Vol.:(0123456789) 1 3 Journal of Thrombosis and Thrombolysis https://doi.org/10.1007/s11239-018-01804-7 Management strategies of the interaction between direct oral anticoagulant and drug-metabolizing enzyme inducers 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 © Springer Science+Business Media, LLC, part of Springer Nature 2019 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 beneft from the advantages of DOACs. This was a retrospective study, evaluating the management of hos- pitalized 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 prescrip- tions for DOACs were identifed. 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 stop- ping 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 difered signifcantly 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 Amichai Perlman and Sarit Hochberg-Klein have contributed equally to this work. * Mordechai Muszkat muszkatm@hadassah.org.il 1 Pharmacy Division, Hadassah Hebrew University Medical Center, Jerusalem, Israel 2 Department of Medicine, Hadassah Hebrew University Medical Center, Mt Scopus, 91540 Jerusalem, Israel 3 Division of Clinical Pharmacy, Institute for Drug Research, School of Pharmacy, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel 4 Department of Cardiology, Hadassah Hebrew University Medical Center, Jerusalem, Israel 5 Department of Oncology, Hadassah Hebrew University Medical Center, Jerusalem, Israel 6 Department of Orthopedics, Hadassah Hebrew University Medical Center, Jerusalem, Israel 7 Department of Epidemiology, Biostatistics, and Occupational Health, Centre for Clinical Epidemiology, Jewish General Hospital, Lady Davis Institute, Montreal, Canada 8 Gerald Bronfman Department of Oncology, McGill University, Montreal, Canada 9 Department of Hematology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel