Single-blind, randomized, prospective study of sequential itraconazole andterbinafine pulse compared with terbinafine pulse for the treatment of toenail onychomycosis

Objective: Efficacy and safety of sequential pulse therapy with itraconazol e and terbinafine were compared with pulse terbinafine alone in the treatme nt of toenail onychomycosis. Methods: This was a 72-week prospective, single-blind, randomized, multicen ter, comparative, parallel group, nonindustry-sponsored trial. A total of 1 90 patients were recruited from 3 outpatient dermatology offices in North A merica. Patients were at least 18 years old and had a clinical and mycologi c diagnosis of dermatophyte toenail onychomycosis. Patients were randomly a ssigned to receive sequential pulse therapy (IIT) with 2 pulses of itracona zole followed by 1 or 2 pulses of terbinafine (itraconazole pulse is 200 mg twice daily for 1 week and terbinafine pulse is 250 mg twice daily for 1 w eek) versus 3 or 4 pulses of terbinafine (TTT). Main outcome measures at we ek 72 evaluated mycologic cure rate (negative light microscopy and culture) , clinical cure (nail appears completely or totally normal), complete cure (clinical and mycologic cure), and effective therapy (mycologic cure and cl inical response with at least: 5 mm of new, uninvolved nail growth). Results: At week 72, in the IIT versus TTT groups, the mycologic cure rate was 54 of 75 (72.0%) versus 44 of 90 (48.9%), clinical cure rate was 42 of 75 (56.0%) versus 35 of 90 (38.9%), effective therapy 49 of 75 (65.3%) vers us 41 of 90 (45.6%), and complete cure 39 of 75 (52.0%) versus 29 of 90 (32 .2%), respectively. Both regimens were well tolerated with no new adverse e ffects being identified. The rate of permanent discontinuation of therapy b ecause of adverse effects was 2 of 81 (2.5%) with IIT and 2 of 95 (2.1%) wi th TTT. Each of the adverse effects normalized over time. The number of pat ients who reported an adverse effect in the 2 groups was 12 of 81 (14.8%) v ersus 22 of 95 (23.2%), respectively. All these adverse effects were revers ible and mild to moderate in severity. Conclusion: Sequential pulse therapy with itraconazole and terbinafine is e ffective and safe for the treatment of dermatophyte toenail onychomycosis.