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Apixaban is a substrate of both CYP3A4 and P-gp. Inhibitors of CYP3A4 and P-gp increase exposure to apixaban and increase the risk of bleeding. Inducers of CYP3A4 and P-gp decrease exposure to apixaban and increase the risk of stroke.
Strong Dual Inhibitors of CYP3A4 and P-gp: The dose of Apixaban should be decreased to 2.5 mg twice daily when it is coadministered with drugs that are strong dual inhibitors of CYP3A4 and P-gp, (e.g., ketoconazole, itraconazole, ritonavir, or clarithromycin).
In patients already taking Apixaban at a dose of 2.5 mg daily, avoid coadministration with strong dual inhibitors of both CYP3A4 and P-gp.
Strong Dual Inducers of CYP3A4 and P-gp: Avoid concomitant use of Apixaban with strong dual inducers of CYP3A4 and P-gp (e.g., rifampin, carbamazepine, phenytoin, St. John's wort) because such drugs will decrease exposure to apixaban.
Anticoagulants and Antiplatelet Agents: Coadministration of antiplatelet agents, fibrinolytics, heparin, aspirin, and chronic NSAID use increases the risk of bleeding.
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