Identification

Name
Rivaroxaban
Accession Number
DB06228  (DB08477)
Type
Small Molecule
Groups
Approved
Description

Rivaroxaban is an anticoagulant and the first orally active direct factor Xa inhibitor. Unlike warfarin, routine lab monitoring of INR is not necessary. However there is no antidote available in the event of a major bleed. Only the 10 mg tablet can be taken without regard to food. The 15 mg and 20 mg tablet should be taken with food. FDA approved on July 1, 2011.

Structure
Thumb
Synonyms
Not Available
External IDs
BAY 59-7939 / BAY-59-7939 / JNJ-39039039 / JNJ39039039
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
XareltoTablet, film coated15 mgOralBayer Ag2008-09-30Not applicableEu
XareltoTablet, film coated10 mgOralBayer Ag2008-09-30Not applicableEu
XareltoTablet, film coated15 mg/1OralAvera McKennan Hospital2015-03-16Not applicableUs50458 0578 30 nlmimage10 444d2239
XareltoTablet, film coated2.5 mgOralBayer Ag2008-09-30Not applicableEu
XareltoTablet, film coated15 mgOralBayer Ag2008-09-30Not applicableEu
XareltoTablet10 mgOralBayer2008-09-16Not applicableCanada
XareltoTablet, film coated20 mgOralBayer Ag2008-09-30Not applicableEu
XareltoTablet, film coated20 mgOralBayer Ag2008-09-30Not applicableEu
XareltoTablet, film coated10 mgOralBayer Ag2008-09-30Not applicableEu
XareltoTablet, film coated10 mgOralBayer Ag2008-09-30Not applicableEu
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
XareltoRivaroxaban (15 mg/1) + Rivaroxaban (20 mg/1)KitJanssen Pharmaceuticals, Inc.2014-09-16Not applicableUs
XareltoRivaroxaban (15 mg) + Rivaroxaban (20 mg)Kit; TabletOralBayer2015-11-02Not applicableCanada
XareltoRivaroxaban (15 mg/1) + Rivaroxaban (20 mg/1)KitJanssen Pharmaceuticals, Inc.2014-09-16Not applicableUs
XareltoRivaroxaban (15 mg) + Rivaroxaban (20 mg)Kit; TabletOralBayer2015-11-02Not applicableCanada
Categories
UNII
9NDF7JZ4M3
CAS number
366789-02-8
Weight
Average: 435.881
Monoisotopic: 435.065569098
Chemical Formula
C19H18ClN3O5S
InChI Key
KGFYHTZWPPHNLQ-AWEZNQCLSA-N
InChI
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
IUPAC Name
5-chloro-N-{[(5S)-2-oxo-3-[4-(3-oxomorpholin-4-yl)phenyl]-1,3-oxazolidin-5-yl]methyl}thiophene-2-carboxamide
SMILES
ClC1=CC=C(S1)C(=O)NC[C@H]1CN(C(=O)O1)C1=CC=C(C=C1)N1CCOCC1=O

Pharmacology

Indication

Rivaroxaban is indicated for the prevention of venous thromboembolic events (VTE) in patients who have undergone total hips replacements and total knee replacement surgery; prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation; treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE); to reduce risk of recurrent DVT and/or PE. Due to a lack of safety studies, it is not recommended for use in those under 18 years old. Its use is also not recommended in those with severe renal impairment (<30mL/min).

Associated Conditions
Pharmacodynamics

Rivaroxaban is an anticoagulant which binds directly to factor Xa. Thereafter, it effectively blocks the amplification of the coagulation cascade, preventing the formation of thrombus. Rivaroxaban is a unqiue anticoagulant for two reasons. First of all, it is does not involve antithrombin III (ATIII) to exert its anticoagulant effects. Secondly, it is an oral agent whereas the widely used unfractionated heparin and low molecular weight heparins are for parenteral use only. Although the activated partial thromboplastin time (aPTT) and HepTest (a test developed to assay low molecular weight heparins) are prolonged in a dose-dependant manner, neither test is recommended for the assessment of the pharmacodynamic effects of rivaroxaban. Anti-Xa activity and inhibition of anti-Xa activity monitoring is also not recommended despite being influenced by rivaroxaban.

