title: Role of agents for reversing the effects of target-specific oral anticoagulants.
abstract: OBJECTIVE
  The available clinical data on target-specific oral anticoagulant (TSOAC) reversal agents that are currently in development or have been approved by the Food and Drug Administration (FDA) are reviewed.
  
  
  CONCLUSIONS
  The development of TSOACs such as dabigatran, rivaroxaban, edoxaban, and apixaban has presented benefits and new challenges. One of the main challenges associated with the use of TSOACs is the lack of suitable agent-specific reversal agents. Several treatment options for the management of life-threatening bleeding events associated with TSOAC use, such as fresh frozen plasma, prothrombin complex concentrates, and recombinant coagulation factor VIIa, have been used, with inconsistent results. Currently, two potential reversal agents for oral direct factor Xa inhibitors (andexanet alfa and ciraparantag) are at various stages of clinical development. Idarucizumab, a reversal agent for the oral direct thrombin inhibitor dabigatran, was approved by FDA in October 2015. Idarucizumab and andexanet alfa have been reported to produce anticoagulation reversal effects within minutes of administration. Ciraparantag was demonstrated to decrease whole blood clotting time to within 10% of baseline values in 10 minutes or less, with a return to baseline hemostasis in 10-30 minutes. TSOAC reversal agents have been generally well tolerated in clinical trials.
  
  
  CONCLUSIONS
  Idarucizumab and other TSOAC reversal agents, such as andexanet alfa and ciraparantag, present the potential for consistent and effective treatment and management options when life-threatening or uncontrolled TSOAC-associated bleeding occurs or when emergency surgery is warranted in patients using TSOACs.
authors.affiliation: Wingate University School of Pharmacy, Hendersonville, NC. ta.riley@wingate.edu.
authors.forename: Tanya R
authors.initials: TR
authors.lastname: Riley
authors.affiliation: Department of Clinical Sciences, School of Pharmacy, University of Louisiana at Monroe, Baton Rouge, LA.
authors.forename: Mary L
authors.initials: ML
authors.lastname: Gauthier-Lewis
authors.affiliation: Department of Pharmacy Practice, University of the Incarnate Word, San Antonio, TX.
authors.forename: Chelsea K
authors.initials: CK
authors.lastname: Sanchez
authors.affiliation: Wingate University School of Pharmacy, Wingate, NC.
authors.forename: Janine S
authors.initials: JS
authors.lastname: Douglas
mesh_terms: D000284:Administration, Oral; D000991:Antithrombins / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000069604:Dabigatran / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D004341:Drug Evaluation; D006470:Hemorrhage / Q000517:prevention & control; D006801:Humans; D011720:Pyrazoles / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D011728:Pyridones / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D000069552:Rivaroxaban / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D013844:Thiazoles / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D000991:Antithrombins; D011720:Pyrazoles; D011725:Pyridines; D011728:Pyridones; D013844:Thiazoles; C522181:apixaban; D000069552:Rivaroxaban; D000069604:Dabigatran; C552171:edoxaban
keywords: andexanet alfa; anticoagulant; antidote; ciraparantag; idarucizumab; reversal