DABIGATRAN CAP,ORAL
Clinical Criteria Summary
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Indications
- Atrial fibrillation/flutter (AF)
- Acute venous thromboembolism (VTE), or prevention of recurrent VTE
- Primary prophylaxis of VTE in patients undergoing hip or knee replacement surgery
- Other indication for anticoagulation (local adjudication required)
Exclusions
- Mechanical heart valve
- Moderate to severe rheumatic mitral valve stenosis (for AF/flutter only)
- Antiphospholipid syndrome (APS)
- Known significant liver disease (e.g., acute clinical hepatitis, cirrhosis [Child-Pugh C], or hepatic disease associated with coagulopathy)
- Pregnancy
- Breastfeeding
Pre-Treatment Assessment & Monitoring
- Assessment of renal function (CrCl) and hemoglobin, hematocrit, and platelets
- Consider liver function testing in patients with a history of or risk for hepatic insufficiency
- Provider must assess DOAC choice, dose, and duration considering patient’s age, renal function, liver function, concurrent medications, and indication
- Identify and address modifiable risk factors for bleeding (e.g., NSAIDs, antiplatelet therapy)
- Document the treatment plan including duration in the patient’s chart
Dosing & Administration Requirements
- For acute VTE: Administer 10 mg twice daily for 7 days as oral loading dose BEFORE starting maintenance doses
- Review drug dosing errors and drug-drug interactions, especially with new starts
Special Populations & Clinical Considerations
- Bioprosthetic heart valve placement in the past 3 months: Appropriate based on shared decision-making process between provider and patient
- Severe renal impairment (CrCl <25-30 ml/min) or hemodialysis: Individual evaluation of risks and benefits recommended; net clinical benefit unclear
- Apixaban may be the preferred DOAC when CrCl is less than 30 ml/min
- For patients who can become pregnant: Counsel on potential risks vs benefits of treatment and use of effective contraception during therapy
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General Principles & Supportive Care
- Reversal agents considered ONLY for severe, life-threatening bleeding 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.
- Supportive care includes: discontinuing anticoagulant, maintaining adequate diuresis, compression, surgical repair, fluid and/or blood replacement, hemodynamic support (hemodialysis for dabigatran).
- Consider 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 reversal agents reserved for patients with known recent exposure to a DOAC.
- Restart anticoagulant therapy as soon as medically appropriate due to elevated risk of thromboembolism.
Idarucizumab (Praxbind) Criteria
- Indication: Reversal of dabigatran in setting of bleeding or emergent surgery/urgent procedures.
- Inclusion Criteria (ALL required):
- Patient taking dabigatran with provider reasonably certain therapeutic anticoagulant levels are present.
- Life-threatening or critical site bleeding (e.g., ICH) OR need for truly emergent procedure that cannot be delayed ≥8 hours requiring normal hemostasis.
- Standard measures for bleeding management (e.g., discontinuing anticoagulant, compression, surgical repair, fluid/blood replacement, hemodynamic support) are insufficient.
- Patient’s risk of thromboembolism deemed less than consequences of continued bleeding or delay of procedure/surgery.
- Safety & Considerations:
- Specific for dabigatran only; will not reverse effects of other anticoagulants including Factor Xa inhibitors (e.g., rivaroxaban, apixaban, edoxaban).
- Thromboembolic events reported (4.8% within 30-day follow-up in REVERSE-AD); consider restarting anticoagulant as soon as medically appropriate (dabigatran can be started 24 hours after administration).
- Hypersensitivity reactions reported.
- Hereditary fructose intolerance due to sorbitol excipient (4g per dose) requires consideration of combined metabolic load.
- Re-elevation of coagulation parameters observed in limited patients; safety/effectiveness of repeat doses not established.
4-Factor Prothrombin Complex Concentrate (4F-PCC/KCetra) Criteria
- Indication: 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 components (heparin, Factors II, VII, IX, X, Proteins C and S, Antithrombin III, human albumin).
- Disseminated intravascular coagulation.
- History of heparin-induced thrombocytopenia (contains heparin).
- Inclusion Criteria (ALL required):
- Patient taking a DOAC with provider reasonably certain therapeutic anticoagulant levels are present.
- Specific reversal agent FDA approved for patient’s condition is not readily available.
- Life-threatening or critical site bleeding (e.g., ICH) OR need for truly emergent procedure that cannot be delayed requiring normal hemostasis.
