Management strategies of the interaction between direct oral anticoagulant and drug-metabolizing enzyme inducers

Amichai Perlman, Sarit Hochberg-Klein, Lotan Choshen Cohen, Gil Dagan, Bruria Hirsh-Raccah, Ehud Horwitz, Gefen Aldouby-Bier, Tamar Negev, Ilan Matok, Laurent Azoulay, Yosef Kalish, Mordechai Muszkat*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


Little is known regarding the management of direct oral anticoagulants (DOACs) in patients with enzyme-inducing drugs (EID). The use of EID may lead to sub-therapeutic concentrations of DOACs and to treatment failure. Thus, many patients on EIDs cannot benefit from the advantages of DOACs. This was a retrospective study, evaluating the management of hospitalized patients with DOACs. Characteristics of hospitalized patients with a prescription for DOACs, with and without EIDs, were summarized and evaluated, and management strategies addressing the potential interaction were documented, including the use of DOAC concentration monitoring. During the period evaluated, 1596 hospitalized patients with prescriptions for DOACs were identified. Most patients received apixaban (n = 1227, 77%), followed by rivaroxaban (240, 15%), and dabigatran (129, 8%). Twenty-two patients (1.4%) had concomitant EIDs. Demographic and clinical characteristics of hospitalized patients with DOACs were similar in those receiving EID and those not. Management strategies included stopping DOAC or EID (41%), and DOAC dose increase (14%). During management of these interactions, DOAC concentrations were measured for 11 of 22 patients and were below the 5th percentile of expected concentration for six of these patients. The management of patients with DOAC concentration measurement differed significantly from those without (p = 0.005), as they were much less likely to have one of the medications stopped and more often had the DOACs’ dose increased. Among hospitalized patients with DOACs, EIDs are not rare. DOAC concentrations are often low in the presence of EIDs. DOAC concentration monitoring may be useful in settings requiring both DOAC and EIDs.

Original languageAmerican English
Pages (from-to)590-595
Number of pages6
JournalJournal of Thrombosis and Thrombolysis
Issue number4
StatePublished - 15 May 2019

Bibliographical note

Publisher Copyright:
© 2019, Springer Science+Business Media, LLC, part of Springer Nature.


  • Antiepileptics
  • Apixaban
  • Dabigatran
  • Direct oral anticoagulants
  • Drug interaction
  • Inducers
  • Rivaroxaban


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