Risk of serious skin disorders among users of oral antifungals: a population-based study

BACKGROUND Serious skin disorders have been associated with the use of oral antifungals in a number of case reports and series of cases. However the incidence of these disorders remains unknown. METHODS We estimated the risk of serious skin disorders in a cohort of users of oral antifungals identified in the general population of the General Practice Research Database in the UK. The cohort included 61,858 patients, 20 to 79 years old, who had received at least one prescription for either oral fluconazole, griseofulvin, itraconazole, ketoconazole, or terbinafine. RESULTS The background rate of serious cutaneous adverse reactions (the one corresponding to non use of oral antifungals) was 3.9 per 10,000 person-years (95% CI 2.9-5.2). Incidence rates for current use were 15.4 per 10,000 person-years (1.9-55.7) for itraconazole, 11.1 (3.0-28.5) for terbinafine, 10.4 (1.3-37.5) for fluconazole, and 4.6 (0.1-25.8) for griseofulvin. Itraconazole was the antifungal associated with the highest relative risk, 3.9 (0.5-15.0), when compared to the risk among non users, followed by terbinafine and fluconazole, with relative risks of 2.8 (0.7-7.8) and 2.6 (0.3-10.1), respectively. CONCLUSIONS We conclude that cutaneous disorders associated with the use of oral antifungals in this study were all of mild severity and that the risk associated with the use of oral antifungals was slightly higher than the risk in non-users. The safety profile of terbinafine regarding cutaneous disorders is similar to other antifungals and in the very low range of risks associated with other drugs.