Andexanet Alfa (Ondexxya)

SOURCE: UK SPC via MHRA Products - ONDEXXYA 200 MG POWDER FOR SOLUTION FOR INFUSION (PLGB179010367), AstraZeneca UK Limited. Section 4.1: 'For adult patients treated with a direct factor Xa (FXa) inhibitor (apixaban or rivaroxaban) when reversal of anticoagulation is needed due to life-threatening or uncontrolled bleeding.' Section 4.2: 'Restricted to hospital use only.' 'Andexanet alfa is administered as an intravenous bolus at a target rate of approximately 30 mg/min over 15 minutes (low dose) or 30 minutes (high dose), followed by administration of a continuous infusion of 4 mg/min (low dose) or 8 mg/min (high dose) for 120 minutes (see Table 1).' Table 1 (columns: initial intravenous bolus; continuous intravenous infusion; total number of 200 mg vials needed): 'Low dose 400 mg at a target rate of 30 mg/min 4 mg/min for 120 minutes (480 mg) 5 High dose 800 mg at a target rate of 30 mg/min 8 mg/min for 120 minutes (960 mg) 9'. STRENGTH (section 2): each vial contains 200 mg of andexanet alfa; after reconstitution each mL of solution contains 10 mg. WHICH REGIMEN: the SPC chooses low or high dose from Table 2 (apixaban) and Table 3 (rivaroxaban), by the anticoagulant, the strength of its last dose and the time since that dose. These are merged-cell tables that flatten ambiguously in the source text, so the selection grid is deliberately NOT reproduced or reconstructed here - read the low/high choice from the SPC's Tables 2-3 before use. Section 4.2: 'If the strength of the last dose of anticoagulant or the interval between the last dosage and the bleeding episode are unknown, no dose recommendation is available. Measurement of baseline anti-FXa-level could support the clinical decision of starting treatment (if level is available in an acceptable timeframe).' NO MAXIMUM DOSE is printed in section 4.2, so none is stored. LIMITATIONS (section 4.4): 'not suitable for pre-treatment of urgent surgery'; 'Use for edoxaban or enoxaparin-reversal is not recommended due to lack of data'; 'will not reverse the effects of non-FXa inhibitors'. RESTARTING ANTITHROMBOTIC THERAPY (section 4.2): re-anticoagulation should be considered after cessation of a major bleed to prevent thrombotic events; it can be re-initiated as soon as medically indicated if the patient is clinically stable and adequate haemostasis has been achieved; a normal degree of anticoagulation from FXa inhibitors or low molecular weight heparin can be expected after 4 hours following end of infusion, based on PK/PD modelling. SPECIAL POPULATIONS (section 4.2): elderly (65 years and over) - no dose adjustment is required; paediatric - 'The safety and efficacy of andexanet alfa in children and adolescents have not been established. No data are available.' ADMINISTRATION (section 4.2): after reconstitution the 10 mg/mL solution is used without further dilution, transferred to sterile large volume syringes (syringe pump) or to suitable empty polyolefin (PO) or polyvinyl chloride (PVC) intravenous bags; a 0.2 or 0.22 micron inline polyethersulfone (PES) or equivalent low protein-binding filter should be used before IV infusion. The eMC text of the same SPC in the bundle was not used for any figure.