Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/11/12 13:21:08」(JST)

wiki en

Edoxaban (DU-176b, trade names Savaysa, Lixiana) is an oral anticoagulant drug which acts as a direct factor Xa inhibitor. It was developed by Daiichi Sankyo and approved in July 2011 in Japan for prevention of venous thromboembolisms (VTE) following lower-limb orthopedic surgery.^[1] It was also approved by the FDA in January 2015 for the prevention of stroke and non–central-nervous-system systemic embolism.^[2]

Medical uses

US FDA-labeled indications:

Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE) following 5 to 10 days of initial therapy with a parenteral anticoagulant.

To reduce the risk of stroke and systemic embolism (SE) in patients with nonvalvular atrial fibrillation (NVAF)

Limitations of use:

Edoxaban should not be used in NVAF patients with CrCl >95 mL/minute because of an increased risk of ischemic stroke compared to warfarin^[3]

Warnings

Premature discontinuation of any oral anticoagulant, including edoxaban, in the absence of adequate alternative anticoagulation increases the risk of ischemic events. If edoxaban is discontinued for reasons other than pathological bleeding or completion of a course of therapy, consider the use of another anticoagulant.^[4]

Do not administer to nonvalvular atrial fibrillation (NVAF) patients with CrCl >95 mL/minute. In clinical trials, these patients had an increased rate of ischemic stroke with edoxaban 60 mg once daily compared to patients treated with warfarin; use another anticoagulant in these patients.^[4]

Spinal or epidural hematomas resulting in long-term or permanent paralysis may occur with neuraxial anesthesia (epidural or spinal anesthesia) or spinal/epidural puncture; the risk is increased by the use of indwelling epidural catheters, concomitant administration of other drugs that affect hemostasis (eg, NSAIDS, platelet inhibitors, other anticoagulants), in patients with a history of traumatic or repeated epidural or spinal punctures, a history of spinal deformity or surgery, or if optimal timing between the administration of edoxaban and neuraxial procedures is not known. Consider the potential benefit versus risk prior to neuraxial intervention in patients who are anticoagulated or scheduled to be anticoagulated for thromboprophylaxis. Monitor frequently for signs and symptoms of neurologic impairment (eg, numbness/weakness of legs, bowel/bladder dysfunction). If neurologic impairment is noted, prompt treatment is necessary.^[4]

Contraindicated in patients with active pathological bleeding.^[5]

Adverse effects

More common

bloody nose
heavy non-menstrual vaginal bleeding
pale skin
troubled breathing with exertion
unusual bleeding or bruising
unusual tiredness or weakness

Less common

bloody or black, tarry stools
vomiting of blood or material that looks like coffee grounds
rash

Rare

confusion
cough
difficulty with speaking
double vision
fever
headache, sudden, severe
inability to move the arms, legs, or facial muscles
inability to speak
nausea and vomiting
slow speech^[6]

Mechanism of action

Edoxaban inhibits free factor Xa and prothrombinase activity and inhibits thrombin-induced platelet aggregation. Inhibition of factor Xa in the coagulation cascade reduces thrombin generation and thrombus formation.^[4]^[5]

Factor Xa

Factor Xa (FXa) is an essential blood coagulation factor^[7] that is responsible for the initiation of the coagulation cascade. FXa cleaves prothrombin to its active form thrombin, which then acts to convert soluble fibrinogen to insoluble fibrin and to activate platelets. Stabilization of the platelet aggregation by fibrin mesh ultimately leads to clot formation.^[8]

Related medications

A number of anticoagulants inhibit the activity of Factor Xa. Unfractionated heparin (UFH), low molecular weight heparin (LMWH), and fondaparinux inhibit the activity of factor Xa indirectly by binding to circulating antithrombin (AT III). These agents must be injected. Warfarin, phenprocoumon, and acenocoumarol are orally active vitamin K antagonists (VKA) which decrease hepatic synthesis of a number of coagulation factors, including Factor X. In recent years, a new series of oral, direct acting inhibitors of Factor Xa have entered clinical development. These include rivaroxaban, apixaban, betrixaban, LY517717, darexaban (YM150), and edoxaban (DU-176b).^[9]

