title: Spontaneous reporting of hepatotoxicity associated with antiandrogens: data from the Spanish pharmacovigilance system.
abstract: OBJECTIVE
  To analyse the type and main features of the hepatotoxicity induced by steroidal and non-steroidal antiandrogens spontaneously reported by physicians, pharmacists and nurses. This analysis could increase the information related to these adverse reactions mainly available from the published isolated cases.
  
  
  METHODS
  Using the Spanish Pharmacovigilance database we searched for spontaneous reports recorded since the date of approval of each antiandrogen up to the present time. We analysed the frequency of liver disorders, the preferred terms coded, the presence of other hepatotoxic drugs, and the characteristics of cases of hepatitis.
  
  
  RESULTS
  Liver disorders were the most common adverse reactions associated with flutamide and bicalutamide, but not with cyproterone acetate. 'Hepatitis' and 'cholestatic hepatitis' were the most frequent terms coded. In 38% of the reports related to cyproterone acetate, 18% of those related to flutamide and 33% of those related to bicalutamide the patient had simultaneously received other hepatotoxic drugs. The disproportionality analysis of hepatitis showed a strong association with flutamide and a weak association with bicalutamide and cyproterone acetate. Mean doses of flutamide and bicalutamide were very close to their defined daily dose (DDD) to treat prostate cancer, although in the case of cyproterone acetate it was slightly higher. The latency period of hepatitis was between 3 and 10 months for the three antiandrogens, and the recovery period was shorter (0.5-3 months). The majority of the reported cases of hepatitis evolved favourably.
  
  
  CONCLUSIONS
  Our results highlight the hepatotoxic potential of flutamide compared to cyproterone acetate. The data related to bicalutamide should be cautiously considered due to the smaller number of reports.
authors.affiliation: Centro de Farmacovigilancia de Asturias, Facultad de Medicina, Oviedo, Spain. gmanso@correo.uniovi.es
authors.forename: Gloria
authors.initials: G
authors.lastname: Manso
authors.forename: Zebron
authors.initials: Z
authors.lastname: Thole
authors.forename: Esther
authors.initials: E
authors.lastname: Salgueiro
authors.forename: Pilar
authors.initials: P
authors.lastname: Revuelta
authors.forename: Agustín
authors.initials: A
authors.lastname: Hidalgo
mesh_terms: D016907:Adverse Drug Reaction Reporting Systems; D000726:Androgen Antagonists / Q000009:adverse effects*; D000813:Anilides / Q000009:adverse effects; D056486:Chemical and Drug Induced Liver Injury / Q000145:classification / Q000209:etiology*; D017373:Cyproterone Acetate / Q000009:adverse effects; D005485:Flutamide / Q000009:adverse effects*; D006801:Humans; D038801:International Classification of Diseases; D008107:Liver Diseases / Q000145:classification / Q000209:etiology*; D009570:Nitriles; D012189:Retrospective Studies; D013030:Spain; D013997:Time Factors; D014105:Tosyl Compounds
chemical_list: D000726:Androgen Antagonists; D000813:Anilides; D009570:Nitriles; D014105:Tosyl Compounds; D017373:Cyproterone Acetate; D005485:Flutamide; C053541:bicalutamide