Vedolizumab
Identification
- Summary
Vedolizumab is an integrin blocker and anti-inflammatory agent used to manage ulcerative colitis and Crohn's disease in adults with inadequate clinical response to immunomodulators.
- Brand Names
- Entyvio
- Generic Name
- Vedolizumab
- DrugBank Accession Number
- DB09033
- Background
Vedolizumab is a recombinant humanized IgG1 monoclonal antibody directed against the human lymphocyte α4β7 integrin, a key mediator of gastrointestinal inflammation. It is used in the treatment of moderate to severe active ulcerative colitis and Crohn's disease for patients who have had an inadequate response with, lost response to, or were intolerant to inhibitors of tumor necrosis factor-alpha (TNF-alpha) or other conventional therapies. By blocking its primary target, α4β7 integrin, vedolizumab reduces inflammation in the gut. Vedolizumab is administered by IV infusion over a period of 30 minutes; after the first dose, it is given again at two and six weeks and then every 8 weeks thereafter.
- Type
- Biotech
- Groups
- Approved
- Biologic Classification
- Protein Based Therapies
Monoclonal antibody (mAb) - Protein Structure
- Protein Chemical Formula
- C6528H10072N1732O2042S42
- Protein Average Weight
- 146837.0 Da
- Sequences
>Heavy Chain Sequence QVQLVQSGAEVKKPGASVKVSCKGSGYTFTSYWMHWVRQAPGQRLEWIGEIDPSESNTNY NQKFKGRVTLTVDISASTAYMELSSLRSEDTAVYYCARGGYDGWDYAIDYWGQGTLVTVS SASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQS SGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELAG APSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQY NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRD ELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
>Light Chain Sequence DVVMTQSPLSLPVTPGEPASISCRSSQSLAKSYGNTYLSWYLQKPGQSPQLLIYGISNRF SGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCLQGTHQPYTFGQGTKVEIKRTVAAPSV FIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSL SSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
Download FASTA Format- Synonyms
- Vedolizumab
- External IDs
- LDP 02
- LDP-02
- LDP02
- MLN-0002
- MLN-02
- MLN0002
- MLN02
Pharmacology
- Indication
Vedolizumab is indicated for adult patients with moderately to severely active UC or CD who have had an inadequate response with, lost response to, or were intolerant to a tumor necrosis factor (TNF) blocker or immunomodulator; or had an inadequate response with, were intolerant to, or demonstrated dependence on corticosteroids.
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- Contraindications & Blackbox Warnings
Avoid life-threatening adverse drug eventsImprove clinical decision support with information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events & improve clinical decision support.- Pharmacodynamics
Non-clinical studies have shown that the pharmacodynamic effects of vedolizumab are reversible upon removal of the antibody: pharmacologic activity of cells inhibited by vedolizumab could be partially restored within 24 hours after removal, with near complete restoration within 4 days. There are no known drug interactions as vedolizumab is a humanized antibody and does not modulate production of cytokines, which is known to affect drug metabolism.
- Mechanism of action
Vedolizumab binds to α4β7 integrin, a key mediator of gastrointestinal inflammation expressed on the surfaces of T and B lymphocytes. By selectively inhibiting the α4β7 integrin, vedolizumab inhibits adhesion of lymphocytes to its natural ligand, mucosal addressin cell adhesion molecule-1 (MAdCAM-1), thereby preventing lymphocytic cells from entering the gut lamina propria and gut-associated lymphoid tissue (GALT). Specifically inhibiting this pathway alleviates GI inflammation without impairing systemic immune responses.
Target Actions Organism AIntegrin alpha-4 antibodyHumans AIntegrin beta-7 antibodyHumans - Absorption
The intended route of administration is intravenous, therefore there is no absorption data and bioavailability is expected to be 100%.
- Volume of distribution
Serum apparent volume of distribution at steady-state has been found to be moderately greater than the serum volume. It is therefore expected to be confined to the systemic circulation, as expected for a high molecular weight protein.
- Protein binding
Vedolizumab binds specifically to α4β7 integrin but does not bind to, or inhibit function of, α4β1 or αEβ7 integrins. Inhibition of the α4β7 integrin is a shared mechanism with natalizumab, however vedolizumab binds solely to the α4β7 but not the α4β1 integrin, unlike natalizumab which binds to both. As a result, natalizumab modulates the systemic immune system and is associated with other side effects such as progressive multifocal leukoencephalopathy (PML).
