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Infections associated with clozapine: a pharmacovigilance study using VigiBase(®)
Introduction: Clozapine is primarily reserved for treatment-resistant schizophrenia due to safety concerns associated with its use. Infections have been reported with clozapine, which may lead to elevated serum levels of the drug. However, the existing literature on this topic is limited. Therefore,...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10577313/ https://www.ncbi.nlm.nih.gov/pubmed/37849735 http://dx.doi.org/10.3389/fphar.2023.1260915 |
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author | Chrétien, Basile Brazo, Perrine Da Silva, Angélique Sassier, Marion Dolladille, Charles Lelong-Boulouard, Véronique Alexandre, Joachim Fedrizzi, Sophie |
author_facet | Chrétien, Basile Brazo, Perrine Da Silva, Angélique Sassier, Marion Dolladille, Charles Lelong-Boulouard, Véronique Alexandre, Joachim Fedrizzi, Sophie |
author_sort | Chrétien, Basile |
collection | PubMed |
description | Introduction: Clozapine is primarily reserved for treatment-resistant schizophrenia due to safety concerns associated with its use. Infections have been reported with clozapine, which may lead to elevated serum levels of the drug. However, the existing literature on this topic is limited. Therefore, we conducted a study using VigiBase(®) to investigate the potential over-reporting of infections associated with clozapine, to explore the presence of dose-dependency, and to investigate the underlying mechanism. Methods: Disproportionality analyses were performed using VigiBase to assess the association between clozapine and all types of infections, the association between clozapine-associated infections and neutropenia, the association between clozapine-associated infections and agranulocytosis, the dose–effect relationship between clozapine and infections, and the interaction between clozapine and the main strong CYP450 inhibitors using reports carried out until 11 April 2023. Results: A statistically significant signal of infections was observed with clozapine, as indicated by an information component of 0.43 [95% CI: (0.41–0.45)]. The most commonly reported infections were respiratory and gastrointestinal in nature. Neutropenia showed weaker association with clozapine-associated reports of infections compared to other clozapine-associated reports [X2 (1, N = 204,073) = 454; p < 0.005], while agranulocytosis demonstrated a stronger association with clozapine-associated reports of infections [X2 (1, N = 204,073) = 56; p < 0.005]. No evidence of dose-dependency was observed. Among the 17 tested CYP inhibitors, significant drug–drug interactions were found with clarithromycin, metronidazole, valproic acid, lansoprazole, omeprazole, amiodarone, and esomeprazole. Discussion: Our study revealed a significant safety signal between clozapine use and infections, predominantly respiratory and gastrointestinal infections. The co-administration of clozapine with valproic acid or proton pump inhibitors may potentially contribute to an increased risk of infection. Further vigilance is warranted in clinical practice, and consideration of therapeutic drug monitoring of clozapine in cases involving concomitant use of these drugs or in the presence of infections may be beneficial. |
format | Online Article Text |
id | pubmed-10577313 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-105773132023-10-17 Infections associated with clozapine: a pharmacovigilance study using VigiBase(®) Chrétien, Basile Brazo, Perrine Da Silva, Angélique Sassier, Marion Dolladille, Charles Lelong-Boulouard, Véronique Alexandre, Joachim Fedrizzi, Sophie Front Pharmacol Pharmacology Introduction: Clozapine is primarily reserved for treatment-resistant schizophrenia due to safety concerns associated with its use. Infections have been reported with clozapine, which may lead to elevated serum levels of the drug. However, the existing literature on this topic is limited. Therefore, we conducted a study using VigiBase(®) to investigate the potential over-reporting of infections associated with clozapine, to explore the presence of dose-dependency, and to investigate the underlying mechanism. Methods: Disproportionality analyses were performed using VigiBase to assess the association between clozapine and all types of infections, the association between clozapine-associated infections and neutropenia, the association between clozapine-associated infections and agranulocytosis, the dose–effect relationship between clozapine and infections, and the interaction between clozapine and the main strong CYP450 inhibitors using reports carried out until 11 April 2023. Results: A statistically significant signal of infections was observed with clozapine, as indicated by an information component of 0.43 [95% CI: (0.41–0.45)]. The most commonly reported infections were respiratory and gastrointestinal in nature. Neutropenia showed weaker association with clozapine-associated reports of infections compared to other clozapine-associated reports [X2 (1, N = 204,073) = 454; p < 0.005], while agranulocytosis demonstrated a stronger association with clozapine-associated reports of infections [X2 (1, N = 204,073) = 56; p < 0.005]. No evidence of dose-dependency was observed. Among the 17 tested CYP inhibitors, significant drug–drug interactions were found with clarithromycin, metronidazole, valproic acid, lansoprazole, omeprazole, amiodarone, and esomeprazole. Discussion: Our study revealed a significant safety signal between clozapine use and infections, predominantly respiratory and gastrointestinal infections. The co-administration of clozapine with valproic acid or proton pump inhibitors may potentially contribute to an increased risk of infection. Further vigilance is warranted in clinical practice, and consideration of therapeutic drug monitoring of clozapine in cases involving concomitant use of these drugs or in the presence of infections may be beneficial. Frontiers Media S.A. 2023-10-02 /pmc/articles/PMC10577313/ /pubmed/37849735 http://dx.doi.org/10.3389/fphar.2023.1260915 Text en Copyright © 2023 Chrétien, Brazo, Da Silva, Sassier, Dolladille, Lelong-Boulouard, Alexandre and Fedrizzi. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Chrétien, Basile Brazo, Perrine Da Silva, Angélique Sassier, Marion Dolladille, Charles Lelong-Boulouard, Véronique Alexandre, Joachim Fedrizzi, Sophie Infections associated with clozapine: a pharmacovigilance study using VigiBase(®) |
title | Infections associated with clozapine: a pharmacovigilance study using VigiBase(®)
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title_full | Infections associated with clozapine: a pharmacovigilance study using VigiBase(®)
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title_fullStr | Infections associated with clozapine: a pharmacovigilance study using VigiBase(®)
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title_full_unstemmed | Infections associated with clozapine: a pharmacovigilance study using VigiBase(®)
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title_short | Infections associated with clozapine: a pharmacovigilance study using VigiBase(®)
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title_sort | infections associated with clozapine: a pharmacovigilance study using vigibase(®) |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10577313/ https://www.ncbi.nlm.nih.gov/pubmed/37849735 http://dx.doi.org/10.3389/fphar.2023.1260915 |
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