Health Canada grants conditional approval for Ondexxya to reverse FXa inhibitor anticoagulant effects

Health Canada has approved AstraZeneca’s Ondexxya (andexanet alfa for injection) for use in adults being treated with Factor Xa (FXa) inhibitors (rivaroxaban or apixaban) who require rapid reversal of anticoagulation due to life-threatening or uncontrolled bleeding. Health Canada gave conditional approval to the drug based on promising evidence of clinical effectiveness; the manufacturer, however, must complete additional clinical trials to verify the drug’s anticipated benefit. Andexanet alfa is an antidote for apixaban or rivaroxaban only. It has not been shown to be effective for (and is not indicated for) the treatment of bleeding related to other FXa inhibitors. Andexanet alfa binds the FXa inhibitors apixaban and rivaroxaban in the plasma, which then frees up endogenous FXa to resume its normal function in hemostasis. The recommended dosing of andexanet alfa is based on the specific FXa inhibitor (i.e., apixaban or rivaroxaban), the dose of FXa inhibitor the patient is taking, and the time since the patient’s last dose (see product monograph for dosing details). The drug is given as an initial intravenous (IV) bolus dose, followed by a two-hour IV infusion. The most common adverse effects of andexanet alfa in adults under treatment with FXa inhibitors are urinary tract infection (10.5%), pneumonia (8.2%), delirium (4.4%), hypotension (4%) and pyrexia (4%). Mild-to moderate infusion-related reactions (flushing, feeling hot, cough, dysgeusia, dyspnea) have also been reported. Serious adverse effects have included pneumonia (4.2%), respiratory failure (2.5%) and ischemic stroke (2.1%). Other thrombotic events (including serious and/or life-threatening events) have also occurred following treatment with andexanet alfa. Reversing FXa inhibitor therapy exposes patients to the thrombotic risk of their underlying disease. To reduce this risk, resumption of anticoagulant therapy should be considered as soon as medically appropriate. No drug–drug interaction studies with andexanet alfa have been performed. However, postmarketing data suggest that its use before heparinization could cause unresponsiveness to heparin. Ondexxya is expected to be introduced in Canada in early 2024. It will be supplied as a white to off-white lyophilized cake or powder in single-use, preservative-free 20 mL vials containing 200 mg andexanet alfa. Unopened vials should be stored in the refrigerator (2°C–8°C). Reference 1. AstraZeneca Canada Inc. Ondexxya (andexanet alfa for injection) product monograph. Mississauga, ON; June 16, 2023. https://pdf.hres.ca/dpd_pm/00071399.PDF (accessed July 7, 2023).

Health Canada grants conditional approval for Ondexxya to reverse FXa inhibitor anticoagulant effects

Register for free access or login.

Related Topics