- Metabolism
The expected consequence of metabolism is proteolytic degradation to small peptides and individual amino acids, and receptor-mediated clearance.
- Route of elimination
Renal clearance is negligible as vedolizumab is a high molecular weight protein.
- Half-life
Vedolizumab has a long terminal elimination half life of 336 to 362 hr.
- Clearance
Vedolizumab has a low clearance of 0.180 to 0.266 ml/hr/kg.
- Adverse Effects
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Long-term studies in animals have not been performed to evaluate the carcinogenic potential, mutagenicity, or possible impairments to fertility. Elevated transaminase levels with or without elevated bilirubin has occurred in patients who have received this drug. Progressive multifocal leukoencephalopathy (PML) has not been reported with use of this drug, however it has occurred in patients who have received different integrin receptor antagonists and is therefore considered a risk for this product. Use of vedolizumab may increase risk of developing infections, and one study found that nasopharyngitis occurs more frequently with vedolizumab than with placebo for CD patients (Wang et al, 2014).
- 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 Vedolizumab. Abciximab The risk or severity of adverse effects can be increased when Abciximab is combined with Vedolizumab. Adalimumab The risk or severity of infection can be increased when Adalimumab is combined with Vedolizumab. Adenovirus type 7 vaccine live The risk or severity of infection can be increased when Adenovirus type 7 vaccine live is combined with Vedolizumab. Aducanumab The risk or severity of adverse effects can be increased when Vedolizumab is combined with Aducanumab. Aldesleukin The risk or severity of adverse effects can be increased when Aldesleukin is combined with Vedolizumab. Alefacept The risk or severity of adverse effects can be increased when Alefacept is combined with Vedolizumab. Alemtuzumab The risk or severity of adverse effects can be increased when Alemtuzumab is combined with Vedolizumab. Alirocumab The risk or severity of adverse effects can be increased when Vedolizumab is combined with Alirocumab. Allogeneic processed thymus tissue The therapeutic efficacy of Allogeneic processed thymus tissue can be decreased when used in combination with Vedolizumab. 
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- No interactions found.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Entyvio Injection, solution 108 mg Subcutaneous Takeda Pharma A/S 2021-02-10 Not applicable EU 
Entyvio Powder, for solution 300 mg / vial Intravenous Takeda 2015-04-21 Not applicable Canada 
Entyvio Injection, powder, lyophilized, for solution 300 mg/5mL Intravenous Takeda Pharmaceuticals America, Inc. 2014-05-20 Not applicable US 
Entyvio Injection, solution 108 mg Subcutaneous Takeda Pharma A/S 2021-02-10 Not applicable EU Entyvio Solution 108 mg / 0.68 mL Subcutaneous Takeda 2020-07-08 Not applicable Canada Entyvio Injection, solution 108 mg Subcutaneous Takeda Pharma A/S 2021-02-10 Not applicable EU Entyvio Injection, solution 108 mg Subcutaneous Takeda Pharma A/S 2021-02-10 Not applicable EU Entyvio Injection, solution 108 mg Subcutaneous Takeda Pharma A/S 2021-02-10 Not applicable EU Entyvio Solution 108 mg / 0.68 mL Subcutaneous Takeda 2020-11-20 Not applicable Canada Entyvio Injection, powder, for solution 300 mg Intravenous Takeda Pharma A/S 2016-09-08 Not applicable EU
Categories
- ATC Codes
- L04AA33 — Vedolizumab
- Drug Categories
- Amino Acids, Peptides, and Proteins
- Antibodies
- Antibodies, Monoclonal
- Antibodies, Monoclonal, Humanized
- Antineoplastic and Immunomodulating Agents
- Blood Proteins
- Cancer immunotherapy
- Gastrointestinal Agents
- Globulins
- Immunoglobulins
- Immunoproteins
- Immunosuppressive Agents
- Immunotherapy
- Integrin Receptor Antagonist
- Miscellaneous GI Drugs
- Proteins
- Selective Immunosuppressants
- 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
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- 9RV78Q2002
- CAS number
- 943609-66-3
References
- General References
