Edoxaban

Edoxaban
Clinical data
Trade names Savaysa, Lixiana
AHFS/Drugs.com Monograph
License data
Pregnancy
category
  • US: C (Risk not ruled out)
    Routes of
    administration    		 Oral
    ATC code
    Legal status
    Legal status
    Pharmacokinetic data
    Bioavailability 62%; Tmax 1–2 hours
    Protein binding 55%
    Metabolism Minimal hepatic
    Elimination half-life 10–14 hours
    Excretion 50% renal; <50% bile
    Identifiers
    CAS Number
    PubChem CID
    IUPHAR/BPS
    DrugBank
    ChemSpider
    UNII
    KEGG
    ChEBI
    Chemical and physical data
    Formula C24H30ClN7O4S
    Molar mass 548.056 g/mol
    3D model (JSmol)
     &#9746;N&#9745;Y (what is this?)  (verify)

    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)

    Contraindications

    Edoxaban is contraindicated in nonvalvular atrial fibrillation (NVAF) patients with a creatinine clearance (CrCl) greater than 95 mL/minute because of an increased risk of ischemic stroke compared to warfarin.[3]

    It is also contraindicated in patients with active pathological bleeding.[4]

    Warnings

    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 (e.g., 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.[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.[5][4]

    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]

    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

    1. ↑ "First market approval in Japan for LIXIANA (Edoxaban)". Press Release. Daiichi Sankyo Europe GmbH. 2011-04-22. Archived from the original on 2013-11-06.
    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. ↑ http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/206316lbl.pdf
    4. 1 2 Savaysa (edoxaban) [prescribing information]. Parsippany, NJ: Daiichi Sankyo; January 2015.
    5. 1 2 lexicomp.com
    6. ↑ https://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
    8. ↑ Katsung, B., S. Masters and A. Trevor. Basic and Clinical Pharmacology 11th Edition. United States: 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.
    This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.