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{{Short description|Anticoagulant medication}}
{{drugbox
{{Use dmy dates|date=March 2022}}
| IUPAC_name = ''N'''-(5-chloropyridin-2-yl)-''N''-thiazolopyridine-2-carbonyl)amino]cyclohexyl]oxamide
{{Drugbox
| image = Edoxaban_skeletal.svg
| Verifiedfields = changed
| width = 200
| Watchedfields = changed
| CAS_number = 912273-65-5
| verifiedrevid = 415900881
| ATC_prefix = none
| image = Edoxaban.svg
| ATC_suffix =
| width = 275
| PubChem = 25022378
| DrugBank = | alt =
| C = 24 | H = 30 | Cl = 1 | N = 7 | O = 4 | S = 1 | caption =

| molecular_weight = 548.056 g/mol
<!-- Clinical data -->
| smiles =
| bioavailability = | pronounce =
| tradename = Savaysa, Lixiana, Roteas, others
| protein_bound =
| Drugs.com = {{drugs.com|monograph|edoxaban-tosylate}}
| metabolism =
| MedlinePlus = a614055
| elimination_half-life =
| DailyMedID = Edoxaban
| excretion =
| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X --> | pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
| pregnancy_AU_comment =
| pregnancy_US = <!-- A / B / C / D / X -->
| pregnancy_category= | pregnancy_category =
| routes_of_administration = ]
| legal_AU = <!-- Unscheduled / S2 / S3 / S4 / S5 / S6 / S7 / S8 / S9 -->
| class =
| legal_CA = <!-- / Schedule I, II, III, IV, V, VI, VII, VIII -->
| ATC_prefix = B01
| legal_UK = <!-- GSL / P / POM / CD / Class A, B, C -->
| ATC_suffix = AF03
| legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V -->

| legal_status =
<!-- Legal status -->
| routes_of_administration =
| legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled -->
| legal_AU_comment =
| legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F -->
| legal_BR_comment =
| legal_CA = Rx-only
| legal_CA_comment = <ref>{{cite web | title=Product monograph brand safety updates | website=Health Canada | date=February 2024 | url=https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/drug-product-database/label-safety-assessment-update/product-monograph-brand-safety-updates.html | access-date=24 March 2024}}</ref><ref>{{cite web | title=Health Canada New Drug Authorizations: 2016 Highlights | website=] | date=14 March 2017 | url=https://www.canada.ca/en/health-canada/services/publications/drugs-health-products/health-canada-new-drug-authorizations-2016-highlights.html | access-date=7 April 2024}}</ref>
| legal_DE = <!-- Anlage I, II, III or Unscheduled -->
| legal_DE_comment =
| legal_NZ = <!-- Class A, B, C -->
| legal_NZ_comment =
| legal_UK = <!-- GSL, P, POM, CD, CD Lic, CD POM, CD No Reg POM, CD (Benz) POM, CD (Anab) POM or CD Inv POM / Class A, B, C -->
| legal_UK_comment =
| legal_US = Rx-only
| legal_US_comment = <ref name="Savaysa FDA label" />
| legal_EU = Rx-only
| legal_EU_comment = <ref name="Lixiana EPAR" /><ref name="Roteas EPAR">{{cite web | title=Roteas EPAR | website=] (EMA) | date=4 May 2017 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/roteas | access-date=25 September 2020}}</ref>
| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV -->
| legal_UN_comment =
| legal_status = Rx-only

<!-- Pharmacokinetic data -->
| bioavailability = 62%; T<sub>max</sub> 1–2 hours<ref name=a/>
| protein_bound = 55%<ref name=a/>
| metabolism = minimal ], ]/], hydrolysis, ]<ref name=a/>
| elimination_half-life = 10–14 hours<ref name=a/>
| excretion = 62% ], 35% ]

