Identification
- Summary
Betrixaban is a Factor Xa inhibitor used for prophylaxis of venous thromboembolism in hospitalized patients.
- Brand Names
- BEVYXXA
- Generic Name
- Betrixaban
- DrugBank Accession Number
- DB12364
- Background
Betrixaban is a non-vitamin K oral anticoagulant whose action is driven by the competitive and reversible inhibition of the factor Xa 1. It was selected among all lead compounds due to its low hERG channel affinity while sustaining its factor Xa inhibition capacity 3. Betrixaban, now developed by Portola Pharmaceuticals Inc., is prescribed as a venous thromboembolism (VTE) prophylactic for adult patients with moderate to severe restricted motility or with other risks for VTE 2. VTE can be manifested as deep vein thrombosis or pulmonary embolism and it is a leading cause of preventable death in hospitalized patients 4.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Betrixaban (DB12364)
- Weight
- Average: 451.91
Monoisotopic: 451.1411173 - Chemical Formula
- C23H22ClN5O3
- Synonyms
- Betrixaban
- N-(5-chloropyridin-2-yl)-2-(4-(N,N-dimethylcarbamimidoyl)benzamido)-5-methoxybenzamide
- N-(5-chloropyridin-2-yl)-2-[[4-(N,N-dimethylcarbamimidoyl)benzoyl]amino]-5-methoxybenzamide
- External IDs
- PRT-054021
- PRT054021
Pharmacology
- Indication
Betrixaban is indicated for prophylaxis of venous thromboembolism (VTE) in conditions of moderate to severe restricted mobility or in patients that qualify as in risk of VTE.
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- Contraindications & Blackbox Warnings
Avoid life-threatening adverse drug eventsImprove clinical decision support with information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events & improve clinical decision support.- Pharmacodynamics
Betrixaban is an oral anticoagulant that excerts its action by preventing thrombin generation without having a direct effect on platelet aggregation 5.
- Mechanism of action
Betrixaban is a cofactor-independent direct inhibitor of the Factor Xa and inhibits free and prothrombinase-bound Factor Xa 1.
Target Actions Organism ACoagulation factor X inhibitorHumans - Absorption
Betrixaban presents a rapid absorption at a dose of 80 mg. Its peak plasma concentration is registered within 3-4 hours after oral administration in healthy humans. The oral bioavailability is 34%, and it can be reduced with the consumption of food4. Specifically, the Cmax and AUC is reduced by an average of 70% and 61% with a low-fat meal, and 50% and 48% with a high-fat meal compared to the fasted state, an effect which is apparent up to six hours following food intake.Label
- Volume of distribution
The apparent volume of distribution os 32 L/kg Label.
- Protein binding
Betrixaban is reported to be present a proteing binding of about 60% 4.
- Metabolism
One of the major characteristics of Betrixaban is its minimal hepatic metabolism (< 1%), preventing potential accumulation with liver impariment. Unchanged Betrixaban is the main form found in human plasma, followed by two hydolitic CYP-independent inactive metabolites (15-18%). The minimal hepatic metabolism produces an unlikely drug-to-drug interaction with inhibitors or agonists of CYP450 4.
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- Route of elimination
Betrixaban is reported to present mainly a gastrointestinal elimination route, it has been shown that even 85% of it gets disposed in the feces and only 11% of it can be found in the urine 1.
- Half-life
Betrixaban presents a long half-life of between 19-27 hours 1.
- Clearance
Betrixaban presents a minimal renal clearance (being 5-7% of the administered dose) 4.
- Adverse Effects
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Betrixaban presents a minimal hepatotoxicity, which is the main adverse effect found in this class of drugs. Some of the major adverse effects of Betrixaban are bleeding or hypersensitivity 4.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbciximab The risk or severity of bleeding can be increased when Abciximab is combined with Betrixaban. Abemaciclib The serum concentration of Abemaciclib can be increased when it is combined with Betrixaban. Abrocitinib The serum concentration of Betrixaban can be increased when it is combined with Abrocitinib. Aceclofenac The risk or severity of bleeding can be increased when Betrixaban is combined with Aceclofenac. Acemetacin The risk or severity of bleeding can be increased when Betrixaban is combined with Acemetacin. Acenocoumarol The risk or severity of bleeding can be increased when Acenocoumarol is combined with Betrixaban. Acetylsalicylic acid The risk or severity of bleeding can be increased when Betrixaban is combined with Acetylsalicylic acid. Adagrasib The serum concentration of Betrixaban can be increased when it is combined with Adagrasib. Afatinib The serum concentration of Betrixaban can be increased when it is combined with Afatinib. Albutrepenonacog alfa The therapeutic efficacy of Albutrepenonacog alfa can be decreased when used in combination with Betrixaban. 
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- Avoid herbs and supplements with anticoagulant/antiplatelet activity. These herbs may increase the risk of bleeding. Examples include garlic, ginger, bilberry, danshen, piracetam, and ginkgo biloba.
