Safety of oral terbinafine: results of a postmarketing surveillance study in 25,884 patients

OBJECTIVE: To broaden the safety database for oral terbinafine by determining the incidence of adverse events, particularly rare risks, that accompany its uncontrolled use in actual clinical practice. DESIGN: Four open, prospective, uncontrolled, postmarketing surveillance studies were conducted in unselected patients in 4 countries. No exclusion criteria were applied. The only treatment instructions participating physicians received were the manufacturer's product information. Physicians monitored patients for adverse events at baseline, during treatment, and at the end of treatment. Serious events were identified according to study protocol, which was consistent for all 4 studies, allowing data to be pooled and analyzed collectively. SETTING: Patients were recruited from dermatology, general, and family practices in the United Kingdom, the Netherlands, Germany, and Austria. PATIENTS: Of the 25884 patients who entered the study, 38.6% had concomitant diseases, 42.8% were taking other medications, and 22.7% were older than 60 years. The predominant indication for terbinafine treatment was onychomycosis (72.2%). INTERVENTIONS: Data on treatment duration was available for 25091 patients. Median duration of treatment was 12 weeks (mean, 13.2 weeks). Treatment extended beyond 6 weeks in 76.0% of patients and for at least 12 weeks in 59.3%. MAIN OUTCOME MEASURES: The incidence of adverse events as reported by physicians, with their opinions regarding relationship to terbinafine therapy. RESULTS: The incidence of adverse events was 10.5%; the majority involved the gastrointestinal system (4.9%) or skin (2.3%). These tended to be mild, transient, and reversible. Terbinafine was considered a possible or probable cause of 11 (0.04%) serious adverse events. No drug interactions were reported, even in patients taking oral antidiabetic agents, astemizole, terfenadine, or cimetidine hydrochloride. CONCLUSIONS: The positive safety profile established during controlled clinical trials of oral terbinafine extends to its uncontrolled use in clinical practice. No previously unrecognized risks were identified.