# Interactions of Enzyme-Inducing Antiepileptic Drugs with Direct-Acting Oral Anticoagulants: Risk of Thromboembolic Events > **NIH NIH F31** · UNIVERSITY OF PENNSYLVANIA · 2024 · $23,314 ## Abstract Project Summary/Abstract Epilepsy affects over 70 million people worldwide, including an estimated 3.4 million in the US. Multiple widely- used antiepileptic drugs (AEDs) have off-target effects inducing key drug metabolizing enzymes, yielding numerous potential drug-drug interactions (DDIs). One such interaction with particularly high real-world relevance, but minimal clinical evidence, has been purported to occur between these enzyme-inducing AEDs (EI-AEDs) and direct-acting oral anticoagulants (DOACs). Co-prescription of AEDs with anticoagulants is common due to the frequent concurrency and causal links between epilepsy and the main indications for DOACs. EI-AEDs induce two crucial components of DOAC absorption and metabolism, which may lead to lower, potentially sub-therapeutic, levels of DOACs, and an increased risk of thromboembolic events. Evidence for these DDIs is composed primarily of in vitro and animal data. Existing human studies have limited real-world applicability due to both: substantial inconsistencies in findings, and methods that put the research at high risk for bias and confounding. Further, these human studies’ narrow focus on pairwise EI-AED/DOAC interactions disregards the potential role of higher-order drug-drug-drug interactions (3DIs), particularly given the high prevalence of polypharmacy in epilepsy populations. The goal of this research plan is to apply methodologically rigorous designs and leverage large-scale administrative claims data to address knowledge gaps regarding real- world DOAC therapeutic failures associated with EI-AED and concomitant drug interactions. In Aim 1, we will use a retrospective incident user cohort design to compare thromboembolic event rates in adults with epilepsy exposed to DOACs with EI-AEDs versus an active comparator group exposed to DOACs with non-enzyme inducing AEDs (NEI-AEDs). Given critical differences in utilization and thrombotic risk, we will separately analyze DOAC use for atrial fibrillation (1A) and deep vein thrombus/pulmonary embolism (1B). To generate effect estimates with vigorous control for observed and unobserved confounders (via proxy-adjustment), data-adaptive high-dimensional propensity scoring will be employed. In Aim 2, we will use a case-crossover design to explore the role of 3DIs in thromboembolic events in adults with epilepsy prescribed EI-AEDs and DOACs. A novel within- person approach to 3DI screening will be undertaken based on the temporal associations of concomitant drugs with thromboembolic events. Estimates will be quantitatively compared to a negative case group prescribed NEI- AEDs with DOACs in order to mitigate the direct effects and confounding by concomitant drugs, as well as to differentiate 3DI from DDI signals. Overall, this research will contribute to the advancement of prescribing standards for epilepsy patients requiring anticoagulation and provide benchmarks for future 3DI investigations. The valuable skills and experiences gained from ... ## Key facts - **NIH application ID:** 10934318 - **Project number:** 5F31NS130952-02 - **Recipient organization:** UNIVERSITY OF PENNSYLVANIA - **Principal Investigator:** Emily Kate Acton - **Activity code:** F31 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2024 - **Award amount:** $23,314 - **Award type:** 5 - **Project period:** 2023-02-03 → 2024-04-05 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10934318 ## Citation > US National Institutes of Health, RePORTER application 10934318, Interactions of Enzyme-Inducing Antiepileptic Drugs with Direct-Acting Oral Anticoagulants: Risk of Thromboembolic Events (5F31NS130952-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10934318. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*