Although other fXa inhibitors had been used in animal studies and phase II trials, the FDA cited differences in pharmacokinetic, pharmacodynamic, and in-vivo/ex-vivo properties between anticoagulants as a reason for limiting andexanet use to agents studied in the phase III trials. 5 Consequently, the FDA did not approve labeling of andexanet as a reversal agent for all fXa inhibitors. 1,4 This indication was based largely on the results of the phase III ANNEXA trials, in which test subjects were given only apixaban or rivaroxaban prior to reversal by andexanet. Comparison of Andexanet Alfa with Factor XaĬurrently, andexanet is FDA-approved for the reversal of anticoagulant effects in the event of life-threatening or uncontrolled bleeding for patients on either apixaban or rivaroxaban therapy. During clinical trials, andexanet was found to possess a procoagulant effect that would potentially increase the risk of thromboembolic events in patients, however, the consequences of this property on clinical outcomes have not been fully studied. An important part of andexanet’s design was the removal of the procoagulant properties of fXa (Figure 2). Andexanet accomplishes this because it is a modified human fXa protein that acts as a decoy for fXa inhibitors.
Interaction of Andexanet Alfa with Drugs and Proteins Involved in the Regulation of fXa Activity.Īndexanet reverses the effects of fXa inhibitors by sequestering these drugs away from fXa, allowing fXa to convert prothrombin into thrombin (Figure 1). Indirect fXa inhibitors (fondaparinux, enoxaparin) act by changing the structure of antithrombin III, which makes it more effective at binding and inhibiting the serine active site (Figure 1).įigure 1. Direct fXa inhibitors (apixaban, rivaroxaban, edoxaban, betrixaban) act by directly inhibiting the serine active site. 1 Given the limited real-world experience in the use of this drug, this overview may serve as useful source for providers to feel more comfortable with its use in practice.įXa inhibitors produce anticoagulant effects by inhibiting the serine active site of fXa, which is responsible for the conversion of prothrombin into activate thrombin during secondary hemostasis. Portola Pharmaceuticals’ andexanet alfa (Andexxa®) has recently garnered significant attention for being the first FDA-approved reversal agent for the factor Xa (fXa) inhibitor class of DOACs. However, like warfarin, DOACs still possess a risk for acute major bleeds. In recent years, direct acting oral anticoagulants (DOACs) have been gaining increased utilization due to fewer drug and food interactions and less frequent blood monitoring required than the traditional anticoagulant of choice, warfarin. Preceptor: Amy Sipe, PharmD, Kansas City VA Medical Center Andexanet Alfa: A Novel Reversal Agent for Factor Xa InhibitorsĪuthor: Christopher Kimes, Pharmacy Student, University of Kansas School of Pharmacy
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