Terbinafine hydrochloride oral granules versus oral griseofulvin suspension in children with tinea capitis: Results of two randomized, investigator-blinded, multicenter, international, controlled trials

• Published in: Journal of the American Academy of Dermatology 2008-07, Vol.59 (1), p.41-54
• Main Authors: Elewski, Boni E., MD, Cáceres, Hector W., MD, DeLeon, Liberation, MD, El Shimy, Saleh, MD, Hunter, Judy A., MD, Korotkiy, Nicolay, MD, Rachesky, Ingrid Johnson, MD, Sanchez-Bal, Victoria, MD, Todd, Gail, MD, Wraith, LindaAnn, MBA, Cai, Bin, MD, Tavakkol, Amir, PhD, Bakshi, Rajesh, MD, Nyirady, Judit, MD, MBA, Friedlander, Sheila Fallon, MD
• Format: Article
• Language: English
• Subjects: Administration, Oral; Antifungal Agents - administration & dosage; Antifungal Agents - adverse effects; Child; Child, Preschool; Dermatology; Dosage Forms; European Continental Ancestry Group; Female; Fever - chemically induced; Griseofulvin - administration & dosage; Griseofulvin - adverse effects; Headache - chemically induced; Humans; Male; Naphthalenes - administration & dosage; Naphthalenes - adverse effects; Nasopharyngitis - chemically induced; Prevalence; Suspensions; Taste Disorders - chemically induced; Tinea Capitis - drug therapy; Tinea Capitis - epidemiology; Tinea Capitis - microbiology; Treatment Outcome; United States - epidemiology
• ISSN: 0190-9622; 1097-6787
• DOI: 10.1016/j.jaad.2008.02.019

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 we