What are the potential interactions between Eliquis (apixaban) and acalabrutinib?

Potential Drug Interaction Between Eliquis (Apixaban) and Acalabrutinib

Acalabrutinib and apixaban should be used together with caution due to potential increased bleeding risk through pharmacodynamic effects, though there is no significant pharmacokinetic interaction requiring dose adjustment.

Mechanism of Potential Interaction

• Apixaban (Eliquis) is a direct oral anticoagulant (DOAC) that is a substrate of both CYP3A4 enzymes and P-glycoprotein (P-gp)/BCRP transporters 1
• Acalabrutinib is a Bruton's tyrosine kinase inhibitor (BTKi) that has been associated with bleeding risk independent of its effect on drug metabolism 1
• Unlike some other small-molecule inhibitors that significantly alter DOAC levels through P-gp inhibition, acalabrutinib does not appear to have clinically significant pharmacokinetic interactions with apixaban 1

Clinical Considerations

• Bleeding of any grade was reported in 39% of patients treated with acalabrutinib in the ELEVATE-TN trial, with grade ≥3 bleeding observed in 2% of patients 1
• The primary concern with this combination is the additive pharmacodynamic effect on bleeding risk rather than a pharmacokinetic interaction 1
• The NCCN guidelines specifically note that "the benefit and risk of ibrutinib or acalabrutinib should be evaluated in patients requiring antiplatelet or anticoagulant therapies" 1

Recommendations for Management

• Monitor patients closely for signs of bleeding when using this combination 1
• Consider the following risk mitigation strategies:
  • Regular clinical assessment for bruising, petechiae, or other signs of bleeding 1
  • Monitor complete blood counts to assess for thrombocytopenia 1
  • Educate patients about bleeding symptoms requiring immediate medical attention 1

Special Considerations

• Patients with atrial fibrillation may require both medications, as BTKi therapy has been associated with atrial fibrillation in 4-6% of patients 1
• NCCN guidelines recommend that "switching to alternate therapy should be considered, especially in patients with atrial fibrillation/hypertension that is not medically controllable" 1
• If a patient develops atrial fibrillation while on acalabrutinib, consider alternative anticoagulation strategies before using apixaban 1

Important Caveats

• Patients requiring warfarin have been excluded from clinical trials evaluating acalabrutinib, and concomitant administration of acalabrutinib with warfarin should be avoided 1
• Unlike some other small-molecule inhibitors used in cancer treatment that have significant pharmacokinetic interactions with apixaban, acalabrutinib does not appear in guidelines as requiring specific dose adjustments when used with apixaban 1
• Over-the-counter medications like NSAIDs or aspirin may further increase bleeding risk when added to this combination and should be avoided if possible 2

By following these recommendations, clinicians can minimize the risk of bleeding complications while providing necessary treatment with both acalabrutinib and apixaban when clinically indicated.