Andexanet Alfa (Ondexxya®): Use in the ED

Background

Andexanet Alfa (Ondexxya®) is licenced for the reversal of patients on direct factor Xa (FXa) inhibitor (apixaban or rivaroxaban) in life-threatening or uncontrolled bleeding.

Andexanet alfa is not licensed for the treatment of bleeding in patients on edoxaban.

In CUH, Andexanet Alfa is stored in the fridge in Pharmacy. In working hours, it can be accessed via Pharmacy. Out of hours, it can be accessed by ADON and Security.

Departmental Position

Andexanet Alfa (Ondexxya®) administration is associated with a significant increased risk of thromboembolic events, particularly acute ischaemic stroke
The European Medication Authority has renewed its Conditional Marketing Authorisation, in view of its overall positive benefit-risk balance (though the FDA has withdrawn from its manufacture and sale in the US)
Careful consideration of each individual patient's risk-benefit balance is required before administration.
Andexanet Alfa should only be given within its licensed indications, as detailed below

Inclusion Criteria

Administration of apixaban or rivaroxaban
and
Acute, life threatening, uncontrolled bleeding with any of:
- Signs and symptoms of haemodynamic compromise e.g.
- ↓↓BP, ↓CRT, confusion or unexplained low cardiac output
- ↓Hb > 2 g/dL or Hb ≤ 8 g/dL if no baseline Hb available
- Bleeding in a critical area or organ e.g. retroperitoneal, intra-articular, pericardial, epidural or intracranial, IM with compartment syndrome
and
Only if within 18 hours after administration of an FXa inhibitor

Exclusion Criteria

Patients < 18 old
Patients who do not meet the eligibility criteria
>18hrs from last FXa inhibitor dose
Print copies Andexanet Alfa HSE Prescribing Guideline July 2023, Andexanet Alfa: Ondexxya®

Cautions

Careful consideration must be given in context of increased risk of thromboembolic events post-Andexanet Alfa. Risk-benefit decision to be made by treating clinician.
Patients requiring emergency surgery within the next 12 hours. Consider discussion with relevant Consultant if vascular or cardiothoracic emergency surgery is likely
Patients requiring treatment with unfractionated heparin in the next 24 hrs e.g. an invasive procedure for ICH with a secondary vascular cause, cardiothoracic surgery
Patients having received PCC within 7 days or recombinant FVIIa within 12 hours

Contraindications

Off-license use
Hypersensitivity to active substance/ingredients
Known allergic reaction to hamster proteins
ICH with GCS < 7

Dose

Dose table 1
Andexanet Alfa	Initial IV bolus	IV Infusion	No. of 200mg vials
Low dose	400 mg @ 30 mg/minute	4 mg/min for 120 minutes (480 mg)	5
High dose	800 mg @ 30 mg/minute	8 mg/min for 120 minutes (960 mg)	9

Dose table 2
FXa inhibitor	Last dose (FXa inhibitor)	Timing of last dose before andexanet alfa initiation
FXa inhibitor	Last dose (FXa inhibitor)	< 8hrs or unknown	≥ 8hrs *
Apixaban	≤ 5mg	Low dose	Low dose
Apixaban	> 5mg / unknown	High dose	Low dose
Rivaroxaban	≤ 10mg	Low dose	Low dose
Rivaroxaban	> 10mg / unknown	High dose	Low dose

Print copies Andexanet Alfa HSE Prescribing Guideline July 2023, Andexanet Alfa: Ondexxya®.

Adverse Rxn/Complications

Please report any suspected adverse reactions.

Infusion reactions

Mild infusion reactions can usually be managed with clinical monitoring
Moderate infusion reactions can be managed by slowing or stopping the infusion temporarily and use of an antihistamine can be considered
Severe infusion reactions should be managed by stopping the infusion and managing the patient specific symptoms

Temporary heparin resistance

Following treatment with andexanet alfa, unfractionated or LMWH will be ineffective for 24 hours
This is especially relevant for patients likely to require an invasive procedure/surgery for which unfractionated heparin will be needed. In this setting, if andexanet alfa has been administered, the patient will be unresponsive to heparin and there is a significant risk of acute, severe thrombosis
Elevation in D-dimers is expected post infusion of andexanet alfa and D-dimers should not be used in the evaluation of possible thrombosis

Thrombosis risk & restarting anticoag.

Reversal of anticoagulation can be associated with an increase in risk of thrombosis for up to 30 days post reversal
This may be especially relevant for patients with a recent (<1 month) Hx of thrombosis and risks and benefits of the use of any reversal agent should be considered on an individual basis

Risk mitigation for thrombosis

See Background for further information
Monitor patients for signs and symptoms of thrombosis post reversal - particularly Acute Ischaemic Stroke (AIS)
Consider restarting anticoagulation when safe to do so, having regard for the individual risks and benefits. Suggested timelines for reintroduction of anticoagulation:
- 7-14 days following a severe, life threatening bleed or ICH

Andexanet Alfa