A Pharmacovigilance Study on Clozapine in the Food and Drug Administration Adverse Event Reporting System: A Regional Comparative Analysis
Masakazu Hatano 1*, Haruna Araki 1, Takeo Saito 2, Shigeki Yamada 1
1Department of Pharmacotherapeutics and informatics, Fujita Health University School of Medicine, 2Department of Psychiatry, Fujita Health University School of Medicine
Received: January 25, 2024; Revised: April 28, 2024; Accepted: May 8, 2024; Published online: May 8, 2024.
© The Korean College of Neuropsychopharmacology. All rights reserved.

Objective: This pharmacovigilance study evaluated the profile of clozapine-related adverse events by region using the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS).
Methods: We categorized each case into five regions (America, Europe/West Asia, Oceania, Asia, and Africa) based on the reporting country information in the FAERS database. The number of clozapine-related adverse events reported in each region was aggregated according to the preferred term (PT) and the Standardized MedDRA Query (SMQ).
Results: A total of 101,872 clozapine-related adverse events were registered in the FAERS database. In America and Europe, leukocyte or neutrophil count abnormalities accounted for half of the top 10 PTs by relative reporting rate. However, Asia had higher relative reporting rates of pyrexia and salivary hypersecretion (13.91% and 10.85%, respectively). Regarding the SMQ, the relative reporting rates of infective pneumonia, convulsions, extrapyramidal syndrome, gastrointestinal obstruction, and hyperglycaemia/new onset diabetes mellitus were higher in Asia than in other regions (5.26%, 9.72%, 12.65%, 5.13%, and 8.26%, respectively), with significant differences even after adjusting for confounding factors using multivariate logistic regression analysis.
Conclusion: Spontaneous reports of adverse events associated with clozapine show regional disparities, particularly in Asia, where concentration-dependent adverse events are more frequently reported. However, the spontaneous reporting system has several limitations, requiring further research for validation.
Keywords: Adverse effects, Antipsychotic agents, Big data, Clozapine, Pharmacovigilance