Tocilizumab
Identification
- Name
- Tocilizumab
- Accession Number
- DB06273
- Description
Tocilizumab is a recombinant humanized monoclonal antibody IL-6 receptor inhibitor used to treat inflammatory and autoimmune conditions.6 It was first described in the literature in 2003 when Chugai, a subsidiary of Roche began developing IL-6 inhibiting monoclonal antibodies.2 It is currently being investigated to treat severely ill patients with COVID-19.1,7,8
Tocilizumab was granted FDA approval on 8 January 2010.6
- Type
- Biotech
- Groups
- Approved
- Biologic Classification
- Protein Based Therapies
Monoclonal antibody (mAb) - Protein Structure
- Protein Chemical Formula
- C6428H9976N1720O2018S42
- Protein Average Weight
- 148000.0 Da
- Sequences
>Tocilizumab light chain: DIQMTQSPSSLSASVGDRVTITCRASQDISSYLNWYQQKPGKAPKLLIYYTSRLHSGVPS RFSGSGSGTDFTFTISSLQPEDIATYYCQQGNTLPYTFGQGTKVEIKRTVAAPSVFIFPP SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
References:
- US Patent US10323095B2: Antibody-fynomer conjugates [Link]
>Tocilizumab heavy chain: QVQLQESGPGLVRPSQTLSLTCTVSGYSITSDHAWSWVRQPPGRGLEWIGYISYSGITTY NPSLKSRVTMLRDTSKNQFSLRLSSVTAADTAVYYCARSLARTTAMDYWGQGSLVTVSSA STKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG LYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGP SVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNS TYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEM TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG
Download FASTA FormatReferences:
- US Patent US10323095B2: Antibody-fynomer conjugates [Link]
- Synonyms
- Atlizumab
- Tocilizumab
- External IDs
- MRA
- MSB-11456
- MSB11456
- R-1569
- RG-1569
- RHPM-1
- RO-4877533
Pharmacology
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- Indication
Tocilizumab is indicated to treat moderate to severe rheumatoid arthritis, giant cell arteritis, polyarticular juvenile idiopathic arthritis, systemic juvenile idiopathic arthritis, and cytokine release syndrome.6
- Associated Conditions
- Contraindications & Blackbox Warnings
- Contraindications & Blackbox WarningsWith our commercial data, access important information on dangerous risks, contraindications, and adverse effects.Our Blackbox Warnings cover Risks, Contraindications, and Adverse Effects
- Pharmacodynamics
Tocilizumab is an IL-6 inhibiting monoclonal antibody used to treat autoimmune and inflammatory conditions.6 Tocilizumab has a long duration of action as it is generally given every 4 weeks and has a wide therapeutic index.6 Patients should be counselled regarding the risk of infections, GI perforation, and hepatotoxicity.6
- Mechanism of action
Interleukin 6 (IL-6) is a pro-inflammatory cytokine produced by cells including T-cells, B-cells, lymphocytes, monocytes, fibroblasts.6 IL-6 rapidly induces C-reactive protein, serum amyloid A, fibrinogen, haptoglobin, and α-1-antichymotrypsin while inhibiting production of fibronectin, albumin, and transferrin.4 IL-6 also induces antibody production, induces cytotoxic T-cell differentiation, and inhibits regulatory T-cell differentiation.4 Tocilizumab binds soluble and membrane bound IL-6 receptors, preventing IL-6 mediated inflammation.6
Target Actions Organism AInterleukin-6 receptor subunit alpha inhibitorantibodyHumans - Absorption
A 162mg subcutaneous dose given weekly has a Cmax of 51.3±23.2µg/mL and an AUC of 8254±3833µg*h/mL.5 A 162mg subcutaneous dose given every 2 weeks has a Cmax of 13±8.3µg/mL and an AUC of 3460±2530µg*h/mL.5 A 162mg subcutaneous dose given every 4 weeks has a Cmax of 154±42µg/mL and an AUC of 39216±14304µg*h/mL.5
- Volume of distribution
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.6 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.6 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.6 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.6
- Protein binding
Data regarding the serum protein binding of tocilizumab is not readily available.6
- Metabolism
Tocilizumab, like other monoclonal antibodies, is expected to be metabolized to smaller proteins and amino acids by proteolytic enzymes.3
- Route of elimination
Data regarding the exact route of elimination of monoclonal antibodies is not readily available.3,6
- Half-life
The half life of tocilizumab is concentration dependent.6 The terminal half life in rheumatoid arthritis patients is 21.5 days.6 The absorption half life in rheumatoid arthritis and giant cell arteritis patients was 4 days, and in polyarticular juvenile idiopathic arthritis patients and systemic juvenile idiopathic arthritis patients was 2 days.6
- 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.6 Clearance is dose dependent and changes from non linear at low doses to linear at higher doses.6
- Adverse Effects
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- Toxicity
Data regarding overdoses of tocilizumab are not readily available.6 Patients experiencing an overdose may develop neutropenia.6 In case of overdose, monitor patients for signs of adverse reactions and provide symptomatic and supportive treatment.6
- Affected organisms
- Humans and other mammals
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbatacept The risk or severity of adverse effects can be increased when Abatacept is combined with Tocilizumab. Abciximab The risk or severity of adverse effects can be increased when Abciximab is combined with Tocilizumab. Abemaciclib The metabolism of Abemaciclib can be increased when combined with Tocilizumab. Acalabrutinib The metabolism of Acalabrutinib can be increased when combined with Tocilizumab. Acebutolol The metabolism of Acebutolol can be increased when combined with Tocilizumab. Acenocoumarol The metabolism of Acenocoumarol can be increased when combined with Tocilizumab. Acetaminophen The metabolism of Acetaminophen can be increased when combined with Tocilizumab. Acetohexamide The metabolism of Acetohexamide can be increased when combined with Tocilizumab. Acetylsalicylic acid The metabolism of Acetylsalicylic acid can be increased when combined with Tocilizumab. Acyclovir The metabolism of Acyclovir can be increased when combined with Tocilizumab. Improve patient outcomesBuild effective decision support tools with the industry’s most comprehensive drug-drug interaction checker.Learn more - Food Interactions
- No interactions found.
