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DDI for warfarin mainly involve moderate to strong inhibitors\/inducers of cytochrome P450 (CYP) 2C9, which is responsible for the elimination of the more potent S-isomer of warfarin. However, inhibitor\/inducers of CYP3A4 and CYP1A2 may also cause DDI with warfarin. Recognition of these precipitating agents along with increased frequency of monitoring when these agents are initiated or discontinued will minimize the impact of warfarin DDI. Direct oral anticoagulants are mainly affected by medications strongly affecting the permeability glycoprotein (P-gp), and to a lesser extent, strong CYP3A4 inhibitors\/inducers. Dabigatran and edoxaban are affected by P-gp modulation. Strong inducers of CYP3A4 or P-gp should be avoided in all patients taking direct oral anticoagulant unless previously proven to be otherwise safe. Simultaneous strong CYP3A4 and P-gp inhibitors should be avoided in patients taking apixaban and rivaroxaban. Concomitant antiplatelet\/anticoagulant use confers additive risk for bleeding, but their combination is unavoidable in many cases. Minimizing duration of concomitant anticoagulant\/antiplatelet therapy as indicated by evidence-based clinical guidelines is the best way to reduce the risk of bleeding.<\/jats:p>","DOI":"10.1161\/circep.121.007956","type":"journal-article","created":{"date-parts":[[2022,5,27]],"date-time":"2022-05-27T12:07:41Z","timestamp":1653653261000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":83,"title":["Drug Interactions Affecting Oral Anticoagulant Use"],"prefix":"10.1161","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3576-0435","authenticated-orcid":true,"given":"Philip L.","family":"Mar","sequence":"first","affiliation":[{"name":"Division of Cardiology, Department of Medicine, St. Louis University, MO (P.L.M., A.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4611-3687","authenticated-orcid":true,"given":"Rakesh","family":"Gopinathannair","sequence":"additional","affiliation":[{"name":"Kansas City Heart Rhythm Institute (R.G., D.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5666-4955","authenticated-orcid":true,"given":"Brooke E.","family":"Gengler","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Saint Louis University Hospital, MO (B.E.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7835-6045","authenticated-orcid":true,"given":"Mina K.","family":"Chung","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Heart, Vascular &amp; 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