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Details

Stereochemistry ACHIRAL
Molecular Formula C25H25N5O4
Molecular Weight 459.4981
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of APIXABAN

SMILES

COc1ccc(cc1)-n2c3c(CCN(c4ccc(cc4)N5CCCCC5=O)C3=O)c(C(=N)O)n2

InChI

InChIKey=QNZCBYKSOIHPEH-UHFFFAOYSA-N
InChI=1S/C25H25N5O4/c1-34-19-11-9-18(10-12-19)30-23-20(22(27-30)24(26)32)13-15-29(25(23)33)17-7-5-16(6-8-17)28-14-3-2-4-21(28)31/h5-12H,2-4,13-15H2,1H3,(H2,26,32)

HIDE SMILES / InChI
Apixaban is an orally active inhibitor of coagulation factor Xa with anticoagulant activity. Apixaban directly inhibits factor Xa, thereby interfering with the conversion of prothrombin to thrombin and preventing formation of cross-linked fibrin clots. Apixaban has been available in Europe since May 2012. An FDA decision on apixaban which was expected on June 28, 2012 was initially delayed before final approval on December 28, 2012. On August 21, 2014, Pfizer announced that apixaban was now FDA approved for treatment and secondary prophylaxis of deep vein thrombosis (DVT) and pulmonary embolism (PE). It is being developed in a joint venture by Pfizer and Bristol-Myers Squibb. It has also been used to lower the risk of developing venous thrombosis post-orthopedic surgical procedures.

CNS Activity

Curator's Comment:: Apixaban is substrate of p-glycoprotein (p-gp), a ubiquitous transmembrane receptor found in the intestinal wall, as well as various other locations in the body, including the blood-brain barrier. P-gp actively transports molecules with diverse conformations, including drugs, across tissue monolayers.

Originator

Curator's Comment:: In 2007, Pfizer and Bristol-Myers Squibb entered into a worldwide collaboration to develop and commercialize apixaban, an oral anticoagulant discovered by Bristol-Myers Squibb. This global alliance combines Bristol-Myers Squibb's long-standing strengths in cardiovascular drug development and commercialization with Pfizer’s global scale and expertise in this field. # Bristol-Myers Squibb

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: P00742
Gene ID: 2159.0
Gene Symbol: F10
Target Organism: Homo sapiens (Human)
0.22 µM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Secondary
ELIQUIS

Approved Use

Indicated to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation; for the prophylaxis of deep vein thrombosis (DVT), which may lead to pulmonary embolism (PE), in patients who have undergone hip or knee replacement surgery; for the treatment of DVT and PE, and for the reduction in the risk of recurrent DVT and PE following initial therapy.

Launch Date

1.35665274E12
Secondary
ELIQUIS

Approved Use

Indicated to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation; for the prophylaxis of deep vein thrombosis (DVT), which may lead to pulmonary embolism (PE), in patients who have undergone hip or knee replacement surgery; for the treatment of DVT and PE, and for the reduction in the risk of recurrent DVT and PE following initial therapy.