<!-- Identifiers -->
| CAS_number_Ref = {{cascite|changed|??}}
| CAS_number = 480449-70-5
| PubChem = 10280735
| IUPHAR_ligand = 7575
| DrugBank_Ref = {{drugbankcite|changed|drugbank}}
| DrugBank = DB09075
| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
| ChemSpiderID = 8456212
| UNII_Ref = {{fdacite|changed|FDA}}
| UNII = NDU3J18APO
| KEGG_Ref = {{keggcite|changed|kegg}}
| KEGG = D09710
| ChEBI_Ref = {{ebicite|changed|EBI}}
| ChEBI = 85973
| ChEMBL_Ref =
| ChEMBL =
| NIAID_ChemDB =
| PDB_ligand =
| synonyms = DU-176b

<!-- Chemical and physical data -->
| IUPAC_name = ''N'''-(5-chloropyridin-2-yl)-''N''-thiazolopyridine-2-carbonyl)amino]cyclohexyl]oxamide
| C=24 | H=30 | Cl=1 | N=7 | O=4 | S=1
| smiles = CN1CCC2=C(C1)SC(=N2)C(=O)N3C(CC3NC(=O)C(=O)NC4=NC=C(C=C4)Cl)C(=O)N(C)C
| StdInChI_Ref = {{stdinchicite|changed|chemspider}}
| StdInChI = 1S/C24H30ClN7O4S/c1-31(2)24(36)13-4-6-15(27-20(33)21(34)30-19-7-5-14(25)11-26-19)17(10-13)28-22(35)23-29-16-8-9-32(3)12-18(16)37-23/h5,7,11,13,15,17H,4,6,8-10,12H2,1-3H3,(H,27,33)(H,28,35)(H,26,30,34)/t13-,15-,17+/m0/s1
| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}
| StdInChIKey = HGVDHZBSSITLCT-JLJPHGGASA-N
}} }}
'''Edoxaban''' (], codenamed '''DU-176b''') is an ] drug which acts as a ]. It is being developed by ]. In animal studies, edoxaban is potent, selective for factor Xa and has good oral bioavailability,<ref name="pmid18624979">{{cite journal |author=Furugohri T, Isobe K, Honda Y, Kamisato-Matsumoto C, Sugiyama N, Nagahara T, Morishima Y, Shibano T |title=DU-176b, a potent and orally active factor Xa inhibitor: in vitro and in vivo pharmacological profiles |journal=Journal of Thrombosis and Haemostasis : JTH |volume=6 |issue=9 |pages=1542–9 |year=2008 |month=September |pmid=18624979 |doi=10.1111/j.1538-7836.2008.03064.x |url=}}</ref> but it has not been approved for use in humans.<ref name="pmid19739042">{{cite journal |author=Sobieraj-Teague M, O'Donnell M, Eikelboom J |title=New anticoagulants for atrial fibrillation |journal=Seminars in Thrombosis and Hemostasis |volume=35 |issue=5 |pages=515–24 |year=2009 |month=July |pmid=19739042 |doi=10.1055/s-0029-1234147 |url=}}</ref>


<!-- Definition and medical uses -->
Several Phase II ]s have been conducted, for example for ] after ]<ref>{{pmid|20589317}}</ref> (phase III early results compare well to ]<ref name=Dec2010>{{cite web |url=http://www.genengnews.com/gen-news-highlights/phase-iii-trial-finds-edoxaban-outclasses-enoxaparin-in-preventing-venous-thromboembolic-events/81244351/ |title=Phase III Trial Finds Edoxaban Outclasses Enoxaparin in Preventing Venous Thromboembolic Events |date=8 Dec 2010 }}</ref>), and for ] prevention in patients with ]<ref>{{pmid|20694273}}</ref> (phase III has completed enrollment<ref name=Dec2010/>).
'''Edoxaban''', sold under the brand name '''Lixiana''' among others, is an ] medication and a ].<ref name="Savaysa FDA label">{{cite web | title=Savaysa- edoxaban tosylate tablet, film coated | website=DailyMed | date=24 April 2020 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e77d3400-56ad-11e3-949a-0800200c9a66 | access-date=23 July 2020}}</ref> It is taken ].<ref name="Savaysa FDA label" />


