{{Short description|Chemical compound}} {{Drugbox | Verifiedfields = changed | Watchedfields = changed | verifiedrevid = 461744356 | IUPAC_name = ''N''-(5-Chloropyridin-2-yl)-2-([4-(''N'',''N''-dimethylcarbamimidoyl)benzoyl]amino)-5-methoxybenzamide | image = Betrixaban.svg | image_class = skin-invert-image | width = 220
<!--Clinical data--> | tradename = Bevyxxa | Drugs.com = {{Drugs.com|parent|bevyxxa}} | synonyms = PRT054021, PRT064445 | pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X --> | pregnancy_US = <!-- A / B / C / D / X --> | pregnancy_category = | legal_AU = <!-- Unscheduled / S2 / S3 / S4 / S5 / S6 / S7 / S8 / S9 --> | legal_CA = <!-- / Schedule I, II, III, IV, V, VI, VII, VIII --> | legal_UK = <!-- GSL / P / POM / CD / Class A, B, C --> | legal_US = Rx-only | legal_status = | routes_of_administration = By mouth
<!--Pharmacokinetic data--> | bioavailability = | protein_bound = 60% | metabolism = | elimination_half-life = 19–27 hrs | duration_of_action = ≥72 hrs | excretion = 85% feces, 11% urine
<!--Identifiers--> | CAS_number_Ref = {{cascite|changed|??}} | CAS_number = 330942-05-7 | ATC_prefix = B01 | ATC_suffix = AF04 | ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL = 512351 | ChEBI = 140421 | PubChem = 10275777 | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank = DB12364 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = 74RWP7W0J9 | KEGG = D08873 | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 18981107
<!--Chemical data--> | C=23 | H=22 | Cl=1 | N=5 | O=3 | smiles = CN(C)C(=N)C1=CC=C(C=C1)C(=O)NC2=C(C=C(C=C2)OC)C(=O)NC3=NC=C(C=C3)Cl | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 1S/C23H22ClN5O3/c1-29(2)21(25)14-4-6-15(7-5-14)22(30)27-19-10-9-17(32-3)12-18(19)23(31)28-20-11-8-16(24)13-26-20/h4-13,25H,1-3H3,(H,27,30)(H,26,28,31) | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = XHOLNRLADUSQLD-UHFFFAOYSA-N }}
'''Betrixaban''' (trade name '''Bevyxxa''') is an oral anticoagulant drug which acts as a direct factor Xa inhibitor.<ref name="pmid19071881">{{cite journal | vauthors = Eriksson BI, Quinlan DJ, Weitz JI | title = Comparative pharmacodynamics and pharmacokinetics of oral direct thrombin and factor xa inhibitors in development | journal = Clinical Pharmacokinetics | volume = 48 | issue = 1 | pages = 1–22 | year = 2009 | pmid = 19071881 | doi = 10.2165/0003088-200948010-00001 | s2cid = 35948814 }}</ref> Betrixaban is FDA approved for venous thrombosis prevention in adults hospitalized for an acute illness who are at risk for thromboembolic complications.<ref>{{Cite web|url=https://www.fda.gov/drugs/informationondrugs/approveddrugs/ucm564422.htm|title=Approved Drugs - FDA approved betrixaban (BEVYXXA, Portola) for the prophylaxis of venous thromboembolism (VTE) in adult patients| work = Center for Drug Evaluation and Research (CDER) | publisher = U.S. Food and Drug Administration |language=en|access-date=2018-10-29}}{{dead link|date=May 2025|bot=medic}}{{cbignore|bot=medic}}</ref> Compared to other directly acting oral anticoagulants betrixaban has relatively low renal excretion and is not metabolized by CYP3A4.<ref>{{cite journal | vauthors = Huisman MV, Klok FA | title = Pharmacological properties of betrixaban | journal = European Heart Journal Supplements | volume = 20 | issue = Suppl E | pages = E12–E15 | date = May 2018 | pmid = 29977164 | pmc = 6016700 | doi = 10.1093/eurheartj/suy016 }}</ref>
== History == Betrixaban was originally developed by Millennium Pharmaceuticals. Portola Pharmaceuticals acquired rights for betrixaban in 2004 and co-developed it with Merck. In 2011 Merck discontinued joint development.<ref>{{cite web|url=http://cardiobrief.org/2011/03/24/merck-abandons-development-of-factor-xa-inhibitor-betrixaban/|title=Merck Abandons Development of Factor Xa Inhibitor Betrixaban| vauthors = Husten H |date=24 March 2011 |publisher=CardioBrief|access-date=11 April 2014}}</ref>
