Clinical Interactions Between Antiseizure Medications and Direct Oral Anticoagulants: A Scoping Review on Therapeutic Failures and Knowledge Gaps

PURPOSE: Antiseizure medications (ASMs) are often coprescribed with direct oral anticoagulants (DOACs). The pharmacokinetic (PK) interactions between ASMs and DOACs may result in altered exposure to anticoagulants, potentially increasing the risk of thromboembolic events or bleeding. This review summarizes the clinical evidence on drug-drug interactions between ASMs and DOACs. METHODS: In accordance with PRISMA-ScR guidelines, a systematic literature search was conducted in PubMed (up to November 2025). All clinical reports and observational datasets reporting the concomitant use of at least 1 ASM and DOAC were included. ASM-DOAC combinations, PK findings, and reported clinical outcomes are presented. RESULTS: Thirty studies were included. Most reports involved enzyme-inducing ASMs (carbamazepine, phenobarbital, primidone, and oxcarbazepine), which were consistently associated with subtherapeutic DOAC plasma concentrations and severe clinical failures. Doubling the DOAC dose did not prevent these events in several cases. Rivaroxaban and apixaban were the most frequently described DOACs, whereas clinical data for edoxaban were limited. Evidence of non-enzyme-inducing ASMs, such as levetiracetam and valproic acid, was limited. CONCLUSIONS: Although enzyme-inducing ASMs compromised DOAC efficacy, the available clinical evidence was fragmented and prone to publication bias. The observed variability in interactions involving noninducing ASMs such as levetiracetam underlines the clinical complexity that may exceed theoretical PK predictions. Given the unpredictability of these interactions and the failure of empirical dose adjustments, a standardized approach for therapeutic drug monitoring and prospective, comparative trials are essential to guide personalized therapy in this high-risk population.