References

^ "First market approval in Japan for LIXIANA (Edoxaban)". Press Release. Daiichi Sankyo Europe GmbH. 2011-04-22.
^ O'Riordan, Michael (9 January 2015). "FDA Approves Edoxaban for Stroke Prevention in AF and DVT/PE Prevention". Medscape. Retrieved 10 January 2015.
^ http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/206316lbl.pdf
^ ^a ^b ^c ^d lexicomp.com
^ ^a ^b Savaysa (edoxaban) [prescribing information]. Parsippany, NJ: Daiichi Sankyo; January 2015.
^ http://www.drugs.com/cons/edoxaban.html
^ Yoshiyuki, I., et al. "Biochemical and pharmalogical profile of darexaban, an oral direct Xa inhibitor." European Journal of Pharmacology (2011): 49-55
^ Katsung, B., S. Masters and A. Trevor. Basic and Clinical Pharmacology 11th Edition. United States of America: McGraw-Hill, 2009
^ Turpie AG (January 2008). "New oral anticoagulants in atrial fibrillation". European Heart Journal 29 (2): 155–65. doi:10.1093/eurheartj/ehm575. PMID 18096568.

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. 直接トロンビン阻害剤および直接Xa因子阻害剤による抗凝固療法 anticoagulation with direct thrombin inhibitors and direct factor xa inhibitors
2. 直接作用型経口抗凝固剤を投与されている患者における出血のマネージメント management of bleeding in patients receiving direct oral anticoagulants
3. 静脈血栓塞栓症の患者における理論的根拠と無期限の抗凝固の適応 rationale and indications for indefinite anticoagulation in patients with venous thromboembolism
4. 外科患者における静脈血栓塞栓症の予防 prevention of venous thromboembolic disease in surgical patients
5. 心房細動：塞栓予防のための抗血栓治療 atrial fibrillation anticoagulant therapy to prevent embolization

English Journal

Non-vitamin K antagonist oral anticoagulants (NOACs) in patients with concomitant atrial fibrillation and heart failure: a systemic review and meta-analysis of randomized trials.

Xiong Q1,2, Lau YC1, Senoo K1, Lane DA1, Hong K2, Lip GY1,3.
European journal of heart failure.Eur J Heart Fail.2015 Sep 3. doi: 10.1002/ejhf.343. [Epub ahead of print]
BACKGROUND: No pooled analysis has been undertaken to assess the efficacy and safety of the non-vitamin K antagonist oral anticoagulants (NOACs) compared with warfarin in the subgroup of patients with atrial fibrillation (AF) and heart failure (HF), including edoxaban data from recent randomized con
PMID 26335355

Dosing of rivaroxaban by indication: getting the right dose for the patient.

Escolar G1, Carne X, Arellano-Rodrigo E.
Expert opinion on drug metabolism & toxicology.Expert Opin Drug Metab Toxicol.2015 Sep 2:1-13. [Epub ahead of print]
INTRODUCTION: Vitamin K antagonists were the only oral anticoagulants available for several decades, but they require frequent coagulation monitoring and dose adjustment. The direct oral anticoagulants rivaroxaban , dabigatran, apixaban, and, most recently, edoxaban have been approved for the manage
PMID 26329812

Net Clinical Benefit of Non-vitamin K Antagonist Oral Anticoagulants Versus Warfarin in Phase III Atrial Fibrillation Trials.

Renda G1, di Nicola M2, De Caterina R3.
The American journal of medicine.Am J Med.2015 Sep;128(9):1007-1014.e2. doi: 10.1016/j.amjmed.2015.03.034. Epub 2015 Apr 22.
OBJECTIVES: The evaluation of the "net clinical benefit" allows an integrated assessment of both the anti-ischemic and the prohemorrhagic effects of non-vitamin K antagonist oral anticoagulants compared with warfarin, and-in the absence of direct comparisons-may inform clinical decisions. We estimat
PMID 25910790

Japanese Journal

第Xa因子阻害薬(リバーロキサバン,開発段階の薬剤) (特集心房細動 : 診断・治療の最新動向) -- (心房細動の治療)

新博次
日本臨床 71(1), 119-125, 2013-01-00
NAID 40019536508

Randomized, Multicenter, Warfarin-Controlled Phase II Study of Edoxaban in Japanese Patients With Non-Valvular Atrial Fibrillation

