Antiseizure medication-induced hypersensitivity reactions: Data from a large healthcare system

Data on hypersensitivity reactions (HR) to individual anti-seizure medications (ASMs), and reactions to additional ASMs, is often limited by sample size. This data is vital in helping clinicians identify initial and subsequent ASMs to use in treating persons with epilepsy (PWE). Using a very large dataset, our study attempts to quantify the occurrence of HR across 31 different ASMs. We also attempt to investigate whether certain pairs of ASMs are associated with a higher frequency of HR.

The Slicer-Dicer tool in the Epic electronic medical records system was used to analyze patients seen between 2012 and 2022 at a large healthcare system in Kentucky with recorded exposures to 31 different ASMs. Incidence of HR with these ASMs were identified, both with single drugs or pairs of drugs, as well as incidence of HR stratified by sex and ASM structure.

A total of 573,571 patients with 967,168 exposures were analyzed. Phenobarbital had the highest rate of HR at 12.9 %. Usage of aromatic ASMs were most associated with patients having HR to other ASMs. HR to 13/31 studied ASMs was more likely to occur in females, while HR was more likely in males with lacosamide. Aromatic ASMs were more likely (p < 0.0001) to be associated with HR compared to non-aromatic ASMs. Carbamazepine and the related drugs oxcarbazepine and eslicarbazepine were associated with the greatest number of drug pairings in which the patient had HR to both medications at any time point.

Our data reveals important patterns in HR to ASMs that may be valuable to clinicians treating PWE. Clinicians should monitor closely for HR when beginning a new ASM in a patient who has taken an aromatic ASM, especially carbamazepine, oxcarbazepine, or eslicarbazepine as well as phenobarbital.