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]
Cerebrovascular ischaemia	8B1Z	Phase 3	[2]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 451.9
  Logarithm of the Partition Coefficient (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 [3]
  Absorption Tmax: The time to maximum plasma concentration (Tmax) is 0.94-2.04 h [3]
  Bioavailability: The bioavailability of drug is 75% [3]
  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 [4]
  Half-life: The concentration or amount of drug in body reduced by one-half in 19 - 27 hours [4]
  Metabolism: The drug is metabolized via the hepatic [5]
  Vd: The volume of distribution (Vd) of drug is 32 L/kg []
• 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
• Repurposed Drugs (RPD): Click to Jump to the Detailed RPD Information of This Drug

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	[6]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[7]

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

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.]	[8]
Tazemetostat	DMWP1BH	Major	Increased risk of bleeding by the combination of Betrixaban and Tazemetostat.	Follicular lymphoma [2A80]	[9]
Avapritinib	DMK2GZX	Major	Increased risk of bleeding by the combination of Betrixaban and Avapritinib.	Gastrointestinal stromal tumour [2B5B]	[10]
Berotralstat	DMWA2DZ	Moderate	Decreased clearance of Betrixaban due to the transporter inhibition by Berotralstat.	Innate/adaptive immunodeficiency [4A00]	[11]
Calaspargase pegol	DMQZBXI	Moderate	Increased risk of bleeding by the combination of Betrixaban and Calaspargase pegol.	Malignant haematopoietic neoplasm [2B33]	[12]
Fedratinib	DM4ZBK6	Major	Increased risk of bleeding by the combination of Betrixaban and Fedratinib.	Myeloproliferative neoplasm [2A20]	[11]
Choline salicylate	DM8P137	Moderate	Increased risk of bleeding by the combination of Betrixaban and Choline salicylate.	Postoperative inflammation [1A00-CA43]	[13]
Curcumin	DMQPH29	Minor	Increased risk of bleeding by the combination of Betrixaban and Curcumin.	Solid tumour/cancer [2A00-2F9Z]	[14]

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

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] ClinicalTrials.gov (NCT01583218) Acute Medically Ill VTE Prevention With Extended Duration Betrixaban Study (The APEX Study). U.S. National Institutes of Health.
• [3] Pharmacodynamics and pharmacokinetics of tolfenamic acid in ruminating calves: evaluation in models of acute inflammation. Vet J. 1998 May;155(3):275-88.
• [4] New oral anticoagulants in atrial fibrillation. Eur Heart J. 2008 Jan;29(2):155-65. Epub 2007 Dec 19.
• [5] Cada DJ, Baker DE: Oritavancin diphosphate. Hosp Pharm. 2014 Dec;49(11):1049-60. doi: 10.1310/hjp4911-1049.
• [6] Company report (Portola)
• [7] Profile of betrixaban and its potential in the prevention and treatment of venous thromboembolism. Vasc Health Risk Manag. 2015 Jun 26;11:343-51.
• [8] 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]
• [9] 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]
• [10] Cerner Multum, Inc. "UK Summary of Product Characteristics.".
• [11] Product Information. Bevyxxa (betrixaban). Portola Pharmaceuticals, South San Francisco, CA.
• [12] 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]
• [13] Fausa O "Salicylate-induced hypoprothrombinemia: a report of four cases." Acta Med Scand 188 (1970): 403-8. [PMID: 5490567]
• [14] Abebe W "Herbal medication: potential for adverse interactions with analgesic drugs." J Clin Pharm Ther 27 (2002): 391-401. [PMID: 12472978]