U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C23H22ClN5O3.C4H4O4
Molecular Weight 567.978
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of BETRIXABAN MALEATE

SMILES

OC(=O)\C=C/C(O)=O.COC1=CC(C(=O)NC2=CC=C(Cl)C=N2)=C(NC(=O)C3=CC=C(C=C3)C(=N)N(C)C)C=C1

InChI

InChIKey=DTSJEZCXVWQKCL-BTJKTKAUSA-N
InChI=1S/C23H22ClN5O3.C4H4O4/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;5-3(6)1-2-4(7)8/h4-13,25H,1-3H3,(H,27,30)(H,26,28,31);1-2H,(H,5,6)(H,7,8)/b;2-1-

HIDE SMILES / InChI

Molecular Formula C23H22ClN5O3
Molecular Weight 451.905
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula C4H4O4
Molecular Weight 116.0722
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 1
Optical Activity NONE

Betrixaban is an anticoagulant drug which acts as a direct factor Xa inhibitor. Betrixaban is now being developed by Portola Pharmaceuticals. Oral, once-daily Factor Xa inhibitor anticoagulant that directly inhibits the activity of Factor Xa, an important validated target in the blood coagulation pathway, to prevent life-threatening thrombosis. U.S. Food and Drug Administration granted Fast Track designation to betrixaban for extended-duration prevention of venous thromboembolism (VTE; blood clots) in acute medically ill patients (i.e., those who are hospitalized for serious medical conditions, such as heart failure, stroke, infection and pulmonary disease). Has the potential to become the first oral Factor Xa inhibitor anticoagulant approved for hospital-to-home prevention of VTE in acute medically ill patients.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Preventing
BEVYXXA

Approved Use

BEVYXXA is indicated for the prophylaxis of venous thromboembolism (VTE) in adult patients hospitalized for an acute medical illness who are at risk for thromboembolic complications due to moderate or severe restricted mobility and other risk factors for VTE.

Launch Date

1.49808965E12
Preventing
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
23.2 ng/mL
40 mg 2 times / day multiple, oral
dose: 40 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
BETRIXABAN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: FASTED
73.1 ng/mL
80 mg 2 times / day multiple, oral
dose: 80 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
BETRIXABAN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: FASTED
122 ng/mL
120 mg 2 times / day multiple, oral
dose: 120 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
BETRIXABAN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: FASTED
38 ng/mL
80 mg single, oral
dose: 80 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
BETRIXABAN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: FASTED
58.2 ng/mL
120 mg single, oral
dose: 120 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
BETRIXABAN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: FASTED
9.37 ng/mL
40 mg single, oral
dose: 40 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
BETRIXABAN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
179 ng × h/mL
40 mg 2 times / day multiple, oral
dose: 40 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
BETRIXABAN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: FASTED
488 ng × h/mL
80 mg 2 times / day multiple, oral
dose: 80 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
BETRIXABAN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: FASTED
821 ng × h/mL
120 mg 2 times / day multiple, oral
dose: 120 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
BETRIXABAN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: FASTED
393 ng × h/mL
80 mg single, oral
dose: 80 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
BETRIXABAN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: FASTED
600 ng × h/mL
120 mg single, oral
dose: 120 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
BETRIXABAN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: FASTED
83.1 ng × h/mL
40 mg single, oral
dose: 40 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
BETRIXABAN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
39.7 h
40 mg 2 times / day multiple, oral
dose: 40 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
BETRIXABAN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: FASTED
37.3 h
80 mg 2 times / day multiple, oral
dose: 80 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
BETRIXABAN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: FASTED
35.9 h
120 mg 2 times / day multiple, oral
dose: 120 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
BETRIXABAN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: FASTED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
40%
40 mg single, oral
dose: 40 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
BETRIXABAN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
550 mg 1 times / day single, oral
Highest studied dose
Dose: 550 mg, 1 times / day
Route: oral
Route: single
Dose: 550 mg, 1 times / day
Sources: Page: dexxience-epar-refusal-public-assessment-report_.pdf - p.50
healthy, adult
n = 59
Health Status: healthy
Age Group: adult
Sex: M
Population Size: 59
Sources: Page: dexxience-epar-refusal-public-assessment-report_.pdf - p.50
Other AEs: Electrocardiogram QTc interval prolonged...
Other AEs:
Electrocardiogram QTc interval prolonged (grade 1, 3.4%)
Sources: Page: dexxience-epar-refusal-public-assessment-report_.pdf - p.50
360 mg 1 times / day single, oral
MTD
Dose: 360 mg, 1 times / day
Route: oral
Route: single
Dose: 360 mg, 1 times / day
Sources: Page: dexxience-epar-refusal-public-assessment-report_.pdf - p.50
healthy, adult
n = 59
Health Status: healthy
Age Group: adult
Sex: M
Population Size: 59
Sources: Page: dexxience-epar-refusal-public-assessment-report_.pdf - p.50
Sources: Page: dexxience-epar-refusal-public-assessment-report_.pdf - p.50
80 mg 1 times / day multiple, oral
Recommended
Dose: 80 mg, 1 times / day
Route: oral
Route: multiple
Dose: 80 mg, 1 times / day
Sources:
unhealthy, median age 76.6 years
n = 3716
Health Status: unhealthy
Condition: Venous thromboembolism
Age Group: median age 76.6 years
Sex: M+F
Population Size: 3716
Sources:
Disc. AE: Haemorrhage, Pulmonary embolism...
AEs leading to
discontinuation/dose reduction:
Haemorrhage (2.4%)
Pulmonary embolism
Thrombosis venous deep
Sources:
80 mg 1 times / day steady, oral
Recommended
Dose: 80 mg, 1 times / day
Route: oral
Route: steady
Dose: 80 mg, 1 times / day
Sources: Page: 208383Orig1s000MedR.pdf - p.76
unhealthy, median age 76.6 years
n = 3716
Health Status: unhealthy
Condition: Venous thromboembolism
Age Group: median age 76.6 years
Sex: M+F
Population Size: 3716
Sources: Page: 208383Orig1s000MedR.pdf - p.76
Other AEs: Gastrointestinal bleeding, Intracranial hemorrhage...
Other AEs:
Gastrointestinal bleeding (major, 19 patients)
Intracranial hemorrhage (major, 2 patients)
Bleeding (grade 5, 1 patient)
Sources: Page: 208383Orig1s000MedR.pdf - p.76
unknown
Other AEs: Epidural hematoma, Spinal hematoma...
Other AEs:
Epidural hematoma
Spinal hematoma
Sources:
AEs

