title: Oseltamivir prescription and regulatory actions vis-à-vis abnormal behavior risk in Japan: drug utilization study using a nationwide pharmacy database.
abstract: BACKGROUND
  In March 2007, a regulatory advisory was issued in Japan to restrict oseltamivir use in children aged 10-19 years because of safety concerns over abnormal behavior. The effectiveness and validity of regulatory risk minimization actions remain to be reviewed, despite their significant public health implications. To assess the impact of the regulatory actions on prescribing practices and safety reporting.  METHODOLOY/PRINICPAL FINDINGS: In this retrospective review of a nationwide pharmacy database, we analyzed 100,344 dispensation records for oseltamivir and zanamivir for the period from November 2006 to March 2009. The time trend in dispensations for these antiviral agents was presented before and after the regulatory actions, contrasted with intensity of media coverage and the numbers of spontaneous adverse reaction reports with regard to antivirals. The 2007 regulatory actions, together with its intense media coverage, reduced oseltamivir dispensation in targeted patients in fiscal year 2008 to 20.4% of that in fiscal year 2006, although influenza activities were comparable between these fiscal years. In contrast, zanamivir dispensation increased approximately nine-fold across all age groups. The number of abnormal behavior reports associated with oseltamivir in children aged 10-19 years decreased from fiscal year 2006 to 2008 (24 to 9 cases); this decline was offset by the increased number of reports of abnormal behavior in children under age 10 (12 to 28 cases). The number of reports associated with zanamivir increased in proportion to increased dispensation of this drug (11 to 114 cases).
  
  
  CONCLUSIONS
  The 2007 actions effectively reduced oseltamivir prescriptions and the number of reports of abnormal behavior in the targeted group. The observed increase in abnormal behavior reports in oseltamivir patients under age 10 and in zanamivir patients suggests that these patient groups may also be at risk, calling into question the validity of the current discrimination by age and agent (Abstract translation is available in Japanese: Appendix S1).
authors.affiliation: Department of Pharmacoepidemiology, Graduate School of Medicine and Public Health, Kyoto University, Kyoto, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Urushihara
authors.forename: Yuko
authors.initials: Y
authors.lastname: Doi
authors.forename: Masaru
authors.initials: M
authors.lastname: Arai
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Matsunaga
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Fujii
authors.forename: Naoko
authors.initials: N
authors.lastname: Iino
authors.forename: Takashi
authors.initials: T
authors.lastname: Kawamura
authors.forename: Koji
authors.initials: K
authors.lastname: Kawakami
mesh_terms: D000293:Adolescent; D000328:Adult; D000998:Antiviral Agents / Q000009:adverse effects / Q000494:pharmacology*; D001519:Behavior / Q000187:drug effects; D002648:Child; D002653:Child Behavior Disorders / Q000139:chemically induced; D016303:Clinical Pharmacy Information Systems; D016208:Databases, Factual; D004363:Drug Utilization; D006801:Humans; D007251:Influenza, Human / Q000188:drug therapy; D007564:Japan; D053139:Oseltamivir / Q000009:adverse effects / Q000494:pharmacology*; D010594:Pharmacies; D012189:Retrospective Studies; D012306:Risk; D012309:Risk-Taking; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D053139:Oseltamivir