Amichai Perlman1,2, Maor Wanounou3, Rachel Goldstein1,3, Lotan Choshen Cohen3, Daniel E Singer4, Mordechai Muszkat5. 1. Division of Clinical Pharmacy, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel. 2. K-Health Inc, Tel Aviv, Israel. 3. Department of Medicine, Hadassah Hebrew University Hospital, Mt. Scopus, P.O. Box 24035, 91240, Jerusalem, Israel. 4. Division of General Internal Medicine, Massachusetts General Hospital, and Harvard Medical School, Boston, MA, USA. 5. Department of Medicine, Hadassah Hebrew University Hospital, Mt. Scopus, P.O. Box 24035, 91240, Jerusalem, Israel. muszkatm@hadassah.org.il.
Abstract
INTRODUCTION: Factor Xa-inhibiting direct oral anticoagulants (FXa-DOACs) undergo hepatic metabolism via cytochrome P-450 (CYP450). Concomitant use of rifampicin, an inducer of these enzymes, with FXa-DOACs, has been shown to decrease FXa-DOAC concentrations in healthy subjects. Several common antiepileptic drugs (AEDs) are known to induce CYP450 enzymes as well. However, little is known regarding the impact of this potential interaction on treatment outcomes with FXa-DOACs. METHODS: We analyzed adverse event cases submitted to the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) from January 2013 to December 2018. We compared the proportion of cases reporting thromboembolic and ischemic adverse events (TAIAEs) with the concomitant use of FXa-DOACs and enzyme-inducing AEDs to the proportion of cases with FXa-DOACs and other AEDs. RESULTS: During this period, 9693 adverse event cases reported concomitant use of FXa-DOACs and AEDs. Almost all reports (> 99%) involved the use of rivaroxaban or apixaban. Compared with other AEDs, enzyme-inducing AEDs were associated with an 86% increase in the odds of reporting TAIAEs [reporting odds ratio (ROR) 1.86, 95% confidence interval (CI) 1.61-2.15; p < 0.0001]. In secondary separate analyses of rivaroxaban and apixaban, enzyme-inducing AEDs were similarly associated with increased reporting of a TAIAE (ROR 1.79, 95% CI 1.50-2.12, and ROR 1.88, 95% CI 1.41-2.48, respectively). CONCLUSION: Using real world data, we observed an increase in the odds of reporting anticoagulation treatment failure among patients treated with FXa-DOACs and concomitant enzyme-inducing AEDs compared to those treated with other AEDs.
INTRODUCTION:Factor Xa-inhibiting direct oral anticoagulants (FXa-DOACs) undergo hepatic metabolism via cytochrome P-450 (CYP450). Concomitant use of rifampicin, an inducer of these enzymes, with FXa-DOACs, has been shown to decrease FXa-DOAC concentrations in healthy subjects. Several common antiepileptic drugs (AEDs) are known to induce CYP450 enzymes as well. However, little is known regarding the impact of this potential interaction on treatment outcomes with FXa-DOACs. METHODS: We analyzed adverse event cases submitted to the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) from January 2013 to December 2018. We compared the proportion of cases reporting thromboembolic and ischemic adverse events (TAIAEs) with the concomitant use of FXa-DOACs and enzyme-inducing AEDs to the proportion of cases with FXa-DOACs and other AEDs. RESULTS: During this period, 9693 adverse event cases reported concomitant use of FXa-DOACs and AEDs. Almost all reports (> 99%) involved the use of rivaroxaban or apixaban. Compared with other AEDs, enzyme-inducing AEDs were associated with an 86% increase in the odds of reporting TAIAEs [reporting odds ratio (ROR) 1.86, 95% confidence interval (CI) 1.61-2.15; p < 0.0001]. In secondary separate analyses of rivaroxaban and apixaban, enzyme-inducing AEDs were similarly associated with increased reporting of a TAIAE (ROR 1.79, 95% CI 1.50-2.12, and ROR 1.88, 95% CI 1.41-2.48, respectively). CONCLUSION: Using real world data, we observed an increase in the odds of reporting anticoagulation treatment failure among patients treated with FXa-DOACs and concomitant enzyme-inducing AEDs compared to those treated with other AEDs.
Authors: Christopher B Granger; John H Alexander; John J V McMurray; Renato D Lopes; Elaine M Hylek; Michael Hanna; Hussein R Al-Khalidi; Jack Ansell; Dan Atar; Alvaro Avezum; M Cecilia Bahit; Rafael Diaz; J Donald Easton; Justin A Ezekowitz; Greg Flaker; David Garcia; Margarida Geraldes; Bernard J Gersh; Sergey Golitsyn; Shinya Goto; Antonio G Hermosillo; Stefan H Hohnloser; John Horowitz; Puneet Mohan; Petr Jansky; Basil S Lewis; Jose Luis Lopez-Sendon; Prem Pais; Alexander Parkhomenko; Freek W A Verheugt; Jun Zhu; Lars Wallentin Journal: N Engl J Med Date: 2011-08-27 Impact factor: 91.245
Authors: Matteo Candeloro; John W Eikelboom; Noel Chan; Vinai Bhagirath; James D Douketis; Sam Schulman Journal: Res Pract Thromb Haemost Date: 2022-02-17