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Trade names | Andexxa, Ondexxya, others |
Other names | Coagulation factor Xa (recombinant), inactivated-zhzo, PRT06445, r-Antidote, PRT4445 |
AHFS/ Drugs.com | Monograph |
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Routes of administration | Intravenous injection |
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Elimination half-life | 5 h to 7 h |
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Andexanet alfa, sold under the brand name Andexxa among others, is an antidote for the medications rivaroxaban and apixaban, when reversal of anticoagulation is needed due to uncontrolled bleeding. [8] It has not been found to be useful for other factor Xa inhibitors. [9] It is given by injection into a vein. [9]
Common side effects include pneumonia and urinary tract infections. [9] Severe side effects may include blood clots, heart attacks, strokes, or cardiac arrest. [9] It works by binding to rivaroxaban and apixaban. [9]
It was approved for medical use in the United States in May 2018. [8] It was developed by Portola Pharmaceuticals. [10]
Andexanet alfa is used to stop life-threatening or uncontrollable bleeding in people who are taking rivaroxaban or apixaban. [8]
There are no randomised clinical trials as of 2019. Studies in healthy volunteers show that the molecule binds factor Xa inhibitors and counters their anti-Xa-activity. [11] The only published clinical trial is a prospective, open label, single group study. [12] This study reports results on 352 people and demonstrates a reduction of anti-Xa-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. [13] The FDA has demanded a randomised clinical trial: the first results are not expected before 2023. [14]
Common side effects include pneumonia and urinary tract infections. [9] Severe side effects may include blood clots or cardiac arrest. [9]
Andexanet alfa has a boxed warning that it is associated with arterial and venous blood clots, ischemic events, cardiac arrest, and sudden deaths. [8]
Andexanet alfa is a biologic agent, a recombinant modified version of human activated factor X (FXa). [15] Andexanet alfa differs from native FXa due to the removal of a 34 residue fragment that contains the Gla domain. This modification reduces andexanet alfa's anticoagulant potential. Additionally, a serine to alanine (S419A) mutation in the active site eliminates its activity as a prothrombin to thrombin catalyst, but still allows the molecule to bind to FXa inhibitors. [16] 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. [10] [17] 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. [18] Its activity is measured using the anti-Xa test, which is utilized to determine the amount of available factor Xa for coagulation [19]
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. [11] As a condition of its accelerated approval there is a study being conducted comparing it to other currently used reversal agents ("usual care"). [12] [20]
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). [21]