| Primary information |
|---|
| ThPP ID | Th1191 |
| Therapeutic Peptide/Protein Name | Vedolizumab |
| Sequence | Heavy Chain Sequence QVQLVQSGAEVKKPGASVKVSCKGSGYTF view full sequnce in fasta |
| Functional Classification | IIa |
| Molecular Weight | 146837 |
| Chemical Formula | C6528H10072N1732O2042S42 |
| Isoelectric Point | 7.6 |
| Hydrophobicity | NA |
| Melting Point (℃) | NA |
| Half Life | 336 to 362 hr. |
| Description | 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. |
| Indication/Disease | It 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. |
| 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. |
| 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 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 |
| Metabolism | The expected consequence of metabolism is proteolytic degradation to small peptides and individual amino acids, and receptor-mediated clearance. |
| 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. |
| Clearance | low clearance of 0.180 to 0.266 ml/hr/kg. |
| Categories | Immunosupressive agent, Antineoplastic agent |
| Patents Number | US2012151248 |
| Date of Issue | 41031 |
| Date of Expiry | 48336 |
| Drug Interaction | Adalimumab, Belimumab, Certolizumab pegol, Denosumab, Etanercept, Golimumab, Infliximab, Leflunomide, Lenalidomide, Natalizumab, Tacrolimus, Thalidomide, Belimumab, Leflunomide, Natalizumab, Sipuleucel-T, Trastuzumab and Tofacitinib |
| Target | Integrin alpha-4, Integrin beta-7 |
| Information of corresponding available drug in the market |
|---|
| Brand Name | Entyvio |
| Company | Takeda Pharmaceuticals America, Inc. |
| Brand Discription | It 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 for | It is indicated for Adult Ulcerative Colitis and Adult Crohn's Disease |
| Chemical Name | NA |
| Formulation | Each 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 Appearnce | Injection, powder, lyophilized, for solution |
| Route of Administration | Intravenous |
| Recommended Dosage | The 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 |
| Contraindication | In 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 Effects | The 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 Link | http://www.rxlist.com/entyvio-drug.htm |
| PubMed ID | 28204866, 27539137, 25484055, 24846335, 24284914, 23727858, 23254906, 21051951, 28296827 |
| 3-D Structure | Th1191 Heavy chianor (Download)Th1191 Light chian (View) or (Download) |