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Comment & Response
February 27, 2018

Drug Interactions With NonVitamin K Oral Anticoagulants

Author Affiliations
  • 1Department of Clinical Pharmacy, University of Colorado, Aurora
  • 2Department of Medicine (Geriatrics), University of Pittsburgh, Pittsburgh, Pennsylvania
JAMA. 2018;319(8):828-829. doi:10.1001/jama.2017.20834

To the Editor The study by Dr Chang and colleagues evaluated bleeding associated with drug-drug interactions with NOACs.1 We believe that the authors provided erroneous information about the mechanisms by which the 12 drugs potentially interact with the 3 NOACs, which was further confused by the use of 3 categories (P-glycoprotein competitors, CYP3A4 inhibitors, or both). Dabigatran is a substrate for the transporter P-glycoprotein, whereas rivaroxaban and apixaban are substrates for both P-glycoprotein and CYP3A4.2 Chronic use of phenytoin and rifampin induces both CYP3A4 and P-glycoprotein as opposed to both being P-glycoprotein competitors and CYP3A4 inhibitors, as stated by the authors.1-4 Other drug interaction errors presented were that digoxin is a competitor of P-glycoprotein and atorvastatin is a dual competitor and inhibitor of P-glycoprotein and CYP3A4; in contrast, both are substrates for P-glycoprotein and atorvastatin is also a CYP3A4 substrate.1-4 All of the remaining drugs are inhibitors of both P-glycoprotein and CYP3A4.2-4