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1797 details
Primary information
ThPP IDTh1191
Therapeutic Peptide/Protein NameVedolizumab
SequenceHeavy Chain Sequence QVQLVQSGAEVKKPGASVKVSCKGSGYTF view full sequnce in fasta
Functional ClassificationIIa
Molecular Weight146837
Chemical FormulaC6528H10072N1732O2042S42
Isoelectric Point7.6
HydrophobicityNA
Melting Point (℃)NA
Half Life336 to 362 hr.
DescriptionVedolizumab 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.
Indication/DiseaseIt 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.
PharmacodynamicsNon-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 ActionVedolizumab 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.
ToxicityLong-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
MetabolismThe expected consequence of metabolism is proteolytic degradation to small peptides and individual amino acids, and receptor-mediated clearance.
AbsorptionThe intended route of administration is intravenous, therefore there is no absorption data and bioavailability is expected to be 100%.
Volume of DistributionSerum 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.
Clearancelow clearance of 0.180 to 0.266 ml/hr/kg.
CategoriesImmunosupressive agent, Antineoplastic agent
Patents NumberUS2012151248
Date of Issue41031
Date of Expiry48336
Drug InteractionAdalimumab, Belimumab, Certolizumab pegol, Denosumab, Etanercept, Golimumab, Infliximab, Leflunomide, Lenalidomide, Natalizumab, Tacrolimus, Thalidomide, Belimumab, Leflunomide, Natalizumab, Sipuleucel-T, Trastuzumab and Tofacitinib
TargetIntegrin alpha-4, Integrin beta-7
Information of corresponding available drug in the market
Brand NameEntyvio
CompanyTakeda Pharmaceuticals America, Inc.
Brand DiscriptionIt is an integrin receptor antagonist, is a humanized IgG1 monoclonal antibody produced in Chinese hamster ovary cells that binds to the human α4β7 integrin. ENTYVIO has an approximate molecular weight of 147 kilodaltons.
Prescribed forIt is indicated for Adult Ulcerative Colitis and Adult Crohn's Disease
Chemical NameNA
FormulationEach single-use vial contains 300 mg vedolizumab, 23 mg L-histidine, 21.4 mg L-histidine monohydrochloride, 131.7 mg L-arginine hydrochloride, 500 mg sucrose and 3 mg polysorbate 80
Physcial AppearnceInjection, powder, lyophilized, for solution
Route of AdministrationIntravenous
Recommended DosageThe recommended dosage of ENTYVIO in adults with ulcerative colitis or Crohn's disease is 300 mg administered by intravenous infusion at zero, two and six weeks and then every eight weeks thereafter
ContraindicationIn patients who have had a known serious or severe hypersensitivity reaction to ENTYVIO or any of its excipients (such as dyspnea, bronchospasm, urticaria, flushing, rash and increased heart rate)
Side EffectsThe most common adverse reactions were nasopharyngitis, headache, arthralgia, nausea, pyrexia, upper respiratory tract infection, fatigue, cough, bronchitis, influenza, back pain, rash, pruritus, sinusitis, oropharyngeal pain and pain in extremities.
Useful Linkhttp://www.rxlist.com/entyvio-drug.htm
PubMed ID28204866, 27539137, 25484055, 24846335, 24284914, 23727858, 23254906, 21051951, 28296827
3-D StructureTh1191 Heavy chianor (Download)Th1191 Light chian (View) or (Download)