Launch Date

1.35665274E12
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
207 ng/mL
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
APIXABAN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
2024 ng × h/mL
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
APIXABAN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
12 h
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
APIXABAN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
50 mg single, oral
Highest studied dose
Dose: 50 mg
Route: oral
Route: single
Dose: 50 mg
Sources:
healthy, 20-39 years
n = 23
Health Status: healthy
Age Group: 20-39 years
Sex: M
Population Size: 23
Sources:
40 mg single, oral
Overdose
Dose: 40 mg
Route: oral
Route: single
Dose: 40 mg
Co-administed with::
digoxin(single 0.75 mg)
Sources:
unknown, 23 months
n = 1
Health Status: unknown
Age Group: 23 months
Sex: M
Population Size: 1
Sources:
Other AEs: Intoxication...
Other AEs:
Intoxication
Sources:
2.5 mg 2 times / day steady, oral
Dose: 2.5 mg, 2 times / day
Route: oral
Route: steady
Dose: 2.5 mg, 2 times / day
Sources:
healthy, 27 years (range: 19-39 years)
n = 6
Health Status: healthy
Age Group: 27 years (range: 19-39 years)
Sex: M
Population Size: 6
Sources:
Disc. AE: Headache, Nausea...
AEs leading to
discontinuation/dose reduction:
Headache (1 patient)
Nausea (1 patient)
Sources:
25 mg 2 times / day steady, oral
Highest studied dose
Dose: 25 mg, 2 times / day
Route: oral
Route: steady
Dose: 25 mg, 2 times / day
Sources:
healthy, 27 years (range: 20-41 years)
n = 8
Health Status: healthy
Age Group: 27 years (range: 20-41 years)
Sex: M
Population Size: 8
Sources:
Other AEs: Haematochezia, Alanine aminotransferase increased...
Other AEs:
Haematochezia (1 patient)
Alanine aminotransferase increased (1 patient)
Sources:
210 mg single, oral
Overdose
Dose: 210 mg
Route: oral
Route: single
Dose: 210 mg
Co-administed with::
levothyroxine(1.5 mg single)
amitriptyline(2.5 mg, single)
Sources:
unknown, 48 years
n = 1
Health Status: unknown
Age Group: 48 years
Sex: F
Population Size: 1
Sources:
Other AEs: Poisoning...
Other AEs:
Poisoning
Sources:
2.5 mg 1 times / day steady, oral
Dose: 2.5 mg, 1 times / day
Route: oral
Route: steady
Dose: 2.5 mg, 1 times / day
Co-administed with::
apixaban(oral; 2.5 mg/12h)
Sources:
unhealthy, 85 years
n = 1
Health Status: unhealthy
Condition: Auricular fibrillation
Age Group: 85 years
Sex: F
Population Size: 1
Sources:
Disc. AE: Hepatotoxicity...
AEs leading to
discontinuation/dose reduction:
Hepatotoxicity (1 patient)
Sources:
25 mg 2 times / day steady, oral
Overdose
Dose: 25 mg, 2 times / day
Route: oral
Route: steady
Dose: 25 mg, 2 times / day
Sources:
healthy
5 mg 2 times / day steady, oral
Recommended
Dose: 5 mg, 2 times / day
Route: oral
Route: steady
Dose: 5 mg, 2 times / day
Sources:
unhealthy
Health Status: unhealthy
Condition: nonvalvular atrial fibrillation
Sources:
Other AEs: Thromboembolic event...
AEs

