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The Impact of Strong Inducers on Direct Oral Anticoagulant Plasma Levels: A Retrospective Study

1Université Catholique de Louvain, CHU UCL Namur, NTHC, NARILIS, Department of Pharmacy, Yvoir, Belgium, 2Université Catholique de Louvain, Cliniques Universitaires Saint-Luc, Department of Internal Medicine, Brussels, Belgium, 3Université Catholique de Louvain, CHU UCL Namur, NTHC, NARILIS, Department of Anesthesiology, Yvoir, Belgium, 4Université Catholique de Louvain, CHU UCL Namur, NTHC, NARILIS, Hematology Laboratory, Yvoir, Belgium, 5Pharmacy Department, NTHC, NARILIS, Université de Namur, Namur, Belgium, 6Clinical Pharmacy Research Group, Louvain Drug Research Institute, Université Catholique de Louvain, Brussels, Belgium

Abstract Number: PB1078

Meeting: ISTH 2021 Congress

Theme: Venous Thromboembolism » Atrial Fibrillation

Background: All direct oral anticoagulants (DOAC) are transported by P-glycoprotein (P-gp), and some of them are metabolized by CYP3A4. Therefore, concomitant use of DOAC and strong CYP3A4/P-gp inducers leads to a potential risk of reduced DOAC levels and therapeutic failure. However, data are scarce in clinical practice.

Aims: To describe DOAC plasma concentrations in patients receiving strong CYP3A4/P-gp inducers, in relation to risk factors for either drug accumulation or loss of efficacy.

Methods: We retrospectively analyzed DOAC measurements performed in clinical practice at the CHU UCL Namur between 2016 and 2021. We included patients receiving simultaneously a DOAC and carbamazepine, phenobarbital, phenytoin, rifampicin or St John’s Wort. Socio-demographic, clinical and medication data were collected. DOAC peak and/or trough levels were estimated at steady-state using specific chromogenic assays. They were compared to on-therapy ranges observed in the pivotal trials. Expected ranges were divided into quartiles, from Q1 (lower) to Q4 (upper). For each patient, risk factors for high or low DOAC levels were identified.

Results: We included 16 patients (median age: 75 years), mainly receiving apixaban (8/16) along with carbamazepine (8/16). Five patients (31%) had peak and/or trough level below the expected range. Among the remaining 11 patients, 8 had at least one measurement in the lower quartile of the range (Q1). The median number of risk factors for drug accumulation was 0 in patients with DOAC levels below the range, compared to 2 in patients with DOAC levels within the range (Figure 1). All DOAC patients aged ≥ 75 years with renal impairment had plasma concentrations within the range.

Individual risk factors for high or low DOAC plasma levels

Conclusions: Our data suggest a significant risk of reduced DOAC levels in patients taking strong CYP3A4/P-gp inducers, especially in patients without risk factors for drug accumulation. In clinical practice, DOAC measurement could help manage the concomitant use of DOAC and strong inducers.    

To cite this abstract in AMA style:

Sennesael A-, Larock A-, Hainaut P, Lessire S, Hardy M, Douxfils J, Spinewine A, Mullier F. The Impact of Strong Inducers on Direct Oral Anticoagulant Plasma Levels: A Retrospective Study [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/the-impact-of-strong-inducers-on-direct-oral-anticoagulant-plasma-levels-a-retrospective-study/. Accessed December 11, 2023.

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