Fluindione and drug reaction with eosinophilia and systemic symptoms: an unrecognised adverse effect?

Abstract

PURPOSE:

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: Amélie Daveluy, Brigitte Milpied, Annick Barbaud, Bénédicte Lebrun-Vignes, Aurore Gouraud, Marie-Laure Laroche, Ecaterina Ciobanu, Bernard Bégaud, Nicholas Moore, Ghada Miremont-Salamé, Françoise Haramburu, French Pharmacovigilance Centres Network and The Toxidermia Group of the French Society of Dermatology
• Journal: European journal of clinical pharmacology (Eur J Clin Pharmacol) Vol. 68 Issue 1 Pg. 101-5 (Jan 2012) ISSN: 1432-1041 [Electronic] Germany
• PMID: 21792562 (Publication Type: Journal Article)

Chemical References

• Anticoagulants
• Vitamin K
• Phenindione
• fluindione

Topics

• Administration, Oral
• Adult
• Adverse Drug Reaction Reporting Systems
• Aged
• Aged, 80 and over
• Anticoagulants (administration & dosage, adverse effects)
• Drug Eruptions (etiology, therapy)
• Drug Hypersensitivity (diagnosis, physiopathology, therapy)
• Eosinophilia (chemically induced, etiology, therapy)
• Female
• France
• Humans
• Male
• Middle Aged
• Pharmacovigilance
• Phenindione (administration & dosage, adverse effects, analogs & derivatives)
• Retrospective Studies
• Severity of Illness Index
• Skin Tests
• Vitamin K (antagonists & inhibitors)