EMed

Andexanet Alfa

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.

It may NOT be clinically appropriate to administer andexanet alfa where last admin. of FXa inhibitor is greater than 18 hours

Inclusions/exclusions

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

Cautions

  • 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

  • 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
< 8hrs or unknown ≥ 8hrs *
Apixaban ≤ 5mg Low dose Low dose
> 5mg / unknown High dose
Rivaroxaban ≤ 10mg Low dose Low dose
> 10mg / unknown High 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

  • Monitor patients for signs and symptoms of thrombosis post reversal
  • 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

Content by Dr Íomhar O' Sullivan. Last review Dr ÍOS 9/05/24.