General Information

Adexxa (andexanet alfa) works by acting as a decoy for Factor Xa inhibitors in the blood, thereby preventing them from inhibiting the activity of native Factor Xa. As a result, the native Factor Xa is available to participate in the coagulation process and restore hemostasis (normal clotting).

Andexxa is specifically indicated for patients treated with rivaroxaban and apixaban, when reversal of anticoagulation is needed due to life-threatening or uncontrolled bleeding.

Andexxa is supplied as a lyophilized powder for solution for intravenous injection. Dose Andexxa based on the specific FXa inhibitor, dose of FXa inhibitor, and time since the patient’s last dose of FXa inhibitor. Administer as an intravenous (IV) bolus, with a target rate of 30 mg/min, followed by continuous infusion for up to 120 minutes.There are two dosing regimens: Low Dose: Initial IV Bolus: 400 mg at a target rate of 30 mg/min 4 mg/min for up to 120 minutes. Follow-On IV Infusion: 4mg/min for up to 120 minutes. High Dose: Initial IV Bolus: 800 mg at a target rate of 30 mg/min. Follow-On IV Infusion: 8mg/min for up to 120 minutes.

Clinical Results

Andexxa was approved under the FDA's Accelerated Approval pathway. Continued approval for this indication may be contingent upon post-marketing study results to demonstrate an improvement in hemostasis in patients. The FDA approval of Andexxa was based on data from two Phase III ANNEXA studies (ANNEXA-R and ANNEXA-A) , which evaluated the safety and efficacy of Andexxa in reversing the anticoagulant activity of the Factor Xa inhibitors rivaroxaban and apixaban in healthy subjects. Results demonstrated that Andexxa rapidly and significantly reversed anti-Factor Xa activity (the anticoagulant mechanism of these medicines). The median decrease in anti-Factor Xa activity from baseline was 97 percent for rivaroxaban and 92 percent for apixaban. Interim data from the ongoing ANNEXA-4 single-arm, open-label study in patients with major bleeding also were assessed by the FDA as part of its review and approval. Data from 185 evaluable patients showed that Andexxa rapidly and significantly reversed anti-Factor Xa activity when administered as a bolus and sustained this reversal when followed by a 120-minute infusion. The median decrease from baseline was 90 percent for rivaroxaban and 93 percent for apixaban.

Side Effects

Adverse effects associated with the use of Andexxa may include, but are not limited to, the following:

urinary tract infections

pneumonia

The Andexxa label comes with the following Boxed Warning:

Treatment with Andexxa has been 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. Monitor for thromboembolic events and initiate anticoagulation when medically appropriate. Monitor for symptoms and signs that precede cardiac arrest and provide treatment as needed.

Mechanism of Action

Andexxa is a recombinant protein specifically designed to bind to Factor Xa inhibitors and rapidly reverse their anticoagulant effect. Andexxa is a modified form of the human Factor Xa molecule, an enzyme that helps blood clot. Andexxa works by acting as a decoy for oral and injectable Factor Xa inhibitors, which target and bind to Factor Xa, which allows them to exert their anticoagulant effect. When Andexxa is given to a patient with Factor Xa inhibitor-related bleeding, it binds to the Factor Xa inhibitor and prevents it from inhibiting the activity of Factor Xa and reverses the anticoagulant effects of the inhibitor.