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Factor Xa Reversal Agent

Andexanet Alfa

Brand names: Ondexxya

Adult dose

Dose: Low dose: 400 mg IV bolus at 30 mg/min, then 480 mg at 4 mg/min for 2 hours. High dose: 800 mg IV bolus at 30 mg/min, then 960 mg at 8 mg/min for 2 hours. Dose depends on anticoagulant (apixaban or rivaroxaban) and last dose timing
Route: Intravenous
Frequency: Single course

Clinical pearls

  • Indicated for reversal of apixaban or rivaroxaban in life-threatening or uncontrolled haemorrhage
  • NICE TA697 (2021): recommended as an option for reversal in adults with life-threatening haemorrhage
  • ANNEXA-4 trial: haemostatic efficacy ~80% in GI bleeding and intracranial haemorrhage
  • High-dose regimen: for rivaroxaban >10 mg or apixaban >5 mg taken within 8 hours
  • Restart anticoagulation as soon as haemostasis achieved and benefit outweighs risk (typically 24–72 hours for AF; individualise for VTE)
  • PCC (prothrombin complex concentrate) remains an alternative where andexanet not available

Contraindications

  • No absolute contraindications in life-threatening haemorrhage
  • Not recommended for reversal of edoxaban or betrixaban (limited data)

Side effects

  • Thromboembolic events (stroke, DVT, PE, MI) — significant risk within 30 days (10–15%)
  • Infusion-related reactions (uncommon)
  • Hyponatraemia and hypophosphataemia (transient)

Interactions

  • Heparin — andexanet transiently inhibits tissue factor pathway inhibitor (TFPI); monitor coagulation
  • Anticoagulants started after reversal — reassess and restart as soon as clinically appropriate

Monitoring

  • Anti-Xa activity levels (to guide dosing and assess reversal)
  • Clinical haemostasis assessment
  • Thromboembolic events post-reversal (restart anticoagulation promptly)
  • INR (if mixed anticoagulation)

Reference: BNF; NICE TA697 (Andexanet alfa for reversing anticoagulation from apixaban or rivaroxaban, 2021); ANNEXA-4 trial (NEJM 2019); BSH guidance on reversal of anticoagulants; https://bnf.nice.org.uk/drugs/andexanet-alfa/. Verify against your local formulary and the latest BNF before prescribing.

Related

Curated clinical cross-links plus same-class fallbacks.