• Andexanet alpha is not FDA approved for non-bleeding patients. If patient requires urgent surgical or invasive procedure discussion with the surgical provider and Hematology is recommended. Determine if procedure can be delayed until 24 hours after rivaroxaban ingestion in patient with normal renal function or 48 hours after ingestion in patient with CrCl < 30 mL/min/1.73 m2, then andexanet may be considered in conjunction with Hematology consultation.
• Andexanet alfa is FDA indicated for reversal of rivaroxaban, but is NOT currently on formulary at St. Vincent. It is recommended for life-threatening bleeding, bleeding into a critical organ. It is a modified human factor Xa decoy protein that binds and sequesters factor Xa inhibitors, but also TFPI. Anti FXa assay results rapidly decrease within 2 minutes after bolus and this is maintained throughout the duration of the continuous infusion. Anti Xa levels returned to placebo levels approximately 2 hours after completion of bolus or infusion. Andexanet alfa is associated with pro-thrombotic risks.
  • Recommended Adult dose:
    Rivaroxaban last dose Timing of rivaroxaban last dose before Andexxa initiation < 8 hrs or Unknown ≥ 8 hrs ≤ 10 mg Low dose: Initial IV Bolus 400 mg at a target rate of 30 mg/min, then IV Infusion: 4 mg/min for up to 100-120 minutes (480 mg) Low dose: Initial IV Bolus 400 mg at a target rate of 30 mg/min; then IV Infusion: 4 mg/min for up to 100-120 minutes > 10 mg or Unknown High dose: Initial IV Bolus: 800 mg at a target rate of 30 mg/min; then IV Infusion: 8 mg/min for up to 100-120 minutes (960 mg)
  • Andexanet Alpha Pediatric dosing: NO reported pediatric dosing is available. Based on limited experience, the following dosing recommendations may be considered when determining risk vs. benefit of reversal of rivaroxaban. Recommend considering the following dosing in patients < 50kg:
    
    Weight Use of rivaroxaban ≤ 24 hours in patients with normal renal function or up to 48 hours in patient with CrCl <30 mL/min/1.73 m2 12 to 30 kg 100 mg bolus, then 1 mg/min for up to 100-120 minutes 30 to < 50 kg 200 mg bolus, then 2 mg/min for up to 100-120 minutes ≥ 50 kg Use Adult dosing above
  • Critical site bleeds: Intracranial hemorrhage, including intraparenchymal, subdural, epidural, and subarachnoid hemorrhages; Other CNS hemorrhage, including intraocular, intra- or extra-axial spinal hemorrhages; Pericardial tamponade; Airway, including posterior epistaxis; Hemothorax, intraabdominal bleeding, and retroperitoneal hemorrhage; Extremity bleeds, including intramuscular and intraarticular bleeding concerning for compartment syndrome, bleeding associated with hemodynamic instability, bleeding in a noncompressible vessel (e.g., subclavian)

Repeat monitoring tests for anticoagulant and platelets, PT, PTT, and fibrinogen after infusing a reversal agent and q 4-6 hours until severe bleeding risk has passed. Determine if and when anticoagulation should be reinitiated and what agent. Monitor patient for thrombosis and bleeding.

Kcentra (prothrombin complex concentrate) 25-50 units/kg/dose (maximum 2000 unit/dose) for severe bleeding or NovoSeven (rFVIIa) 90 mcg/kg may be considered. FEIBA (activated PCC) 50 units/kg would be a last resort due to higher thrombosis risk. They are on formulary at PMCH but are not labeled by the manufacturer for reversal of rivaroxaban.

In the setting of overdose, also consider administration of activated charcoal (50 g) if within 2 hours of dose.

Rivaroxaban is NOT dialyzable because it is mostly protein bound.