AEs

AESignificanceDosePopulation
Electrocardiogram QTc interval prolonged grade 1, 3.4%
550 mg 1 times / day single, oral
Highest studied dose
Dose: 550 mg, 1 times / day
Route: oral
Route: single
Dose: 550 mg, 1 times / day
Sources: Page: dexxience-epar-refusal-public-assessment-report_.pdf - p.50
healthy, adult
n = 59
Health Status: healthy
Age Group: adult
Sex: M
Population Size: 59
Sources: Page: dexxience-epar-refusal-public-assessment-report_.pdf - p.50
Haemorrhage 2.4%
Disc. AE
80 mg 1 times / day multiple, oral
Recommended
Dose: 80 mg, 1 times / day
Route: oral
Route: multiple
Dose: 80 mg, 1 times / day
Sources:
unhealthy, median age 76.6 years
n = 3716
Health Status: unhealthy
Condition: Venous thromboembolism
Age Group: median age 76.6 years
Sex: M+F
Population Size: 3716
Sources:
Pulmonary embolism Disc. AE
80 mg 1 times / day multiple, oral
Recommended
Dose: 80 mg, 1 times / day
Route: oral
Route: multiple
Dose: 80 mg, 1 times / day
Sources:
unhealthy, median age 76.6 years
n = 3716
Health Status: unhealthy
Condition: Venous thromboembolism
Age Group: median age 76.6 years
Sex: M+F
Population Size: 3716
Sources:
Thrombosis venous deep Disc. AE
80 mg 1 times / day multiple, oral
Recommended
Dose: 80 mg, 1 times / day
Route: oral
Route: multiple
Dose: 80 mg, 1 times / day
Sources:
unhealthy, median age 76.6 years
n = 3716
Health Status: unhealthy
Condition: Venous thromboembolism
Age Group: median age 76.6 years
Sex: M+F
Population Size: 3716
Sources:
Bleeding grade 5, 1 patient
80 mg 1 times / day steady, oral
Recommended
Dose: 80 mg, 1 times / day
Route: oral
Route: steady
Dose: 80 mg, 1 times / day
Sources: Page: 208383Orig1s000MedR.pdf - p.76
unhealthy, median age 76.6 years
n = 3716
Health Status: unhealthy
Condition: Venous thromboembolism
Age Group: median age 76.6 years
Sex: M+F
Population Size: 3716
Sources: Page: 208383Orig1s000MedR.pdf - p.76
Gastrointestinal bleeding major, 19 patients
80 mg 1 times / day steady, oral
Recommended
Dose: 80 mg, 1 times / day
Route: oral
Route: steady
Dose: 80 mg, 1 times / day
Sources: Page: 208383Orig1s000MedR.pdf - p.76
unhealthy, median age 76.6 years
n = 3716
Health Status: unhealthy
Condition: Venous thromboembolism
Age Group: median age 76.6 years
Sex: M+F
Population Size: 3716
Sources: Page: 208383Orig1s000MedR.pdf - p.76
Intracranial hemorrhage major, 2 patients
80 mg 1 times / day steady, oral
Recommended
Dose: 80 mg, 1 times / day
Route: oral
Route: steady
Dose: 80 mg, 1 times / day
Sources: Page: 208383Orig1s000MedR.pdf - p.76
unhealthy, median age 76.6 years
n = 3716
Health Status: unhealthy
Condition: Venous thromboembolism
Age Group: median age 76.6 years
Sex: M+F
Population Size: 3716
Sources: Page: 208383Orig1s000MedR.pdf - p.76
Epidural hematoma
unknown
Spinal hematoma
unknown
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no
no
no
no
no
no
no
no
no
no
no
no
no
yes [IC50 11.6 uM]
yes [IC50 11.6 uM]
yes [Inhibition 10 uM]
Drug as victimTox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
Oral factor Xa inhibitors for venous thromboembolism prevention in major orthopedic surgery: a review.
2008
Emergence of new oral antithrombotics: a critical appraisal of their clinical potential.
2008
New oral anticoagulants in atrial fibrillation.
2008 Jan
The prevention and treatment of venous thromboembolism with LMWHs and new anticoagulants.
2009
Factor Xa inhibitors--new anticoagulants for secondary haemostasis.
2009 Aug
A randomized evaluation of betrixaban, an oral factor Xa inhibitor, for prevention of thromboembolic events after total knee replacement (EXPERT).
2009 Jan
New anticoagulants for atrial fibrillation.
2009 Jul
New anticoagulants: focus on venous thromboembolism.
2009 Jul
Rivaroxaban -- an oral, direct Factor Xa inhibitor: lessons from a broad clinical study programme.
2009 May
Emerging antithrombotic agents for thromboprophylaxis, clinical potential and patient considerations.
2010
Post-operative thromboprophylaxis: new oral thrombin and factor X inhibitors and their place in clinical practice.
2010 May 24
New anticoagulants for the prevention of venous thromboembolism.
2010 May 25
Role of orally available antagonists of factor Xa in the treatment and prevention of thromboembolic disease: focus on rivaroxaban.
2010 Sep
Patents

