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Valproic Acid and Fatalities in Children: A Review of Individual Case Safety Reports in VigiBase

INTRODUCTION: Valproic acid is an effective first line drug for the treatment of epilepsy. Hepatotoxicity is a rare and potentially fatal adverse reaction for this medicine. OBJECTIVE: Firstly to characterise valproic acid reports on children with fatal outcome and secondly to determine reporting ov...

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Autores principales: Star, Kristina, Edwards, I. Ralph, Choonara, Imti
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4193865/
https://www.ncbi.nlm.nih.gov/pubmed/25302991
http://dx.doi.org/10.1371/journal.pone.0108970
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author Star, Kristina
Edwards, I. Ralph
Choonara, Imti
author_facet Star, Kristina
Edwards, I. Ralph
Choonara, Imti
author_sort Star, Kristina
collection PubMed
description INTRODUCTION: Valproic acid is an effective first line drug for the treatment of epilepsy. Hepatotoxicity is a rare and potentially fatal adverse reaction for this medicine. OBJECTIVE: Firstly to characterise valproic acid reports on children with fatal outcome and secondly to determine reporting over time of hepatotoxicity with fatal outcome. METHODS: Individual case safety reports (ICSRs) for children ≤17 years with valproic acid and fatal outcome were retrieved from the WHO Global ICSR database, VigiBase, in June 2013. Reports were classified into hepatotoxic reactions or other reactions. Shrinkage observed-to-expected ratios were used to explore the relative reporting trend over time and for patient age. The frequency of polytherapy, i.e. reports with more than one antiepileptic medicine, was investigated. RESULTS: There have been 268 ICSRs with valproic acid and fatal outcome in children, reported from 25 countries since 1977. A total of 156 fatalities were reported with hepatotoxicity, which has been continuously and disproportionally reported over time. There were 31 fatalities with pancreatitis. Other frequently reported events were coma/encephalopathy, seizures, respiratory disorders and coagulopathy. Hepatotoxicity was disproportionally and most commonly reported in children aged 6 years and under (104/156 reports) but affected children of all ages. Polytherapy was significantly more frequently reported for valproic acid with fatal outcome (58%) compared with non-fatal outcome (34%). CONCLUSION: Hepatotoxicity remains a considerable problem. The risk appears to be greatest in young children (6 years and below) but can occur at any age. Polytherapy is commonly reported and seems to be a risk factor for hepatotoxicity, pancreatitis and other serious adverse drug reactions with valproic acid.
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spelling pubmed-41938652014-10-14 Valproic Acid and Fatalities in Children: A Review of Individual Case Safety Reports in VigiBase Star, Kristina Edwards, I. Ralph Choonara, Imti PLoS One Research Article INTRODUCTION: Valproic acid is an effective first line drug for the treatment of epilepsy. Hepatotoxicity is a rare and potentially fatal adverse reaction for this medicine. OBJECTIVE: Firstly to characterise valproic acid reports on children with fatal outcome and secondly to determine reporting over time of hepatotoxicity with fatal outcome. METHODS: Individual case safety reports (ICSRs) for children ≤17 years with valproic acid and fatal outcome were retrieved from the WHO Global ICSR database, VigiBase, in June 2013. Reports were classified into hepatotoxic reactions or other reactions. Shrinkage observed-to-expected ratios were used to explore the relative reporting trend over time and for patient age. The frequency of polytherapy, i.e. reports with more than one antiepileptic medicine, was investigated. RESULTS: There have been 268 ICSRs with valproic acid and fatal outcome in children, reported from 25 countries since 1977. A total of 156 fatalities were reported with hepatotoxicity, which has been continuously and disproportionally reported over time. There were 31 fatalities with pancreatitis. Other frequently reported events were coma/encephalopathy, seizures, respiratory disorders and coagulopathy. Hepatotoxicity was disproportionally and most commonly reported in children aged 6 years and under (104/156 reports) but affected children of all ages. Polytherapy was significantly more frequently reported for valproic acid with fatal outcome (58%) compared with non-fatal outcome (34%). CONCLUSION: Hepatotoxicity remains a considerable problem. The risk appears to be greatest in young children (6 years and below) but can occur at any age. Polytherapy is commonly reported and seems to be a risk factor for hepatotoxicity, pancreatitis and other serious adverse drug reactions with valproic acid. Public Library of Science 2014-10-10 /pmc/articles/PMC4193865/ /pubmed/25302991 http://dx.doi.org/10.1371/journal.pone.0108970 Text en © 2014 Star et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Star, Kristina
Edwards, I. Ralph
Choonara, Imti
Valproic Acid and Fatalities in Children: A Review of Individual Case Safety Reports in VigiBase
title Valproic Acid and Fatalities in Children: A Review of Individual Case Safety Reports in VigiBase
title_full Valproic Acid and Fatalities in Children: A Review of Individual Case Safety Reports in VigiBase
title_fullStr Valproic Acid and Fatalities in Children: A Review of Individual Case Safety Reports in VigiBase
title_full_unstemmed Valproic Acid and Fatalities in Children: A Review of Individual Case Safety Reports in VigiBase
title_short Valproic Acid and Fatalities in Children: A Review of Individual Case Safety Reports in VigiBase
title_sort valproic acid and fatalities in children: a review of individual case safety reports in vigibase
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4193865/
https://www.ncbi.nlm.nih.gov/pubmed/25302991
http://dx.doi.org/10.1371/journal.pone.0108970
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