Compared with ] it has fewer ]s.<ref name=a>{{cite journal | vauthors = Parasrampuria DA, Truitt KE | title = Pharmacokinetics and Pharmacodynamics of Edoxaban, a Non-Vitamin K Antagonist Oral Anticoagulant that Inhibits Clotting FactorXa | journal = Clinical Pharmacokinetics | volume = 55 | issue = 6 | pages = 641–55 | date = June 2016 | pmid = 26620048 | pmc = 4875962 | doi = 10.1007/s40262-015-0342-7 }}</ref>
==References==

<!-- History and culture -->
It was developed by ] and approved in July 2011, in Japan for prevention of ]s following lower-limb ].<ref name="url_Daiichi_Sankyo_Europe_GmbH">{{cite press release |url=http://www.daiichi-sankyo.eu/media/press-news-in-english/news-detail/article/first-market-approval-in-japan-for-lixianaR-edoxaban.html |title=First market approval in Japan for Lixiana (Edoxaban) |date=22 April 2011 |work=Daiichi Sankyo Europe GmbH |url-status=dead |archive-url=https://web.archive.org/web/20131106002948/http://www.daiichi-sankyo.eu/media/press-news-in-english/news-detail/article/first-market-approval-in-japan-for-lixianaR-edoxaban.html |archive-date=6 November 2013 }}</ref> It was also approved in the United States by the ] (FDA) in January 2015, for the prevention of stroke and non–central-nervous-system systemic ].<ref>{{cite web | url=http://www.medscape.com/viewarticle/837837 | title=FDA Approves Edoxaban for Stroke Prevention in AF and DVT/PE Prevention | work=Medscape | date=9 January 2015 | access-date=10 January 2015 | last = O'Riordan | first = Michael | name-list-style = vanc }}</ref><ref>{{cite web | title=Drug Approval Package: Savaysa (edoxaban tosylate) Tablets NDA #206316 | website=U.S. ] (FDA) | date=13 February 2015 | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206316Orig1Orig2s000TOC.cfm | access-date=23 July 2020}}</ref> It was approved for use in the European Union in June 2015.<ref name="Lixiana EPAR" /> It is on the ].<ref name="WHO22nd">{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 22nd list (2021) | year = 2021 | hdl = 10665/345533 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MHP/HPS/EML/2021.02 | hdl-access=free }}</ref>

==Medical uses==
In the United States, edoxaban is ] to treat ] and ] following five to ten days of initial therapy with a ] anticoagulant.<ref name="Savaysa FDA label" /> It is also indicated to reduce the risk of blood clots in people with ].<ref name="Savaysa FDA label" /><ref>{{cite journal | vauthors = Lowenstern A, Al-Khatib SM, Sharan L, Chatterjee R, Allen LaPointe NM, Shah B, Borre ED, Raitz G, Goode A, Yapa R, Davis JK, Lallinger K, Schmidt R, Kosinski AS, Sanders GD | display-authors = 6 | title = Interventions for Preventing Thromboembolic Events in Patients With Atrial Fibrillation: A Systematic Review | journal = Annals of Internal Medicine | volume = 169 | issue = 11 | pages = 774–787 | date = December 2018 | pmid = 30383133 | pmc = 6825839 | doi = 10.7326/M18-1523 | doi-access = free | title-link = doi }}</ref>

In the European Union, edoxaban is indicated for preventing blood clots in people with nonvalvular atrial fibrillation who also have at least one risk factor, such as having had a previous ], ] (hypertension), ], ] or being 75 years of age or older. It is also used to treat deep vein thrombosis and pulmonary embolism and to prevent either of these from reoccurring.<ref name="Lixiana EPAR">{{cite web | title=Lixiana EPAR | website=] (EMA) | date=3 July 2015 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/lixiana | access-date=23 July 2020}}</ref>

==Contraindications and notes==
Edoxaban is often contraindicated in people (incomplete list):

*with active pathological bleeding<ref name="Lixiana EMA PI"/>
*who are ] or ]<ref name="Lixiana EMA PI"/>
*who have conditions that increase bleeding risks. Examples: ] associated with ] and relevant bleeding risk, current or recent gastrointestinal ulceration, malignant ]s at high risk of bleeding, recent ] or ], recent brain, spinal or ophthalmic surgery, known or suspected ], ]s, ]s or major intraspinal or intracerebral vascular abnormalities<ref name="Lixiana EMA PI"/>
*who have uncontrolled and severe ]<ref name="Lixiana EMA PI"/>
*who use any other ]s<ref name="Lixiana EMA PI"/>

