Ischemic and Thrombotic Events Associated with Concomitant Xa-inhibiting Direct Oral Anticoagulants and Antiepileptic Drugs: Analysis of the FDA Adverse Event Reporting System (FAERS)

Amichai Perlman, Maor Wanounou, Rachel Goldstein, Lotan Choshen Cohen, Daniel E. Singer, Mordechai Muszkat*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

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.

Original languageAmerican English
Pages (from-to)1223-1228
Number of pages6
JournalCNS Drugs
Volume33
Issue number12
DOIs
StatePublished - 1 Dec 2019

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© 2019, Springer Nature Switzerland AG.

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