Details of the Drug

General Information of Drug (ID: DM2C4RF)

Drug Name
Betrixaban
Synonyms
Betrixaban; 330942-05-7; Bevyxxa; PRT054021; UNII-74RWP7W0J9; PRT 054021; 74RWP7W0J9; betrixaban maleate; Betrixaban [USAN:INN]; betrixaban/; Betrixaban (USAN); D0J0BU; SCHEMBL158591; QCR-99; GTPL9602; EX-A358; MolPort-009-682-948; ZINC3
Indication
Disease Entry ICD 11 Status REF
Venous thromboembolism BD72 Approved [1], [2]
Cerebrovascular ischaemia 8B1Z Phase 3 [3]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 451.9
Topological Polar Surface Area (xlogp) 3.6
Rotatable Bond Count (rotbonds) 7
Hydrogen Bond Donor Count (hbonddonor) 3
Hydrogen Bond Acceptor Count (hbondacc) 5
ADMET Property
Absorption AUC
The area under the plot of plasma concentration (AUC) of drug is 13-50 mgh/L [4]
Absorption Tmax
The time to maximum plasma concentration (Tmax) is 0.94-2.04 h [4]
Bioavailability
The bioavailability of drug is 75% [4]
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 [5]
Half-life
The concentration or amount of drug in body reduced by one-half in 19 - 27 hours [5]
Metabolism
The drug is metabolized via the hepatic [6]
Vd
The volume of distribution (Vd) of drug is 32 L/kg [7]
Chemical Identifiers
Formula
C23H22ClN5O3
IUPAC Name
N-(5-chloropyridin-2-yl)-2-[[4-(N,N-dimethylcarbamimidoyl)benzoyl]amino]-5-methoxybenzamide
Canonical 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)
InChIKey
XHOLNRLADUSQLD-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
10275777
ChEBI ID
CHEBI:140421
CAS Number
330942-05-7
DrugBank ID
DB12364
TTD ID
D0J0BU
VARIDT ID
DR00216
ACDINA ID
D00067

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Coagulation factor Xa (F10) TTCIHJA FA10_HUMAN Modulator [8]

Drug Transporter (DTP)
DTP Name DTP ID UniProt ID MOA REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [9]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Venous thromboembolism
ICD Disease Classification BD72
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Coagulation factor Xa (F10) DTT F10 4.84E-02 -0.28 -0.9
P-glycoprotein 1 (ABCB1) DTP P-GP 2.04E-02 -1.13E+00 -1.00E+00
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Betrixaban (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Apigenin DMI3491 Minor Increased risk of bleeding by the combination of Betrixaban and Apigenin. Discovery agent [N.A.] [25]
Tazemetostat DMWP1BH Major Increased risk of bleeding by the combination of Betrixaban and Tazemetostat. Follicular lymphoma [2A80] [26]
Avapritinib DMK2GZX Major Increased risk of bleeding by the combination of Betrixaban and Avapritinib. Gastrointestinal stromal tumour [2B5B] [27]
Berotralstat DMWA2DZ Moderate Decreased clearance of Betrixaban due to the transporter inhibition by Berotralstat. Innate/adaptive immunodeficiency [4A00] [28]
Calaspargase pegol DMQZBXI Moderate Increased risk of bleeding by the combination of Betrixaban and Calaspargase pegol. Malignant haematopoietic neoplasm [2B33] [29]
Fedratinib DM4ZBK6 Major Increased risk of bleeding by the combination of Betrixaban and Fedratinib. Myeloproliferative neoplasm [2A20] [28]
Choline salicylate DM8P137 Moderate Increased risk of bleeding by the combination of Betrixaban and Choline salicylate. Postoperative inflammation [1A00-CA43] [30]
Curcumin DMQPH29 Minor Increased risk of bleeding by the combination of Betrixaban and Curcumin. Solid tumour/cancer [2A00-2F9Z] [31]
⏷ Show the Full List of 8 DDI Information of This Drug

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG
DIG Name DIG ID PubChem CID Functional Classification
FD&C blue no. 1 E00263 19700 Colorant
Carmellose sodium E00625 Not Available Disintegrant
Dextrose monohydrate E00538 22814120 Binding agent; Diluent; Flavoring agent; Tonicity agent
Ferric hydroxide oxide yellow E00539 23320441 Colorant
Ferrosoferric oxide E00231 14789 Colorant
Magnesium stearate E00208 11177 lubricant
Titanium dioxide E00322 26042 Coating agent; Colorant; Opacifying agent
⏷ Show the Full List of 7 Pharmaceutical Excipients of This Drug
Pharmaceutical Formulation
Formulation Name Drug Dosage Dosage Form Route
Betrixaban 80 mg capsule 80 mg Oral Capsule Oral
Betrixaban 40 mg capsule 40 mg Oral Capsule Oral
Jump to Detail Pharmaceutical Formulation Page of This Drug