Mechanism of action

Rivaroxaban competitively inhibits free and clot bound factor Xa. Factor Xa is needed to activate prothrombin (factor II) to thrombin (factor IIa). Thrombin is a serine protease that is required to activate fibrinogen to fibrin, which is the loose meshwork that completes the clotting process. Since one molecule of factor Xa can generate more than 1000 molecules of thrombin, selective inhibitors of factor Xa are profoundly useful in terminating the amplification of thrombin generation. The action of rivaroxaban is irreversible.

TargetActionsOrganism
ACoagulation factor X
antagonist
Human
Absorption

Following oral administration, rivaroxaban is rapidly absorbed and reaches peak plasma concentration in 2-4 hours. Bioavailability of the 10 mg dose is >80%. However, the 15-20 mg dose have a lower bioavailability if taken in the fasted state and consequently should be taken with food.

Volume of distribution

The steady state Vd is 50 L

Protein binding

Plasma protein binding is about 92% to 95%

Metabolism

Approximately two-thirds of the dose is metabolized. It is metabolized by CYP3A4, CYP3A5, CYP2J2 and CYP-independant mechanisms

Route of elimination

Approximately two-thirds of rivaroxaban is excreted into urine (via active tubular secretion in which approximately 36% as unchanged drug and 30% as inactive metabolism). The remaining third of the administered dose is excreted via feces in which 7% is in the form of unchanged drug and 21% as inactive metabolites.

Half life

The terminal half life is 5-9 hours in adults and 11-13 hours in the elderly.

Clearance

Systemic clearance is approximately 10 L/h, so rivaroxaban is considered a drug with low clearance. Renal clearance is ~3-4 L/h.

Toxicity

Excessive bleeding. Overdosages should be treated using activated charcoal and supportive measures such as mechanical compression and hemodynamic support. If bleeding is not controlled, the following procoagulants can be administered: activated prothrombin complex concentrate, prothrombin complex concentrate and recombinant factor VIIa. There is also a higher chance of post procedural hemorrhage compared to enoxaparin (1.55% vs. 1.39% respectively).

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(4R)-limonene(4R)-limonene may increase the anticoagulant activities of Rivaroxaban.
AbacavirThe serum concentration of Abacavir can be decreased when it is combined with Rivaroxaban.
AbciximabAbciximab may increase the anticoagulant activities of Rivaroxaban.
AceclofenacAceclofenac may increase the anticoagulant activities of Rivaroxaban.
AcemetacinThe risk or severity of bleeding can be increased when Rivaroxaban is combined with Acemetacin.
AcenocoumarolAcenocoumarol may increase the anticoagulant activities of Rivaroxaban.
AcetaminophenThe serum concentration of Rivaroxaban can be increased when it is combined with Acetaminophen.
Acetyl sulfisoxazoleThe metabolism of Rivaroxaban can be decreased when combined with Acetyl sulfisoxazole.
Acetylsalicylic acidAcetylsalicylic acid may increase the anticoagulant activities of Rivaroxaban.
AlclofenacAlclofenac may increase the anticoagulant activities of Rivaroxaban.
Food Interactions
  • Food should be taken with the 15 mg and 20 mg tablet. Food increases the bioavailability of the 20 mg dose.
  • Foods with antiplatelet/anticoagulants properties such as horseradish, gingko, ginger, garlic, feverfew
  • St. John's Wort is a CYP3A4 inducer and will decrease levels of rivaroxaban

References

Synthesis Reference

Prabhudas BODHURI, Gamini Weeratunga, "PROCESSES FOR THE PREPARATION OF RIVAROXABAN AND INTERMEDIATES THEREOF." U.S. Patent US20100273790, issued October 28, 2010.