Edoxaban (incomplete list):

*is enhanced by the following strong ] (P-gp) inhibitors: ], ], ] or ]. Concomitant use of these and edoxaban may require 30&nbsp;mg doses of edoxaban (instead of 60&nbsp;mg). The efficacy of edoxaban may decrease when it is used with strong P-gp inducers such as ], ], ] or ]. If these medications are used with edoxaban, caution is advised.<ref name="Lixiana EMA PI"/>
*interacts with ], ], ] and ].<ref name="Lixiana EMA PI"/>
*inferior to ] in nonvalvular ] with a ] (CrCl) greater than 95&nbsp;ml/min.<ref name="Savaysa FDA label" />

==Adverse effects==
May affect up to 1 in 10 people:<ref name="Lixiana EMA PI">{{Cite web|url=https://www.ema.europa.eu/en/documents/product-information/lixiana-epar-product-information_en.pdf|title=Lixiana, INN-edoxaban|url-status=live|archive-url=https://web.archive.org/web/20191106140905/https://www.ema.europa.eu/en/documents/product-information/lixiana-epar-product-information_en.pdf|archive-date=6 November 2019|access-date=6 November 2019}}</ref>

*stomach ache
*abnormal results of blood tests that measure liver function
*]
*bleeding from the skin, nose, vagina, bowel, mouth, throat or stomach
*rash
*]
*dizziness
*feeling sick
*headache
*itching

May affect up to 1 in 100 people:<ref name="Lixiana EMA PI"/>

*bleeding in the eyes, brain, after a surgical operation or other types of bleeding
*blood in the spit when coughing
*reduced number of ] in blood
*]
*]

May affect up to 1 in 1000 people: bleeding in the muscles, joints, abdomen, heart or inside the skull.<ref name="Lixiana EMA PI"/>

==Overdose==
Edoxaban overdose can cause serious bleeding.<ref name="Lixiana EPAR" /> No approved antidotes for edoxaban overdose exist {{as of|2021|04|lc=on}}.<ref name="Lixiana EPAR" /> ] does not significantly contribute to edoxaban clearance.<ref name="Savaysa FDA label" /><ref name="Lixiana EMA PI"/> ] has been studied as an antidote for edoxaban overdose, but has only been approved for reversing ] and ] effects by the FDA and the EMA as of 2019.<ref>{{Cite web |url= https://www.fda.gov/media/113954/download |title=Summary basis for regulatory action - ANDEXXA |last=Ovanesov |first=Mikhail |website=] | name-list-style = vanc |date=3 August 2017|access-date=6 November 2019}}</ref><ref>{{Cite web|url=https://www.ema.europa.eu/en/medicines/human/EPAR/ondexxya|title=Ondexxya|date=27 February 2019|website=European Medicines Agency|url-status=live|access-date=6 November 2019|archive-url=https://web.archive.org/web/20190716153654/https://www.ema.europa.eu/en/medicines/human/EPAR/ondexxya |archive-date=16 July 2019 }}</ref>

==Mechanism of action==
Edoxaban is a direct, ], reversible and competitive ] of human ], with an ] (K<sub>i</sub>) value of&nbsp;0.561 ]. In ], uninhibited factor Xa forms a ] complex with ] on ] surfaces. Prothrombinases turn prothrombins to ]. Thrombins turn blood-soluble ] to insoluble ], which are the main components of blood clots.<ref name=a/>

==Pharmacokinetics==
In human, 15–150&nbsp;mg oral doses of edoxaban reach their maximum concentrations in blood 1–2&nbsp;hours after ingestion. With 60&nbsp;mg doses of ] edoxaban, 97% of the total radiation was detected after oral administration, with 62% from feces and 35% from urine. 49% of the total radiation from the feces and 24% from the urine were from edoxaban, the rest from its metabolites.<ref name=a/>

