A Pharmacovigilance Study on Clozapine in the Food and Drug Administration Adverse Event Reporting System: A Regional Comparative Analysis
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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.
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.
참고문헌 (33)
- Barnes TR, "Evidence-based guidelines for the pharmacological treatment of schizophrenia : updated recommendations from the British Association for Psychopharmacology", J Psychopharmacol, 34, pp.3~78 (2020)
- Galletly C, "Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for the management of schizophrenia and related disorders", Aust N Z J Psychiatry, 50, pp.410~472 (2016)
- Keepers GA, "The American Psychiatric Association practice guideline for the treatment of patients with schizophrenia", Am J Psychiatry, 177, pp.868~872 (2020)
- Huhn M, "Comparative efficacy and tolerability of 32 oral antipsychotics for the acute treatment of adults with multi-episode schizophrenia : a systematic review and network meta-analysis", Lancet, 394, pp.939~951 (2019)
- Masuda T, "Association with hospitalization and all-cause discontinuation among patients with schizophrenia on clozapine vs other oral second-generation antipsychotics : a systematic review and meta-analysis of cohort studies", JAMA Psychiatry, 76, pp.1052~1062 (2019)
- Bachmann CJ, "International trends in clozapine use : a study in 17 countries", Acta Psychiatr Scand, 136, pp.37~51 (2017)
- Xu SW, "Clozapine prescription pattern in patients with schizophrenia in Asia : the REAP survey(2016)", Psychiatry Res, 287, pp.112271~ (2020)
- Moore TJ, "Serious adverse drug events reported to the Food and Drug Administration, 1998-2005", Arch Intern Med, 167, pp.1752~1759 (2007)
- Wiciński M, "Clozapine-induced agranulocytosis", granulocytopenia : mechanisms and monitoring, 2018, pp.25, 22~28
- Ronaldson KJ, "A new monitoring protocol for clozapine-induced myocarditis based on an analysis of 75 cases and 94 controls", Aust N Z J Psychiatry, 45, pp.458~465 (2011)
- de Leon J, "An international adult guideline for making clozapine titration safer by using six ancestry-based personalized dosing titrations, CRP, and clozapine levels", Pharmacopsychiatry, 55, pp.73~86 (2022)
- De Leon J, "Data from the World Health Organization's pharmacovigilance database supports the prominent role of pneumonia in mortality associated with clozapine adverse drug reactions", Schizophr Bull, 46, pp.1~3 (2020)
- Kumlien E, "Seizure risk associated with neuroactive drugs : data from the WHO adverse drug reactions database", Seizure, 19, pp.69~73 (2010)
- Lertxundi U, "Antipsychotics and seizures : higher risk with atypicals?", Seizure, 22, pp.141~143 (2013)
- Schoretsanitis G, "Blood levels to optimize antipsychotic treatment in clinical practice : a joint consensus statement of the American Society of Clinical Psychopharmacology and the Therapeutic Drug Monitoring Task Force of the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie", J Clin Psychiatry, 81, pp.19~ (2020)
- Polcwiartek C, "The clinical potentials of adjunctive fluvoxamine to clozapine treatment : a systematic review", Psychopharmacology(Berl), 233, pp.741~750 (2016)
- de Leon J, "Do Asian patients require only half of the clozapine dose prescribed for Caucasians? A critical overview", Indian J Psychol Med, 42, pp.4~10 (2020)
- Ruan CJ, "Clozapine metabolism in East Asians and Caucasians : a pilot exploration of the prevalence of poor metabolizers and a systematic review", J Clin Psychopharmacol, 39, pp.135~144 (2019)
- Singh R, ""Asian"phenotype underestimates the genetic diversity of asia yet overstates its impact on variability in drug disposition and pharmacodynamics", Clin Pharmacol Ther, 105, pp.802~805 (2019)
- "Medical Dictionary for Regulatory Activities/Japanese version (MedDRA/J) version 25.0" (2022)[URL]
- Yasui-Furukori N, "Japanese patients need slower, personalized clozapine titrations : a comment on the case described by Kikuchi et al", PCN Rep, 2, pp.e70~ (2023)
- Kikuchi Y, "Slower clozapine titration than the official Japanese protocol led to fewer inflammatory adverse effects: a retrospective chart review of seven hospitals", Schizophr Res (2023)[DOI]
- Kang N, "Association between initial pattern of clozapine titration, concentration-to-dose ratio, and incidence of fever in patients with schizophrenia spectrum disorders in a Korean tertiary hospital", Schizophr Res (2023)[DOI]
- Kang N, "Association between initial clozapine titration and pneumonia risk among patients with schizophrenia in a Korean tertiary hospital", Schizophr Res (2023)[DOI]
- Gallego JA, "Safety and tolerability of antipsychotic polypharmacy", Expert Opin Drug Saf, 11, pp.527~542 (2012)
- Hatano M, "Analysis of clozapine-induced seizures using the Japanese Adverse Drug Event Report database", PLoS One, 18, pp.e0287122~ (2023)
- Lee JW, "Trends in the prevalence of type 2 diabetes in Asians versus whites : results from the United States National Health Interview Survey, 1997-2008", Diabetes Care, 34, pp.353~357 (2011)
- De Las Cuevas C, "Clozapine-associated myocarditis in the World Health Organization's pharmacovigilance database : focus on reports from various countries", Rev Psiquiatr Salud Ment(Engl Ed), 15, pp.238~250 (2022)
- Winckel K, "Clozapine-induced myocarditis : separating the wheat from the chaff", Aust N Z J Psychiatry, 49, pp.188~ (2015)
- Wagner E, "Impact of smoking behavior on clozapine blood levels-a systematic review and meta-analysis", Acta Psychiatr Scand, 142, pp.456~466 (2020)
- Hägg S, "Effect of caffeine on clozapine pharmacokinetics in healthy volunteers", Br J Clin Pharmacol, 49, pp.59~63 (2000)
- Noguchi Y, "Detection algorithms and attentive points of safety signal using spontaneous reporting systems as a clinical data source", Brief Bioinform, 22, pp.bbab347~ (2021)
- De Las Cuevas C, "Adverse drug reactions and their fatal outcomes in clozapine patients in VigiBase:comparing the top four reporting countries (US, UK, Canada and Australia)", Schizophr Res (2023)[DOI]
