Description

Simple

A medication used to treat inflammatory conditions in the bowels.

Clinical

An integrin blocker and anti-inflammatory agent used to manage ulcerative colitis and Crohn's disease in adults with inadequate clinical response to immunomodulators.

Overview

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.

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... Read more

Pharmacodynamic

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... Read more

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)... Read more

Absorption

The intended route of administration is intravenous, therefore there is no absorption data and bioavailability is expected to be 100%.

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... Read more

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.

Clearance

Vedolizumab has a low clearance of 0.180 to 0.266 ml/hr/kg.

Half life

Vedolizumab has a long terminal elimination half life of 336 to 362 hr.

Route of elimination

Renal clearance is negligible as vedolizumab is a high molecular weight protein.

Toxicity

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 leukoencephal... Read more

Adverse Effects

Contraindications

Information currently not available.

Food Interactions

    Information currently not available.

Interactions

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  • Paracetamol(acetaminophen)
  • Paxil(paroxetine)
  • Pamelor(nortriptyline)
  • Panadol(acetaminophen)
  • Patanol(olopatadine ophthalmic)
  • Pataday(olopatadine ophthalmic)
  • Parnate(tranylcypromine)
  • Pazeo(olopatadine ophthalmic)
2-Methoxyethanol
The risk or severity of adverse effects can be increased when 2-Methoxyethanol is combined with Vedolizumab.
9-(N-methyl-L-isoleucine)-cyclosporin A
The risk or severity of adverse effects can be increased when Vedolizumab is combined with 9-(N-methyl-L-isoleucine)-cyclosporin A.
Abatacept
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.
Abetimus
The risk or severity of adverse effects can be increased when Abetimus is combined with Vedolizumab.
Abituzumab
The risk or severity of adverse effects can be increased when Vedolizumab is combined with Abituzumab.
Abrilumab
The risk or severity of adverse effects can be increased when Vedolizumab is combined with Abrilumab.
Acteoside
The risk or severity of adverse effects can be increased when Vedolizumab is combined with Acteoside.
Adalimumab
The risk or severity of infection can be increased when Adalimumab is combined with Vedolizumab.
Adecatumumab
The risk or severity of adverse effects can be increased when Adecatumumab 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.
Afelimomab
The risk or severity of infection can be increased when Afelimomab is combined with Vedolizumab.
Aldesleukin
The risk or severity of adverse effects can be increased when Aldesleukin is combined with Vedolizumab.
Aldosterone
The risk or severity of adverse effects can be increased when Aldosterone 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.
Altretamine
The risk or severity of adverse effects can be increased when Altretamine is combined with Vedolizumab.
Amatuximab
The risk or severity of adverse effects can be increased when Vedolizumab is combined with Amatuximab.
4 References
  1. 1 . Ardizzone S, Bianchi Porro G: Biologic therapy for inflammatory bowel disease. Drugs. 2005;65(16):2253-86.PubMed: 16266194
  2. 2 . 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.PubMed: 19509315
  3. 3 . 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.PubMed: 25552903
  4. 4 . 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.PubMed: 25526490