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10578 details
Primary information
ID10578
Therapeutic IDTh1119
Protein NameTocilizumab
Sequence>Th1119_Tocilizumab QVQLQESGPGLVRPSQTLSLTCTVSGYSITSDHAWSWVRQPPGRGLEWIGYISYSGITTYNPSLKSRVTMLRDTSKNQFSLRLSSVTAADTAVYYCARSLARTTAMDYWGQGSLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
Molecular Weight148000
Chemical FormulaC6428H9976N1720O2018S42
Isoelectric PointNA
HydrophobicityNA
Melting pointNA
Half-life11 days for 4 mg/kg and up to 13 days for 8 mg/kg
DescriptionRecombinant, 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/DiseaseIndicated 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.
PharmacodynamicsA 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 ActionInterleukin (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.
ToxicityData 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]
MetabolismTocilizumab, like other monoclonal antibodies, is expected to be metabolized to smaller proteins and amino acids by proteolytic enzymes.[A19126]
AbsorptionA 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]
ClearanceThe 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]
CategoriesNA
Patents NumberCA2201781
Date of Issue1-Dec-2010
Date of Expiry6-Jul-2015
Drug InteractionNA
TargetInterleukin-6 receptor subunit alpha
Brand NameACTEMRA
CompanyGenentech
Brand DescriptionGenentech
Prescribed ForACTEMRA (tocilizumab) is indicated for the treatment ofRheumatoid Arthritis, Polyarticular Juvenile Idiopathic Arthritis (PJIA), Juvenile Idiopathic Arthritis (SJIA).
Chemical NameNA
FormulationSingle-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 AdministrationIntravenous infusion, Subcutaneous
Recommended DosageRheumatoid 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.
Contraindicationcontraindicated in patients with known hypersensitivity to ACTEMRA
Side EffectsSerious Infections, Gastrointestinal Perforations, Infusion Reactions, Anaphylaxis, Neutropenia, Thrombocytopenia, Elevated Liver Enzymes, Immunogenicity, Malignancies.
Useful Link 1Link
Useful Link 2NA
RemarksNA