US20100273790
General References
  1. Piccini JP, Patel MR, Mahaffey KW, Fox KA, Califf RM: Rivaroxaban, an oral direct factor Xa inhibitor. Expert Opin Investig Drugs. 2008 Jun;17(6):925-37. doi: 10.1517/13543784.17.6.925 . [PubMed:18491993]
  2. Alban S: Pharmacological strategies for inhibition of thrombin activity. Curr Pharm Des. 2008;14(12):1152-75. [PubMed:18473863]
  3. Stevenson M, Scope A, Holmes M, Rees A, Kaltenthaler E: Rivaroxaban for the prevention of venous thromboembolism: a single technology appraisal. Health Technol Assess. 2009 Oct;13 Suppl 3:43-8. doi: 10.3310/hta13suppl3/07. [PubMed:19846028]
  4. Imberti D, Dall'Asta C, Pierfranceschi MG: Oral factor Xa inhibitors for thromboprophylaxis in major orthopedic surgery: a review. Intern Emerg Med. 2009 Dec;4(6):471-7. doi: 10.1007/s11739-009-0293-9. [PubMed:19696978]
  5. Alexander D, Jeremias A: Rivaroxaban in the contemporary treatment of acute coronary syndromes. Expert Opin Investig Drugs. 2011 Jun;20(6):849-57. doi: 10.1517/13543784.2011.580274. Epub 2011 May 10. [PubMed:21554163]
  6. Cabral KP: Pharmacology of the new target-specific oral anticoagulants. J Thromb Thrombolysis. 2013 Aug;36(2):133-40. doi: 10.1007/s11239-013-0929-5. [PubMed:23645472]
External Links
KEGG Drug
D07086
PubChem Compound
9875401
PubChem Substance
175427064
ChemSpider
8051086
BindingDB
7840
ChEBI
68579
ChEMBL
CHEMBL198362
HET
RIV
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Rivaroxaban
ATC Codes
B01AF01 — Rivaroxaban
AHFS Codes
  • 20:12.04.92 — Miscellaneous Anticoagulants
PDB Entries
2w26 / 5vof
FDA label
Download (537 KB)
MSDS
Download (480 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableHealthy Volunteers1
1CompletedNot AvailablePediatrics / Thrombosis, Venous1
1CompletedNot AvailablePharmacokinetics1
1CompletedNot AvailableTherapeutic Equivalency1
1CompletedNot AvailableThrombosis, Venous1
1CompletedOtherBiological Availability1
1CompletedOtherHealthy Volunteers1
1CompletedOtherThrombosis1
1CompletedPreventionProphylaxis of Venous Thromboembolic Events2
1CompletedTreatmentBioavailability / Healthy Participants / Pharmacokinetics1
1CompletedTreatmentEmbolism, Atrial Fibrillation and Venous Thrombosis2
1CompletedTreatmentEnd-Stage Renal Disease (ESRD)1
1CompletedTreatmentHaemorrhage1
1CompletedTreatmentHealthy Volunteers3
1CompletedTreatmentHealthy Volunteers / Impaired Renal Function1
1CompletedTreatmentThrombosis1
1TerminatedTreatmentGastric Bypass Status1
1, 2Active Not RecruitingPreventionNeoplasms1
1, 2CompletedOtherThromboembolism1
2CompletedPreventionCardiovascular Disease, Coronary Artery Disease1
2CompletedPreventionNonvalvular Atrial Fibrillation3
2CompletedPreventionPrevention / Thromboembolism1
2CompletedPreventionProphylaxis of Venous Thromboembolic Events1
2CompletedPreventionVenous Thromboembolism (VTE)4
2CompletedTreatmentAcute Coronary Syndromes (ACS)2
2CompletedTreatmentDeep Vein Thrombosis (DVT) / Thrombosis, Venous2
2CompletedTreatmentHealthy Volunteers1
2CompletedTreatmentStroke, Ischemic / Transient Ischaemic Attack (TIA)1
2CompletedTreatmentThrombosis, Venous1
2CompletedTreatmentVenous Thromboembolism (VTE)2
2Enrolling by InvitationTreatmentSickle Cell Disorders / Sickle Cell-Beta0-Thalassemia / Sickle Cell-beta^0^-Thalassemia1
2Not Yet RecruitingTreatmentCerebral Venous Thrombosis1
2RecruitingPreventionPost-gastrointestinal bypass surgery1
2RecruitingTreatmentCancer-associated Thrombosis / Duodenal Cancer / Esophageal Cancers / Hepatobiliary Cancers / Malignant Neoplasm of Pancreas / Malignant Neoplasm of Stomach1
2RecruitingTreatmentHaemorrhage1
2RecruitingTreatmentValvular Heart Disease1
