Drug-associated hyperammonaemia: a Bayesian analysis of the WHO Pharmacovigilance Database.
Journal
Annals of intensive care
ISSN: 2110-5820
Titre abrégé: Ann Intensive Care
Pays: Germany
ID NLM: 101562873
Informations de publication
Date de publication:
18 Jun 2022
18 Jun 2022
Historique:
received:
14
01
2022
accepted:
29
05
2022
entrez:
18
6
2022
pubmed:
19
6
2022
medline:
19
6
2022
Statut:
epublish
Résumé
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. 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 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. 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.
Sections du résumé
BACKGROUND
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
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
RESULTS
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
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.
Identifiants
pubmed: 35716335
doi: 10.1186/s13613-022-01026-4
pii: 10.1186/s13613-022-01026-4
pmc: PMC9206694
doi:
Types de publication
Journal Article
Langues
eng
Pagination
55Subventions
Organisme : SRLF voucher
ID : TC00845191
Informations de copyright
© 2022. The Author(s).
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