What are alternative anticoagulants for a patient intolerant of Eliquis (apixaban) and Xarelto (rivaroxaban)?

Alternative Anticoagulants for Patients Intolerant to Apixaban and Rivaroxaban

For patients intolerant to both Eliquis (apixaban) and Xarelto (rivaroxaban), dabigatran (Pradaxa) is the recommended alternative direct oral anticoagulant, with edoxaban and warfarin as additional options depending on specific patient factors.

Alternative Direct Oral Anticoagulants (DOACs)

Dabigatran (Pradaxa)

• First-line alternative when Factor Xa inhibitors (apixaban and rivaroxaban) cannot be used
• Direct thrombin inhibitor with a different mechanism of action than Factor Xa inhibitors
• Dosing:
  • 150 mg twice daily if CrCl >30 mL/min
  • 75 mg twice daily if CrCl 15-30 mL/min 1
• Advantages:
  • Has specific reversal agent (idarucizumab) for emergency situations 2
  • Different mechanism of action may avoid cross-intolerance with Factor Xa inhibitors

Edoxaban

• Alternative Factor Xa inhibitor with different pharmacokinetic profile
• Recommended by American College of Cardiology/American Heart Association guidelines as an effective alternative 2
• May be considered if intolerance to apixaban/rivaroxaban was not due to class effect

Non-DOAC Alternatives

Warfarin (Vitamin K Antagonist)

• Traditional anticoagulant with extensive clinical experience
• Requires regular INR monitoring (target 2.0-3.0)
• Optimal INR range of 2.0-2.5 provides best balance between stroke prevention and bleeding risk 3
• Monitoring requirements:
  • Weekly during initiation
  • At least monthly when stable 2

Fondaparinux

• Synthetic pentasaccharide that inhibits Factor Xa
• Administered as subcutaneous injection once daily
• Dosing based on weight:
  • 5 mg if <50 kg
  • 7.5 mg if 50-100 kg
  • 10 mg if >100 kg 2
• Not recommended in severe renal impairment 2

Decision Algorithm for Selecting Alternative Anticoagulant

1. Determine reason for intolerance to apixaban/rivaroxaban:

   • If bleeding-related: Consider dabigatran or warfarin
   • If GI symptoms: Consider warfarin or edoxaban
   • If rash/allergic reaction: Consider switching to different class (dabigatran)

2. Assess renal function:

   • CrCl >30 mL/min: All options available
   • CrCl 15-30 mL/min: Reduced-dose dabigatran (75mg BID), warfarin
   • CrCl <15 mL/min: Warfarin only

3. Consider need for reversal agent:

   • If high bleeding risk: Dabigatran (idarucizumab available) or warfarin (vitamin K/PCC available)

4. Consider monitoring capabilities:

   • Limited access to monitoring: DOACs preferred
   • Good access to monitoring: Warfarin acceptable

Special Considerations

Antiphospholipid Syndrome

• Avoid rivaroxaban in high-risk antiphospholipid syndrome patients (triple positive)
• Warfarin is preferred in this population 4

Elderly Patients

• Apixaban and edoxaban may have better safety profiles in elderly
• If both are contraindicated, consider reduced-dose dabigatran or warfarin with careful monitoring 5

Concomitant Medications

• Check for drug interactions with P-glycoprotein inhibitors if considering dabigatran 1
• Avoid antiplatelet agents if possible to minimize bleeding risk 1

Monitoring Recommendations

• For dabigatran: Regular renal function monitoring, especially in elderly patients 1
• For warfarin: INR monitoring at least weekly during initiation and monthly when stable 2
• For all alternatives: Monitor for signs of bleeding, particularly when transitioning between agents

Practical Considerations

• When switching between anticoagulants, ensure appropriate overlap to maintain anticoagulation
• Document the specific nature of the intolerance to apixaban and rivaroxaban to guide future therapy
• Consider consultation with hematology for complex cases or multiple drug intolerances

Remember that the choice of alternative anticoagulant should prioritize reduction in morbidity and mortality while minimizing adverse effects that led to intolerance of the previous agents.