2TerminatedTreatmentAnticoagulants / Aortic Valve Disorder / Heart Valve Prosthesis Implantation1
2Unknown StatusPreventionHaemorrhage / Venous Thromboembolism (VTE)1
2, 3Not Yet RecruitingTreatmentMultiple Myeloma in Relapse / Multiple Myeloma Progression / Multiple Myeloma Stage I / Multiple Myeloma Stage II / Multiple Myeloma Stage III / Multiple Myeloma With Failed Remission1
2, 3RecruitingTreatmentAnticoagulants and Bleeding Disorders / Prostheses and Implants / Strokes / Valve Heart Disease1
2, 3RecruitingTreatmentMenstruation / Venous Thromboembolism (VTE)1
2, 3Unknown StatusTreatmentStroke, Ischemic / Transient Ischaemic Attack (TIA)1
3Active Not RecruitingPreventionCancers / Neoplasms1
3Active Not RecruitingPreventionPeripheral Artery Disease (PAD)1
3Active Not RecruitingPreventionPrevention & Control1
3Active Not RecruitingPreventionTranscatheter Aortic Valve Replacement1
3Active Not RecruitingTreatmentChronic Portal Vein Thrombosis / Deep Vein Thrombosis (DVT)1
3Active Not RecruitingTreatmentType 2 Diabetic Patients1
3CompletedPreventionArthritis / Knee Osteoarthritis (Knee OA) / Osteoarthritis, Hip / Thromboembolism1
3CompletedPreventionHeart Failure, Unspecified / Infectious Diseases / Respiratory Insufficiency / Rheumatic Diseases / Stroke, Acute1
3CompletedPreventionNonvalvular Atrial Fibrillation2
3CompletedPreventionNonvalvular Atrial Fibrillation / Strokes / Systemic Embolism1
3CompletedPreventionPrevention / Venous Thromboembolism (VTE)1
3CompletedPreventionPulmonary Embolism (PE) / Thromboembolism / Thrombosis / Thrombosis, Venous / Venous Thromboembolism (VTE)1
3CompletedPreventionVenous Thromboembolism (VTE)7
3CompletedTreatmentAcute Coronary Syndromes (ACS) / Myocardial Infarction / Myocardial Ischemia / Unstable Angina (UA)1
3CompletedTreatmentAntiphospholipid Syndrome1
3CompletedTreatmentCoronary Artery Disease / Heart Failure, Unspecified1
3CompletedTreatmentDeep Vein Thrombosis (DVT)1
3CompletedTreatmentHematoma1
3CompletedTreatmentNeoplasms / Venous Thromboembolism (VTE)1
3CompletedTreatmentNonvalvular Atrial Fibrillation2
3CompletedTreatmentNonvalvular Atrial Fibrillation / Percutaneous Coronary Intervention1
3CompletedTreatmentPrevention / Venous Thromboembolism (VTE)1
3CompletedTreatmentPulmonary Embolism (PE)2
3CompletedTreatmentSuperficial Vein Thrombosis1
3CompletedTreatmentThrombosis, Venous1
3CompletedTreatmentVenous Thromboembolism (VTE)1
3Not Yet RecruitingPreventionAcute Coronary Syndromes (ACS) / Nonvalvular Atrial Fibrillation1
3Not Yet RecruitingPreventionCancers / Central Venous Catheter Thrombosis / Upper Extremity Deep Vein Thrombosis1
3Not Yet RecruitingPreventionRheumatic Heart Disease1
3Not Yet RecruitingTreatmentCoronary Artery Disease / Saphenous Vein Graft Patency1
3Not Yet RecruitingTreatmentNonvalvular Atrial Fibrillation1
3Not Yet RecruitingTreatmentVenous Thromboembolism (VTE)1
3RecruitingDiagnosticAortic Valve Stenosis / Cardiovascular Disease (CVD) / Heart Valve Diseases / Thrombosis / Ventricular Outflow Obstruction1
3RecruitingPreventionAtrial Flutter / Intracranial Hemorrhage, Hypertensive / Intracranial Hemorrhages / Intraventricular Hemorrhage / Microhaemorrhage / Nonvalvular Atrial Fibrillation / Small Vessel Cerebrovascular Disease / Subarachnoid Hemorrhage / Subdural haematoma1
3RecruitingPreventionNonvalvular Atrial Fibrillation1
3RecruitingPreventionPrevention of Venous Thromboembolism1
3RecruitingPreventionRadial Artery Occlusion1
3RecruitingPreventionRheumatic Heart Disease1
3RecruitingPreventionThrombosis1
3RecruitingTreatmentCancers / Venous Thromboembolism (VTE)1
3RecruitingTreatmentDeep Vein Thrombosis (DVT)1
3RecruitingTreatmentDeep Venous Thrombosis1
3RecruitingTreatmentImpaired Renal Function1
