Safety profile of etifoxine: A French pharmacovigilance survey
Abstract
Etifoxine chlorhydrate is a benzoxazine derivative approved for the treatment of psychosomatic manifestations of anxiety since 1979. Previously labeled adverse drug reactions (ADRs) only include drowsiness, benign cutaneous reactions, and acute hypersensitivity reactions. The objectives were to examine recent data on etifoxine-related ADR by reviewing Individual Case Safety Reports (ICSRs) recorded in France especially unexpected ADRs. Etifoxine-related ICSRs were extracted from the French Pharmacovigilance database from 1 January 2000 to 30 April 2012 and data from the marketing authorization holder up to 31 December 2011 were also obtained. Of the 350 cases retained for analysis, 123 (35%) were considered serious. Dermatological or acute hypersensitivity reactions were the most frequent ADRs (59%) mainly isolated cutaneous eruptions. However, there were 24 cases of severe toxidermia (DRESS in 5, erythema multiforme in 10 and Stevens-Johnson syndrome in 5) with etifoxine as the most suspected drug in 11 patients, and seven cases of vasculitis or serum sickness-like reaction. Liver disorders were reported in 34 patients of whom 25 developed acute hepatitis with a cytolytic biological pattern in 16. Other unexpected ADRs included 16 reversible cases of metrorrhagia with positive rechallenge in 5, and three cases of biopsy-proven microscopic colitis of which one recurred after etifoxine re-administration. Although etifoxine has been marketed for more than 30 years, this survey identified a number of unexpected and sometimes serious ADRs, in particularly severe toxidermia and acute cytolytic hepatitis. A recent update of the French etifoxine summary of the product characteristics (SPC) was based on these findings.
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Etifoxine use is limited by reports of adverse effects such as cutaneous reactions, hepatotoxicity, colitis and metrorrhagia in a substantial number of people.
“Although its use is limited by reports of the occurrence of adverse effects such cutaneous reactions, hepatotoxicity, colitis and metrorrhagia in a substantial number of people (Cottin et al., 2016), the therapeutic profile of this drug is interesting for drug development.”
From Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders (2019) · cites this paper as Cottin et al., 2016
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- Authors
- Cottin, J., Gouraud, A., Jean‐Pastor, M., Dautriche, A. D., Boulay, C., Geniaux, H., Auffret, M., Bernard, N., Descotes, J., & Vial, T.
- Affiliations
- Hospices Civils de Lyon (FR)
- Regional Pharmacovigilance Center of Marseille Hôpital Sainte‐Marguerite, University Hospitals (AP‐HM), 270 Boulevard de Sainte‐Marguerite 13274 Marseille Cedex 09 France
- CHU Dijon Bourgogne (FR)
- Regional Pharmacovigilance Center of Rouen University Hospitals Service de pharmacologie, 76 031 Rouen Cedex France
- Centre Hospitalier Universitaire de Bordeaux (FR)
- Centre Hospitalier Universitaire de Lille (FR)
- Corresponding author
- Cottin, Judith
- Venue
- Fundamental & Clinical Pharmacology
- Publisher
- Wiley
- Published
- 2016-01-26
- Volume
- 30
- Issue
- 2
- Pages
- 147-152
- ISSN
- 0767-3981 (ISSN-L)
- 1472-8206
- OpenAlex
- W2321375336
- Cited by
- 22
- References
- 12
- Citations by year
- 2026: 3 · 2024: 1 · 2023: 4 · 2020: 4 · 2019: 3 · 2018: 3 · 2017: 2 · 2016: 2
- FWCI
- 1.85
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Fundamental and Clinical Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Pharmacovigilance and Adverse Drug Reactions
- Health Sciences › Medicine › Pharmacology › Drug-Induced Adverse Reactions
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
- Keywords
- etifoxine, adverse drug reactions, pharmacovigilance, benzoxazine derivatives, anxiety, DRESS syndrome, erythema multiforme, Stevens-Johnson syndrome, serum sickness-like reaction, vasculitis, acute hepatitis, cytolytic hepatitis, liver disease, drug-induced skin reaction, microscopic colitis, metrorrhagia, drug safety
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Child, Female, France, Humans, Male, Middle Aged, Oxazines, Surveys and Questionnaires, Databases, Factual, Adverse Drug Reaction Reporting Systems, Young Adult, Pharmacovigilance, Drug-Related Side Effects and Adverse Reactions
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