Betrixaban

Betrixaban (trade name Bevyxxa) is an oral anticoagulant drug which acts as a direct factor Xa inhibitor.[1] Betrixaban is FDA approved for venous thrombosis prevention in adults hospitalized for an acute illness who are at risk for thromboembolic complications.[2] Compared to other directly acting oral anticoagulantss betrixaban has relatively low renal excretion and is not metabolized by CYP3A4.[3]

Betrixaban

Clinical data
Trade names	Bevyxxa
Other names	PRT054021, PRT064445
AHFS/Drugs.com	bevyxxa
Routes of administration	By mouth
ATC code	B01AF04 (WHO)
Legal status
Legal status	US: ℞-only
Pharmacokinetic data
Protein binding	60%
Elimination half-life	19–27 hrs
Duration of action	≥72 hrs
Excretion	85% feces, 11% urine
Identifiers
IUPAC name N-(5-Chloropyridin-2-yl)-2-([4-(N,N-dimethylcarbamimidoyl)benzoyl]amino)-5-methoxybenzamide
CAS Number	330942-05-7
PubChem CID	10275777
DrugBank	DB12364
ChemSpider	18981107
UNII	74RWP7W0J9
KEGG	D08873
ChEBI	CHEBI:140421
ChEMBL	ChEMBL512351
CompTox Dashboard (EPA)	DTXSID10954727
ECHA InfoCard	100.207.746
Chemical and physical data
Formula	C23H22ClN5O3
Molar mass	451.905 g·mol^−1
3D model (JSmol)	Interactive image
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) Key:XHOLNRLADUSQLD-UHFFFAOYSA-N
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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.[4]

The drug has undergone clinical trials for prevention of embolism after knee surgery[5] and for prevention of stroke following non-valvular atrial fibrillation.[6][7] Betrixaban was also studied in a large phase III clinical trial for extended duration thromboprophylaxis in acute ill patients.[8] Previously apixaban and rivaroxaban have failed to show positive risk/benefit ratio in this indication compared to enoxaparin.[9][10] 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.[11] Based on these results betrixaban was approved by FDA on June 23rd, 2017 becoming the first DOAC approved for extended prophylaxis in hospitalized patients.[12]

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.[13]

See also

• Rivaroxaban
• Apixaban
• Edoxaban
• Enoxaparin

References

1. Eriksson BI, Quinlan DJ, Weitz JI (2009). "Comparative pharmacodynamics and pharmacokinetics of oral direct thrombin and factor xa inhibitors in development". Clinical Pharmacokinetics. 48 (1): 1–22. doi:10.2165/0003088-200948010-00001. PMID 19071881. S2CID 35948814.
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. Retrieved 2018-10-29.
3. 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.
4. Husten, Harry. "Merck Abandons Development of Factor Xa Inhibitor Betrixaban". CardioBrief. Retrieved 11 April 2014.
5. 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.
6. 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.
7. 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.
8. 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.
9. 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.
10. 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.
11. 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.
12. "FDA approved betrixaban (BEVYXXA, Portola) for the prophylaxis of venous thromboembolism (VTE) in adult patients". Retrieved 28 June 2017.
13. "CHMP decision" (PDF).