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, François Mullier

Research output: Contribution to journalArticlepeer-review

Abstract

PURPOSE: The concomitant use of direct oral anticoagulants (DOAC) and strong P-gp and 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.

METHODS: We retrospectively identified hospitalized patients receiving simultaneously 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 to on-therapy ranges observed in pivotal trials. Individual risk factors for high or low DOAC levels were identified.

RESULTS: We 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).

CONCLUSION: Our 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.

Original languageEnglish
JournalThe American journal of medicine
DOIs
Publication statusE-pub ahead of print - 25 Jun 2021

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