title: Spontaneous reporting of serious cutaneous reactions with protein kinase inhibitors.
abstract: OBJECTIVE
  Our aim was to describe all serious cutaneous adverse drug reactions (ADRs) spontaneously reported in France for all oral protein kinase inhibitors, their characteristics and whether they were labeled (reported in the Summary of Product Characteristics) or not.
  
  
  METHODS
  We performed a retrospective observational study in the French PharmacoVigilance Database, selecting for analysis serious cutaneous reactions of patients due to treatment with oral protein kinase inhibitors (erlotinib, gefitinib, imatinib, nilotinib, dasatinib, sunitinib, sorafenib, pazopanib, lapatinib, everolimus) between 1 January 2008 and 31 December 31 2010.
  
  
  RESULTS
  Ninety-four patients suffered from 115 serious cutaneous reactions due to oral protein kinase inhibitors. Serious cutaneous reactions more frequently reported were maculo-papular rash (mostly with imatinib), followed by hand-foot syndrome (specifically with sorafenib) and papulopustular rash (particularly with erlotinib). Patients were mostly males (63 %) with a mean age of 62.6 ± 15.4 years. Drug withdrawal was observed in 73.1 % of cases because of these cutaneous reactions. Delay of occurrence of the ADR varied from 11.5 to 58.5 days. Unlabeled serious reactions were found (17.4 %), including skin ulceration, vasculitis or purpura with sorafenib or sunitinib and drug rash with eosinophilia and systemic symptoms with imatinib.
  
  
  CONCLUSIONS
  Some of the serious ADRs spontaneously reported with oral protein kinase inhibitors are labeled and commonly reported in the literature, but others occur only rarely and unlabeled. In our study, most serious ADRs occurred in males within the 2 first months of treatment and were responsible for the withdrawal of therapy with protein kinase inhibitors.
authors.affiliation: Laboratoire de Pharmacologie Médicale et Clinique, Equipe de PharmacoEpidémiologie INSERM U 1027, Faculté de Médecine de l'Université de Toulouse, 37 allées Jules-Guesde, 31000, Toulouse, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Faye
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Bondon-Guitton
authors.forename: Pascale
authors.initials: P
authors.lastname: Olivier-Abbal
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Montastruc
mesh_terms: D016907:Adverse Drug Reaction Reporting Systems / Q000592:standards / Q000706:statistics & numerical data; D062313:Databases, Pharmaceutical; D003875:Drug Eruptions / Q000453:epidemiology / Q000209:etiology*; D005602:France; D006801:Humans; D047428:Protein Kinase Inhibitors / Q000009:adverse effects*; D012189:Retrospective Studies; D012720:Severity of Illness Index
chemical_list: D047428:Protein Kinase Inhibitors