3RecruitingTreatmentLiver Cirrhosis1
3RecruitingTreatmentMesenteric Vein Thrombosis / Portal Vein Thrombosis / Splenic Vein Thrombosis1
3RecruitingTreatmentPortal Vein Thrombosis1
3RecruitingTreatmentVenous Thromboembolism (VTE)1
3SuspendedTreatmentSymptomatic Superficial Vein Thrombosis1
3TerminatedPreventionNon-major Orthopaedic Surgery1
3TerminatedPreventionStrokes1
3TerminatedTreatmentAntiphospholipid Syndrome1
3TerminatedTreatmentCardiac surgery, heparin-induced thrombocytopenia and thrombosis syndrome1
4Active Not RecruitingBasic ScienceAtrial Fibrillation or Pulmonary Embolism / Existent Coronary or Valvular Calcification, or Both and Agatston Score > 50 in at Least One Location / Need of Long Term Oral Anticoagulation Therapy (OAT)1
4CompletedBasic ScienceAcute Coronary Syndromes (ACS) / Nonvalvular Atrial Fibrillation1
4CompletedBasic ScienceVenous Thromboembolism (VTE)1
4CompletedOtherAntiphospholipid Antibody Syndrome1
4CompletedPreventionAtherosclerosis1
4CompletedPreventionFemur Head Necrosis / Fracture of Neck of Femur / Osteoarthritis, Hip1
4CompletedPreventionKnee Osteoarthritis (Knee OA)1
4CompletedPreventionNonvalvular Atrial Fibrillation1
4CompletedTreatmentCancer-associated Thrombosis / Haemorrhage / Recurrences / Rivaroxaban1
4CompletedTreatmentCentral Venous Catheter Thrombosis / Neoplasms1
4CompletedTreatmentChronic Renal Failure (CRF)1
4CompletedTreatmentHaemorrhage / Nonvalvular Atrial Fibrillation / Strokes / Thrombo-embolism1
4CompletedTreatmentPulmonary Embolism (PE)1
4CompletedTreatmentVenous Thromboembolism (VTE)1
4Not Yet RecruitingPreventionKnee Osteoarthritis (Knee OA)2
4Not Yet RecruitingPreventionNonvalvular Atrial Fibrillation / Strokes1
4Not Yet RecruitingTreatmentAcute Heart Failure (AHF)1
4RecruitingOtherSpinal Cord Injuries (SCI) / Thromboembolism1
4RecruitingPreventionAortic Valve Insufficiency / Aortic Valve Stenosis / Thrombosis1
4RecruitingPreventionCalcifications, Vascular1
4RecruitingPreventionNonvalvular Atrial Fibrillation2
4RecruitingPreventionNonvalvular Atrial Fibrillation / Strokes1
4RecruitingSupportive CarePulmonary Embolism (PE) / Thrombosis, Venous1
4RecruitingTreatmentAcute Coronary Syndromes (ACS) / Myocardial Infarction / Myocardial Ischemia / Unstable Angina (UA)1
4RecruitingTreatmentAnticoagulating Treatment on a Duration at Least 12-month-old Superior / Anticoagulation Treatment at Least > or = to 12-month / Permanent Atrial Fibrillation / Pulmonary Embolism (PE) / Thrombosis, Venous1
4RecruitingTreatmentDeep Vein Thrombosis (DVT) / Post Thrombotic Syndrome1
4RecruitingTreatmentDeep Vein Thrombosis (DVT) / Pulmonary Embolism (PE)1
4RecruitingTreatmentDiabetes Mellitus (DM)1
4RecruitingTreatmentNonvalvular Atrial Fibrillation3
4RecruitingTreatmentVenous Thromboembolism (VTE)1
4TerminatedTreatmentPulmonary Embolism (PE) / Thrombosis, Venous1
4Unknown StatusNot AvailableAnticoagulant Overdosage / Anticoagulant-induced Bleeding / Hemorrhage / Thrombosis1
4Unknown StatusTreatmentNonvalvular Atrial Fibrillation1
4WithdrawnTreatmentComplications; Arthroplasty1
4WithdrawnTreatmentCoronary Heart Disease (CHD) / Non ST Segment Elevation Myocardial Infarction (NSTEMI) / ST Elevation Myocardial Infarction (STEMI) / Stable Angina (SA) / Unstable Angina (UA)1
Not AvailableActive Not RecruitingNot AvailableAcute Coronary Syndromes (ACS) / Nonvalvular Atrial Fibrillation / Pulmonary Embolism (PE) / Thrombosis, Venous1
Not AvailableActive Not RecruitingNot AvailableAll-cause Mortality / Major Bleeding / Myocardial Infarction / Nonvalvular Atrial Fibrillation / Stroke, Ischemic / Systemic Embolization1
Not AvailableActive Not RecruitingNot AvailableAnticoagulation1
