increase to every week based on clinical response, Patients at or above 100 kg weight = 162 mg administered subcutaneously every week. |
| Contraindication | contraindicated in patients with known hypersensitivity to ACTEMRA |
| Side Effects | Serious Infections, Gastrointestinal Perforations, Infusion Reactions, Anaphylaxis, Neutropenia, Thrombocytopenia, Elevated Liver Enzymes, Immunogenicity, Malignancies. |
| Useful Link 1 | Link |
| Useful Link 2 | NA |
| Remarks | NA |