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


METHODS
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.


CONCLUSIONS
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.
Elewski
Boni E
BE
Department of Dermatology, University of Alabama, Birmingham, Alabama 35294-0009, USA. beelewski@aol.com
Cáceres
Hector W
HW
DeLeon
Liberation
L
El Shimy
Saleh
S
Hunter
Judy A
JA
Korotkiy
Nicolay
N
Rachesky
Ingrid Johnson
IJ
Sanchez-Bal
Victoria
V
Todd
Gail
G
Wraith
LindaAnn
L
Cai
Bin
B
Tavakkol
Amir
A
Bakshi
Rajesh
R
Nyirady
Judit
J
Friedlander
Sheila Fallon
SF
D000284:Administration, Oral; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D004304:Dosage Forms; D005260:Female; D005334:Fever / Q000139:chemically induced; D006118:Griseofulvin / Q000008:administration & dosage* / Q000009:adverse effects; D006261:Headache / Q000139:chemically induced; D006801:Humans; D008297:Male; D009281:Naphthalenes / Q000008:administration & dosage* / Q000009:adverse effects; D009304:Nasopharyngitis / Q000139:chemically induced; D015995:Prevalence; D013535:Suspensions; D013651:Taste Disorders / Q000139:chemically induced; D000077291:Terbinafine; D014006:Tinea Capitis / Q000188:drug therapy* / Q000453:epidemiology / Q000382:microbiology; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology; D044465:White People
D000935:Antifungal Agents; D004304:Dosage Forms; D009281:Naphthalenes; D013535:Suspensions; D006118:Griseofulvin; D000077291:Terbinafine