IDARUCIZUMAB INJ,SOLN
Clinical Criteria Summary
Criteria for Idarucizumab (Praxbind)
- Applies to: Dabigatran
- Indication/Use: Reversal of dabigatran in the setting of bleeding or emergent surgery/urgent procedures.
- Inclusion Criteria (ALL must be met):
- Patient has been taking dabigatran, and provider is reasonably certain that therapeutic anticoagulant levels are present (e.g., patient history and timing of last dose, laboratory testing if available).
- Patient has life-threatening or critical site bleeding (e.g., ICH) OR is in need of a truly emergent procedure that cannot be delayed for at least 8 hours and where normal hemostasis is required.
- If reversal is desired in the setting of bleeding, standard measures for bleeding management (e.g., discontinuing anticoagulant, compression, surgical repair, fluid and/or blood replacement, hemodynamic support) are insufficient.
- Patient’s risk of thromboembolism is deemed less than the consequences of continued bleeding or delay of the procedure or surgery.
- Issues for Consideration:
- Specific for dabigatran only; will not reverse effects of other anticoagulants including Factor Xa inhibitors (e.g., rivaroxaban, apixaban, edoxaban) or other direct thrombin inhibitors (e.g., argatroban, bivalirudin).
- Not known to exhibit procoagulant effects.
- Reversing anticoagulation exposes patients to thrombotic risk of underlying disease; 4.8% experienced a thromboembolic event within 30-day follow-up in REVERSE-AD. Consider restarting anticoagulant therapy as soon as medically appropriate (dabigatran can be started 24 hours after idarucizumab administration).
- Hypersensitivity reactions have been reported.
- Patients with hereditary fructose intolerance: Serious adverse reactions/death reported with parenteral sorbitol; recommended dose contains 4 g of sorbitol excipient. Consider combined metabolic load from all sources.
- Re-elevation of coagulation parameters observed in limited patients; safety and effectiveness of repeat doses not established.
- Dose and Administration:
- Single dose of 5 gm (2 vials, each containing 2.5 gm).
- Administered IV as 2 consecutive infusions or by bolus injection of both vials via syringe.
- Supplied in packages of 2 single-use, 2.5 gm vials requiring refrigeration.
Criteria for 4-Factor Prothrombin Complex Concentrate (4F-PCC) (Kcentra)
- Applies to: Apixaban, Rivaroxaban, Edoxaban, Dabigatran (used as nonspecific reversal agent when specific agents unavailable)
- Indication/Use: Use in DOAC associated life-threatening bleeding or need for emergent surgery/urgent procedures. (Off-label)
- Exclusion Criteria (ANY present -> NOT receive):
- Known anaphylactic or severe systemic reaction to 4F-PCC or any components (heparin, Factors II, VII, IX, X, Proteins C and S, Antithrombin III, human albumin).
- Disseminated intravascular coagulation.
- History of heparin induced thrombocytopenia (4F-PCC contains heparin).
- Inclusion Criteria (ALL must be met):
- Patient has been taking a DOAC, and provider is reasonably certain that therapeutic anticoagulant levels are present (e.g., patient history and timing of last dose, laboratory testing if available).
- Specific reversal agent (idarucizumab for dabigatran) FDA approved for the patient’s condition is not readily available.
- Patient has life-threatening or critical site bleeding (e.g., ICH) OR is in need of a truly emergent procedure that cannot be delayed and where normal hemostasis is required.
- If reversal is desired in the setting of bleeding, standard measures for bleeding management (e.g., compression, surgical repair, volume replacement, hemodynamic support) are insufficient.
- Patient’s risk of thromboembolism is deemed less than the consequences of continued bleeding or delay of the procedure or surgery.
- Issues for Consideration:
- Off-label use: FDA approved for urgent reversal of vitamin K antagonists (VKA); used as nonspecific reversal agent for DOACs when specific agent unavailable. Evidence on use for DOAC reversal is low quality. Specific reversal agent preferred if available.
- Boxed Warning: Arterial and Venous Thromboembolic complications (fatal and nonfatal). Reversing anticoagulation exposes patients to thrombotic risk of underlying disease. Consider restarting anticoagulant therapy as soon as medically appropriate. More thromboembolic events occurred in trials vs plasma, especially in patients with history of thromboembolic event. Patients with recent thromboembolic event (past 3 months) excluded from trials; may not be suitable for such patients.
- Hypersensitivity reactions observed.
- Transmission risk: Blood-derived product manufactured using two virus reduction steps but still carries risk of transmitting infection.
- If 4F-PCC unavailable, activated PCC (aPCC, FEIBA) may be considered. Contains mainly nonactivated Factors II, IX, and X and mainly activated Factor VII. Generally less well studied than 4F-PCC for DOAC reversal. Single dose of 50 units per kg has been used.
- Dose and Administration:
- Doses vary: Single dose of 25 to 50 units per kg or fixed dose of 2,000 units IV.
- Dosing calculated based on quantity (international units) of factor IX in product (varies from vial to vial).
- Administered by IV infusion at rate of 0.12 ml/kg/min (~3 units/kg/min) up to maximum rate of 8.4 ml/min (~210 units/min).
- Supplied in single vials of 500 units and 1000 units requiring reconstitution; can be stored at 2-25°C.
General Principles for DOAC Reversal Agents
- Applies to: Apixaban, Rivaroxaban, Edoxaban, Dabigatran
- Use of reversal agents should be considered ONLY in severe, life-threatening bleeding and where potential risk of thromboembolism is deemed less than consequences of continued bleeding.
- DOACs have relatively short half-lives; bleeding often managed by temporarily discontinuing anticoagulant and providing supportive care (discontinuing anticoagulant, maintaining adequate diuresis, compression, surgical repair, fluid and/or blood replacement, hemodynamic support, and hemodialysis for dabigatran).
- Consider administration of activated charcoal for known recent DOAC ingestion within past 2-4 hours.
- Consider presence of other antithrombotic drugs (e.g., antiplatelet agents) and discontinue as appropriate.
- Use reserved for patients with known recent exposure to a DOAC.
- Consider restarting anticoagulant therapy as soon as medically appropriate due to elevated risk of thromboembolism.
- High quality data lacking; no randomized trial evidence demonstrating that administration of reversal agents improves clinical outcomes.
- No FDA approved products indicated for reversal of apixaban, rivaroxaban, or edoxaban (factor Xa inhibitors). Use of nonspecific agent such as 4F-PCC may be considered as part of treatment strategy (evidence limited). If 4F-PCC unavailable, aPCC (FEIBA) may be considered. Note: 4F-PCC and some aPCC contraindicated in patients with history of heparin induced thrombocytopenia (HIT).
- Facilities expected to have reversal agents readily and emergently available when clinically necessary; restrict to or oversee by locally designated specialty service(s) (e.g., Hematology, Critical care, Emergency Medicine, Neurology, Neurosurgery).