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:

1. US Patent US10323095B2: Antibody-fynomer conjugates [Link]

>Tocilizumab heavy chain:
QVQLQESGPGLVRPSQTLSLTCTVSGYSITSDHAWSWVRQPPGRGLEWIGYISYSGITTY
NPSLKSRVTMLRDTSKNQFSLRLSSVTAADTAVYYCARSLARTTAMDYWGQGSLVTVSSA
STKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG
LYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGP
SVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNS
TYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEM
TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQ
QGNVFSCSVMHEALHNHYTQKSLSLSPG

References:

1. US Patent US10323095B2: Antibody-fynomer conjugates [Link]

Download FASTA Format

Synonyms

• Atlizumab

External IDs

• MRA
• MSB-11456
• MSB11456
• R-1569
• RG-1569
• RHPM-1
• RO-4877533

Pharmacology

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

• Cytokine Release Syndrome caused by CAR-T Cell Therapy
• Giant Cell Arteritis (GCA)
• Moderate to Severe Rheumatoid Arthritis
• Polyarticular Juvenile Idiopathic Arthritis
• Systemic Juvenile Idiopathic Arthritis (SJIA)

Contraindications & Blackbox Warnings

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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	inhibitor antibody	Humans

Absorption

A 162mg subcutaneous dose given weekly has a C_max 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 C_max of 13±8.3µg/mL and an AUC of 3460±2530µg*h/mL.⁵ A 162mg subcutaneous dose given every 4 weeks has a C_max 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.

• Approved
• Vet approved
• Nutraceutical
• Illicit
• Withdrawn
• Investigational
• Experimental
• All Drugs

Drug	Interaction
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Abatacept	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.

Additional Data Available

Extended Description
Extended Description
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Severity
Severity
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Evidence Level
Evidence Level
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Action
Action
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Food Interactions

No interactions found.

Products

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International/Other Brands

RoActemra

Brand Name Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End	Region	Image
Unlock Additional Data
Actemra	Solution	400 mg	Intravenous	Hoffmann La Roche	2010-05-26	Not applicable
Actemra	Injection, solution, concentrate	20 mg/1mL	Intravenous	Genentech, Inc.	2010-01-08	Not applicable
Actemra	Solution	162 mg	Subcutaneous	Hoffmann La Roche	2019-01-15	Not applicable
Actemra	Solution	200 mg	Intravenous	Hoffmann La Roche	2010-05-26	Not applicable
Actemra	Injection, solution	180 mg/1mL	Subcutaneous	Genentech, Inc.	2013-10-21	Not applicable
Actemra	Injection, solution, concentrate	20 mg/1mL	Intravenous	Genentech, Inc.	2010-01-08	Not applicable
Actemra	Solution	162 mg	Subcutaneous	Hoffmann La Roche	2014-05-30	Not applicable
Actemra	Solution	80 mg	Intravenous	Hoffmann La Roche	2010-05-26	Not applicable
Actemra	Injection, solution, concentrate	20 mg/1mL	Intravenous	Genentech, Inc.	2010-01-08	Not applicable
Actemra ACTPen	Injection, solution	180 mg/1mL	Subcutaneous	Genentech, Inc.	2018-11-19	Not applicable

Additional Data Available

Application Number
Application Number
Available for Purchase
A unique ID assigned by the FDA when a product is submitted for approval by the labeller.
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Product Code
Product Code
Available for Purchase
A governmentally-recognized ID which uniquely identifies the product within its regulatory market.
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Categories

ATC Codes

L04AC07 — Tocilizumab

• L04AC — Interleukin inhibitors
• L04A — IMMUNOSUPPRESSANTS
• L04 — IMMUNOSUPPRESSANTS
• L — ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS

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

1. 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]
2. Ding C, Jones G: Technology evaluation: MRA, Chugai. Curr Opin Mol Ther. 2003 Feb;5(1):64-9. [PubMed:12669473]
3. 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]
4. 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]
5. 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]
6. FDA Approved Drug Products: Actemra Tocilizumab Intravenous or Subcutaneous Injection [Link]
7. Clinical Trials: TOCIVID-19 [Link]
8. Clinical Trials: COVACTA [Link]

External Links

KEGG Drug

D02596

PubChem Substance

347910344

RxNav

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	3
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	19
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
Injection, solution		162 mg/0.9mL
Injection, solution	Subcutaneous	180 mg/1mL
Injection, solution, concentrate	Intravenous	20 mg/1mL
Injection, solution, concentrate	Intravenous	400 mg/20mL
Injection, solution, concentrate	Intravenous	80 mg/4mL
Solution	Intravenous	200 mg
Solution	Intravenous	400 mg
Solution	Intravenous	80 mg
Injection, solution	Subcutaneous	162 mg/0.9ml
Injection, solution	Intravenous	200 mg/10ml
Injection, solution	Intravenous	400 mg/20ml
Injection, solution	Intravenous	80 mg/4ml
Solution	Subcutaneous	162 mg
Injection, solution	Cutaneous; Parenteral	162 MG
Injection, solution, concentrate	Intravenous	20 MG/ML

Prices

Not Available

Patents

Patent Number	Pediatric Extension	Approved	Expires (estimated)	Region
Unlock Additional Data
CA2201781	No	2010-01-12	2015-06-07
CA1341152	No	2000-12-12	2017-12-12

Additional Data Available

Filed On
Filed On
Available for Purchase
The date on which a patent was filed with the relevant government.
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Properties

State

Liquid

Experimental Properties

Not Available

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Drug created on March 19, 2008 10:20 / Updated on November 30, 2020 13:38