The drug has undergone clinical trials for prevention of embolism after knee surgery<ref name="pmid19132191">{{cite journal | vauthors = Turpie AG, Bauer KA, Davidson BL, Fisher WD, Gent M, Huo MH, Sinha U, Gretler DD | display-authors = 6 | title = A randomized evaluation of betrixaban, an oral factor Xa inhibitor, for prevention of thromboembolic events after total knee replacement (EXPERT) | journal = Thrombosis and Haemostasis | volume = 101 | issue = 1 | pages = 68–76 | date = January 2009 | pmid = 19132191 | doi = 10.1160/th08-07-0460 | s2cid = 21670373 }}</ref> and for prevention of stroke following non-valvular atrial fibrillation.<ref>{{cite journal | vauthors = Piccini JP, Lopes RD, Mahaffey KW | title = Oral factor Xa inhibitors for the prevention of stroke in atrial fibrillation | journal = Current Opinion in Cardiology | volume = 25 | issue = 4 | pages = 312–320 | date = July 2010 | pmid = 20520539 | doi = 10.1097/HCO.0b013e32833a524f | s2cid = 25718628 }}</ref><ref>{{cite journal | vauthors = Sobieraj-Teague M, O'Donnell M, Eikelboom J | title = New anticoagulants for atrial fibrillation | journal = Seminars in Thrombosis and Hemostasis | volume = 35 | issue = 5 | pages = 515–524 | date = July 2009 | pmid = 19739042 | doi = 10.1055/s-0029-1234147 | doi-access = free }}</ref> Betrixaban was also studied in a large phase III clinical trial for extended duration thromboprophylaxis in acute ill patients.<ref>{{cite journal | vauthors = Cohen AT, Harrington R, Goldhaber SZ, Hull R, Gibson CM, Hernandez AF, Kitt MM, Lorenz TJ | display-authors = 6 | title = The design and rationale for the Acute Medically Ill Venous Thromboembolism Prevention with Extended Duration Betrixaban (APEX) study | journal = American Heart Journal | volume = 167 | issue = 3 | pages = 335–341 | date = March 2014 | pmid = 24576517 | doi = 10.1016/j.ahj.2013.11.006 | doi-access = free }}</ref> Previously apixaban and rivaroxaban have failed to show positive risk/benefit ratio in this indication compared to enoxaparin.<ref>{{cite journal | vauthors = Cohen AT, Spiro TE, Büller HR, Haskell L, Hu D, Hull R, Mebazaa A, Merli G, Schellong S, Spyropoulos AC, Tapson V | display-authors = 6 | title = Rivaroxaban for thromboprophylaxis in acutely ill medical patients | language = EN | journal = The New England Journal of Medicine | volume = 368 | issue = 6 | pages = 513–523 | date = February 2013 | pmid = 23388003 | doi = 10.1056/nejmoa1111096 | hdl-access = free | hdl = 10447/96593 }}<!--http://espace.library.uq.edu.au/view/UQ:382389/UQ382389_OA.pdf--></ref><ref>{{cite journal | vauthors = Goldhaber SZ, Leizorovicz A, Kakkar AK, Haas SK, Merli G, Knabb RM, Weitz JI | title = Apixaban versus enoxaparin for thromboprophylaxis in medically ill patients | language = EN | journal = The New England Journal of Medicine | volume = 365 | issue = 23 | pages = 2167–2177 | date = December 2011 | pmid = 22077144 | doi = 10.1056/nejmoa1110899 | hdl-access = free | hdl = 2437/127244 }}</ref>{{npsn|date=November 2020}} APEX trial compared betrixaban with enoxaparin and included 7513 patients. Lower rate of VTE events was found in betrixaban arm with no increase in major bleedings compared to enoxaparin.<ref>{{cite journal | vauthors = Cohen AT, Harrington RA, Goldhaber SZ, Hull RD, Wiens BL, Gold A, Hernandez AF, Gibson CM | display-authors = 6 | title = Extended Thromboprophylaxis with Betrixaban in Acutely Ill Medical Patients | language = EN | journal = The New England Journal of Medicine | volume = 375 | issue = 6 | pages = 534–544 | date = August 2016 | pmid = 27232649 | doi = 10.1056/nejmoa1601747 | doi-access = free | hdl = 11573/884978 | hdl-access = free }}</ref> Based on these results betrixaban was approved by FDA on June 23, 2017, becoming the first DOAC approved for extended prophylaxis in hospitalized patients.<ref>{{cite web|title=FDA approved betrixaban (BEVYXXA, Portola) for the prophylaxis of venous thromboembolism (VTE) in adult patients|website=Food and Drug Administration |url=https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm564422.htm|access-date=28 June 2017}}{{dead link|date=May 2025|bot=medic}}{{cbignore|bot=medic}}</ref>
Betrixaban has been also reviewed by EMA but didn't receive marketing approval in EU mainly due to concerns of increased bleeding risk and absence of reversal agent.<ref>{{Cite web|url=https://www.ema.europa.eu/documents/smop-initial/questions-answers-refusal-marketing-authorisation-dexxience-betrixaban_en.pdf|title=Refusal of the marketing authorisation for Dexxience (betrixaban): Outcome of re-examination | work = Committee for Medicinal Products for Human Use (CHMP) | publisher = European Medicines Agency | date = 27 July 2018 }}</ref>
== See also == * Edoxaban * Enoxaparin
== References == {{reflist}}
{{Antithrombotics}}
Category:Direct Xa inhibitors Category:2-Aminopyridines Category:Amides Category:Amidines Category:Benzene derivatives Category:Chloropyridines Category:Methoxy compounds