Not AvailableActive Not RecruitingNot AvailableIschemia, Brain1
Not AvailableActive Not RecruitingNot AvailableNonvalvular Atrial Fibrillation6
Not AvailableActive Not RecruitingNot AvailableVenous Thrombosis and Pulmonary Embolism1
Not AvailableActive Not RecruitingSupportive CareNon-valvular Atrial Fibrillation (NVAF)1
Not AvailableCompletedNot AvailableAll-cause Mortality / Major Bleeding / Myocardial Infarction / Nonvalvular Atrial Fibrillation / Stroke, Ischemic / Systemic Embolization1
Not AvailableCompletedNot AvailableArthroplasty, Replacement, Hip / Arthroplasty, Replacement, Knee1
Not AvailableCompletedNot AvailableAtrial Fibrillation (Prevention of Stroke)1
Not AvailableCompletedNot AvailableBlood Clots1
Not AvailableCompletedNot AvailableDeep Vein Thrombosis (DVT) and / or Pulmonary Embolism (PE) / Venous Thromboembolism (VTE)1
Not AvailableCompletedNot AvailableDeep Vein Thrombosis (DVT) / Thrombosis, Venous1
Not AvailableCompletedNot AvailableIschemia, Brain1
Not AvailableCompletedNot AvailableMajor Bleeding / Venous Thromboembolism (VTE)1
Not AvailableCompletedNot AvailableNonvalvular Atrial Fibrillation18
Not AvailableCompletedNot AvailableStroke, Ischemic1
Not AvailableCompletedNot AvailableStrokes1
Not AvailableCompletedNot AvailableThrombosis, Venous2
Not AvailableCompletedNot AvailableUnsuspected Pulmonary Embolism1
Not AvailableCompletedNot AvailableVenous Thromboembolism (VTE)3
Not AvailableCompletedTreatmentPortal Vein Thrombosis1
Not AvailableEnrolling by InvitationTreatmentAcute DVT of Lower Extremity1
Not AvailableNo Longer AvailableNot AvailableProsthesis; Cardiac, Heart, Functional Disturbance as Result / Thromboembolism1
Not AvailableNot Yet RecruitingTreatmentAcute Exacerbation Copd / Venous Thromboembolism (VTE)1
Not AvailableRecruitingNot AvailableAcute Coronary Syndromes (ACS) / Nonvalvular Atrial Fibrillation / Pulmonary Embolism (PE) / Thrombosis, Venous3
Not AvailableRecruitingNot AvailableAnticoagulants and Bleeding Disorders / Venous Thromboembolism (VTE)1
Not AvailableRecruitingNot AvailableHeart Failure, Unspecified1
Not AvailableRecruitingNot AvailableNonvalvular Atrial Fibrillation2
Not AvailableRecruitingNot AvailablePulmonary Embolism (PE)1
Not AvailableRecruitingNot AvailableStrokes1
Not AvailableRecruitingNot AvailableVenous Thromboembolism (VTE)1
Not AvailableRecruitingHealth Services ResearchNeoplasms / Thrombosis, Venous1
Not AvailableRecruitingPreventionNonvalvular Atrial Fibrillation / Strokes1
Not AvailableRecruitingSupportive CareHemorrhage / Nonvalvular Atrial Fibrillation / Periodontal Diseases1
Not AvailableRecruitingTreatmentBlood Clots / Cancers / Deep Vein Thrombosis (DVT) / Pulmonary Embolism (PE) / Venous Thromboembolism (VTE)1
Not AvailableRecruitingTreatmentDeep Venous Thrombosis1
Not AvailableUnknown StatusSupportive CareBlood Loss / Osteoarthritis, Hip1
Not AvailableUnknown StatusTreatmentIleofemoral Deep Vein Thrombosis1
Not AvailableWithdrawnNot AvailableKnee Replacement Surgery / Prophylaxis of Venous Thromboembolic Events / Total Hip Replacement1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Kit
Kit; tabletOral
TabletOral10 mg
TabletOral15 mg
TabletOral20 mg
Tablet, film coatedOral10 mg/1
Tablet, film coatedOral10 mg
Tablet, film coatedOral15 mg/1
Tablet, film coatedOral15 mg
Tablet, film coatedOral2.5 mg
Tablet, film coatedOral20 mg
Tablet, film coatedOral20 mg/1
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA2396561No2008-10-142020-12-11Canada
CA2547113No2012-01-242024-11-13Canada
US7157456No2001-02-082021-02-08Us
US7585860No2000-12-112020-12-11Us
US7592339No2000-12-112020-12-11Us
US9539218No2014-02-172034-02-17Us
US9415053No2004-11-132024-11-13Us