Metabolism occurs mostly via ], ], ] and enzymatic ]. CES1 oxidizes the ] ] carbons of edoxabans to ] groups. CYP3A4 and CYP3A5 oxidize edoxabans via ] or ]. In hydrolysis, ] moiety of edoxaban is removed. ] occurs to a lesser extent via ].<ref name=a/>

== References ==
{{reflist}} {{reflist}}


{{Antithrombotics}} {{Antithrombotics}}
{{Portal bar | Medicine}}


] ]
] ]
]

]
{{blood-drug-stub}}

Latest revision as of 05:24, 7 September 2024

Anticoagulant medication

Pharmaceutical compound
Edoxaban
Clinical data
Trade namesSavaysa, Lixiana, Roteas, others
Other namesDU-176b
AHFS/Drugs.comMonograph
MedlinePlusa614055
License data
Routes of
administration		By mouth
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability62%; Tmax 1–2 hours
Protein binding55%
Metabolismminimal CES1, CYP3A4/5, hydrolysis, glucuronidation
Elimination half-life10–14 hours
Excretion62% feces, 35% urine
Identifiers
IUPAC name
  • N'-(5-chloropyridin-2-yl)-N-thiazolopyridine-2-carbonyl)amino]cyclohexyl]oxamide
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC24H30ClN7O4S
Molar mass548.06 g·mol
3D model (JSmol)
SMILES
  • CN1CCC2=C(C1)SC(=N2)C(=O)N3C(CC3NC(=O)C(=O)NC4=NC=C(C=C4)Cl)C(=O)N(C)C
InChI
  • InChI=1S/C24H30ClN7O4S/c1-31(2)24(36)13-4-6-15(27-20(33)21(34)30-19-7-5-14(25)11-26-19)17(10-13)28-22(35)23-29-16-8-9-32(3)12-18(16)37-23/h5,7,11,13,15,17H,4,6,8-10,12H2,1-3H3,(H,27,33)(H,28,35)(H,26,30,34)/t13-,15-,17+/m0/s1
  • Key:HGVDHZBSSITLCT-JLJPHGGASA-N
  (what is this?)  (verify)

Edoxaban, sold under the brand name Lixiana among others, is an anticoagulant medication and a direct factor Xa inhibitor. It is taken by mouth.

Compared with warfarin it has fewer drug interactions.

It was developed by Daiichi Sankyo and approved in July 2011, in Japan for prevention of venous thromboembolisms following lower-limb orthopedic surgery. It was also approved in the United States by the Food and Drug Administration (FDA) in January 2015, for the prevention of stroke and non–central-nervous-system systemic embolism. It was approved for use in the European Union in June 2015. It is on the World Health Organization's List of Essential Medicines.

Medical uses

In the United States, edoxaban is indicated to treat deep vein thrombosis and pulmonary embolism following five to ten days of initial therapy with a parenteral anticoagulant. It is also indicated to reduce the risk of blood clots in people with nonvalvular atrial fibrillation.

In the European Union, edoxaban is indicated for preventing blood clots in people with nonvalvular atrial fibrillation who also have at least one risk factor, such as having had a previous stroke, high blood pressure (hypertension), diabetes mellitus, congestive heart failure or being 75 years of age or older. It is also used to treat deep vein thrombosis and pulmonary embolism and to prevent either of these from reoccurring.

Contraindications and notes

Edoxaban is often contraindicated in people (incomplete list):

Edoxaban (incomplete list):

Adverse effects

May affect up to 1 in 10 people:

  • stomach ache
  • abnormal results of blood tests that measure liver function
  • anemia
  • bleeding from the skin, nose, vagina, bowel, mouth, throat or stomach
  • rash
  • bloody urine
  • dizziness
  • feeling sick
  • headache
  • itching

May affect up to 1 in 100 people:

  • bleeding in the eyes, brain, after a surgical operation or other types of bleeding
  • blood in the spit when coughing
  • reduced number of platelets in blood
  • allergic reaction
  • hives

May affect up to 1 in 1000 people: bleeding in the muscles, joints, abdomen, heart or inside the skull.

