Post-Marketing Assessment of Neuropsychiatric Adverse Events in Influenza Patients Treated with Oseltamivir: An Updated ReviewReport as inadecuate

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Advances in Therapy

, Volume 29, Issue 10, pp 826–848

First Online: 02 October 2012Received: 08 June 2012


A 2008 review by our group concluded that the risk of neuropsychiatric adverse events NPAEs in influenza patients was not increased by oseltamivir exposure, and did not identify any mechanism by which oseltamivir or its metabolites could cause or worsen such events. The current article reviews new information on this topic. Between September 16, 2007 and May 15, 2010, 1,805 spontaneously-reported NPAEs were identified in 1,330 patients receiving oseltamivir: 767 42.5% from Japan, 296 16.4% from the USA, and 742 41.1% from other countries. NPAEs were more common in children: 1,072 59.4% events were in those aged ≤16 years. NPAEs often occurred within 48 h of treatment initiation 953 events; 52.8%. Nearly half of the events were serious in nature 838; 46.4%. The three largest categories of events were abnormal behavior 457 events, 25.3%, miscellaneous psychiatric events 370; 20.5%, and delusions-perceptual disturbances 316 events, 17.5%. A total of 1,545 events 85.6% in eight different categories were considered to be delirium or delirium-like. Twenty-eight suicide-related events were reported. A US healthcare claims database analysis showed that the risk of NPAEs in 7,798 oseltamivir-treated patients was no higher than that in 10,411 patients not on antivirals, but a study on oseltamivir and abnormal behavior in Japan was less conclusive. NPAE frequency in oseltamivir-exposed Japanese and Taiwanese children with influenza was the same as in unexposed children. New analysis of the UK General Practice Research Database showed that the relative adjusted risk of NPAEs in influenza patients was 2.18-times higher than in the general population. Other epidemiology studies report frequent occurrence of encephalitis and similar disorders in influenza patients independently of oseltamivir exposure. The new data support the findings of the original assessment. Evidence suggests that influenza-related encephalopathies are caused by influenza-induced inflammatory responses, but more work is needed to confirm the underlying mechanisms.

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KeywordsAdverse events Central nervous system Influenza Neuropsychiatric Oseltamivir Safety Tolerability To view enhanced content go to

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Electronic Supplementary MaterialSupplementary material is available for this article at 10.1007-s12325-012-0050-8 and is accessible for authorized users.

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Author: Stephen Toovey - Eric P. Prinssen - Craig R. Rayner - Bharat T. Thakrar - Regina Dutkowski - Annette Koerner - Tom Chu -


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