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

Details

Stereochemistry ABSOLUTE
Molecular Formula C19H18ClN3O5S
Molecular Weight 435.8831
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of RIVAROXABAN

SMILES

c1cc(ccc1N2CCOCC2=O)N3C[C@]([H])(CNC(=O)c4ccc(Cl)s4)OC3=O

InChI

InChIKey=KGFYHTZWPPHNLQ-AWEZNQCLSA-N
InChI=1S/C19H18ClN3O5S/c20-16-6-5-15(29-16)18(25)21-9-14-10-23(19(26)28-14)13-3-1-12(2-4-13)22-7-8-27-11-17(22)24/h1-6,14H,7-11H2,(H,21,25)/t14-/m0/s1

HIDE SMILES / InChI

Molecular Formula C19H18ClN3O5S
Molecular Weight 435.8831
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment:: http://www.biospace.com/News/bayer-healthcares-xarelto-rivaroxaban-becomes/244131

Rivaroxaban (trade name Xarelto) is an oral anticoagulant. It is the first available orally active direct factor Xa inhibitor. Upon oral administration, rivaroxaban selectively binds to both free factor Xa and factor Xa bound in the prothrombinase complex. This interferes with the conversion of prothrombin (factor II) to thrombin and eventually prevents the formation of cross-linked fibrin clots. Rivaroxaban does not affect existing thrombin levels. Activation of factor X to factor Xa (FXa) via the intrinsic and extrinsic pathways plays a central role in the cascade of blood coagulation. Xarelto is indicated to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, treatment and prophylaxis of deep vein thrombosis (DVT) which may lead to PE in patients undergoing knee or hip replacement surgery, pulmonary embolism (PE) and for the reduction in the risk of recurrence of deep vein thrombosis and of pulmonary embolism following initial 6 months treatment for DVT and/or PE.

CNS Activity

Curator's Comment:: Rivaroxaban is distributed heterogeneously to tissues and organs, exhibiting only moderate tissue affinity and does not substantially penetrate the blood-brain barrier.

Originator

Curator's Comment:: Rivaroxaban was discovered in Bayer HealthCare Pharmaceuticals' Wuppertal laboratories in Germany, and is being jointly developed by Bayer HealthCare and Johnson & Johnson Pharmaceutical. # Bayer HealthCare Pharmaceuticals

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
0.400000000000000022 nM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Secondary
XARELTO

Approved Use

Indicated to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, for the treatment of deep vein thrombosis (DVT), pulmonary embolism (PE), and for the reduction in the risk of recurrence of DVT and of PE for the prophylaxis of DVT, which may lead to PE in patients undergoing knee or hip replacement surgery.

Launch Date

1309478400000
Cmax

Cmax

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

AUC

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

T1/2

ValueDoseCo-administeredAnalytePopulation
10.77 h
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
RIVAROXABAN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
9 h
20 mg 1 times / day unknown, oral
dose: 20 mg
route of administration: Oral
experiment type: UNKNOWN
co-administered:
RIVAROXABAN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
5%
20 mg 1 times / day unknown, oral
dose: 20 mg
route of administration: Oral
experiment type: UNKNOWN
co-administered:
RIVAROXABAN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
80 mg single, oral
Highest studied dose
Dose: 80 mg
Route: oral
Route: single
Dose: 80 mg
Sources:
healthy, 19-45
Health Status: healthy
Age Group: 19-45
Sex: M
Sources:
50 mg single, oral
Studied dose
Dose: 50 mg
Route: oral
Route: single
Dose: 50 mg
Sources:
healthy, 60-76
Health Status: healthy
Age Group: 60-76
Sex: M+F
Sources:
20 mg 1 times / day multiple, oral
Recommended
Dose: 20 mg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg, 1 times / day
Sources:
unhealthy
Disc. AE: Bleeding...
AEs leading to
discontinuation/dose reduction:
Bleeding (2%)
Sources:
20 mg 1 times / day multiple, oral
Recommended
Dose: 20 mg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg, 1 times / day
Sources:
unhealthy
Disc. AE: Bleeding...
AEs leading to
discontinuation/dose reduction:
Bleeding (grade 3-5, 4.3%)
Sources:
20 mg 1 times / day multiple, oral
Recommended
Dose: 20 mg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg, 1 times / day
Sources:
unhealthy
Disc. AE: Spinal epidural hematoma...
AEs leading to
discontinuation/dose reduction:
Spinal epidural hematoma
Sources:
20 mg 2 times / day multiple, oral
Recommended
Dose: 20 mg, 2 times / day
Route: oral
Route: multiple
Dose: 20 mg, 2 times / day
Sources:
unhealthy
Disc. AE: Bleeding...
AEs leading to
discontinuation/dose reduction:
Bleeding (1.7%)
Sources:
AEs

