Adverse Cutaneous Reactions to Selective Cyclooxygenase 2 Inhibitors: Experience of an Italian Drug-Surveillance Center

Abstract

Background: Selective cyclooxygenase (COX) 2 nonsteroidal anti-inflammatory drugs (NSAIDs) have been associated with a general lower incidence of side effects compared with nonselective NSAIDs. Postmarketing information has highlighted the need to reassess the risk evaluation for specific organs, including the skin. Objective: A prospective databank to record all cases of adverse cutaneous reactions associated with the use of COX inhibitors was conducted at the Centre for Drug Surveillance of the Dermatology Department of Cagliari University. Material and Methods: An intensive surveillance program from November 2000 to October 2004, adopting the World Health Organization Collaborating Centre for Drug Monitoring causality assessment criteria and algorithm. Results: Seventeen cases, 4 male and 13 female, were studied. None had previously presented any drug intolerance or allergy. Clinical manifestations were mainly maculopapular exanthema followed by urticaria-angioedema. A severe case of leukocytoclastic vasculitis was also observed. Responsible drugs were celecoxib (13 cases; 76%), rofecoxib (3 cases; 18%), and etoricoxib (1 case; 6%). All cases recovered with drug withdrawal. Causality was probable for all eruptions, except for the fixed drug eruption, for which causality was certain. Discussion: Although most cases were associated with celecoxib, the observation of severe eruptions owing to rofecoxib and etoricoxib in this prospective study is consistent with a class effect of COX inhibitors on the skin, which merits further studies to explain the fine underlying mechanisms.