Betrixaban

Betrixaban
Names
Trade namesBevyxxa, Dexxience, other
Other namesPRT054021, PRT064445
IUPAC name
  • N-(5-Chloropyridin-2-yl)-2-([4-(N,N-dimethylcarbamimidoyl)benzoyl]amino)-5-methoxybenzamide
Clinical data
Drug classAnticoagulant (direct factor Xa inhibitor)[1]
Main usesDiscontinued[1]
Side effectsBleeding[1]
WHO AWaReUnlinkedWikibase error: ⧼unlinkedwikibase-error-statements-entity-not-set⧽
Routes of
use		By mouth
Duration of action≥72 hrs
External links
AHFS/Drugs.comMonograph
Legal
Legal status
Pharmacokinetics
Protein binding60%
Elimination half-life19–27 hrs
Excretion85% feces, 11% urine
Chemical and physical data
FormulaC23H22ClN5O3
Molar mass451.905 g·mol−1
3D model (JSmol)
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
InChI
  • InChI=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) checkY
  • Key:XHOLNRLADUSQLD-UHFFFAOYSA-N checkY

Betrixaban, sold under the brand name Bevyxxa among others, was an anticoagulant used to prevent blood clots in veins in at risk adults, hospitalized for an illness.[2] It has a higher rate of bleeding compared to enoxaparin.[3] It was taken by mouth.[2]

Common side effects include bleeding.[1] Other side effects may include allergic reactions.[1] Safety in pregnancy is unclear.[1] It is a direct factor Xa inhibitor.[1]

Betrixaban was approved for medical use in the United States in 2017; however, has been subsequently discontinued.[1] It was refused approval in Europe in 2018 due to concerns regarding effectiveness and safety.[3]

Mechanism of action

Compared to other directly acting oral anticoagulants it has relatively low kidney excretion and is not metabolized by CYP3A4.[4]

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.[5]

The drug has undergone clinical trials for prevention of embolism after knee surgery[6] and for prevention of stroke following non-valvular atrial fibrillation.[7][8] Betrixaban was also studied in a large phase III clinical trial for extended duration thromboprophylaxis in acute ill patients.[9] Previously apixaban and rivaroxaban have failed to show positive risk/benefit ratio in this indication compared to enoxaparin.[10][11] 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.[12] Based on these results betrixaban was approved by FDA on June 23rd, 2017 becoming the first DOAC approved for extended prophylaxis in hospitalized patients.[13]

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.[14]

See also

References

  1. 1 2 3 4 5 6 7 8 "Betrixaban Monograph for Professionals". Drugs.com. Archived from the original on 25 January 2021. Retrieved 10 January 2022.
  2. 1 2 Research, Center for Drug Evaluation and. "Approved Drugs - FDA approved betrixaban (BEVYXXA, Portola) for the prophylaxis of venous thromboembolism (VTE) in adult patients". www.fda.gov. Archived from the original on 2018-07-25. Retrieved 2018-10-29.
  3. 1 2 "Dexxience". Archived from the original on 10 April 2021. Retrieved 10 January 2022.
  4. ↑ Huisman, Menno V; Klok, Frederikus A (2018-05-01). "Pharmacological properties of betrixaban". European Heart Journal Supplements. 20 (suppl_E): E12–E15. doi:10.1093/eurheartj/suy016. ISSN 1520-765X. PMC 6016700. PMID 29977164.
  5. ↑ Husten, Harry. "Merck Abandons Development of Factor Xa Inhibitor Betrixaban". CardioBrief. Archived from the original on 13 April 2014. Retrieved 11 April 2014.
  6. ↑ Turpie AG, Bauer KA, Davidson BL, Fisher WD, Gent M, Huo MH, Sinha U, Gretler DD (January 2009). "A randomized evaluation of betrixaban, an oral factor Xa inhibitor, for prevention of thromboembolic events after total knee replacement (EXPERT)". Thrombosis and Haemostasis. 101 (1): 68–76. doi:10.1160/th08-07-0460. PMID 19132191.
  7. ↑ Piccini, J. P.; Lopes, R. D.; Mahaffey, K. W. (2010). "Oral factor Xa inhibitors for the prevention of stroke in atrial fibrillation". Current Opinion in Cardiology. 25 (4): 312–20. doi:10.1097/HCO.0b013e32833a524f. PMID 20520539. S2CID 25718628.
  8. ↑ Sobieraj-Teague, M.; O’donnell, M.; Eikelboom, J. (2009). "New Anticoagulants for Atrial Fibrillation". Seminars in Thrombosis and Hemostasis. 35 (5): 515–24. doi:10.1055/s-0029-1234147. PMID 19739042.
  9. ↑ Cohen, Alexander T.; Harrington, Robert; Goldhaber, Samuel Z.; Hull, Russell; Gibson, C. Michael; Hernandez, Adrian F.; Kitt, Michael M.; Lorenz, Todd J. (2014-01-01). "The design and rationale for the Acute Medically Ill Venous Thromboembolism Prevention with Extended Duration Betrixaban (APEX) study". American Heart Journal. 167 (3): 335–41. doi:10.1016/j.ahj.2013.11.006. PMID 24576517.
  10. ↑ Cohen, Alexander T.; Spiro, Theodore E.; Büller, Harry R.; Haskell, Lloyd; Hu, Dayi; Hull, Russell; Mebazaa, Alexandre; Merli, Geno; Schellong, Sebastian (2013-02-07). "Rivaroxaban for Thromboprophylaxis in Acutely Ill Medical Patients" (PDF). New England Journal of Medicine. 368 (6): 513–523. doi:10.1056/nejmoa1111096. hdl:10447/96593. ISSN 0028-4793. PMID 23388003. Archived (PDF) from the original on 2021-11-04. Retrieved 2021-05-31.
  11. ↑ Goldhaber, Samuel Z.; Leizorovicz, Alain; Kakkar, Ajay K.; Haas, Sylvia K.; Merli, Geno; Knabb, Robert M.; Weitz, Jeffrey I. (2011-12-08). "Apixaban versus Enoxaparin for Thromboprophylaxis in Medically Ill Patients" (PDF). New England Journal of Medicine. 365 (23): 2167–2177. doi:10.1056/nejmoa1110899. hdl:2437/127244. ISSN 0028-4793. PMID 22077144. Archived from the original on 2021-11-04. Retrieved 2021-05-31.
  12. ↑ Cohen, Alexander T.; Harrington, Robert A.; Goldhaber, Samuel Z.; Hull, Russell D.; Wiens, Brian L.; Gold, Alex; Hernandez, Adrian F.; Gibson, C. Michael (2016-08-11). "Extended Thromboprophylaxis with Betrixaban in Acutely Ill Medical Patients". New England Journal of Medicine. 375 (6): 534–544. doi:10.1056/nejmoa1601747. hdl:11573/884978. ISSN 0028-4793. PMID 27232649.
  13. ↑ "FDA approved betrixaban (BEVYXXA, Portola) for the prophylaxis of venous thromboembolism (VTE) in adult patients". Archived from the original on 25 July 2018. Retrieved 28 June 2017.
  14. ↑ "CHMP decision" (PDF). Archived (PDF) from the original on 2018-10-02. Retrieved 2021-05-31.
Identifiers:
This article is issued from Offline. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.