AEs

AESignificanceDosePopulation
Bleeding 2%
Disc. AE
20 mg 1 times / day multiple, oral
Recommended
Dose: 20 mg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg, 1 times / day
Sources:
unhealthy
Bleeding grade 3-5, 4.3%
Disc. AE
20 mg 1 times / day multiple, oral
Recommended
Dose: 20 mg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg, 1 times / day
Sources:
unhealthy
Spinal epidural hematoma Disc. AE
20 mg 1 times / day multiple, oral
Recommended
Dose: 20 mg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg, 1 times / day
Sources:
unhealthy
Bleeding 1.7%
Disc. AE
20 mg 2 times / day multiple, oral
Recommended
Dose: 20 mg, 2 times / day
Route: oral
Route: multiple
Dose: 20 mg, 2 times / day
Sources:
unhealthy
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no
no
no
no
no
no
no
no
no
no
no
no
no
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
yes
yes
yes
yes (co-administration study)
Comment: ketoconazole increased cmax of rivaroxaban 0.7x, auc 1.6x
Page: 9
yes
yes (co-administration study)
Comment: ketoconazole increased cmax of rivaroxaban 0.7x, auc 1.6x
Page: 9
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
New issues in oral anticoagulants.
2008
New compounds in the management of venous thromboembolism after orthopedic surgery: focus on rivaroxaban.
2008
Brave new world: the current and future use of novel anticoagulants.
2008
The top 4 advances in antithrombotic care in the last year.
2008
Pharmacological strategies for inhibition of thrombin activity.
2008
Gateways to clinical trials.
2008 Apr
Potent anticoagulants are associated with a higher all-cause mortality rate after hip and knee arthroplasty.
2008 Aug
Rivaroxaban: an oral direct inhibitor of factor Xa.
2008 Aug 15
[Summary and perspectives. Rivaroxaban].
2008 Dec
[Rivaroxaban (Xarelto): efficacy and safety].
2008 Dec
[Perioperative venous thromboembolism prophylaxis: short review and recommendations].
2008 Dec
[Rivaroxaban: clinical pharmacology].
2008 Dec
[Rivaroxaban: a decisive step forward in the management of postoperative thromboembolic disease?].
2008 Dec
[Pharmacology of heparins and direct anticoagulants].
2008 Dec
The laboratory diagnosis and clinical management of patients with heparin-induced thrombocytopenia: an update.
2008 Feb
Current and future prospects for anticoagulant therapy: inhibitors of factor Xa and factor IIa.
2008 Feb
Gateways to clinical trials.
2008 Jan-Feb
Selective factor Xa inhibition for thromboprophylaxis.
2008 Jul 5
Extended duration rivaroxaban versus short-term enoxaparin for the prevention of venous thromboembolism after total hip arthroplasty: a double-blind, randomised controlled trial.
2008 Jul 5
Gateways to clinical trials.
2008 Jun
[Hematology 2008].
2008 Jun
Rivaroxaban, an oral direct factor Xa inhibitor.
2008 Jun
New anticoagulants--the path from discovery to clinical practice.
2008 Jun 26
Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty.
2008 Jun 26
Rivaroxaban versus enoxaparin for thromboprophylaxis after hip arthroplasty.
2008 Jun 26
Preventing venous thromboembolism through risk assessment approaches.
2008 Jun 26-Jul 9
[New oral anticoagulants: molecular characteristics, mechanisms of action, pharmacokinetics and pharmacodynamics].
2008 Nov
[Anaesthesia and thromboembolic disease].
2008 Nov
[Thromboembolic disease in orthopedic surgery].
2008 Nov
[Rivaroxaban. The first factor Xa inhibitor].
2008 Nov
Controversies in the antiphospholipid syndrome: can we ever stop warfarin?
2008 Nov 11
Rivaroxaban for thromboprophylaxis.
2008 Nov 13
Rivaroxaban for thromboprophylaxis.
2008 Nov 13
Rivaroxaban for thromboprophylaxis.
2008 Nov 13
Rivaroxaban for thromboprophylaxis.
2008 Nov 13
Thromboprophylaxis with rivaroxaban or enoxaparin did not differ for major bleeding in knee arthroplasty.
2008 Nov-Dec
Orally administered factor xa inhibitor, rivaroxaban: a novel thromboembolic prophylaxis agent.
2008 Oct
[Always more amputations in Germany?].
2008 Oct
More effective, simpler-to-use clot-buster is on the way. Clot-prevention drug could save lives after joint replacement.
2008 Oct
[Prophylaxis of venous thromboembolism].
2008 Oct
Dose-escalation study of the pharmacokinetics and pharmacodynamics of rivaroxaban in healthy elderly subjects.
2008 Oct
Differences in urinary prothrombin fragment 1 + 2 levels after total hip replacement in relation to venous thromboembolism and bleeding events.
2008 Oct
Rivaroxaban--an oral, direct Factor Xa inhibitor--has potential for the management of patients with heparin-induced thrombocytopenia.
2008 Oct
Polyphosphate as a general procoagulant agent.
2008 Oct
New developments in anticoagulation for atrial fibrillation.
2008 Sep
Population pharmacokinetics and pharmacodynamics of once- and twice-daily rivaroxaban for the prevention of venous thromboembolism in patients undergoing total hip replacement.
2008 Sep
Determination of rivaroxaban--a novel, oral, direct Factor Xa inhibitor--in human plasma by high-performance liquid chromatography-tandem mass spectrometry.
2008 Sep 1
A dose-ranging study evaluating once-daily oral administration of the factor Xa inhibitor rivaroxaban in the treatment of patients with acute symptomatic deep vein thrombosis: the Einstein-DVT Dose-Ranging Study.
2008 Sep 15
Comparative pharmacodynamics and pharmacokinetics of oral direct thrombin and factor xa inhibitors in development.
2009
Rivaroxaban: a novel, oral, direct factor Xa inhibitor.
2009 Feb
Patents

