• Am. J. Med. · Oct 2021

    The impact of strong inducers on direct oral anticoagulant levels.

    • Anne-Laure Sennesael, Anne-Sophie Larock, Philippe Hainaut, Sarah Lessire, Michael Hardy, Jonathan Douxfils, Anne Spinewine, and François Mullier.
    • Department of Pharmacy, Centre Hospitalier Universitaire (CHU) UCL Namur, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for Life Sciences (NARILIS), Université catholique de Louvain, Yvoir, Belgium; Clinical Pharmacy Research Group, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium. Electronic address: anne-laure.sennesael@uclouvain.be.
    • Am. J. Med. 2021 Oct 1; 134 (10): 1295-1299.

    PurposeThe concomitant use of direct oral anticoagulants (DOAC) and strong P-glycoprotein (P-gp) and cytochrome P450 3A4 (CYP3A4) inducers may lead to reduced DOAC levels and therapeutic failure. This study aimed to describe DOAC concentrations in patients receiving strong P-gp and CYP3A4 inducers, in relation to individual risk factors for high or low DOAC levels.MethodsWe retrospectively identified hospitalized patients simultaneously receiving a DOAC and carbamazepine, phenobarbital, phenytoin, or rifampicin between 2016 and 2021. Among them, patients who underwent DOAC measurement at steady state were included. DOAC peak or trough levels were compared with on-therapy ranges observed in pivotal trials. Individual risk factors for high or low DOAC levels were identified.ResultsWe included 17 patients (median age 75 years), mainly receiving apixaban and carbamazepine. For 5 patients (29%), DOAC trough or peak level was below the expected range. Among the remaining 12 patients, 8 had at least one measurement in the lower quartile of the range. The median number of risk factors for drug accumulation was 0 (range 0-1) in patients with ≥1 measurement below the range and 2 (range 0-3) in other patients. DOAC measurement led to treatment adjustments in 9 patients (DOAC dose increase or switch).ConclusionOur data suggest a significant risk of reduced DOAC levels in patients taking strong P-gp and CYP3A4 inducers, especially those without risk factors for drug accumulation. DOAC measurement could help manage this relevant drug-drug interaction.Copyright © 2021 Elsevier Inc. All rights reserved.

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