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.01 mg/mLALOGPS
logP1.74ALOGPS
logP1.9ChemAxon
logS-4.6ALOGPS
pKa (Strongest Acidic)13.6ChemAxon
pKa (Strongest Basic)-1.6ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area88.18 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity104.74 m3·mol-1ChemAxon
Polarizability43.41 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9966
Blood Brain Barrier+0.9462
Caco-2 permeable+0.6822
P-glycoprotein substrateNon-substrate0.5691
P-glycoprotein inhibitor IInhibitor0.6325
P-glycoprotein inhibitor IIInhibitor0.5601
Renal organic cation transporterNon-inhibitor0.7562
CYP450 2C9 substrateNon-substrate0.7866
CYP450 2D6 substrateNon-substrate0.8761
CYP450 3A4 substrateSubstrate0.5964
CYP450 1A2 substrateNon-inhibitor0.6469
CYP450 2C9 inhibitorNon-inhibitor0.7035
CYP450 2D6 inhibitorNon-inhibitor0.7516
CYP450 2C19 inhibitorInhibitor0.6475
CYP450 3A4 inhibitorNon-inhibitor0.6667
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.7463
Ames testNon AMES toxic0.6162
CarcinogenicityNon-carcinogens0.8838
BiodegradationNot ready biodegradable0.9844
Rat acute toxicity2.4353 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8938
hERG inhibition (predictor II)Inhibitor0.6205
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as phenylmorpholines. These are aromatic compounds containing a morpholine ring and a benzene ring linked to each other through a CC or a CN bond.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Oxazinanes
Sub Class
Morpholines
Direct Parent
Phenylmorpholines
Alternative Parents
Thiophene carboxamides / 2-heteroaryl carboxamides / 2,5-disubstituted thiophenes / Oxazolidinones / Aryl chlorides / Benzene and substituted derivatives / Tertiary carboxylic acid amides / Carbamate esters / Heteroaromatic compounds / Secondary carboxylic acid amides
show 11 more
Substituents
Phenylmorpholine / 2-heteroaryl carboxamide / Thiophene carboxamide / Thiophene carboxylic acid or derivatives / 2,5-disubstituted thiophene / Aryl chloride / Aryl halide / Monocyclic benzene moiety / Oxazolidinone / Benzenoid
show 25 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
monocarboxylic acid amide, organochlorine compound, thiophenes, lactam, aromatic amide, morpholines, oxazolidinone (CHEBI:68579)