- Take at the same time every day.
- Take with food. Betrixaban should be taken with food. The Cmax and AUC of betrixaban are decreased by approximately 60% and 55% when administered together with a 900 calorie meal.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Bevyxxa Capsule, gelatin coated 80 mg/1 Oral Portola Pharmaceuticals, Inc. 2017-07-07 Not applicable US 
Bevyxxa Capsule, gelatin coated 40 mg/1 Oral Portola Pharmaceuticals, Inc. 2017-07-07 Not applicable US
Categories
- ATC Codes
- B01AF04 — Betrixaban
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as benzanilides. These are aromatic compounds containing an anilide group in which the carboxamide group is substituted with a benzene ring. They have the general structure RNC(=O)R', where R,R'= benzene.
- Kingdom
- Organic compounds
- Super Class
- Benzenoids
- Class
- Benzene and substituted derivatives
- Sub Class
- Anilides
- Direct Parent
- Benzanilides
- Alternative Parents
- Benzamides / Methoxyanilines / Anisoles / Phenoxy compounds / Benzoyl derivatives / Methoxybenzenes / Alkyl aryl ethers / Aryl chlorides / Pyridines and derivatives / Imidolactams show 10 more
- Substituents
- Alkyl aryl ether / Amidine / Anisole / Aromatic heteromonocyclic compound / Aryl chloride / Aryl halide / Azacycle / Benzamide / Benzanilide / Benzoic acid or derivatives show 25 more
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 74RWP7W0J9
- CAS number
- 330942-05-7
- InChI Key
- XHOLNRLADUSQLD-UHFFFAOYSA-N
- 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)
- IUPAC Name
- N-(5-chloropyridin-2-yl)-2-[4-(N,N-dimethylcarbamimidoyl)benzamido]-5-methoxybenzamide
- SMILES
- COC1=CC=C(NC(=O)C2=CC=C(C=C2)C(=N)N(C)C)C(=C1)C(=O)NC1=CC=C(Cl)C=N1
References
- General References
- Turpie AG: New oral anticoagulants in atrial fibrillation. Eur Heart J. 2008 Jan;29(2):155-65. Epub 2007 Dec 19. [Article]
- Connolly SJ, Eikelboom J, Dorian P, Hohnloser SH, Gretler DD, Sinha U, Ezekowitz MD: Betrixaban compared with warfarin in patients with atrial fibrillation: results of a phase 2, randomized, dose-ranging study (Explore-Xa). Eur Heart J. 2013 May;34(20):1498-505. doi: 10.1093/eurheartj/eht039. Epub 2013 Mar 13. [Article]
- Zhang P, Huang W, Wang L, Bao L, Jia ZJ, Bauer SM, Goldman EA, Probst GD, Song Y, Su T, Fan J, Wu Y, Li W, Woolfrey J, Sinha U, Wong PW, Edwards ST, Arfsten AE, Clizbe LA, Kanter J, Pandey A, Park G, Hutchaleelaha A, Lambing JL, Hollenbach SJ, Scarborough RM, Zhu BY: Discovery of betrixaban (PRT054021), N-(5-chloropyridin-2-yl)-2-(4-(N,N-dimethylcarbamimidoyl)benzamido)-5-methoxybenz amide, a highly potent, selective, and orally efficacious factor Xa inhibitor. Bioorg Med Chem Lett. 2009 Apr 15;19(8):2179-85. doi: 10.1016/j.bmcl.2009.02.111. Epub 2009 Mar 3. [Article]
- Chan NC, Bhagirath V, Eikelboom JW: Profile of betrixaban and its potential in the prevention and treatment of venous thromboembolism. Vasc Health Risk Manag. 2015 Jun 26;11:343-51. doi: 10.2147/VHRM.S63060. eCollection 2015. [Article]
- Cabral KP, Ansell JE: The role of factor Xa inhibitors in venous thromboembolism treatment. Vasc Health Risk Manag. 2015 Jan 30;11:117-23. doi: 10.2147/VHRM.S39726. eCollection 2015. [Article]
- External Links
- PubChem Compound
- 10275777
- PubChem Substance
- 347828616
- ChemSpider
- 18981107
- BindingDB
- 50249298
- 1927851
- ChEBI
- 140421
- ChEMBL
- CHEMBL512351
- ZINC
- ZINC000030691754
- Wikipedia
- Betrixaban
- FDA label
- Download (548 KB)
- MSDS
- Download (24.5 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 3 Completed Prevention Venous Thromboembolism 1 2 Completed Prevention Thromboembolism 1 2 Completed Treatment Atrial Fibrillation 1 2 Completed Treatment Atrial Fibrillation / Atrial Flutter 1 2 Terminated Treatment Bleeding 1 1 Completed Basic Science Health Volunteers 1 1 Completed Basic Science Healthy Subjects (HS) 1 1 Completed Other Healthy Subjects (HS) 1 1 Completed Prevention Hepatic Impairment 1 1 Completed Treatment Impaired Renal Function 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Capsule, gelatin coated Oral 40 mg/1 Capsule, gelatin