- Ardizzone S, Bianchi Porro G: Biologic therapy for inflammatory bowel disease. Drugs. 2005;65(16):2253-86. [Article]
- Soler D, Chapman T, Yang LL, Wyant T, Egan R, Fedyk ER: The binding specificity and selective antagonism of vedolizumab, an anti-alpha4beta7 integrin therapeutic antibody in development for inflammatory bowel diseases. J Pharmacol Exp Ther. 2009 Sep;330(3):864-75. doi: 10.1124/jpet.109.153973. Epub 2009 Jun 9. [Article]
- Krupka N, Baumgart DC: Designing biologic selectivity for inflammatory bowel disease--role of vedolizumab. Drug Des Devel Ther. 2014 Dec 17;9:147-54. doi: 10.2147/DDDT.S50348. eCollection 2015. [Article]
- Wang MC, Zhang LY, Han W, Shao Y, Chen M, Ni R, Wang GN, Wei FX, Zhang YW, Xu XD, Zhang YC: PRISMA--efficacy and safety of vedolizumab for inflammatory bowel diseases: a systematic review and meta-analysis of randomized controlled trials. Medicine (Baltimore). 2014 Dec;93(28):e326. doi: 10.1097/MD.0000000000000326. [Article]
- External Links
- KEGG Drug
- D08083
- PubChem Substance
- 347910392
- 1538097
- ChEMBL
- CHEMBL1743087
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Vedolizumab
- FDA label
- Download (281 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Active Not Recruiting Treatment Crohn's Disease (CD) 1 4 Active Not Recruiting Treatment Crohn's Disease (CD) / Ulcerative Colitis 1 4 Completed Treatment Crohn's Disease (CD) 1 4 Completed Treatment Crohn's Disease (CD) / Ulcerative Colitis 1 4 Completed Treatment Pouchitis 1 4 Completed Treatment Ulcerative Colitis 2 4 Not Yet Recruiting Basic Science Inflammatory Bowel Diseases (IBD) / Psoriasis (PsO) 1 4 Not Yet Recruiting Treatment Crohn's Disease (CD) / Ulcerative Colitis 1 4 Recruiting Treatment Crohn Disease of Small Intestine 1 4 Recruiting Treatment Crohn's Disease (CD) 2
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection, powder, for solution Intravenous Injection, powder, for solution Intravenous; Parenteral 300 MG Injection, powder, lyophilized, for solution Intravenous 300 mg/5mL Injection, solution Subcutaneous 108 MG Powder, for solution Intravenous 300 mg / vial Solution Subcutaneous 108 mg / 0.68 mL Powder Intravenous Injection, powder, lyophilized, for solution Intravenous Injection, powder, for solution Intravenous 300 mg Injection, solution, concentrate Intravenous 300 mg/1vial - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US2012151248 No 2012-05-02 2032-05-02 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source isoelectric point 7.6 European Medicines Agency Assessment Report (Procedure No.: EMEA/H/C/002782/0000)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antibody
- General Function
- Metal ion binding
- Specific Function
- Integrins alpha-4/beta-1 (VLA-4) and alpha-4/beta-7 are receptors for fibronectin. They recognize one or more domains within the alternatively spliced CS-1 and CS-5 regions of fibronectin. They are...
- Gene Name
- ITGA4
- Uniprot ID
- P13612
- Uniprot Name
- Integrin alpha-4
- Molecular Weight
- 114898.745 Da
References
- Soler D, Chapman T, Yang LL, Wyant T, Egan R, Fedyk ER: The binding specificity and selective antagonism of vedolizumab, an anti-alpha4beta7 integrin therapeutic antibody in development for inflammatory bowel diseases. J Pharmacol Exp Ther. 2009 Sep;330(3):864-75. doi: 10.1124/jpet.109.153973. Epub 2009 Jun 9. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antibody
- General Function
- Virus receptor activity
- Specific Function
- Integrin alpha-4/beta-7 (Peyer patches-specific homing receptor LPAM-1) is an adhesion molecule that mediates lymphocyte migration and homing to gut-associated lymphoid tissue (GALT). Integrin alph...
- Gene Name
- ITGB7
- Uniprot ID
- P26010
- Uniprot Name
- Integrin beta-7
- Molecular Weight
- 86902.415 Da
References
- Soler D, Chapman T, Yang LL, Wyant T, Egan R, Fedyk ER: The binding specificity and selective antagonism of vedolizumab, an anti-alpha4beta7 integrin therapeutic antibody in development for inflammatory bowel diseases. J Pharmacol Exp Ther. 2009 Sep;330(3):864-75. doi: 10.1124/jpet.109.153973. Epub 2009 Jun 9. [Article]
Drug created on February 20, 2015 22:30 / Updated on October 20, 2021 19:48