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

Accepted 13 February 2007. published online 31 March 2008.

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.

Abbreviations used: AEs, adverse events, ALT/SGPT, alanine aminotransferase/serum glutamic pyruvic transaminase, AST/SGOT, aspartate aminotransferase/serum glutamic oxaloacetic transaminase, BUN, blood urea nitrogen, CMH, Cochran Mantel Haenszel, GGT, gamma glutamyl transpeptidase, mITT, modified intent-to-treat, TSSS, total signs and symptoms score

a Department of Dermatology, University of Alabama, Birmingham, Alabama

b Instituto de Salud Especializado del Niño, Lima, Peru

c Center for Clinical Trials, LLC, Paramount, Calif

d Dermatology Department, Misr University of Science and Technology, Cairo, Egypt

e Health Care Partners Medical Group, Torrance, Calif

f Department of Dermatology, Russian Medical Children's Hospital, Moscow, Russia

g The Clinical Research Center of Northwest Florida, Panama City, Florida

h private practice, Bellflower, Calif

i Division of Dermatology, University of Cape Town, Cape Town, South Africa

j Novartis Pharmaceuticals Corporation, East Hanover, NJ

k Novartis Pharma AG, Basel, Switzerland

l Division of Pediatric Dermatology, Children's Hospital, San Diego, Calif

Reprint requests: Boni E. Elewski, MD, Department of Dermatology, University of Alabama at Birmingham School of Medicine, EFH 414 1530, 3rd Avenue South, Birmingham, AL 35294-0009.

Supported by Novartis Pharmaceuticals Corporation.

Disclosures: Drs Elewski, Cáceres, DeLeon, El Shimy, Hunter, Korotkiy, Rachesky, Sanchez-Bal, Todd, and Friedlander were study investigators and received grants or other financial support from Novartis Pharmaceuticals Corporation. Drs Cai, Tavakkol, and Nyirady and Ms Wraith are employees of Novartis Pharmaceuticals Corporation, East Hanover, NJ. Dr Bakshi is an employee of Novartis Pharma AG, Basel, Switzerland. They receive salary, stock (A.T., J.N.), stock option (A.T., J.N.), and other financial benefits from the company.

Portions of the data were presented at the Annual Congress of the European Academy of Dermatology and Venereology in Vienna, Austria, May 16-20, 2007.

∗A list of all study investigators and other contributors to the study may be found at the end of the article.

PII: S0190-9622(08)00252-1

doi:10.1016/j.jaad.2008.02.019

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