- Standard measures for bleeding management are insufficient.
- Patient’s risk of thromboembolism deemed less than consequences of continued bleeding or delay of procedure/surgery.
- Safety & Considerations:
- Boxed warning for arterial and venous thromboembolic complications; higher thromboembolic events vs plasma in VKA trials, especially with history of thromboembolism.
- Not suitable for patients with thromboembolic events in prior 3 months.
- Hypersensitivity reactions observed.
- Risk of transmitting infection from human blood source.
- No FDA-approved products indicated for reversal of apixaban, rivaroxaban, or edoxaban; use of nonspecific agent such as 4F-PCC may be considered though evidence is limited. If 4F-PCC unavailable, activated PCC (aPCC/FEIBA) may be considered.
Dosing & Administration
- Idarucizumab: Single dose 5 gm (2 vials x 2.5 gm). Administered IV as 2 consecutive infusions or bolus injection. Requires refrigeration.
- 4F-PCC: Doses vary: single dose 25-50 units/kg or fixed dose 2,000 units IV. Dosing calculated based on quantity of factor IX in product. Administered by IV infusion at rate up to 8.4 ml/min (~210 units/min). Supplied in 500 or 1000 unit vials requiring reconstitution; store at 2-25°C.
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FDA Approved Adult Indications
- Non-valvular atrial fibrillation
- Treatment of DVT and PE (after 5-10 days of parenteral anticoagulant)
- Reduction in the risk of recurrent DVT and PE following initial therapy
- Post-surgical VTE prophylaxis following hip replacement surgery
- Post-surgical VTE prophylaxis following knee replacement surgery
Oversight & Initiation
- Chronic DOAC therapy requires initial assessment, education, and follow-up by locally designated staff (e.g., anticoagulation management program or other designees).
- Facilities should utilize decision support tools and/or anticoagulation staff for upfront review to verify appropriate candidate selection, agent choice, and dosing upon initiation.
- Short-term treatment (e.g., post-surgical VTE prophylaxis) or very low dose regimens should follow education/monitoring protocols similar to alternative agents in that setting.
Laboratory Monitoring
- Baseline: Serum creatinine (SCr) to estimate creatinine clearance (CrCl); CrCl estimated using Cockcroft-Gault equation with actual body weight for apixaban trials. Hemoglobin, hematocrit, and platelets required. Liver function tests may be considered for patients with history/risk of hepatic insufficiency. PT/aPTT may be obtained for emergency reference. Baseline values drawn within 1-3 months are acceptable per provider clinical judgment based on age/health status/comorbidities.
- Follow-up: SCr monitored at least annually (more frequently if CrCl < 60 ml/min, concomitant illness worsening renal function, or age ≥ 75 years). Hemoglobin, hematocrit, and platelets monitored at least annually or as clinically dictated. Liver function testing considered for underlying liver disease or clinical indication.
Patient Education
- Initial and periodic education must cover: capsule/tablet identification, proper storage, therapy indication, risks/benefits, anticipated duration, daily dose/dosing changes (e.g., loading doses), administration considerations, drug interactions, monitoring requirements, adherence importance, management of missed/extra doses, signs/symptoms of bleeding/thromboembolic events, avoidance of major bleeding risk medications (e.g., NSAIDs, antiplatelets) unless instructed, non-bleeding adverse events, fall risks/mitigation, medication supply acquisition, pre-procedure provider notification for peri-procedural management, anticoagulation provider contact information, and gender-specific considerations for women of childbearing age (menstrual difficulties, pregnancy, contraception).
Adherence Monitoring
- Monitor adherence, refill history, and medication tolerance, especially at therapy initiation.
- Utilize population management tools, telephone follow-up, face-to-face visits, secure messaging, or combinations based on site resources.
Follow-up Care
- Initial: Within 2-4 weeks of initiation (or sooner if clinically indicated) to assess tolerance, bleeding, thromboembolic events, other adverse events (e.g., GI intolerance), adherence, correct dosing (e.g., transition from high-intensity initiation dosing for acute VTE), duplicate therapy, and reinforce education.
- Periodic/Long-term: Reassess adherence, screen for drug interactions, monitor labs as needed. Time points, methods, and responsible staff determined locally per VHA Directive 1108.16(1).
Quality Assurance
- Incorporate DOACs into ongoing quality assurance plans per VHA Directive 1108.16(1).
- Report adverse events per local protocols and P&T Committee; enter into VA ADERS.