title: Fluindione and drug reaction with eosinophilia and systemic symptoms: an unrecognised adverse effect?
abstract: OBJECTIVE
  Fluindione is an oral vitamin K antagonist (indanedione derivative) exclusively marketed in France and Luxembourg, known to have immuno-allergic adverse effects such as hepatitis, fever or interstitial nephritis. A few cases of drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported with fluindione. The aim of the present study was to investigate fluindione-induced DRESS cases reported in France and to describe their characteristics.
  
  
  METHODS
  We searched for potential cases of DRESS with fluindione reported in the French pharmacovigilance database since 2000.
  
  
  RESULTS
  Thirty-six cases of DRESS were included and concerned 17 women and 19 men. The mean age was 65 years (median: 68 years, range: 28-95 years). Kidneys and liver were the most frequent organs involved. Thirty-five cases were serious. In 5 cases, the effect was life-threatening. Most of the patients recovered. Fluindione was the only medicine suspected in 26 cases. Skin patch tests, performed in 10 cases, were positive with fluindione in 9 cases.
  
  
  CONCLUSIONS
  Fluindione is not known to be a frequent cause of DRESS. However, the number of reports found is probably underestimated. The seriousness of DRESS, as all immuno-allergic adverse effects, contraindicates fluindione reintroduction. Coumarinic derivatives are the alternatives in patients who need oral anticoagulant treatment.
authors.affiliation: Université de Bordeaux, U657, 33000, Bordeaux, France. amelie.daveluy@u-bordeaux2.fr
authors.forename: Amélie
authors.initials: A
authors.lastname: Daveluy
authors.forename: Brigitte
authors.initials: B
authors.lastname: Milpied
authors.forename: Annick
authors.initials: A
authors.lastname: Barbaud
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Lebrun-Vignes
authors.forename: Aurore
authors.initials: A
authors.lastname: Gouraud
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Laroche
authors.forename: Ecaterina
authors.initials: E
authors.lastname: Ciobanu
authors.forename: Bernard
authors.initials: B
authors.lastname: Bégaud
authors.forename: Nicholas
authors.initials: N
authors.lastname: Moore
authors.forename: Ghada
authors.initials: G
authors.lastname: Miremont-Salamé
authors.forename: Françoise
authors.initials: F
authors.lastname: Haramburu
mesh_terms: D000284:Administration, Oral; D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects*; D003875:Drug Eruptions / Q000209:etiology* / Q000628:therapy; D004342:Drug Hypersensitivity / Q000175:diagnosis / Q000503:physiopathology* / Q000628:therapy; D004802:Eosinophilia / Q000139:chemically induced / Q000209:etiology* / Q000628:therapy; D005260:Female; D005602:France; D006801:Humans; D008297:Male; D008875:Middle Aged; D060735:Pharmacovigilance; D010630:Phenindione / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D012189:Retrospective Studies; D012720:Severity of Illness Index; D012882:Skin Tests; D014812:Vitamin K / Q000037:antagonists & inhibitors*
chemical_list: D000925:Anticoagulants; D014812:Vitamin K; D010630:Phenindione; C017673:fluindione