Pharmacogenetics and Oxcarbazepine in Children and Adolescents: Beyond HLA-B*15:02

Document Type

Article

Publication Date

2-2024

Identifier

DOI: 10.1089/cap.2023.0064

Abstract

Background: Oxcarbazepine is thought to be better-tolerated and less susceptible to drug-drug interactions than its predecessor, carbamazepine. Genetic testing for HLA-B*15:02 is recommended in specific populations to identify those at high risk of severe hypersensitivity reactions; however, other pharmacologic and pharmacogenetic factors that can impact drug disposition may be involved. Methods: We present a case of an 8-year-old boy treated with oxcarbazepine who developed drug reaction with eosinophilia and systemic symptoms (DRESS) with Stevens-Johnsons syndrome overlap and was negative for HLA-B*15:02. We review the extant literature related to oxcarbazepine disposition, and potential pharmacogenetic variants in aldoketoreductase 1C (AKR1C)2-4 that may contribute to this risk. Results: Genetic variability in oxcarbazepine disposition pathways may contribute to tolerability and toxicity, including the development of hypersensitivity reactions. Conclusions: While preemptive genetic testing for HLA-B*15:02 in individuals of Asian ancestry is recommended to prevent severe hypersensitivity reactions to oxcarbazepine, oxcarbazepine concentrations and AKR1C variation may contribute to the risk of severe adverse reactions. We provide recommendations for future study to elucidate whether these individual factors are important for reducing the risk of severe adverse events.

Journal Title

Journal of child and adolescent psychopharmacology

Volume

34

Issue

1

First Page

61

Last Page

66

MeSH Keywords

Male; Child; Adolescent; Humans; Oxcarbazepine; Anticonvulsants; Pharmacogenetics; HLA-B Antigens; Stevens-Johnson Syndrome

Keywords

AKR1C; HLA-B; hypersensitivity; oxcarbazepine; pharmacogenetics; tolerability

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