The first Factor Xa inhibitor reversal agent, andexanet alfa (brand name of AndexXa®) received FDA approval in early May 2018. Aandexanet alfa is indicated for patients who have been treated with rivaroxaban (Xarelto®) or apixaban (Eliquis®), and are in need of anticoagulation reversal due to life-threatening or uncontrolled bleeding. Andexanet alfa is a recombinant modified human Factor Xa protein that is catalytically inactive. It works as a reversal agent by binding and sequestering Factor Xa inhibitors. In addition, it inhibits the activity of Tissue Factor Pathway Inhibitor (TFPI), increasing tissue factor-initiated thrombin generation.
The completed trial in healthy volunteers and ongoing research trial with patients with acute major bleeds show overall efficacy in the agent’s ability to decrease anti-FXa activity. The package insert for AndexXa® states an improvement in hemostasis has not been established.
The side effect profile is low, however andexanet does carry the following warning that the drug is associated with serious and life-threatening adverse events, including:
- Arterial and venous thromboembolic events
- Ischemic events, including myocardial infarction and ischemic stroke
- Cardiac arrest
- Sudden deaths
The package insert recommends to monitor for thromboembolic events and initiate anticoagulation when medically appropriate. Also, monitor for symptoms and signs that precede cardiac arrest and provide treatment as needed. To reduce thromboembolic risk, resume anticoagulant therapy as soon as medically appropriate following treatment with AndexXa®.
FDA gave this drug an accelerated approval and is the only approved product for reversal of apixaban and rivaroxaban. Continued approval for this indication may be contingent upon the results of studies to demonstrate an improvement in hemostasis in patients.
Connolly SJ, Milling, Jr, TJ., Eikelboom, et al. Andexanet Alfa for Acute Major Bleeding Associated with Factor Xa Inhibitors. NEJM. 2016;375(2):1131-1141
AnedexXa [package insert]. San Francisco, CA: Portola Pharmaceuticals, Inc; May 2018.