Patents

Sample Use Guides

80 mg PO QD for 35 day + 7 days.
Route of Administration: Oral
In a tissue factor-induced thrombin-generation assay, betrixaban, in concentrations ranging between 5 and 25 ng/ml, inhibited thrombin generation to trough and peak levels comparable to those achieved by 2.5 mg of fondaparinux.
Substance Class Chemical
Created
by admin
on Sat Dec 16 13:59:03 UTC 2023
Edited
by admin
on Sat Dec 16 13:59:03 UTC 2023
Record UNII
28Z3021TMU
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
BETRIXABAN MALEATE
Common Name English
BEVYXXA
Brand Name English
BENZAMIDE, N-(5-CHLORO-2-PYRIDINYL)-2-((4-((DIMETHYLAMINO)IMINOMETHYL)BENZOYL)AMINO)-5-METHOXY-, (2Z)-2-BUTENEDIOATE (1:1)
Systematic Name English
Betrixaban maleate [WHO-DD]
Common Name English
BETRIXABAN MALEATE [MI]
Common Name English
Code System Code Type Description
RXCUI
1927955
Created by admin on Sat Dec 16 13:59:03 UTC 2023 , Edited by admin on Sat Dec 16 13:59:03 UTC 2023
PRIMARY
MERCK INDEX
m12019
Created by admin on Sat Dec 16 13:59:03 UTC 2023 , Edited by admin on Sat Dec 16 13:59:03 UTC 2023
PRIMARY
SMS_ID
100000166595
Created by admin on Sat Dec 16 13:59:03 UTC 2023 , Edited by admin on Sat Dec 16 13:59:03 UTC 2023
PRIMARY
FDA UNII
28Z3021TMU
Created by admin on Sat Dec 16 13:59:03 UTC 2023 , Edited by admin on Sat Dec 16 13:59:03 UTC 2023
PRIMARY
PUBCHEM
16069304
Created by admin on Sat Dec 16 13:59:03 UTC 2023 , Edited by admin on Sat Dec 16 13:59:03 UTC 2023
PRIMARY
CAS
936539-80-9
Created by admin on Sat Dec 16 13:59:03 UTC 2023 , Edited by admin on Sat Dec 16 13:59:03 UTC 2023
PRIMARY
Related Record Type Details
PARENT -> SALT/SOLVATE
Related Record Type Details
ACTIVE MOIETY