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Post-Marketing Assessment of Neuropsychiatric Adverse Events in Influenza Patients Treated with Oseltamivir: An Updated Review
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  • Open Access
  • Published: 02 October 2012

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

  • Stephen Toovey1,
  • Eric P. Prinssen1,
  • Craig R. Rayner2,
  • Bharat T. Thakrar1,
  • Regina Dutkowski1,
  • Annette Koerner1,
  • Tom Chu3,
  • Alexandra Sirzen-Zelenskaya1,
  • Markus Britschgi1,
  • Sudhir Bansod1 &
  • …
  • Barbara Donner1 

Advances in Therapy volume 29, pages 826–848 (2012)Cite this article

  • 2088 Accesses

  • 45 Citations

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Abstract

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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Authors and Affiliations

  1. F. Hoffmann-La Roche Ltd., PBMT Bldg. 74/3O Z01.05, CH-4070, Basel, Switzerland

    Stephen Toovey, Eric P. Prinssen, Bharat T. Thakrar, Regina Dutkowski, Annette Koerner, Alexandra Sirzen-Zelenskaya, Markus Britschgi, Sudhir Bansod & Barbara Donner

  2. Roche Products Pty. Ltd., Melbourne, Australia

    Craig R. Rayner

  3. Hoffmann-La Roche, Inc., Nutley, NJ, USA

    Tom Chu

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Toovey, S., Prinssen, E.P., Rayner, C.R. et al. Post-Marketing Assessment of Neuropsychiatric Adverse Events in Influenza Patients Treated with Oseltamivir: An Updated Review. Adv Therapy 29, 826–848 (2012). https://doi.org/10.1007/s12325-012-0050-8

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  • Received: 08 June 2012

  • Published: 02 October 2012

  • Issue Date: October 2012

  • DOI: https://doi.org/10.1007/s12325-012-0050-8

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Keywords

  • Adverse events
  • Central nervous system
  • Influenza
  • Neuropsychiatric
  • Oseltamivir
  • Safety
  • Tolerability
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