Products
- Comprehensive & structured drug product infoFrom application numbers to product codes, connect different identifiers through our commercial datasets.Easily connect various identifiers back to our datasets
- International/Other Brands
- RoActemra
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Actemra Injection, solution 180 mg/1mL Subcutaneous Genentech, Inc. 2013-10-21 Not applicable US Actemra Solution 162 mg Subcutaneous Hoffmann La Roche 2019-01-15 Not applicable Canada Actemra Solution Intravenous Hoffmann La Roche 2010-05-26 Not applicable Canada Actemra Injection, solution, concentrate 20 mg/1mL Intravenous Genentech, Inc. 2010-01-08 Not applicable US Actemra Solution Subcutaneous Hoffmann La Roche 2014-05-30 Not applicable Canada Actemra Injection, solution, concentrate 20 mg/1mL Intravenous Genentech, Inc. 2010-01-08 Not applicable US Actemra Solution Intravenous Hoffmann La Roche 2010-05-26 Not applicable Canada Actemra Injection, solution, concentrate 20 mg/1mL Intravenous Genentech, Inc. 2010-01-08 Not applicable US Actemra Solution Intravenous Hoffmann La Roche 2010-05-26 Not applicable Canada Actemra ACTPen Injection, solution 180 mg/1mL Subcutaneous Genentech, Inc. 2018-11-19 Not applicable US
Categories
- ATC Codes
- L04AC07 — Tocilizumab
- Drug Categories
- Agents reducing cytokine levels
- Amino Acids, Peptides, and Proteins
- Antibodies
- Antibodies, Monoclonal
- Antineoplastic and Immunomodulating Agents
- Antirheumatic Agents
- Biologics for Rheumatoid Arthritis Treatment
- Blood Proteins
- Cytochrome P-450 CYP3A Inducers
- Cytochrome P-450 CYP3A4 Inducers
- Cytochrome P-450 CYP3A4 Inducers (strength unknown)
- Cytochrome P-450 CYP3A4 Inducers (weak)
- Cytochrome P-450 Enzyme Inducers
- Disease-modifying Antirheumatic Agents
- Experimental Unapproved Treatments for COVID-19
- Globulins
- Immunoglobulins
- Immunoproteins
- Immunosuppressive Agents
- Interleukin Inhibitors
- Interleukin-6 Receptor Antagonist
- Proteins
- Serum Globulins
- Chemical TaxonomyProvided by Classyfire
- Description
- Not Available
- Kingdom
- Organic Compounds
- Super Class
- Organic Acids
- Class
- Carboxylic Acids and Derivatives
- Sub Class
- Amino Acids, Peptides, and Analogues
- Direct Parent
- Peptides
- Alternative Parents
- Not Available
- Substituents
- Not Available
- Molecular Framework
- Not Available
- External Descriptors
- Not Available
Chemical Identifiers
- UNII
- I031V2H011
- CAS number
- 375823-41-9
References
- General References
- Cellina M, Orsi M, Bombaci F, Sala M, Marino P, Oliva G: Favorable changes of CT findings in a patient with COVID-19 pneumonia after treatment with tocilizumab. Diagn Interv Imaging. 2020 Mar 31. pii: S2211-5684(20)30087-5. doi: 10.1016/j.diii.2020.03.010. [PubMed:32278585]
- Ding C, Jones G: Technology evaluation: MRA, Chugai. Curr Opin Mol Ther. 2003 Feb;5(1):64-9. [PubMed:12669473]
- Keizer RJ, Huitema AD, Schellens JH, Beijnen JH: Clinical pharmacokinetics of therapeutic monoclonal antibodies. Clin Pharmacokinet. 2010 Aug;49(8):493-507. doi: 10.2165/11531280-000000000-00000. [PubMed:20608753]
- Tanaka T, Narazaki M, Kishimoto T: IL-6 in inflammation, immunity, and disease. Cold Spring Harb Perspect Biol. 2014 Sep 4;6(10):a016295. doi: 10.1101/cshperspect.a016295. [PubMed:25190079]
- Abdallah H, Hsu JC, Lu P, Fettner S, Zhang X, Douglass W, Bao M, Rowell L, Burmester GR, Kivitz A: Pharmacokinetic and Pharmacodynamic Analysis of Subcutaneous Tocilizumab in Patients With Rheumatoid Arthritis From 2 Randomized, Controlled Trials: SUMMACTA and BREVACTA. J Clin Pharmacol. 2017 Apr;57(4):459-468. doi: 10.1002/jcph.826. Epub 2016 Nov 17. [PubMed:27599663]
