|Systematic (IUPAC) name|
|Mol. mass||548.056 g/mol|
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Edoxaban (INN, codenamed DU-176b, trade name Lixiana) is an anticoagulant drug which acts as a direct factor Xa inhibitor. It is being developed by Daiichi Sankyo. It is an oral, once-daily, direct factor Xa inhibitor under investigation for stroke prevention in patients with atrial fibrillation and for treatment and secondary prevention of venous thromboembolism. It was approved in July 2011 in Japan for prevention of venous thromboembolisms (VTE) following lower-limb orthopedic surgery.
In animal studies, edoxaban is potent, selective for factor Xa and has good oral bioavailability.
Edoxaban has a bioavailability of over 60%, reaches peak plasma level 1–2 h after administration, and has a half-life between 9 and 10 h (multiple daily doses of 60–120 mg). Edoxaban is eliminated through multiple pathways, but renal clearance represents 49% of total edoxaban clearance. Exposure to edoxaban increases in patients with renal dysfunction and in individuals with low body weight (≤60 kg)
Several Phase II clinical trials have been conducted, for example for thromboprophylaxis after total hip replacement (phase III early results compare well to enoxaparin), and a phase 3, randomized, double-blind, multinational trial for stroke prevention in patients with atrial fibrillation. Those papers follow similar recent major trials showing similar results for the other new factor Xa inhibitors, rivaroxaban and apixaban.
A double blinded phase III trial showed that edoxaban was noninferior to warfarin in preventing recurrent venous thromboembolic events after pretreatment of venous thromboembolism with heparin of at least 5 days. Major bleedings were not different and fatal and fatal intracranial bleedings were lower.
- "First market approval in Japan for LIXIANA (Edoxaban)". Press Release. Daiichi Sankyo Europe GmbH. 2011-04-22.
- Furugohri T, Isobe K, Honda Y, Kamisato-Matsumoto C, Sugiyama N, Nagahara T, Morishima Y, Shibano T (September 2008). "DU-176b, a potent and orally active factor Xa inhibitor: in vitro and in vivo pharmacological profiles". J. Thromb. Haemost. 6 (9): 1542–9. doi:10.1111/j.1538-7836.2008.03064.x. PMID 18624979.
- Ogata K, Mendell-Harary J, Tachibana M, Masumoto H, Oguma T, Kojima M, Kunitada S: Clinical safety, tolerability, pharmacokinetics, and pharmacodynamics of the novel factor Xa inhibitor edoxaban in healthy volunteers. J Clin Pharmacol 2010, 50(7):743-753 http://www.ncbi.nlm.nih.gov/pubmed/20081065?dopt=Abstract&holding=f1000,f1000m,isrctn
- Matsushima N, Lee F, Sato T, Weiss D, Mendel J: Absolute bioavailability of edoxaban in healthy subjects. AAPS J 2011, 13(Suppl 2):T2362. OpenURL
- A new era of stroke prevention in atrial fibrillation: comparing a new generation of oral anticoagulants with warfarin Bruce S Stambler International Archives of Medicine 2013, 6:46 doi:10.1186/1755-7682-6-46 http://www.intarchmed.com/content/6/1/46#B51
- Raskob, G.; Cohen, A. T.; Eriksson, B. I.; Puskas, D.; Shi, M.; Bocanegra, T.; Weitz, J. I. (2010). "Oral direct factor Xa inhibition with edoxaban for thromboprophylaxis after elective total hip replacement". Thrombosis and Haemostasis 104 (3): 642–649. doi:10.1160/TH10-02-0142. PMID 20589317.
- "Phase III Trial Finds Edoxaban Outclasses Enoxaparin in Preventing Venous Thromboembolic Events". 8 Dec 2010.
- Weitz JI, Connolly SJ, Patel I, Salazar D, Rohatagi S, Mendell J, Kastrissios H, Jin J, Kunitada S (September 2010). "Randomised, parallel-group, multicentre, multinational phase 2 study comparing edoxaban, an oral factor Xa inhibitor, with warfarin for stroke prevention in patients with atrial fibrillation". Thromb. Haemost. 104 (3): 633–41. doi:10.1160/TH10-01-0066. PMID 20694273.
- Edoxaban versus Warfarin in Patients with Atrial Fibrillation Robert P. Giugliano, M.D., Christian T. Ruff, M.D., M.P.H., Eugene Braunwald, M.D., Sabina A. Murphy, M.P.H., Stephen D. Wiviott, M.D., Jonathan L. Halperin, M.D., Albert L. Waldo, M.D., Michael D. Ezekowitz, M.D., D.Phil., Jeffrey I. Weitz, M.D., Jindřich Špinar, M.D., Witold Ruzyllo, M.D., Mikhail Ruda, M.D., Yukihiro Koretsune, M.D., Joshua Betcher, Ph.D., Minggao Shi, Ph.D., Laura T. Grip, A.B., Shirali P. Patel, B.S., Indravadan Patel, M.D., James J. Hanyok, Pharm.D., Michele Mercuri, M.D., and Elliott M. Antman, M.D. for the ENGAGE AF-TIMI 48 Investigators article doi:10.1056/NEJMoa1310907
- "Edoxaban versus Warfarin for the Treatment of Symptomatic Venous Thromboembolism". N. Engl. J. Med. 369 (15): 1406–15. August 2013. doi:10.1056/NEJMoa1306638. PMID 23991658.
- Edoxaban Hokusai VTE study, 2013 trialresultscenter