Teratogenicity of zonisamide and other little-used antiseizure medications

Frank J E Vajda; Terence J O'Brien; Janet E Graham; Alison A Hitchcock; Piero Perucca; Cecilie M Lander; Mervyn J Eadie

doi:10.1016/j.seizure.2024.03.002

Teratogenicity of zonisamide and other little-used antiseizure medications

Seizure. 2024 Apr:117:198-201. doi: 10.1016/j.seizure.2024.03.002. Epub 2024 Mar 2.

Authors

Frank J E Vajda¹, Terence J O'Brien², Janet E Graham³, Alison A Hitchcock³, Piero Perucca⁴, Cecilie M Lander⁵, Mervyn J Eadie⁵

Affiliations

¹ Departments of Medicine and Neurosciences, The Royal Melbourne Hospital, The University of Melbourne, Parkville, VIC 3050, Australia; Department of Neuroscience, Monash University, Melbourne, VIC 3004, Australia. Electronic address: [email protected].
² Department of Neuroscience, Monash University, Melbourne, VIC 3004, Australia; Department of Neurology, Alfred Health, Melbourne, VIC 3004, Australia.
³ Departments of Medicine and Neurosciences, The Royal Melbourne Hospital, The University of Melbourne, Parkville, VIC 3050, Australia.
⁴ Departments of Medicine and Neurosciences, The Royal Melbourne Hospital, The University of Melbourne, Parkville, VIC 3050, Australia; Department of Neuroscience, Monash University, Melbourne, VIC 3004, Australia; Department of Neurology, Alfred Health, Melbourne, VIC 3004, Australia; Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, VIC 3084, Australia; Bladin-Berkovic Comprehensive Epilepsy Program, Austin Health, Heidelberg, VIC 3084, Australia.
⁵ Royal Brisbane and Women's Hospital and School of Medicine and Biomedical Science, University of Queensland, Brisbane, QLD 4027, Australia.

PMID: 38460459
DOI: 10.1016/j.seizure.2024.03.002

Abstract

Purpose: To investigate the risk of teratogenesis occurring in relation to intrauterine exposure to infrequently used antiseizure medications in Australia.

Methods: Analysis of data contained in the Raoul Wallenberg Australian Pregnancy Register of Antiepileptic Drugs.

Results: There was statistically significant evidence that zonisamide, but not any other of nine infrequently used antiseizure medications in Australia, was associated with a risk of teratogenesis related to the maternal dose of the drug taken in at least the earlier half of pregnancy.

Conclusions: The teratogenesis associated with zonisamide, like that associated with topiramate and possibly acetazolamide, may be an expression of a class effect shared among sulphonamide-derived carbonic anhydrase inhibitors that possess anti-seizure activity.

Keywords: Acetazolamide; Foetal malformation; Pregnancy; Teratogenesis; Topiramate; Zonisamide.

MeSH terms

Abnormalities, Drug-Induced / etiology
Adult
Anticonvulsants* / adverse effects
Australia
Epilepsy / drug therapy
Female
Humans
Isoxazoles / adverse effects
Pregnancy
Registries
Zonisamide* / adverse effects

Substances

Zonisamide
Anticonvulsants
Isoxazoles