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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 MuszkatEmail author
Article

Abstract

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.

Keywords

Direct oral anticoagulants Apixaban Rivaroxaban Dabigatran Inducers Antiepileptics Drug interaction 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The study was approved by the institutional review board (365-15-HMO).

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Amichai Perlman
    • 1
    • 2
    • 3
  • Sarit Hochberg-Klein
    • 2
    • 7
  • Lotan Choshen Cohen
    • 2
  • Gil Dagan
    • 2
  • Bruria Hirsh-Raccah
    • 1
    • 3
    • 4
  • Ehud Horwitz
    • 1
    • 2
  • Gefen Aldouby-Bier
    • 1
    • 5
  • Tamar Negev
    • 1
    • 6
  • Ilan Matok
    • 3
  • Laurent Azoulay
    • 7
    • 8
  • Yosef Kalish
    • 9
  • Mordechai Muszkat
    • 2
    Email author
  1. 1.Pharmacy DivisionHadassah Hebrew University Medical CenterJerusalemIsrael
  2. 2.Department of MedicineHadassah Hebrew University Medical CenterJerusalemIsrael
  3. 3.Division of Clinical Pharmacy, Institute for Drug Research, School of Pharmacy, Faculty of MedicineHebrew University of JerusalemJerusalemIsrael
  4. 4.Department of CardiologyHadassah Hebrew University Medical CenterJerusalemIsrael
  5. 5.Department of OncologyHadassah Hebrew University Medical CenterJerusalemIsrael
  6. 6.Department of OrthopedicsHadassah Hebrew University Medical CenterJerusalemIsrael
  7. 7.Department of Epidemiology, Biostatistics, and Occupational Health, Centre for Clinical EpidemiologyJewish General Hospital, Lady Davis InstituteMontrealCanada
  8. 8.Gerald Bronfman Department of OncologyMcGill UniversityMontrealCanada
  9. 9.Department of HematologyHadassah-Hebrew University Medical CenterJerusalemIsrael

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