AEs

AESignificanceDosePopulation
Intoxication
40 mg single, oral
Overdose
Dose: 40 mg
Route: oral
Route: single
Dose: 40 mg
Co-administed with::
digoxin(single 0.75 mg)
Sources:
unknown, 23 months
n = 1
Health Status: unknown
Age Group: 23 months
Sex: M
Population Size: 1
Sources:
Headache 1 patient
Disc. AE
2.5 mg 2 times / day steady, oral
Dose: 2.5 mg, 2 times / day
Route: oral
Route: steady
Dose: 2.5 mg, 2 times / day
Sources:
healthy, 27 years (range: 19-39 years)
n = 6
Health Status: healthy
Age Group: 27 years (range: 19-39 years)
Sex: M
Population Size: 6
Sources:
Nausea 1 patient
Disc. AE
2.5 mg 2 times / day steady, oral
Dose: 2.5 mg, 2 times / day
Route: oral
Route: steady
Dose: 2.5 mg, 2 times / day
Sources:
healthy, 27 years (range: 19-39 years)
n = 6
Health Status: healthy
Age Group: 27 years (range: 19-39 years)
Sex: M
Population Size: 6
Sources:
Alanine aminotransferase increased 1 patient
25 mg 2 times / day steady, oral
Highest studied dose
Dose: 25 mg, 2 times / day
Route: oral
Route: steady
Dose: 25 mg, 2 times / day
Sources:
healthy, 27 years (range: 20-41 years)
n = 8
Health Status: healthy
Age Group: 27 years (range: 20-41 years)
Sex: M
Population Size: 8
Sources:
Haematochezia 1 patient
25 mg 2 times / day steady, oral
Highest studied dose
Dose: 25 mg, 2 times / day
Route: oral
Route: steady
Dose: 25 mg, 2 times / day
Sources:
healthy, 27 years (range: 20-41 years)
n = 8
Health Status: healthy
Age Group: 27 years (range: 20-41 years)
Sex: M
Population Size: 8
Sources:
Poisoning
210 mg single, oral
Overdose
Dose: 210 mg
Route: oral
Route: single
Dose: 210 mg
Co-administed with::
levothyroxine(1.5 mg single)
amitriptyline(2.5 mg, single)
Sources:
unknown, 48 years
n = 1
Health Status: unknown
Age Group: 48 years
Sex: F
Population Size: 1
Sources:
Hepatotoxicity 1 patient
Disc. AE
2.5 mg 1 times / day steady, oral
Dose: 2.5 mg, 1 times / day
Route: oral
Route: steady
Dose: 2.5 mg, 1 times / day
Co-administed with::
apixaban(oral; 2.5 mg/12h)
Sources:
unhealthy, 85 years
n = 1
Health Status: unhealthy
Condition: Auricular fibrillation
Age Group: 85 years
Sex: F
Population Size: 1
Sources:
Thromboembolic event
5 mg 2 times / day steady, oral
Recommended
Dose: 5 mg, 2 times / day
Route: oral
Route: steady
Dose: 5 mg, 2 times / day
Sources:
unhealthy
Health Status: unhealthy
Condition: nonvalvular atrial fibrillation
Sources:
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
minor [IC50 20 uM]
no
no
no
no
no
no
no
no
no
no
no
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
minor
minor
minor
minor
minor
no
no
no
no
no
no
yes
yes
yes (co-administration study)
Comment: ketoconazole increased cmax of apixaban 1.5x, auc 2x
Page: 9.0
yes
yes (co-administration study)
Comment: ketoconazole increased cmax of apixaban 1.5x, auc 2x
Page: 9.0
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
Oral factor Xa inhibitors for venous thromboembolism prevention in major orthopedic surgery: a review.
2008
The prevention and treatment of venous thromboembolism with LMWHs and new anticoagulants.
2009
Selecting the optimal antithrombotic regimen for patients with acute coronary syndromes undergoing percutaneous coronary intervention.
2009
Factor Xa inhibitors--new anticoagulants for secondary haemostasis.
2009 Aug
Use of emerging oral anticoagulants in clinical practice: translating results from clinical trials to orthopedic and general surgical patient populations.
2009 Aug
Apixaban or enoxaparin for thromboprophylaxis after knee replacement.
2009 Aug 6
Oral anticoagulation with Factor Xa and thrombin inhibitors: Is there an alternative to warfarin?
2009 Dec
Oral factor Xa inhibitors for thromboprophylaxis in major orthopedic surgery: a review.
2009 Dec
New anticoagulants for atrial fibrillation.
2009 Jul
New anticoagulants: focus on venous thromboembolism.
2009 Jul
Gateways to clinical trials.
2009 Nov
Apixaban or enoxaparin for thromboprophylaxis.
2009 Nov 19
Gateways to clinical trials.
2009 Oct
New antithrombotic drugs: potential for use in oncology.
2009 Oct 10
[New developments in antithrombotic care].
2009 Sep
Novel anticoagulant therapy: principle and practice.
2010
New oral anticoagulants in development: potential for improved safety profiles.
2010
Potential of new anticoagulants in patients with cancer.
2010 Apr
Antithrombotic treatment failures in antiphospholipid syndrome: the new anticoagulants?
2010 Apr
Primary prevention of venous thromboembolism in medical and surgical oncology patients.
2010 Apr 13
Treatment of thromboembolism in cancer patients.
2010 Aug
Apixaban, a direct factor Xa inhibitor, inhibits tissue-factor induced human platelet aggregation in vitro: comparison with direct inhibitors of factor VIIa, XIa and thrombin.
2010 Aug
Antithrombotic and anticoagulant profiles of TAK-442, a novel factor Xa inhibitor, in a rabbit model of venous thrombosis.
2010 Aug
New oral anticoagulants: a practical guide for clinicians.
2010 Feb
Phenyltriazolinones as potent factor Xa inhibitors.
2010 Feb 15
Metabolism, pharmacokinetics and pharmacodynamics of the factor Xa inhibitor apixaban in rabbits.
2010 Jan
The new oral anticoagulants.
2010 Jan 7
Oral factor Xa inhibitors for the prevention of stroke in atrial fibrillation.
2010 Jul
Gateways to clinical trials.
2010 Jun
Drug and dietary interactions of the new and emerging oral anticoagulants.
2010 Jun
Old versus new anticoagulants: focus on pharmacology.
2010 Jun
Effect of the direct factor Xa inhibitor apixaban in rat models of thrombosis and hemostasis.
2010 Jun
[A new deal with new anticoagulants?].
2010 Jun
[Pulmonary circulation: contributions of the year 2009].
2010 Mar
Rationale and design of AVERROES: apixaban versus acetylsalicylic acid to prevent stroke in atrial fibrillation patients who have failed or are unsuitable for vitamin K antagonist treatment.
2010 Mar
Apixaban for reduction in stroke and other ThromboemboLic events in atrial fibrillation (ARISTOTLE) trial: design and rationale.
2010 Mar
Antithrombotic drugs for patients with ischaemic stroke and transient ischaemic attack to prevent recurrent major vascular events.
2010 Mar
Comparative efficacy and safety of the novel oral anticoagulants dabigatran, rivaroxaban and apixaban in preclinical and clinical development.
2010 Mar
In vitro assessment of metabolic drug-drug interaction potential of apixaban through cytochrome P450 phenotyping, inhibition, and induction studies.
2010 Mar
Apixaban versus enoxaparin for thromboprophylaxis after knee replacement (ADVANCE-2): a randomised double-blind trial.
2010 Mar 6
Apixaban to prevent venous thromboembolism after knee replacement.
2010 Mar 6
Emerging anticoagulants for venous thromboembolism prevention.
2010 May 15
Forecasting drug utilization and expenditure in a metropolitan health region.
2010 May 17
New anticoagulants for the prevention of venous thromboembolism.
2010 May 25
New options with dabigatran etexilate in anticoagulant therapy.
2010 May 25
New antithrombotics for atrial fibrillation.
2010 Oct
Novel oral anticoagulants: implications in the perioperative setting.
2010 Sep
Quantification of apixaban's therapeutic utility in prevention of venous thromboembolism: selection of phase III trial dose.
2010 Sep
New antithrombotic agents--insights from clinical trials.
2010 Sep
Role of orally available antagonists of factor Xa in the treatment and prevention of thromboembolic disease: focus on rivaroxaban.
2010 Sep
Patents

