Antidote – recombinant, inactive factor Xa decoy (apixaban, rivaroxaban)
EU – conditional marketing authorisation still valid (no suspension or withdrawal known, as of 10/2026). USA – off the market since 22.12.2025 (FDA: risks outweigh benefits). Clarify availability in your own hospital/depot.
Preparation: 200 mg powder, reconstituted in 20 ml water for injection = 10 mg/ml
Life-threatening bleeding on apixaban or rivaroxaban
- Apixaban last dose ≤ 5 mg → low; > 5 mg and < 8 h → HIGH; > 5 mg and ≥ 8 h → low. Rivaroxaban ≤ 10 mg → low; > 10 mg and < 8 h → HIGH; > 10 mg and ≥ 8 h → low. Dose or timing unknown – the EU SmPC gives no recommendation. Dose selection[234]
- 400 mg low dose – i.v. bolus at approx. 30 mg/min[234]200 mg powder, reconstituted in 20 ml water for injection = 10 mg/ml · = 40 ml
- 480 mg low dose – followed by infusion 4 mg/min over 120 min[234]200 mg powder, reconstituted in 20 ml water for injection = 10 mg/ml · = 48 ml
- 800 mg high dose – i.v. bolus at approx. 30 mg/min[234]200 mg powder, reconstituted in 20 ml water for injection = 10 mg/ml · = 80 ml
- 960 mg high dose – followed by infusion 8 mg/min over 120 min[234]200 mg powder, reconstituted in 20 ml water for injection = 10 mg/ml · = 96 ml
European Trauma Guideline 2023 – suggestion (2C) in life-threatening bleeding, especially traumatic brain injury. ESAIC 2024 – andexanet and PCC are equivalent options. In spontaneous intracranial haemorrhage NCS/SCCM 2026 prefers 4-factor PCC (conditional recommendation); ESO/EANS 2025 – only in highly selected patients (more thromboembolic events, no proven functional benefit in ANNEXA-I). Not licensed for edoxaban (use PCC there).
Contraindications
- Hypersensitivity to the active substance or any of the excipients
- Known allergic reaction to hamster proteins
Notes
- Thromboembolism – ANNEXA-I (intracerebral haemorrhage): thromboses 10.3 % vs. 5.6 % with standard care (publication 2024), 14.6 % vs. 6.9 % after FDA re-analysis. EU SmPC 06/2025 updated with the ANNEXA-I final results; withdrawn from the US market for this reason (22.12.2025).
- Heparin resistance – do not give before planned heparinisation (e.g. cardiopulmonary bypass, vascular surgery) (DHPC 11/2020).
- Commercial anti-Xa assays are unsuitable after administration – do not guide therapy by them (DHPC 06/2020).
- Benefit > 18 h after the last factor Xa inhibitor dose not established.