The mechanisms of sudden‐onset type adverse reactions to oseltamivir
Oseltamivir is contraindicated for people aged 10–19 in principle in Japan, due to concern about abnormal behaviours. Sudden death is another concern. This review examines growing evidence of their association and discusses underlying mechanisms of these sudden‐onset type reactions to oseltamivir. F...
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| Format: | Online |
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John Wiley and Sons Inc.
2016
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5201449/ |
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pubmed-52014492017-01-24 The mechanisms of sudden‐onset type adverse reactions to oseltamivir Hama, R. Bennett, C. L. Review Article Oseltamivir is contraindicated for people aged 10–19 in principle in Japan, due to concern about abnormal behaviours. Sudden death is another concern. This review examines growing evidence of their association and discusses underlying mechanisms of these sudden‐onset type reactions to oseltamivir. First, the importance of animal models and the concept of human equivalent dose (HED) is summarized. Second, the specific condition for oseltamivir use, influenza infection, is reviewed. Third, findings from toxicity studies conducted prior to and after the marketing of oseltamivir are reported on to provide context on the observation of a possible causal association. Fourth, similarity and consistency of toxicity in humans with that in other animals is described. Finally, coherence of toxicokinetic and molecular level of evidence (channels, receptors and enzymes), including differences from the toxicity of other neuraminidase inhibitors, is reviewed. It is concluded that unchanged oseltamivir has various effects on the central nervous system (CNS) that may be related to clinical findings including hypothermia, abnormal behaviours including with fatal outcome, and sudden death. Among receptors and enzymes related to CNS action, it is known that oseltamivir inhibits nicotinic acetylcholine receptors, which are closely related to hypothermia, as well as human monoamine oxidase‐A (MAO‐A), which is closely related to abnormal or excitatory behaviours. Receptors such as GABAA, GABAB and NMDA and their related receptors/channels including Na+ and Ca2+ channels are thought to be other candidates for investigation related to respiratory suppression followed by sudden death and psychotic reactions (both acute and chronic), respectively. John Wiley and Sons Inc. 2016-06-30 2017-02 /pmc/articles/PMC5201449/ /pubmed/27364959 http://dx.doi.org/10.1111/ane.12629 Text en © 2016 The Authors. Acta Neurologica Scandinavica Published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs (http://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Hama, R. Bennett, C. L. |
| spellingShingle |
Hama, R. Bennett, C. L. The mechanisms of sudden‐onset type adverse reactions to oseltamivir |
| author_facet |
Hama, R. Bennett, C. L. |
| author_sort |
Hama, R. |
| title |
The mechanisms of sudden‐onset type adverse reactions to oseltamivir |
| title_short |
The mechanisms of sudden‐onset type adverse reactions to oseltamivir |
| title_full |
The mechanisms of sudden‐onset type adverse reactions to oseltamivir |
| title_fullStr |
The mechanisms of sudden‐onset type adverse reactions to oseltamivir |
| title_full_unstemmed |
The mechanisms of sudden‐onset type adverse reactions to oseltamivir |
| title_sort |
mechanisms of sudden‐onset type adverse reactions to oseltamivir |
| description |
Oseltamivir is contraindicated for people aged 10–19 in principle in Japan, due to concern about abnormal behaviours. Sudden death is another concern. This review examines growing evidence of their association and discusses underlying mechanisms of these sudden‐onset type reactions to oseltamivir. First, the importance of animal models and the concept of human equivalent dose (HED) is summarized. Second, the specific condition for oseltamivir use, influenza infection, is reviewed. Third, findings from toxicity studies conducted prior to and after the marketing of oseltamivir are reported on to provide context on the observation of a possible causal association. Fourth, similarity and consistency of toxicity in humans with that in other animals is described. Finally, coherence of toxicokinetic and molecular level of evidence (channels, receptors and enzymes), including differences from the toxicity of other neuraminidase inhibitors, is reviewed. It is concluded that unchanged oseltamivir has various effects on the central nervous system (CNS) that may be related to clinical findings including hypothermia, abnormal behaviours including with fatal outcome, and sudden death. Among receptors and enzymes related to CNS action, it is known that oseltamivir inhibits nicotinic acetylcholine receptors, which are closely related to hypothermia, as well as human monoamine oxidase‐A (MAO‐A), which is closely related to abnormal or excitatory behaviours. Receptors such as GABAA, GABAB and NMDA and their related receptors/channels including Na+ and Ca2+ channels are thought to be other candidates for investigation related to respiratory suppression followed by sudden death and psychotic reactions (both acute and chronic), respectively. |
| publisher |
John Wiley and Sons Inc. |
| publishDate |
2016 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5201449/ |
| _version_ |
1613848114041454592 |