- FDA Approved Drug Products: Actemra Tocilizumab Intravenous or Subcutaneous Injection [Link]
- Clinical Trials: TOCIVID-19 [Link]
- Clinical Trials: COVACTA [Link]
- External Links
- KEGG Drug
- D02596
- PubChem Substance
- 347910344
- 612865
- ChEMBL
- CHEMBL1237022
- PharmGKB
- PA165292659
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Tocilizumab
- AHFS Codes
- 92:36.00 — Disease-modifying Antirheumatic Agents
- FDA label
- Download (512 KB)
- MSDS
- Download (482 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Active Not Recruiting Treatment Rheumatoid Arthritis 2 4 Completed Not Available Healthy Volunteers 1 4 Completed Device Feasibility Rheumatoid Arthritis 1 4 Completed Other Rheumatoid Arthritis 1 4 Completed Treatment Juvenile Idiopathic Arthritis (JIA) 1 4 Completed Treatment Rheumatoid Arthritis 20 4 Completed Treatment Schizoaffective Disorders / Schizophrenia 1 4 Enrolling by Invitation Treatment Rheumatoid Arthritis 1 4 Not Yet Recruiting Treatment Antibody-mediated Rejection 1 4 Recruiting Treatment Adalimumab / Takayasu's Disease / Tocilizumab / Treatments 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection Intravenous 162 mg/0.9ml Injection Intravenous 20 MG/ML Injection, solution Subcutaneous 180 mg/1mL Injection, solution, concentrate Intravenous 20 mg/1mL Solution Intravenous Solution Subcutaneous Injection, solution Injection, solution Subcutaneous 162 mg/0.9ml Injection, solution, concentrate Intravenous 20 mg/mL Injection, solution Intravenous 200 mg/10ml Injection, solution Intravenous 400 mg/20ml Injection, solution Intravenous 80 mg/4ml Solution Intravenous 80 mg Solution Intravenous 400 mg Solution Subcutaneous 162 mg Injection, solution Parenteral; Subcutaneous 162 MG Injection, solution Subcutaneous 162 mg Injection, solution, concentrate Intravenous - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region CA2201781 No 2010-01-12 2015-06-07 Canada CA1341152 No 2000-12-12 2017-12-12 Canada
Properties
- State
- Liquid
- Experimental Properties
- Not Available
Targets

- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- InhibitorAntibody
- General Function
- Protein homodimerization activity
- Specific Function
- Part of the receptor for interleukin 6. Binds to IL6 with low affinity, but does not transduce a signal. Signal activation necessitate an association with IL6ST. Activation may lead to the regulati...
- Gene Name
- IL6R
- Uniprot ID
- P08887
- Uniprot Name
- Interleukin-6 receptor subunit alpha
- Molecular Weight
- 51547.015 Da
References
- Smolen JS, Maini RN: Interleukin-6: a new therapeutic target. Arthritis Res Ther. 2006;8 Suppl 2:S5. Epub 2006 Jul 28. [PubMed:16899109]
- Betts BC, St Angelo ET, Kennedy M, Young JW: Anti-IL6-receptor-alpha (tocilizumab) does not inhibit human monocyte-derived dendritic cell maturation or alloreactive T-cell responses. Blood. 2011 Nov 10;118(19):5340-3. doi: 10.1182/blood-2011-06-363390. Epub 2011 Sep 22. [PubMed:21940820]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inducer
- General Function
- Vitamin d3 25-hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- Long TJ, Cosgrove PA, Dunn RT 2nd, Stolz DB, Hamadeh H, Afshari C, McBride H, Griffith LG: Modeling Therapeutic Antibody-Small Molecule Drug-Drug Interactions Using a Three-Dimensional Perfusable Human Liver Coculture Platform. Drug Metab Dispos. 2016 Dec;44(12):1940-1948. doi: 10.1124/dmd.116.071456. Epub 2016 Sep 12. [PubMed:27621203]
- FDA Approved Drug Products: Actemra Tocilizumab Intravenous or Subcutaneous Injection [Link]
Drug created on March 19, 2008 16:20 / Updated on March 01, 2021 12:05