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Background: Although griseofulvin is currently considered the primary antifungal agent used to treat tinea capitis in many countries, increasingly higher doses and longer durations of treatment are becoming necessary to achieve effective treatment. Alternative antifungal therapies with shorter/simpler treatment regimens may be important to develop for this indication., Objective: To compare the efficacy and safety of a new pediatric formulation of terbinafine hydrochloride oral granules with griseofulvin oral suspension in the treatment of tinea capitis., Method: Children (4-12 years of age) with clinically diagnosed and potassium hydroxide microscopy-confirmed tinea capitis were randomized in two identical studies (trial 1, trial 2) to once-daily treatment with terbinafine (5-8 mg/kg; n = 1040) or griseofulvin administered per label (10-20 mg/kg; n = 509) for a period of 6 weeks followed by 4 weeks of follow-up. End-of-study complete cure (negative fungal culture and microscopy with Total Signs and Symptoms Score [TSSS] = 0), and mycologic (negative culture and microscopy) and clinical cure (TSSS = 0) were primary and secondary efficacy variables, respectively. Efficacy analysis was based on pooled data using modified intent-to-treat population (those who received at least one dose of study drug and had positive baseline fungal culture, N = 1286). Safety assessments included monitoring of the frequency and severity of adverse events (AEs)., Results: Rates of complete cure and mycologic cure were significantly higher for terbinafine than for griseofulvin (45.1% vs 39.2% and 61.5% vs 55.5%, respectively; P < .05). A majority (86.7%) of patients received griseofulvin, 10 to 19.9 mg/kg per day; complete cure rate was not found to be higher among patients who received griseofulvin more than 20 mg/kg per day compared with those who received less than 20 mg/kg per day. Complete cure rate was statistically significantly greater for terbinafine compared to griseofulvin in trial 1 (46.23% vs 34.01%) but not in trial 2 (43.99% vs 43.46%). On the basis of pooled data, clinical cure was higher for terbinafine than for griseofulvin, but the difference was not found to be statistically significant (P = .10). Subgroup analyses revealed that terbinafine was significantly better than griseofulvin for all cure rates--mycologic, clinical, and complete--among patients with Trichophyton tonsurans but not Microsporum canis (P < .001). For M. canis, mycologic and clinical cure rates were significantly better with griseofulvin than with terbinafine (P < .05). Approximately 50% of patients in each group reported an AE; almost all were mild or moderate in severity. Nasopharyngitis, headache, and pyrexia were most common in both groups. There were no drug-related serious AEs, no deaths, and no significant effects on weight or laboratory parameters, including liver transaminases., Limitations: In retrospect, a difference in the distribution of infecting microorganisms between the two trials was a limitation. Stringent adherence to griseofulvin doses recommended by prescribing information but smaller than those used in current clinical practice, and exclusion of adjuvant therapies such as shampoos or topical agents, which are routinely used in practice, are other limitations., Conclusions: Data from this largest pediatric trial of terbinafine to date indicate that terbinafine is efficacious and well tolerated in the treatment of tinea capitis. Terbinafine is an effective alternative to griseofulvin against T. tonsurans tinea capitis.

Objectives: An open-label study was performed to assess the efficacy and safety of terbinafine in the treatment of eumycetoma., Methods: Single-center, open-label study, including 27 patients with signs and symptoms of eumycetoma which had developed within 5 years and was confirmed by mycological examination. The intention-to-treat population (n=23) received 500 mg of terbinafine bid for 24-48 weeks. Efficacy evaluations included clinical signs and symptoms (e.g. sinuses open or closed, degree of tumefaction, and emission of grains either present or absent); mycological examinations from Week 24 onwards; and investigators' overall assessment of efficacy (cure, improved since baseline, unchanged since baseline, or deterioration since baseline). Safety evaluations included monitoring of adverse events, laboratory assessments, vital signs and physical examinations., Results: Good clinical improvement was seen in patients who completed the study (n=20). Tumefaction was absent or improved in 80% of patients; sinuses were closed in 50% of patients, and grain emissions were absent in 65% of patients. Of the 16 patients who had repeat mycological assessment, four (25%) were mycologically cured. In the investigators' overall opinion at the end of the study, five (25%) were cured and 11 (55%) were clinically improved. The majority of adverse events reported were mild to moderate, and consistent with the known tolerability profile of terbinafine., Conclusion: High-dose terbinafine (1,000 mg/day) is well tolerated and clinically effective in patients with eumycetoma, a difficult-to-treat subcutaneous mycoses.

Background: Terbinafine is an established drug for the treatment of toenail onychomycosis. Minimizing the total dose of terbinafine and giving it intermittently could improve tolerability as well as compliance, provided efficacy is not compromised., Objective: Two identical trials were conducted to compare the efficacy, safety and tolerability of the current standard regimen of terbinafine 250 mg daily with a new formulation of terbinafine given intermittently for three cycles of 2 weeks of treatment (350 mg daily) followed by 2 weeks off treatment., Methods: A total of 2005 patients with a clinical diagnosis of subungual onychomycosis of the large toenail confirmed by microscopy and culture for a dermatophyte were recruited into the two trials and treated for 12 weeks., Results: Patients with onychomycosis of prolonged duration (mean 9 years) and a median nail involvement of 63% with or without spikes, lateral involvement and white superficial onychomycosis (WSO) were included in the trial. The studies found a significant difference (p<0.05) in favour of standard daily dosing with terbinafine. Response rates for the primary variable complete cure (mycological and clinical cure) were lower with the new formulation in both Trial I (-5.8%; 95% CI -11.8, 0.07) and Trial II (difference -5.9%; 95% CI -12, 0.1). Both treatments were equally well tolerated, with approximately 11% of patients in both groups reporting at least one treatment-related adverse event., Conclusions: Pulsed dosing with terbinafine did not provide any clear safety advantages and was significantly less effective. Consequently, continuous treatment with terbinafine tablets remains the optimal therapy for onychomycosis.