Topiramate Increases Risk of Hyperammonemia in Epilepsy Patients with Valproic Acid Therapy
Abstract number :
2.278
Submission category :
7. Anti-seizure Medications / 7D. Drug Side Effects
Year :
2023
Submission ID :
11
Source :
www.aesnet.org
Presentation date :
12/3/2023 12:00:00 AM
Published date :
Authors :
Presenting Author: Dong Won Kwack, MD – Konkuk University Medical Center
Dong Wook Kim, MD, PhD – Neurology – Konkuk University Medical Center
Rationale: Hyperammonemia can occur after acute overdose or chronic use of valproic acid (VPA). Although VPA-related hyperammonemic encephalopathy (VHE) is a rare complication of VPA therapy, early recognition of VHE and identifying its risk factors are important because VHE can lead to loss of consciousness and increased seizure frequency. The purpose of our study is to evaluate the risk factors of hyperammonemia in epilepsy patients during the treatment with VPA therapy.
Methods: We reviewed the medical records of 1,084 adult patients with epilepsy and enrolled 116 patients with VPA therapy who had results of blood levels of ammonia over a three year period. Hyperammonemia was defined as a blood ammonia level exceeding 80 ug/dL. Correlations of blood levels of ammonia with dosages and blood levels of VPA were evaluated. We further performed univariate and multivariate linear regression analyses to identify risk factors for hyperammonemia in epilepsy patients treated with VPA therapy.
Results: Blood levels of ammonia were correlated with dosages of VPA (p = 0.036) but not with blood levels of VPA (p = 0.463). Hyperammonemia was more common in patients with higher VPA dosage and higher total drug loads of concurrent antiseizure medications (ASMs). Hyperammonemia was also associated with the use of topiramate, levetiracetam, and several ASMs with metabolic inducing properties. In multivariate analysis, we identified total drug loads of ASMs (p = 0.003) and use of topiramate (p = 0,007) as independent predictors of hyperammonemia. Four patients (4/116, 3.4%) had clinical symptoms of VHE. Three of them had hyperammonemia while other patient had normal blood level of ammonia with a high blood level of VPA.
Conclusions: Higher total drug loads of concurrent ASMs and use of topiramate were independent risk factors of hyperammonemia in epilepsy patients with VPA therapy. Although the incidence of VHE was not high in our study, clinicians should be aware of this potential adverse effect of VPA therapy, especially in patients with polytherapy of ASMs including topiramate.
Funding: The authors confirm that there are no conflicts of interest to disclose.
Anti-seizure Medications