Chiara Cancellerini

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.

Objective: Capillary microsampling offers a minimally invasive alternative to venipuncture for therapeutic drug monitoring (TDM) of anti‐seizure medications (ASMs). We evaluated the feasibility and reliability of volumetric absorptive microsampling (VAMS) and quantitative dried blood spot (qDBS) devices for ambulatory self‐collection and at‐home use in persons with epilepsy (PwE). Methods: PwE attending the Epilepsy Centre of the IRCCS‐Istituto delle Scienze Neurologiche di Bologna (Italy) were enrolled between October 2023 and October 2024. Participants performed supervised self‐collection using VAMS and qDBS in ambulatory setting and at‐home self‐collection with VAMS devices. Sample quality, delivery success, and patient‐reported outcomes (ease, pain, and clarity of instructions) were recorded. Carbamazepine, lacosamide, lamotrigine, and levetiracetam were quantified using a validated ultra‐high performance liquid chromatography‐tandem mass spectrometry (UHPLC–MS/MS) method. Reliability was assessed by comparing at‐home VAMS with ambulatory VAMS and cross‐validating qDBS with VAMS and venous plasma samples using Bland–Altman analysis and linear regression. Results: A total of 105 PwE (66% female, mean age 41 years) performed at‐home and ambulatory self‐collection using VAMS and qDBS devices. Most at‐home VAMS samples (88%) were received by the laboratory within 7 days, and 86.8% met high‐quality criteria. For lacosamide, lamotrigine, and levetiracetam, we found strong correlations between at‐home and ambulatory VAMS (Pearson's r ranging from .88 to .98) and low mean bias (60 years impacted sampling quality, particularly for qDBS ( p = .04). Significance: VAMS‐based self‐collection is feasible and reliable for at‐home TDM, provided that high‐quality sampling is ensured. qDBS represents a reliable alternative for ambulatory monitoring. Future work should focus on optimizing sampling procedures for older adults and improving logistics for home‐based microsampling.

This study describes the development and validation of a fully automated workflow for serum sample preparation, enabling the quantitative determination of cannabidiol (CBD) and its active metabolite, 7-hydroxy-CBD, via liquid chromatography coupled with tandem mass spectrometry (LC–MS/MS) analysis. Implemented on an automated platform, the workflow performs key steps such as solvent dispensing, mixing, centrifugation, filtration, and supernatant transfer, producing 96-well plates ready for analysis. Human serum samples were obtained from patients with epilepsy treated with CBD. All samples were processed using both manual and automated methods to evaluate method agreement. Quantification was performed by LC–MS/MS with CBD-d₃ as the internal standard (IS). Method validation was conducted in accordance with European Medicine Agency (EMA) guidelines, confirming that the automated protocol meets the recommended acceptance criteria for both intraday and interday precision and accuracy. Calibration curves demonstrated excellent linearity across the concentration ranges. Comparative analysis using Passing–Bablok regression and Bland–Altman plots demonstrated strong agreement between the methods. These findings support the clinical applicability of the automated method for the therapeutic drug monitoring (TDM) of CBD and 7-hydroxy-CBD, and its robust performance and scalability provide a solid foundation for the development of an expanded analytical panel covering a broader range of antiseizure medications (ASMs), enabling more standardized TDM protocols in clinical practice.