Factors associated with subtherapeutic levels of valproic acid in hospitalized patients with epilepsy: A retrospective cohort study

Valproic acid (VPA) is a commonly used anti-seizure medication, owing to its efficacy and cost-effectiveness. However, maintaining appropriate serum levels is crucial due to the narrow therapeutic window, as subtherapeutic levels can lead to treatment failure or adverse outcomes. This study aimed to identify the factors associated with subtherapeutic serum levels of valproic acid in patients undergoing treatment. This retrospective cohort study was performed at a tertiary care hospital and involved inpatients aged ≥ 18 years who were receiving valproic acid for epilepsy treatment. Data were obtained through chart reviews and a Therapeutic Drug Monitoring database. Subtherapeutic VPA levels were defined as < 50 mg/L. Logistic regression was used to identify risk factors for subtherapeutic levels. Of the 152 patients, 96 (63.2%) had subtherapeutic VPA levels (<50 mg/L). Males were more likely than females to have subtherapeutic levels (OR 2.45, 95% CI: 1.15-5.22; P = .02). Previous use of phenytoin significantly increased the risk of subtherapeutic VPA levels (OR 2.58, 95% CI: 1.16-5.71; P = .02). VPA administration by syrup and doses below 15 mg/kg/day were associated with subtherapeutic levels (OR 3.28 and 2.34, respectively). Additionally, co-medications, such as topiramate and meropenem, also increased this risk (OR 5.09 and 4.64, respectively). This study identified several factors significantly associated with subtherapeutic levels of valproic acid, including males, prior phenytoin use, co-medications, such as topiramate and meropenem, and lower VPA dosages. These findings underscore the importance of careful monitoring and individualized treatment plans to maintain therapeutic VPA levels in clinical practice. Further research is needed to explore the clinical implications and to develop strategies to minimize the risk of subtherapeutic levels in patients receiving VPA.