Below is a summary of relevant drug interactions taken from the prescribing information for each agent:
- Antagonized by P-gp inducers (eg, rifampin); avoid.
- Increased dabigatran levels with P-gp inhibitors (eg, dronedarone, ketoconazole, verapamil, amiodarone, quinidine, clarithromycin).
- Concomitant NSAIDs, platelet inhibitors, heparin, fibrinolytic therapy: increased risk of bleeding.
- Increased risk of bleeding with concomitant aspirin, P2Y12 platelet inhibitors, other antithrombotic agents, fibrinolytic therapy, NSAIDs, clopidogrel; avoid.
- Avoid with concomitant combined P-gp and strong CYP3A4 inhibitors (eg, ketoconazole, itraconazole, lopinavir/ritonavir, ritonavir, indinavir/ritonavir, conivaptan).
- Avoid with concomitant combined P-gp and strong CYP3A4 inducers (eg, carbamazepine, phenytoin, rifampin, St. John’s wort).
- May be potentiated with concomitant renal impairment and combined P-gp and weak or moderate CYP3A4 inhibitors (eg, erythromycin, azithromycin, diltiazem, verapamil, quinidine, ranolazine, dronedarone, amiodarone, felodipine).
- Concomitant strong dual inhibitors of CYP3A4 and P-gp (eg, ketoconazole, itraconazole, ritonavir, clarithromycin): 2.5mg twice daily; if already on 2.5mg twice daily, coadministration should be avoided.
- Potentiated by dual inhibitors of CYP3A4 and P-gp.
- Antagonized by concomitant strong dual inducers of CYP3A4 and P-gp (eg, rifampin, carbamazepine, phenytoin, St. John’s wort); avoid.
- Increased risk of bleeding with concomitant aspirin, antiplatelet agents, fibrinolytics, other anticoagulants, heparin, thrombolytic agents, selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, NSAIDs.
All physicians, including cardiologists, need to become more familiar with potential DDIs between commonly used agents. Zhou et al posit that one of the drivers of DDIs is lack of coordination among healthcare providers and suggest a model of “integrated care, in a dynamic continuum.”
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