coated Oral 80 mg/1 - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US8557852 No 2013-10-15 2028-09-08 US US6376515 No 2002-04-23 2020-09-15 US US8691847 No 2014-04-08 2020-09-15 US US9629831 No 2017-04-25 2020-09-15 US US9555023 No 2017-01-31 2026-11-07 US US8404724 No 2013-03-26 2031-03-29 US US8987463 No 2015-03-24 2030-12-28 US US7598276 No 2009-10-06 2026-11-08 US US6835739 No 2004-12-28 2020-09-15 US US8518977 No 2013-08-27 2020-09-15 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 200-212 ºC Vincent, et al. Crystalline forms of a Factor Xa inhibitor. Patent application number WO 2012031017 A1 water solubility 2.5-2.7 mg/ml Vincent, et al. Crystalline forms of a Factor Xa inhibitor. Patent application number WO 2012031017 A1 - Predicted Properties
Property Value Source Water Solubility 0.0163 mg/mL ALOGPS logP 2.86 ALOGPS logP 3.03 Chemaxon logS -4.4 ALOGPS pKa (Strongest Acidic) 11.63 Chemaxon pKa (Strongest Basic) 10.91 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 6 Chemaxon Hydrogen Donor Count 3 Chemaxon Polar Surface Area 107.41 Å2 Chemaxon Rotatable Bond Count 6 Chemaxon Refractivity 138.29 m3·mol-1 Chemaxon Polarizability 47.62 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Serine-type endopeptidase activity
- Specific Function
- Factor Xa is a vitamin K-dependent glycoprotein that converts prothrombin to thrombin in the presence of factor Va, calcium and phospholipid during blood clotting.
- Gene Name
- F10
- Uniprot ID
- P00742
- Uniprot Name
- Coagulation factor X
- Molecular Weight
- 54731.255 Da
References
- Connolly SJ, Eikelboom J, Dorian P, Hohnloser SH, Gretler DD, Sinha U, Ezekowitz MD: Betrixaban compared with warfarin in patients with atrial fibrillation: results of a phase 2, randomized, dose-ranging study (Explore-Xa). Eur Heart J. 2013 May;34(20):1498-505. doi: 10.1093/eurheartj/eht039. Epub 2013 Mar 13. [Article]
- Zhang P, Huang W, Wang L, Bao L, Jia ZJ, Bauer SM, Goldman EA, Probst GD, Song Y, Su T, Fan J, Wu Y, Li W, Woolfrey J, Sinha U, Wong PW, Edwards ST, Arfsten AE, Clizbe LA, Kanter J, Pandey A, Park G, Hutchaleelaha A, Lambing JL, Hollenbach SJ, Scarborough RM, Zhu BY: Discovery of betrixaban (PRT054021), N-(5-chloropyridin-2-yl)-2-(4-(N,N-dimethylcarbamimidoyl)benzamido)-5-methoxybenz amide, a highly potent, selective, and orally efficacious factor Xa inhibitor. Bioorg Med Chem Lett. 2009 Apr 15;19(8):2179-85. doi: 10.1016/j.bmcl.2009.02.111. Epub 2009 Mar 3. [Article]
- Chan NC, Bhagirath V, Eikelboom JW: Profile of betrixaban and its potential in the prevention and treatment of venous thromboembolism. Vasc Health Risk Manag. 2015 Jun 26;11:343-51. doi: 10.2147/VHRM.S63060. eCollection 2015. [Article]
- Cabral KP, Ansell JE: The role of factor Xa inhibitors in venous thromboembolism treatment. Vasc Health Risk Manag. 2015 Jan 30;11:117-23. doi: 10.2147/VHRM.S39726. eCollection 2015. [Article]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Xenobiotic-transporting atpase activity
- Specific Function
- Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- Multidrug resistance protein 1
- Molecular Weight
- 141477.255 Da
References
- Chan NC, Bhagirath V, Eikelboom JW: Profile of betrixaban and its potential in the prevention and treatment of venous thromboembolism. Vasc Health Risk Manag. 2015 Jun 26;11:343-51. doi: 10.2147/VHRM.S63060. eCollection 2015. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization
- Specific Function
- Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel. Channel properties are modulated by cAMP and subunit assembly. Mediates the rapidly activating component of the ...
- Gene Name
- KCNH2
- Uniprot ID
- Q12809
- Uniprot Name
- Potassium voltage-gated channel subfamily H member 2
- Molecular Weight
- 126653.52 Da
References
- Chan NC, Bhagirath V, Eikelboom JW: Profile of betrixaban and its potential in the prevention and treatment of venous thromboembolism. Vasc Health Risk Manag. 2015 Jun 26;11:343-51. doi: 10.2147/VHRM.S63060. eCollection 2015. [Article]
Drug created at October 20, 2016 22:05 / Updated at October 07, 2021 12:09