References

1 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2018
2 2017 FDA drug approvals.Nat Rev Drug Discov. 2018 Feb;17(2):81-85.
3 ClinicalTrials.gov (NCT01583218) Acute Medically Ill VTE Prevention With Extended Duration Betrixaban Study (The APEX Study). U.S. National Institutes of Health.
4 Pharmacodynamics and pharmacokinetics of tolfenamic acid in ruminating calves: evaluation in models of acute inflammation. Vet J. 1998 May;155(3):275-88.
5 New oral anticoagulants in atrial fibrillation. Eur Heart J. 2008 Jan;29(2):155-65. Epub 2007 Dec 19.
6 Cada DJ, Baker DE: Oritavancin diphosphate. Hosp Pharm. 2014 Dec;49(11):1049-60. doi: 10.1310/hjp4911-1049.
7 An FDA phase I clinical trial of quinacrine sterilization (QS). Int J Gynaecol Obstet. 2003 Oct;83 Suppl 2:S45-9.
8 Company report (Portola)
9 Profile of betrixaban and its potential in the prevention and treatment of venous thromboembolism. Vasc Health Risk Manag. 2015 Jun 26;11:343-51.
10 Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
11 MDR1 (ABCB1) G1199A (Ser400Asn) polymorphism alters transepithelial permeability and sensitivity to anticancer agents. Cancer Chemother Pharmacol. 2009 Jun;64(1):183-8.
12 Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett. 2016 Jan 1;370(1):153-64.
13 Folate transporter expression decreases in the human placenta throughout pregnancy and in pre-eclampsia. Pregnancy Hypertens. 2012 Apr;2(2):123-31.
14 Comparative studies on in vitro methods for evaluating in vivo function of MDR1 P-glycoprotein. Pharm Res. 2001 Dec;18(12):1660-8.
15 Antiestrogens and steroid hormones: substrates of the human P-glycoprotein. Biochem Pharmacol. 1994 Jul 19;48(2):287-92.
16 Association of genetic polymorphisms in the influx transporter SLCO1B3 and the efflux transporter ABCB1 with imatinib pharmacokinetics in patients with chronic myeloid leukemia. Ther Drug Monit. 2011 Apr;33(2):244-50.
17 Pfizer. Product Development Pipeline. March 31 2009.
18 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
19 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2359).
20 Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
21 Serum zinc concentrations: contamination from laboratory equipment. JPEN J Parenter Enteral Nutr. 1979 May-Jun;3(3):179-81.
22 Biochemistry and clinical pharmacology of new anticoagulant agents. Pathophysiol Haemost Thromb. 2002 Sep-Dec;32(5-6):218-24.
23 Effect of factor X inhibition on coagulation activation and cytokine induction in human systemic inflammation. J Infect Dis. 2002 Nov 1;186(9):1270-6.
24 Haemophilia B: Christmas disease. Expert Opin Pharmacother. 2005 Aug;6(9):1517-24.
25 Heck AM, DeWitt BA, Lukes AL "Potential interactions between alternative therapies and warfarin." Am J Health Syst Pharm 57 (2000): 1221-7 quiz 1228-30. [PMID: 10902065]
26 Bodiford AB, Kessler FO, Fermo JD, Ragucci KR "Elevated international normalized ratio with the consumption of grapefruit and use of warfarin." SAGE Open Med Case Rep 0 (2013): 1-3. [PMID: 27489634]
27 Cerner Multum, Inc. "UK Summary of Product Characteristics.".
28 Product Information. Bevyxxa (betrixaban). Portola Pharmaceuticals, South San Francisco, CA.
29 Caruso V, Iacoviello L, Di Castelnuovo A, et.al "Thrombotic complications in childhood acute lymphoblastic leukemia: a meta-analysis of 17 prospective studies comprising 1752 pediatric patients." Blood 108 (2006): 2216-22. [PMID: 16804111]
30 Fausa O "Salicylate-induced hypoprothrombinemia: a report of four cases." Acta Med Scand 188 (1970): 403-8. [PMID: 5490567]
31 Abebe W "Herbal medication: potential for adverse interactions with analgesic drugs." J Clin Pharm Ther 27 (2002): 391-401. [PMID: 12472978]