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. 2024 Aug 31;22(3):442-450.
doi: 10.9758/cpn.24.1174. Epub 2024 Jun 7.

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
Affiliations

A Pharmacovigilance Study on Clozapine in the Food and Drug Administration Adverse Event Reporting System: A Regional Comparative Analysis

Masakazu Hatano et al. Clin Psychopharmacol Neurosci. .

Abstract

Objective: This pharmacovigilance study evaluated the profile of clozapine-related adverse events by region using the Food and Drug Administration 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 Medical Dictionary for Regulatory Activities (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: Antipsychotic agents; Big data; Clozapine; Long term adverse effects; Pharmacovigilance.

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Conflict of interest statement

Conflicts of Interest

The authors have no competing interests to declare. The interests from the past three years are as follows. Masakazu Hatano received honoraria from Ishiyaku Publishers, Inc., Meiji Seika Pharma Co., Ltd., Medical Friend. Co., Ltd., Nanzando Co., Ltd., Sumitomo Pharma Co., Ltd., and WELCIA Holdings Co., Ltd. Takeo Saito received honoraria from Meiji Seika Pharma Co., Ltd. and Kyowa Pharmaceutical Industry Co., Ltd. Shigeki Yamada received honoraria from AstraZeneca K.K., Daiichi Sankyo Co., Ltd., EA Pharma Co., Ltd., Eisai Co., Ltd., Meiji Seika Pharma Co., Ltd., Nippon Shinyaku Co., Ltd., Nipro Corporation, Otsuka Pharmaceutical Factory, Pfizer Japan Inc., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Toa Eiyo Ltd., and Towa Pharmaceutical Co., Ltd. And funding from EA Pharma Co., Ltd., Kissei Pharmaceutical Co., Ltd., Mochida Pharmaceutical Co., Ltd., SUGI Holdings Co., Ltd., and Otsuka Pharmaceutical Factory.

Figures

Fig. 1
Fig. 1
Reporting odds ratios of relative reporting rates by region for each SMQ. SMQ, Standardized MedDRA Query; MedDRA, Medical Dictionary for Regulatory Activities.
See this image and copyright information in PMC

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