YAMASHITA Takeshi,KORETSUNE Yukihiro,YASAKA Masahiro,INOUE Hiroshi,KAWAI Yohko,YAMAGUCHI Takenori,UCHIYAMA Shinichiro,MATSUMOTO Masayasu,OGAWA Satoshi
Circulation journal : official journal of the Japanese Circulation Society 76(8), 1840-1847, 2012-07-25
… Edoxaban is a once-daily (QD) oral, direct factor Xa inhibitor in clinical development for the prevention of stroke in patients with non-valvular atrial fibrillation (NVAF). … The aim of this study was to evaluate the safety of edoxaban in Japanese patients with NVAF. … A total of 536 NVAF patients (CHADS2 ≥1) were randomized to receive double-blinded edoxaban 30, 45, or 60mg QD or open-label warfarin (international normalized ratio [INR] 2.0-3.0 for age <70 years; …
NAID 10030504266

Edoxaban in Japanese Patients With Nonvalvular Atrial Fibrillation : Not the Same Dose for Everybody

ROLDAN Vanessa,MARIN Francisco,LIP Gregory Y. H.
Circulation journal : official journal of the Japanese Circulation Society 76(8), 1826-1827, 2012-07-25
NAID 10030504159

Related Pictures

Savaysa (Edoxaban Tablet) Wins US FDA Edoxaban Is FDA Approved As Anticoagulant Image of Edoxaban Chemical Structure compounds api edoxaban edoxaban home Edoxaban - 480449-70-5 - Antia TM) (edoxaban) Tablets NDA to the U.S. FDA Sankyo's edoxaban will 'shake things up

★リンクテーブル★

リンク元

「エドキサバン」

Edoxaban
Systematic (IUPAC) name
	N'-(5-chloropyridin-2-yl)-N-[(1S,2R,4S)-4-(dimethylcarbamoyl)-2-[(5-methyl-6,7-dihydro-4H-[1,3]thiazolo[5,4-c]pyridine-2-carbonyl)amino]cyclohexyl]oxamide
Clinical data
Trade names	Savaysa, Lixiana
AHFS/Drugs.com	Monograph
Pregnancy; category	US: C (Risk not ruled out); ;
Legal status	US: ℞-only;
Routes of; administration	Oral
Pharmacokinetic data
Bioavailability	62%; Tmax 1–2 hours
Protein binding	55%
Metabolism	Minimal hepatic
Biological half-life	10–14 hours
Excretion	50% renal; <50% bile
Identifiers
CAS Registry Number	912273-65-5
ATC code	None
PubChem	CID: 25022378
IUPHAR/BPS	7575
ChemSpider	8456212
UNII	NDU3J18APO
KEGG	D09710
ChEBI	CHEBI:85973
Chemical data
Formula	C24H30ClN7O4S
Molecular mass	548.056 g/mol
	SMILES CN1CCC2=C(C1)SC(=N2)C(=O)N[C@@H]3C[C@H](CC[C@@H]3NC(=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)

　　[★]

英: edoxaban
化: エドキサバントシル酸塩水和物 edoxaban tosilate hydrate
商: リクシアナ
関: 血液凝固阻止剤

[url_Daiichi_Sankyo_Europe_GmbH-1] "First market approval in Japan for LIXIANA (Edoxaban)". Press Release. Daiichi Sankyo Europe GmbH. 2011-04-22.

[2] O'Riordan, Michael (9 January 2015). "FDA Approves Edoxaban for Stroke Prevention in AF and DVT/PE Prevention". Medscape. Retrieved 10 January 2015.

[3] ttp://www.accessdata.fda.gov/drugsatfda_docs/label/2015/206316lbl.pdf

[lexicomp-4] xicomp.com

[PI-5] Savaysa (edoxaban) [prescribing information]. Parsippany, NJ: Daiichi Sankyo; January 2015.

[6] ttp://www.drugs.com/cons/edoxaban.html

[7] Yoshiyuki, I., et al. "Biochemical and pharmalogical profile of darexaban, an oral direct Xa inhibitor." European Journal of Pharmacology (2011): 49-55

[Katsung-8] Katsung, B., S. Masters and A. Trevor. Basic and Clinical Pharmacology 11th Edition. United States of America: McGraw-Hill, 2009

[9] Turpie AG (January 2008). "New oral anticoagulants in atrial fibrillation". European Heart Journal 29 (2): 155–65. doi:10.1093/eurheartj/ehm575. PMID 18096568.

匿名

検索

案内

案内

edoxaban