| Clinical data | |
|---|---|
| Trade names | Andexxa, Ondexxya, others |
| Other names | Coagulation factor Xa (recombinant), inactivated-zhzo, PRT06445, r-Antidote, PRT4445 |
| AHFS/Drugs.com | Monograph |
| License data | |
| Pregnancy category | |
| Routes of administration | Intravenous injection |
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| Pharmacokinetic data | |
| Eliminationhalf-life | 5 h to 7 h |
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Andexanet alfa, sold under the brand nameAndexxa among others, is anantidote for the medicationsrivaroxaban andapixaban, when reversal ofanticoagulation is needed due to uncontrolled bleeding.[7] It has not been found to be useful for otherfactor Xa inhibitors.[9] It is given byinjection into a vein.[9]
Common side effects includepneumonia andurinary tract infections.[9] Severe side effects may includeblood clots,heart attacks,strokes, orcardiac arrest.[9] It works by binding to rivaroxaban and apixaban.[9]
It was approved for medical use in the United States in May 2018.[7] It was developed byPortola Pharmaceuticals.[10]
Andexanet alfa is used to stop life-threatening or uncontrollable bleeding in people who are takingrivaroxaban orapixaban.[7]
Studies in healthy volunteers show that the molecule bindsfactor Xa inhibitors and counters their anti-Xa-activity.[11] The first published clinical trial was 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 demanded a randomised clinical trial[14] which resulted in publication in 2024.[15] The ANNEXA-I trial included 530 patients with intracerebral hemorrhage who were receiving factor Xa inhibitors. Andexanet resulted in better control of hematoma expansion than usual care, but was associated with thrombotic events, including ischemic stroke. ANNEXA-I did not have sufficient power or information to draw conclusions about the effect of andexanet on mortality, clinical deterioration, or the need for rescue therapy.[16]
Common side effects include pneumonia and urinary tract infections.[9] Severe side effects may includeblood clots orcardiac arrest.[9]
Andexanet alfa has aboxed warning that it is associated with arterial and venous blood clots,ischemic events, cardiac arrest, and sudden deaths.[7]
Andexanet alfa is abiologic agent, arecombinant modified version of human activatedfactor X (FXa).[17] Andexanet alfa differs from native FXa due to the removal of a 34 residue fragment that contains theGla 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.[18]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 effectivehemostasis.[10][19] In other words, it acts as adecoy receptor. Andexanet alfa reverses effect of all anticoagulants that act directly through FXa or by bindingantithrombin III. The drug is not effective againstfactor IIa inhibitordabigatran.[20] Its activity is measured using the anti-Xa test, which is utilized to determine the amount of available factor Xa for coagulation[21]
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, the ANNEXA-I study was conducted comparing it to other currently used reversal agents ("usual care").[12][22]
Initial pricing (AWP) is $58,000 per reversal (800 mgbolus + 960 mg infusion, $3,300 per 100 mgvial) which is higher than reversal agents for otherDOAC agents (idarucizumab for use indabigatran reversal is $4,200 per reversal).[23]
