PURPOSE: The properties of three oral anticoagulant-specific reversal agents are 
reviewed, and guidance is presented to assist pharmacists in planning for the 
agents' introduction to the market.
SUMMARY: Idarucizumab, which received Food and Drug Administration approval in 
October 2015, is a humanized monoclonal antibody fragment that immediately 
neutralizes the anticoagulant effect of dabigatran, as evidenced by reduced 
unbound dabigatran concentrations and normalized coagulation tests. Preliminary 
Phase III trial results demonstrated a median maximum reversal of 100%, a median 
time to bleeding cessation of 11.4 hours, and normal intraoperative hemostasis 
in 92% of patients requiring anticoagulation reversal before an urgent 
procedure. Andexanet alfa is a factor Xa (FXa) decoy that binds to direct and 
indirect FXa inhibitors. In Phase III trials in healthy volunteers, andexanet 
alfa reduced anti-FXa activity by more than 90%, reduced the concentration of 
unbound direct FXa inhibitor, and inhibited thrombin generation. Ciraparantag is 
a reversal agent under development for reversal of anticoagulation with direct 
and indirect FXa inhibitors and certain factor IIa inhibitors; it exerts its 
effect through hydrogen bonding. Concerns for thromboembolic events directly 
related to administration of idarucizumab, andexanet alfa, or ciraparantag have 
not arisen. Pharmacists need to begin preparing for the introduction of these 
specific reversal agents through protocol development and provider education; in 
addition, pharmacy departments need to plan for procurement and storage. The 
specific reversal agents should be incorporated into antithrombotic stewardship 
or other clinical pharmacy programs for surveillance.
CONCLUSION: As agents that provide rapid reversal of direct oral anticoagulant 
activity become available, advance planning will help hospitals to optimize 
their use.