Targets

Details
1. Coagulation factor X
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Serine-type endopeptidase activity
Specific Function
Factor Xa is a vitamin K-dependent glycoprotein that converts prothrombin to thrombin in the presence of factor Va, calcium and phospholipid during blood clotting.
Gene Name
F10
Uniprot ID
P00742
Uniprot Name
Coagulation factor X
Molecular Weight
54731.255 Da
References
  1. Melillo SN, Scanlon JV, Exter BP, Steinberg M, Jarvis CI: Rivaroxaban for thromboprophylaxis in patients undergoing major orthopedic surgery. Ann Pharmacother. 2010 Jun;44(6):1061-71. doi: 10.1345/aph.1M681. Epub 2010 Apr 27. [PubMed:20424181]
  2. Ufer M: Comparative efficacy and safety of the novel oral anticoagulants dabigatran, rivaroxaban and apixaban in preclinical and clinical development. Thromb Haemost. 2010 Mar;103(3):572-85. doi: 10.1160/TH09-09-0659. Epub 2010 Feb 2. [PubMed:20135071]
  3. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Mismetti P, Laporte S: [Rivaroxaban: clinical pharmacology]. Ann Fr Anesth Reanim. 2008 Dec;27 Suppl 3:S16-21. doi: 10.1016/S0750-7658(08)75142-6. [PubMed:19185782]
  2. Ufer M: Comparative efficacy and safety of the novel oral anticoagulants dabigatran, rivaroxaban and apixaban in preclinical and clinical development. Thromb Haemost. 2010 Mar;103(3):572-85. doi: 10.1160/TH09-09-0659. Epub 2010 Feb 2. [PubMed:20135071]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
This enzyme metabolizes arachidonic acid predominantly via a NADPH-dependent olefin epoxidation to all four regioisomeric cis-epoxyeicosatrienoic acids. One of the predominant enzymes responsible f...
Gene Name
CYP2J2
Uniprot ID
P51589
Uniprot Name
Cytochrome P450 2J2
Molecular Weight
57610.165 Da
References
  1. Ufer M: Comparative efficacy and safety of the novel oral anticoagulants dabigatran, rivaroxaban and apixaban in preclinical and clinical development. Thromb Haemost. 2010 Mar;103(3):572-85. doi: 10.1160/TH09-09-0659. Epub 2010 Feb 2. [PubMed:20135071]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. Cabral KP: Pharmacology of the new target-specific oral anticoagulants. J Thromb Thrombolysis. 2013 Aug;36(2):133-40. doi: 10.1007/s11239-013-0929-5. [PubMed:23645472]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Walenga JM, Adiguzel C: Drug and dietary interactions of the new and emerging oral anticoagulants. Int J Clin Pract. 2010 Jun;64(7):956-67. doi: 10.1111/j.1742-1241.2009.02286.x. [PubMed:20584229]
  2. Chen T, Lam S: Rivaroxaban: an oral direct factor Xa inhibitor for the prevention of thromboembolism. Cardiol Rev. 2009 Jul-Aug;17(4):192-7. doi: 10.1097/CRD.0b013e3181aa2154. [PubMed:19525681]

Drug created on March 19, 2008 10:18 / Updated on September 22, 2018 22:34