Overdose

Edoxaban overdose can cause serious bleeding. No approved antidotes for edoxaban overdose exist as of April 2021. Hemodialysis does not significantly contribute to edoxaban clearance. Andexanet alfa has been studied as an antidote for edoxaban overdose, but has only been approved for reversing rivaroxaban and apixaban effects by the FDA and the EMA as of 2019.

Mechanism of action

Edoxaban is a direct, selective, reversible and competitive inhibitor of human factor Xa, with an inhibitory constant (Ki) value of 0.561 nM. In coagulation, uninhibited factor Xa forms a prothrombinase complex with factor Va on platelet surfaces. Prothrombinases turn prothrombins to thrombins. Thrombins turn blood-soluble fibrinogens to insoluble fibrins, which are the main components of blood clots.

Pharmacokinetics

In human, 15–150 mg oral doses of edoxaban reach their maximum concentrations in blood 1–2 hours after ingestion. With 60 mg doses of isotope labeled edoxaban, 97% of the total radiation was detected after oral administration, with 62% from feces and 35% from urine. 49% of the total radiation from the feces and 24% from the urine were from edoxaban, the rest from its metabolites.

Metabolism occurs mostly via CES1, CYP3A4, CYP3A5 and enzymatic hydrolysis. CES1 oxidizes the tertiary amide carbonyl carbons of edoxabans to carboxylic acid groups. CYP3A4 and CYP3A5 oxidize edoxabans via hydroxylation or demethylation. In hydrolysis, 2-amino-5-chloropyridine moiety of edoxaban is removed. Glucuronidation occurs to a lesser extent via glucuronosyltransferases.

References

  1. "Product monograph brand safety updates". Health Canada. February 2024. Retrieved 24 March 2024.
  2. "Health Canada New Drug Authorizations: 2016 Highlights". Health Canada. 14 March 2017. Retrieved 7 April 2024.
  3. ^ "Savaysa- edoxaban tosylate tablet, film coated". DailyMed. 24 April 2020. Retrieved 23 July 2020.
  4. ^ "Lixiana EPAR". European Medicines Agency (EMA). 3 July 2015. Retrieved 23 July 2020.
  5. "Roteas EPAR". European Medicines Agency (EMA). 4 May 2017. Retrieved 25 September 2020.
  6. ^ Parasrampuria DA, Truitt KE (June 2016). "Pharmacokinetics and Pharmacodynamics of Edoxaban, a Non-Vitamin K Antagonist Oral Anticoagulant that Inhibits Clotting FactorXa". Clinical Pharmacokinetics. 55 (6): 641–55. doi:10.1007/s40262-015-0342-7. PMC 4875962. PMID 26620048.
  7. "First market approval in Japan for Lixiana (Edoxaban)". Daiichi Sankyo Europe GmbH (Press release). 22 April 2011. Archived from the original on 6 November 2013.
  8. O'Riordan M (9 January 2015). "FDA Approves Edoxaban for Stroke Prevention in AF and DVT/PE Prevention". Medscape. Retrieved 10 January 2015.
  9. "Drug Approval Package: Savaysa (edoxaban tosylate) Tablets NDA #206316". U.S. Food and Drug Administration (FDA). 13 February 2015. Retrieved 23 July 2020.
  10. World Health Organization (2021). World Health Organization model list of essential medicines: 22nd list (2021). Geneva: World Health Organization. hdl:10665/345533. WHO/MHP/HPS/EML/2021.02.
  11. Lowenstern A, Al-Khatib SM, Sharan L, Chatterjee R, Allen LaPointe NM, Shah B, et al. (December 2018). "Interventions for Preventing Thromboembolic Events in Patients With Atrial Fibrillation: A Systematic Review". Annals of Internal Medicine. 169 (11): 774–787. doi:10.7326/M18-1523. PMC 6825839. PMID 30383133.
  12. ^ "Lixiana, INN-edoxaban" (PDF). Archived (PDF) from the original on 6 November 2019. Retrieved 6 November 2019.
  13. Ovanesov M (3 August 2017). "Summary basis for regulatory action - ANDEXXA". Food and Drug Administration. Retrieved 6 November 2019.
  14. "Ondexxya". European Medicines Agency. 27 February 2019. Archived from the original on 16 July 2019. Retrieved 6 November 2019.
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