Enexanet

Enexanet, more commonly known as andexanet alfa and marketed under the brand name AndexXa, is a pharmacologic reversal agent designed to counteract the anticoagulant effects of direct Factor Xa inhibitors. It is a recombinant modified human Factor Xa decoy protein that binds Factor Xa inhibitors with high affinity, sequestering them and restoring the activity of the endogenous coagulation cascade.

Medical use and indications: Andexanet alfa is indicated for adults with life-threatening or uncontrolled bleeding associated with direct Factor Xa inhibitors, notably rivaroxaban, apixaban, and edoxaban. It is not intended for routine reversal or prevention of bleeding. Dosing and administration follow regulatory labeling and depend on the specific Xa inhibitor involved and the timing of the last dose. The product is given intravenously as a bolus, followed by an infusion in many regimens.

Mechanism of action: The agent acts as a decoy receptor for Factor Xa inhibitors. By binding the inhibitors, andexanet alfa neutralizes their anticoagulant effect and allows the body's normal coagulation pathways to function, providing rapid reversal of anticoagulation. Because the agent is cleared from circulation relatively quickly, the reversal effect is transient and clinicians monitor for reemergence of anticoagulation as the inhibitor is eliminated or redistributed.

Administration and safety: The reversal is performed in emergency settings, with rapid onset of action and short duration. Safety considerations include the risk of thromboembolic events after reversal and the need to resume anticoagulation when bleeding is controlled to minimize thrombotic risk. Careful patient selection and monitoring are essential.

History and regulatory status: Andexanet alfa was developed to address the absence of specific antidotes for Factor Xa inhibitors and received FDA approval in 2018 for certain life-threatening bleedings. Regulatory status and labeling may vary by country, and updates may reflect broader use with additional Xa inhibitors.