Ondexxya

/ Alexion

Andexanet alfa is administered as an intravenous bolus at a target rate of approximately 30 mg/min over 15 minutes (low dose) or 30 minutes (high dose), followed by administration of a continuous infusion of 4 mg/min (low dose) or 8 mg/min (high dose) for 120 minutes.
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For adult patients treated with a direct factor Xa (FXa) inhibitor (apixaban or rivaroxaban) when reversal of anticoagulation is needed due to life-threatening or uncontrolled bleeding.

* Hypersensitivity to the active substance or to any other ingredients
* Known allergic reaction to hamster proteins

Limitations of use: Andexanet alfa is not suitable for pre-treatment of urgent surgery. Use for edoxaban or enoxaparin-reversal is not recommended due to lack of data.
Andexanet alfa will not reverse the effects of non-FXa inhibitors.
Treatment monitoring should be based mainly on clinical parameters indicative of
appropriate response (i.e., achievement of haemostasis), lack of efficacy (i.e., re-bleeding),
and adverse events (i.e., thromboembolic events). Treatment monitoring of andexanet alfa
should not be based on anti-FXa-activity. Commercial anti-FXa-activity assays are
unsuitable for measuring anti-FXa activity following administration of andexanet alfa as
these assays result in erroneously elevated anti-FXa activity levels, thereby causing a
substantial underestimation of the reversal activity of andexanet alfa.
Thrombotic events: Serious arterial and venous thromboembolic events have been reported following treatment with andexanet alfa including frequent reports of early manifestation (within 72 hours) after reversal. Patients with prior history of stroke, myocardial infarction or heart failure may be at higher risk of thrombotic events. Reversing FXa inhibitor therapy exposes patients to the thrombotic risk of their underlying disease. In addition, independent pro-coagulant effect of andexanet alfa, mediated by inhibition of tissue factor pathway inhibitor (TFPI), has been demonstrated, which may pose an additional risk of developing thrombosis. The duration of this effect in bleeding patients is not known. Laboratory parameters as anti- FXa activity, endogenous thrombotic potential (ETP), or markers of thrombosis might not be reliable for guidance. To reduce this risk, resumption of anticoagulant therapy should be considered as soon as medically appropriate after completion of treatment.
Use of andexanet alfa in conjunction with other supportive measures: Andexanet alfa can be used in conjunction with standard haemostatic supportive measures, which should be considered as medically appropriate. Pro-coagulant factor treatments (e.g., 3- or 4-factor prothrombin complex concentrate (PCC)/activated PCC, recombinant factor VIIa, fresh frozen plasma) and whole blood should be avoided unless absolutely required, due to lack of data in combination with these treatments.
Interaction with heparin: Use of andexanet alfa prior to heparinisation e.g. during surgeries or procedures should be avoided as andexanet alfa causes unresponsiveness to heparin. Use of andexanet alfa as an antidote for heparin or low-molecular weight heparin has not been evaluated and is not recommended.
Infusion-related reactions: In case of mild or moderate infusion reactions, careful observation may be sufficient. For moderate symptoms, consideration may be given to a brief interruption or slowing of the infusion with resumption of the infusion after symptoms subside. Diphenhydramine may be administered.
See prescribing information for full details.

Common: Ischaemic stroke, Myocardial infarction, Deep vein thrombosis, Pulmonary Embolism, Pyrexia.
See prescribing information for full details.

No interaction studies with andexanet alfa have been performed.
See prescribing information for full details.

Pregnancy: There are no data from the use of andexanet alfa in pregnant women. Andexanet alfa is not recommended during pregnancy or in women of childbearing potential not using
contraception.
Lactation: It is unknown whether andexanet alfa is excreted in human milk. A risk to newborns/infants cannot be excluded. Breast-feeding should be discontinued during treatment with andexanet alfa.

There is no clinical experience with overdose of andexanet alfa. No dose-limiting toxicities have been observed during clinical studies.