Sample Use Guides

The recommended dose is 5 mg orally twice daily. In patients with at least 2 of the following characteristics: age 80 years, body weight 60 kg, or serum creatinine 1.5 mg/dL, the recommended dose is 2.5 mg orally twice daily.
Route of Administration: Oral
In Vitro Use Guide
Unknown
Name Type Language
APIXABAN
DASH   EMA EPAR   INN   JAN   MART.   MI   ORANGE BOOK   USAN   VANDF   WHO-DD  
INN   USAN  
Official Name English
APIXABAN [EMA EPAR]
Common Name English
APIXABAN [VANDF]
Common Name English
1-(4-METHOXYPHENYL)-7-OXO-6-(4-(2-OXOPIPERIDIN-1-YL)PHENYI)-4,5,6,7-TETRAHYDRO-1H-PYRAZOLO(3,4-C)PYRIDINE-3-CARBOXAMIDE
Common Name English
APIXABAN [JAN]
Common Name English
APIXABAN [MART.]
Common Name English
BMS-562247
Code English
APIXABAN [MI]
Common Name English
BMS-562247-01
Code English
APIXABAN [ORANGE BOOK]
Common Name English
1H-PYRAZOLO(3,4-C)PYRIDINE-3-CARBOXAMIDE, 4,5,6,7-TETRAHYDRO-1-( 4-METHOXYPHENYL)-7-OXO-6-(4-(2-OXO-1-PIPERIDINYL)PHENYL)-
Common Name English
APIXABAN [WHO-DD]
Common Name English
ELIQUIS
Brand Name English
APIXABAN [INN]
Common Name English
APIXABAN [USAN]
Common Name English
Classification Tree Code System Code
LIVERTOX 59
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WHO-ATC B01AF02
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NCI_THESAURUS C263
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EMA ASSESSMENT REPORTS ELIQUIS (AUTHORIZED: ARTHROPLASTY)
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LOINC 74214-8
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WHO-VATC QB01AF02
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EMA ASSESSMENT REPORTS ELIQUIS (AUTHORIZED: VENOUS THROMBOEMBOLISM)
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NDF-RT N0000175637
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Code System Code Type Description
IUPHAR
6390
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PRIMARY
FDA UNII
3Z9Y7UWC1J
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PRIMARY
EVMPD
SUB25425
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PRIMARY
INN
8626
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PRIMARY
JAPANESE REVIEW
ELIQUIS
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PRIMARY APPROVED DECEMBER 2012
MESH
C522181
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PRIMARY
ChEMBL
CHEMBL231779
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PRIMARY
MERCK INDEX
M1993
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PRIMARY Merck Index
CAS
503612-47-3
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PRIMARY
LACTMED
Apixaban
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PRIMARY
HSDB
8223
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PRIMARY
PUBCHEM
10182969
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PRIMARY
WIKIPEDIA
APIXABAN
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PRIMARY
RXCUI
1364430
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PRIMARY RxNorm
DRUG BANK
DB06605
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PRIMARY
NCI_THESAURUS
C61308
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PRIMARY
EPA CompTox
503612-47-3
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PRIMARY
DRUG CENTRAL
4298
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PRIMARY