|Trade names||Andexxa, Ondexxya, others|
|Other names||Coagulation factor Xa (recombinant), inactivated-zhzo, PRT06445, r-Antidote, PRT4445|
|Main uses||Reversal of rivaroxaban or apixaban|
|Side effects||Feeling hot, shortness of breath, blood clots|
|Elimination half-life||5 h to 7 h|
Andexanet alfa, sold under the trade name Andexxa among others, is an antidote for the medications rivaroxaban and apixaban, when reversal of anticoagulation is needed due to uncontrolled bleeding. Evidence of benefit is not definitive as of 2021. It has not been found to be useful for other factor Xa inhibitors. It is given by injection into a vein.
Common side effects include pneumonia, urinary tract infection, feeling hot, and shortness of breath. Severe side effects may include blood clots, heart attacks, strokes, or cardiac arrest. It works by binding to rivaroxaban and apixaban.
Andexanet alfa was approved for medical use in the United States in 2018. It was developed by Portola Pharmaceuticals. The typical cost of using the medications per person is 25,000 to 50,000 USD in the United States as of 2019. In the United Kingdom it costs the NHS about £15,000 as of 2020.
There are no randomised clinical trials as of 2019. Studies in healthy volunteers show that the molecule binds fXa-inhibitors and counters their anti-fXa-activity. The only published clinical trial is a prospective, open label, single group study. This study reports results on 352 people and demonstrates a reduction of anti-fXa-activity while also showing an excellent or good hemostatic efficacy in 82%. While people who were expected to die in 30 days were excluded from the study, 14% of participants died. There was no relationship between hemostatic efficacy and reduced anti-Xa-activity. The FDA has demanded a randomised clinical trial: the first results are not expected before 2023.
Mechanism of action
Andexanet alfa is a biologic agent, a recombinant modified version of human activated factor X (FXa). FXa inhibitors bind to andexanet alfa with the same affinity as to natural FXa. As a consequence in the presence of andexanet alfa natural FXa is partially freed, which can lead to effective hemostasis. In other words, it acts as a decoy receptor. Andexanet alfa reverses effect of all anticoagulants that act directly through FXa or by binding antithrombin III. The drug is not effective against factor IIa inhibitor dabigatran.
It was approved in the United States in 2018 based on data from two phase III studies on reversing the anticoagulant activity of FXa inhibitors rivaroxaban and apixaban in healthy volunteers. As a condition of its accelerated approval there is a study being conducted comparing it to other currently used reversal agents ("usual care").
Society and culture
Initial pricing (AWP) is $58,000 per reversal (800 mg bolus + 960 mg infusion, $3,300 per 100 mg vial) which is higher than reversal agents for other DOAC agents (idarucizumab for use in dabigatran reversal is $4,200 per reversal).
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