Sample Use Guides

15 mg and 20 mg tablets with food; take 10 mg tablets with or without food. For patients with CrCl >50 mL/min 20 mg orally, once daily and for patients with CrCl 15 - 50 mL/min 15 mg orally, once daily with the evening meal.
Route of Administration: Oral
To evaluate the influence of prothrombin complex concentrate (PCC) on the anticoagulant effects of rivaroxaban as measured by prothrombin time (PT) and thrombin generation tests plasma and whole blood samples from healthy volunteers were spiked with Rivaroxaban (up to 800 ug/L) and prothrombin complex concentrate (PCC) was added to these samples in concentration ranges as used clinically to reverse the effects of vitamin K antagonists. Prothrombin complex concentrate does not neutralize the
Substance Class Chemical
Created
by admin
on Fri Jun 25 21:06:40 UTC 2021
Edited
by admin
on Fri Jun 25 21:06:40 UTC 2021
Record UNII
9NDF7JZ4M3
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
RIVAROXABAN
DASH   EMA EPAR   INN   JAN   MART.   MI   ORANGE BOOK   USAN   VANDF   WHO-DD  
INN   USAN  
Official Name English
RIVAROXABAN [EMA EPAR]
Common Name English
JNJ-39039039
Code English
RIVAROXABAN [ORANGE BOOK]
Common Name English
RIVAROXABAN [MI]
Common Name English
RIVAROXABAN [USP-RS]
Common Name English
RIVAROXABAN [INN]
Common Name English
RIVAROXABAN [WHO-DD]
Common Name English
RIVAROXABAN [MART.]
Common Name English
2-THIOPHENECARBOXAMIDE, 5-CHLORO-N-(((5S)-2-OXO-3-(4-(3-OXO-4-MORPHOLINYL)PHENYL)-5-OXAZOLIDINYL)METHYL)-
Systematic Name English
RIVAROXABAN [VANDF]
Common Name English
JNJ39039039
Code English
RIVAROXABAN [JAN]
Common Name English
BAY 59-7939
Code English
RIVAROXABAN [USAN]
Common Name English
RIVAROXABAN [EP MONOGRAPH]
Common Name English
XARELTO
Brand Name English
5-CHLORO-N-(((5S)-2-OXO-3-(4-(3-OXOMORPHOLIN-4-YL)PHENYL)-1,3-OXAZOLIDIN-5-YL)METHYL)THIOPHENE-2-CARBOXAMIDE
Systematic Name English
BAY-59-7939
Code English
Classification Tree Code System Code
EMA ASSESSMENT REPORTS XARELTO (AUTHORIZED: ARTHROPLASTY, REPLACEMENT)
Created by admin on Fri Jun 25 21:06:40 UTC 2021 , Edited by admin on Fri Jun 25 21:06:40 UTC 2021
NCI_THESAURUS C263
Created by admin on Fri Jun 25 21:06:40 UTC 2021 , Edited by admin on Fri Jun 25 21:06:40 UTC 2021
WHO-ATC B01AF01
Created by admin on Fri Jun 25 21:06:40 UTC 2021 , Edited by admin on Fri Jun 25 21:06:40 UTC 2021
NDF-RT N0000175637
Created by admin on Fri Jun 25 21:06:40 UTC 2021 , Edited by admin on Fri Jun 25 21:06:40 UTC 2021
EMA ASSESSMENT REPORTS XARELTO (AUTHORIZED: VENOUS THROMBOEMBOLISM)
Created by admin on Fri Jun 25 21:06:40 UTC 2021 , Edited by admin on Fri Jun 25 21:06:40 UTC 2021
WHO-ATC B01AX06
Created by admin on Fri Jun 25 21:06:40 UTC 2021 , Edited by admin on Fri Jun 25 21:06:40 UTC 2021
