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{{Short description|Anticoagulant medication}} |
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{{drugbox |
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{{Use dmy dates|date=March 2022}} |
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| verifiedrevid = 401316371 |
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{{Drugbox |
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| IUPAC_name = ''N'''-(5-chloropyridin-2-yl)-''N''-thiazolopyridine-2-carbonyl)amino]cyclohexyl]oxamide |
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| Verifiedfields = changed |
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| image = Edoxaban_skeletal.svg |
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| Watchedfields = changed |
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| width = 200 |
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| verifiedrevid = 415900881 |
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| CAS_number = 912273-65-5 |
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| image = Edoxaban.svg |
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| ATC_prefix = none |
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| width = 275 |
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| ATC_suffix = |
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| PubChem = 25022378 |
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| alt = |
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| DrugBank = |
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| caption = |
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| C = 24 | H = 30 | Cl = 1 | N = 7 | O = 4 | S = 1 |
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<!-- Clinical data --> |
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| molecular_weight = 548.056 g/mol |
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| smiles = |
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| pronounce = |
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| tradename = Savaysa, Lixiana, Roteas, others |
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| bioavailability = |
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| Drugs.com = {{drugs.com|monograph|edoxaban-tosylate}} |
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| protein_bound = |
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| MedlinePlus = a614055 |
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| metabolism = |
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| DailyMedID = Edoxaban |
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| elimination_half-life = |
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| excretion = |
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| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X --> |
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| pregnancy_AU_comment = |
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| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X --> |
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| pregnancy_category = |
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| pregnancy_US = <!-- A / B / C / D / X --> |
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| routes_of_administration = ] |
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| pregnancy_category= |
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| class = |
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| legal_AU = <!-- Unscheduled / S2 / S3 / S4 / S5 / S6 / S7 / S8 / S9 --> |
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| ATC_prefix = B01 |
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| legal_CA = <!-- / Schedule I, II, III, IV, V, VI, VII, VIII --> |
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| ATC_suffix = AF03 |
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| legal_UK = <!-- GSL / P / POM / CD / Class A, B, C --> |
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| legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V --> |
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<!-- Legal status --> |
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| legal_status = |
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| legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled --> |
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| routes_of_administration = |
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| legal_AU_comment = |
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| legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F --> |
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| legal_BR_comment = |
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| legal_CA = Rx-only |
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| 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> |
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| legal_DE = <!-- Anlage I, II, III or Unscheduled --> |
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| legal_DE_comment = |
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| legal_NZ = <!-- Class A, B, C --> |
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| legal_NZ_comment = |
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| 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 --> |
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| legal_UK_comment = |
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| legal_US = Rx-only |
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| legal_US_comment = <ref name="Savaysa FDA label" /> |
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| legal_EU = Rx-only |
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| 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> |
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| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV --> |
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| legal_UN_comment = |
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| legal_status = Rx-only |
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<!-- Pharmacokinetic data --> |
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| bioavailability = 62%; T<sub>max</sub> 1–2 hours<ref name=a/> |
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| protein_bound = 55%<ref name=a/> |
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| metabolism = minimal ], ]/], hydrolysis, ]<ref name=a/> |
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| elimination_half-life = 10–14 hours<ref name=a/> |
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| excretion = 62% ], 35% ] |
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<!-- Identifiers --> |
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| CAS_number_Ref = {{cascite|changed|??}} |
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| CAS_number = 480449-70-5 |
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| PubChem = 10280735 |
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| IUPHAR_ligand = 7575 |
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| DrugBank_Ref = {{drugbankcite|changed|drugbank}} |
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| DrugBank = DB09075 |
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| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}} |
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| ChemSpiderID = 8456212 |
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| UNII_Ref = {{fdacite|changed|FDA}} |
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| UNII = NDU3J18APO |
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| KEGG_Ref = {{keggcite|changed|kegg}} |
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| KEGG = D09710 |
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| ChEBI_Ref = {{ebicite|changed|EBI}} |
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| ChEBI = 85973 |
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| ChEMBL_Ref = |
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| ChEMBL = |
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| NIAID_ChemDB = |
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| PDB_ligand = |
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| synonyms = DU-176b |
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<!-- Chemical and physical data --> |
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| IUPAC_name = ''N'''-(5-chloropyridin-2-yl)-''N''-thiazolopyridine-2-carbonyl)amino]cyclohexyl]oxamide |
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| C=24 | H=30 | Cl=1 | N=7 | O=4 | S=1 |
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| smiles = CN1CCC2=C(C1)SC(=N2)C(=O)N3C(CC3NC(=O)C(=O)NC4=NC=C(C=C4)Cl)C(=O)N(C)C |
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| StdInChI_Ref = {{stdinchicite|changed|chemspider}} |
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| 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 |
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| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}} |
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| StdInChIKey = HGVDHZBSSITLCT-JLJPHGGASA-N |
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}} |
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}} |
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'''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> |
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<!-- Definition and medical uses --> |
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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/>). |
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'''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" /> |
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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> |
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==References== |
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<!-- History and culture --> |
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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> |
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==Medical uses== |
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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> |
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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> |
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==Contraindications and notes== |
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Edoxaban is often contraindicated in people (incomplete list): |
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*with active pathological bleeding<ref name="Lixiana EMA PI"/> |
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*who are ] or ]<ref name="Lixiana EMA PI"/> |
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*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"/> |
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*who have uncontrolled and severe ]<ref name="Lixiana EMA PI"/> |
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*who use any other ]s<ref name="Lixiana EMA PI"/> |
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Edoxaban (incomplete list): |
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*is enhanced by the following strong ] (P-gp) inhibitors: ], ], ] or ]. Concomitant use of these and edoxaban may require 30 mg doses of edoxaban (instead of 60 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"/> |
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*interacts with ], ], ] and ].<ref name="Lixiana EMA PI"/> |
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*inferior to ] in nonvalvular ] with a ] (CrCl) greater than 95 ml/min.<ref name="Savaysa FDA label" /> |
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==Adverse effects== |
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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> |
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*stomach ache |
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*abnormal results of blood tests that measure liver function |
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*] |
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*bleeding from the skin, nose, vagina, bowel, mouth, throat or stomach |
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*rash |
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*] |
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*dizziness |
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*feeling sick |
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*headache |
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*itching |
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May affect up to 1 in 100 people:<ref name="Lixiana EMA PI"/> |
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*bleeding in the eyes, brain, after a surgical operation or other types of bleeding |
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*blood in the spit when coughing |
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*reduced number of ] in blood |
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*] |
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*] |
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May affect up to 1 in 1000 people: bleeding in the muscles, joints, abdomen, heart or inside the skull.<ref name="Lixiana EMA PI"/> |
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==Overdose== |
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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> |
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==Mechanism of action== |
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Edoxaban is a direct, ], reversible and competitive ] of human ], with an ] (K<sub>i</sub>) value of 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/> |
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==Pharmacokinetics== |
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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 ] 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/> |
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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/> |
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== References == |
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{{reflist}} |
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{{reflist}} |
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{{Antithrombotics}} |
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{{Antithrombotics}} |
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{{Portal bar | Medicine}} |
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{{blood-drug-stub}} |
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