Andexanet alfa

ANDEXXA is indicated for patients treated with rivaroxaban or apixaban, when reversal of anticoagulation is needed due to life-threatening or uncontrolled bleeding. This indication is approved under accelerated approval based on the change from baseline in anti-FXa activity in healthy volunteers. An improvement in hemostasis has not been established. Continued approval for this indication may be contingent upon the results of studies that demonstrate an improvement in hemostasis in patients. ANDEXXA (coagulation factor Xa (recombinant), inactivated-zhzo) is a recombinant modified human factor Xa (FXa) protein indicated for patients treated with rivaroxaban or apixaban, when reversal of anticoagulation is needed due to life-threatening or uncontrolled bleeding.

Coagulation factor Xa (recombinant), inactivated-zhzo exerts its procoagulant effect by binding and sequestering the FXa inhibitors, rivaroxaban and apixaban. Another observed procoagulant effect of the ANDEXXA protein is its ability to bind to, and inhibit the activity of, Tissue Factor Pathway Inhibitor (TFPI). Inhibition of TFPI activity can increase tissue factor (TF)-initiated thrombin generation.

For intravenous (IV) use only. • 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 IV bolus, with a target rate of 30 mg/min, followed by continuous infusion for 120 minutes. • There are two dosing regimens: Dose The safety and effectiveness of more than one dose have not been evaluated. Initial IV Bolus Follow-On IV Infusion Low Dose 400 mg at a target rate of 30 mg/min 4 mg/min for 120 minutes High Dose 800 mg at a target rate of 30 mg/min 8 mg/min for 120 minutes

None. None.

Boxed warning (thromboembolic risks, ischemic risks, cardiac arrest, and sudden deaths): 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. • Arterial and venous thromboembolic events, ischemic events, and cardiac events, including sudden death, have occurred during treatment with ANDEXXA. Resume anticoagulant therapy as soon as medically appropriate following treatment with ANDEXXA. • Unresponsiveness to unfractionated heparin has been reported following ANDEXXA administration. • Re-elevation or incomplete reversal of anticoagulant activity can occur.

The most common adverse reactions (≥ 5%) in bleeding patients receiving ANDEXXA were urinary tract infections and pneumonia.

Do not use unfractionated heparin following ANDEXXA administration due to unresponsiveness characterized by non-prolongation of activated clotting times. See full prescribing information for details on drug interactions.

DO NOT FREEZE. Prior to reconstitution Unopened vials should be stored refrigerated at 2°C to 8°C (36°F to 46°F) until the expiration date indicated on the label. After reconstitution • Reconstituted ANDEXXA in vials is stable at room temperature for up to 8 hours, or may be stored for up to 24 hours at 2°C to 8°C (36°F to 46°F). • Reconstituted ANDEXXA in IV bags is stable at room temperature for up to 8 hours. • Discard any unused portion of reconstituted solution.