WHO-VATC QB01AF01
Created by admin on Fri Jun 25 21:06:40 UTC 2021 , Edited by admin on Fri Jun 25 21:06:40 UTC 2021
LIVERTOX 855
Created by admin on Fri Jun 25 21:06:40 UTC 2021 , Edited by admin on Fri Jun 25 21:06:40 UTC 2021
LOINC 74871-5
Created by admin on Fri Jun 25 21:06:40 UTC 2021 , Edited by admin on Fri Jun 25 21:06:40 UTC 2021
Code System Code Type Description
EPA CompTox
366789-02-8
Created by admin on Fri Jun 25 21:06:40 UTC 2021 , Edited by admin on Fri Jun 25 21:06:40 UTC 2021
PRIMARY
NCI_THESAURUS
C77995
Created by admin on Fri Jun 25 21:06:40 UTC 2021 , Edited by admin on Fri Jun 25 21:06:40 UTC 2021
PRIMARY
DRUG BANK
DB06228
Created by admin on Fri Jun 25 21:06:40 UTC 2021 , Edited by admin on Fri Jun 25 21:06:40 UTC 2021
PRIMARY
MERCK INDEX
M9638
Created by admin on Fri Jun 25 21:06:40 UTC 2021 , Edited by admin on Fri Jun 25 21:06:40 UTC 2021
PRIMARY Merck Index
USP_CATALOG
1604530
Created by admin on Fri Jun 25 21:06:40 UTC 2021 , Edited by admin on Fri Jun 25 21:06:40 UTC 2021
PRIMARY USP-RS
WIKIPEDIA
RIVAROXABAN
Created by admin on Fri Jun 25 21:06:40 UTC 2021 , Edited by admin on Fri Jun 25 21:06:40 UTC 2021
PRIMARY
FDA UNII
9NDF7JZ4M3
Created by admin on Fri Jun 25 21:06:40 UTC 2021 , Edited by admin on Fri Jun 25 21:06:40 UTC 2021
PRIMARY
INN
8428
Created by admin on Fri Jun 25 21:06:40 UTC 2021 , Edited by admin on Fri Jun 25 21:06:40 UTC 2021
PRIMARY
IUPHAR
6388
Created by admin on Fri Jun 25 21:06:40 UTC 2021 , Edited by admin on Fri Jun 25 21:06:40 UTC 2021
PRIMARY
ChEMBL
CHEMBL198362
Created by admin on Fri Jun 25 21:06:40 UTC 2021 , Edited by admin on Fri Jun 25 21:06:40 UTC 2021
PRIMARY
RXCUI
1114195
Created by admin on Fri Jun 25 21:06:40 UTC 2021 , Edited by admin on Fri Jun 25 21:06:40 UTC 2021
PRIMARY RxNorm
CAS
366789-02-8
Created by admin on Fri Jun 25 21:06:40 UTC 2021 , Edited by admin on Fri Jun 25 21:06:40 UTC 2021
PRIMARY
DRUG CENTRAL
4182
Created by admin on Fri Jun 25 21:06:40 UTC 2021 , Edited by admin on Fri Jun 25 21:06:40 UTC 2021
PRIMARY
MESH
C503223
Created by admin on Fri Jun 25 21:06:40 UTC 2021 , Edited by admin on Fri Jun 25 21:06:40 UTC 2021
PRIMARY
PUBCHEM
9875401
Created by admin on Fri Jun 25 21:06:40 UTC 2021 , Edited by admin on Fri Jun 25 21:06:40 UTC 2021
PRIMARY
LACTMED
Rivaroxaban
Created by admin on Fri Jun 25 21:06:40 UTC 2021 , Edited by admin on Fri Jun 25 21:06:40 UTC 2021
PRIMARY
HSDB
8149
Created by admin on Fri Jun 25 21:06:40 UTC 2021 , Edited by admin on Fri Jun 25 21:06:40 UTC 2021
PRIMARY
EVMPD
SUB29263
Created by admin on Fri Jun 25 21:06:40 UTC 2021 , Edited by admin on Fri Jun 25 21:06:40 UTC 2021
PRIMARY
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