Cargando…

Drug-associated hyperammonaemia: a Bayesian analysis of the WHO Pharmacovigilance Database

BACKGROUND: Hyperammonaemia is frequent in Intensive Care Unit patients. Some drugs have been described as associated with this condition, but there are no large-scale studies investigating this topic and most descriptions only consist of case-reports. METHODS: We performed a disproportionality anal...

Descripción completa

Detalles Bibliográficos
Autores principales: Balcerac, Alexander, Bihan, Kevin, Lebrun-Vignes, Bénédicte, Thabut, Dominique, Salem, Joe-Elie, Weiss, Nicolas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9206694/
https://www.ncbi.nlm.nih.gov/pubmed/35716335
http://dx.doi.org/10.1186/s13613-022-01026-4
_version_ 1784729387112857600
author Balcerac, Alexander
Bihan, Kevin
Lebrun-Vignes, Bénédicte
Thabut, Dominique
Salem, Joe-Elie
Weiss, Nicolas
author_facet Balcerac, Alexander
Bihan, Kevin
Lebrun-Vignes, Bénédicte
Thabut, Dominique
Salem, Joe-Elie
Weiss, Nicolas
author_sort Balcerac, Alexander
collection PubMed
description BACKGROUND: Hyperammonaemia is frequent in Intensive Care Unit patients. Some drugs have been described as associated with this condition, but there are no large-scale studies investigating this topic and most descriptions only consist of case-reports. METHODS: We performed a disproportionality analysis using VigiBase, the World Health Organization Pharmacovigilance Database, using the information component (IC). The IC compares observed and expected values to find associations between drugs and hyperammonaemia using disproportionate Bayesian reporting. An IC(0.25) (lower end of the IC 95% credibility interval) > 0 is considered statistically significant. The main demographic and clinical features, confounding factors, and severity of cases have been recorded. RESULTS: We identified 71 drugs with a disproportionate reporting in 2924 cases of hyperammonaemia. Most of the suspected drugs could be categorised into 4 main therapeutic classes: oncologic drugs, anti-epileptic drugs, immunosuppressants and psychiatric drugs. The drugs most frequently involved were valproic acid, fluorouracil, topiramate, oxaliplatin and asparaginase. In addition to these molecules known to be responsible for hyperammonaemia, our study reported 60 drugs not previously identified as responsible for hyperammonaemia. These include recently marketed molecules including anti-epileptics such as cannabidiol, immunosuppressants such as basiliximab, and anti-angiogenics agents such as tyrosine kinase inhibitors (sunitinib, sorafenib, regorafenib, lenvatinib) and monoclonal antibodies (bevacizumab, ramucirumab). The severity of cases varies depending on the drug class involved and high mortality rates are present when hyperammonaemia occurs in patients receiving immunosuppressant and oncologic drugs. CONCLUSIONS: This study constitutes the first large-scale study on drug-associated hyperammonaemia. This description may prove useful for clinicians in patients’ care as well as for trial design. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13613-022-01026-4.
format Online
Article
Text
id pubmed-9206694
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Springer International Publishing
record_format MEDLINE/PubMed
spelling pubmed-92066942022-06-20 Drug-associated hyperammonaemia: a Bayesian analysis of the WHO Pharmacovigilance Database Balcerac, Alexander Bihan, Kevin Lebrun-Vignes, Bénédicte Thabut, Dominique Salem, Joe-Elie Weiss, Nicolas Ann Intensive Care Research BACKGROUND: Hyperammonaemia is frequent in Intensive Care Unit patients. Some drugs have been described as associated with this condition, but there are no large-scale studies investigating this topic and most descriptions only consist of case-reports. METHODS: We performed a disproportionality analysis using VigiBase, the World Health Organization Pharmacovigilance Database, using the information component (IC). The IC compares observed and expected values to find associations between drugs and hyperammonaemia using disproportionate Bayesian reporting. An IC(0.25) (lower end of the IC 95% credibility interval) > 0 is considered statistically significant. The main demographic and clinical features, confounding factors, and severity of cases have been recorded. RESULTS: We identified 71 drugs with a disproportionate reporting in 2924 cases of hyperammonaemia. Most of the suspected drugs could be categorised into 4 main therapeutic classes: oncologic drugs, anti-epileptic drugs, immunosuppressants and psychiatric drugs. The drugs most frequently involved were valproic acid, fluorouracil, topiramate, oxaliplatin and asparaginase. In addition to these molecules known to be responsible for hyperammonaemia, our study reported 60 drugs not previously identified as responsible for hyperammonaemia. These include recently marketed molecules including anti-epileptics such as cannabidiol, immunosuppressants such as basiliximab, and anti-angiogenics agents such as tyrosine kinase inhibitors (sunitinib, sorafenib, regorafenib, lenvatinib) and monoclonal antibodies (bevacizumab, ramucirumab). The severity of cases varies depending on the drug class involved and high mortality rates are present when hyperammonaemia occurs in patients receiving immunosuppressant and oncologic drugs. CONCLUSIONS: This study constitutes the first large-scale study on drug-associated hyperammonaemia. This description may prove useful for clinicians in patients’ care as well as for trial design. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13613-022-01026-4. Springer International Publishing 2022-06-18 /pmc/articles/PMC9206694/ /pubmed/35716335 http://dx.doi.org/10.1186/s13613-022-01026-4 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research
Balcerac, Alexander
Bihan, Kevin
Lebrun-Vignes, Bénédicte
Thabut, Dominique
Salem, Joe-Elie
Weiss, Nicolas
Drug-associated hyperammonaemia: a Bayesian analysis of the WHO Pharmacovigilance Database
title Drug-associated hyperammonaemia: a Bayesian analysis of the WHO Pharmacovigilance Database
title_full Drug-associated hyperammonaemia: a Bayesian analysis of the WHO Pharmacovigilance Database
title_fullStr Drug-associated hyperammonaemia: a Bayesian analysis of the WHO Pharmacovigilance Database
title_full_unstemmed Drug-associated hyperammonaemia: a Bayesian analysis of the WHO Pharmacovigilance Database
title_short Drug-associated hyperammonaemia: a Bayesian analysis of the WHO Pharmacovigilance Database
title_sort drug-associated hyperammonaemia: a bayesian analysis of the who pharmacovigilance database
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9206694/
https://www.ncbi.nlm.nih.gov/pubmed/35716335
http://dx.doi.org/10.1186/s13613-022-01026-4
work_keys_str_mv AT balceracalexander drugassociatedhyperammonaemiaabayesiananalysisofthewhopharmacovigilancedatabase
AT bihankevin drugassociatedhyperammonaemiaabayesiananalysisofthewhopharmacovigilancedatabase
AT lebrunvignesbenedicte drugassociatedhyperammonaemiaabayesiananalysisofthewhopharmacovigilancedatabase
AT thabutdominique drugassociatedhyperammonaemiaabayesiananalysisofthewhopharmacovigilancedatabase
AT salemjoeelie drugassociatedhyperammonaemiaabayesiananalysisofthewhopharmacovigilancedatabase
AT weissnicolas drugassociatedhyperammonaemiaabayesiananalysisofthewhopharmacovigilancedatabase