Guidance for rivaroxaban, apixaban and edoxaban rapid reversal using andexanet alfa (Ondexxya)

Objectives

To provide guidance for rapid reversal of apixaban, rivaroxaban and edoxaban using andexanet alfa (Ondexxya©) in adults (at or over 18 years old) who have taken either drug in the last 48 hours, presenting with life/limb-threatening bleeding or requiring emergency surgery.

This guidance is not applicable for use with any other anticoagulants.

Indication

The decision to use Andexanet alfa (Ondexxya) should be made by the physician-in-charge at STR grade or higher following risk:benefit consideration.

Definition of life/limb-threatening bleeding

Any of the following:

Intracranial (CT or MRI documented)
Retroperitoneal (CT or MRI documented)
Intra-ocular (excludes conjunctival)
Spontaneous muscle haematoma associated with compartment syndrome
Pericardial
Non-traumatic intra-articular
Any invasive procedure to stop bleeding
Active bleeding from any orifice plus BP≤90mmHg systolic, or oliguria or ≥20g/l fall in Hb

Stock will be kept in the Acute Medical Unit and the A&E Resuscitation area in Ninewells and in A&E at Perth Royal Infirmary.

Dose and mode of administration

Patients who had either

apixaban less than or equal to 5mg
rivaroxaban less than or equal to 10mg
edoxaban less than or equal to 30mg

or if more than 8 hours previously

apixaban more than 5mg
rivaroxaban more than 10mg
edoxaban more than 30mg

should be given

low dose andexanet alfa 400mg intravenous (IV) bolus (30mg/minute) followed by
480mg as an IV infusion over two hours (4mg/minute).

Patients who had

apixaban more than 5mg
rivaroxaban more than 10mg
edoxaban more than 30mg

within the preceding 8 hours or at an unknown time

should be given

high dose andexanet alfa 800mg IV bolus (30mg/minute) followed by
960mg as an IV infusion over two hours (8mg/minute).

Andexanet alfa is restricted to hospital use only

Monitoring

Monitoring for efficacy is clinical. We recommend sending a citrate (blue) coagulation tubes and requesting PT, APTT, and fibrinogen pre and 30 mins post-andexanet alfa.

Contraindications

Previous life-threatening reaction to andexanet alfa.

Caution

The safety and efficacy of andexanet alfa is not established for children below age of 18, pregnancy or lactation. There is a potential thrombotic risk from andexanet and/or from reversing rivaroxaban, apixaban or edoxaban in prothrombotic patients. There is little data on re-exposure to andexanet alfa.

Note that use for reversing edoxaban is off licence but national consensus supports this use in view of the absence of a licenced alternative.

Restarting anticoagulation

When clinically stable with adequate haemostasis, anticoagulation can be re-commenced at 24 hours. Clinical review of the risk:benefit of and the timing of re-starting anticoagulation should be carried out by the clinical team in charge of the patient with input from haematology colleagues if required.

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