Which anticoagulant carries the lowest risk of metabolic drug-drug interactions?
The new oral anticoagulants (NOACs) are less likely than warfarin to interact with other drugs, but agents that affect the cytochrome P450 (CYP) 3A4 enzyme or the P-glycoprotein (P-gp) can change the plasma concentrations of NOACs and ultimately alter their impact on anticoagulation. Dabigatran has a very low potential for drug-drug interactions because its plasma levels are affected only by P-gp, noted Dr. Jean M. Connors, medical director of anticoagulation management service at Brigham and Women's Hospital and the Dana-Farber Cancer Institute in Boston. Although providers don’t have to worry about combining dabigatran with drugs that inhibit or induce CYP3A4, co-administering dabigatran with other anticoagulants and antiplatelet agents could increase bleeding risks. Dr. Connors said strong CYP3A4 and P-gp inhibitors or inducers could result in substantial changes in the plasma concentrations of rivaroxaban and, to some degree, apixaban.
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Dr. Connors has focused on the effective anticoagulation of cancer patients, who she said are at increased risk for thrombotic events and 2 to 6 times more likely to suffer bleeding events while on anticoagulants. A recent report she co-authored tagged enzalutamide (an androgen receptor antagonist used to treat castration-resistant prostate cancer) and dexamethasone (a glucocorticoid used for its antitumor effects in many lymphoid malignancies) as strong inhibitors of CYP3A4 that can impact the anticoagulant effects of NOACs. The report also noted that the anti-cancer therapies paclitaxel, vemurafenib, prednisone, and bexarotene cause moderate induction of CYP3A4 activity and have little impact on P-gp, meaning combining the agents with rivaroxaban or apixaban could decrease the plasma concentrations of the anticoagulants but wouldn’t impact the concentration of dabigatran. The report said providers should weigh the risk of bleeding against the benefit of preventing thromboembolic events in cancer patients who are candidates for anticoagulation therapy, and noted that the safety of combining cancer therapies with NOACs must be assessed based on their interactions with CYP3A4 and P-gp.
Short NJ, Connors JM. New Oral Anticoagulants and the Cancer Patient. Oncologist. 2014;19(1):82-93.