Comparative analysis of adverse drug reactions to tetracyclines: results of a French national survey and review of the literature

Summary Background  The question of quantitative and qualitative differences between adverse drug reactions (ADRs) to tetracyclines was raised many years ago, especially for minocycline and doxycycline. Objectives  To assess and compare ADRs related to tetracyclines according to sales figures in France through a national survey. Methods  ADR data were collected from the French Pharmacovigilance Database (FPD), marketing authorization holders (MAH) and the literature. Sales analyses were based on MAH data provided annually to the French Drugs Agency. Results  Among the tetracyclines available in France, doxycycline and minocycline are the most frequently used. However, their sales decreased between 1995 and 2007, more sharply for minocycline than doxycycline. According to the FPD, based on MAH data and published reports, minocycline-associated ADRs were more serious and were reported more frequently than for the other tetracyclines. Minocycline and doxycycline ADR patterns differed: gastrointestinal disorders (especially oesophageal lesions) predominated with doxycycline, while intracranial hypertension and hepatic disorders were primarily reported with minocycline. Autoimmune disorders, drug reaction with eosinophilia and systemic symptoms (DRESS) and other hypersensitivity reactions were also more frequent with minocycline. ADRs reported with lymecycline and metacycline were essentially cutaneous and gastrointestinal disorders. Conclusions  In the absence of markedly better efficacy against the various indications for tetracyclines, the minocycline benefit/risk ratio was clearly lower than that of doxycycline, and possibly those of lymecycline and metacycline. In light of these findings, minocycline should no longer be considered first-line therapy for inflammatory skin disorders, especially acne.