Tinea (pityriasis) versicolor is a non-contagious
infection of the skin caused by Pityrosporum orbiculare (Malassezia
furfur). This commensal organism is part of the normal skin flora. In
susceptible individuals the condition is often recurrent and may give rise to
hyperpigmented or hypopigmented patches on the trunk which may extend to the
neck, arms and upper thighs. Treatment of the infection may not immediately
result in restoration of pigment to the affected sites. Normalization of
pigment following successful therapy is variable and may take months, depending
on individual skin type and incidental skin exposure. The rate of recurrence of
infection is variable.
NIZORAL® (ketoconazole) was not detected in plasma in 39 patients
who shampooed 4-10 times per week for 6 months, or in 33 patients who shampooed
2-3 times per week for 3-26 months (mean: 16 months).
An exaggerated use washing test on the sensitive
antecubital skin of 10 subjects twice daily for five consecutive days showed
that the irritancy potential of ketoconazole 2% shampoo was significantly less than
that of 2.5% selenium sulfide shampoo.
A human sensitization test, a phototoxicity study, and a
photoallergy study conducted in 38 male and 22 female volunteers showed no
contact sensitization of the delayed hypersensitivity type, no phototoxicity and
no photoallergenic potential due to NIZORAL (ketoconazole) 2% Shampoo.
Mode Of Action
Interpretations of in vivo studies suggest that
ketoconazole impairs the synthesis of ergosterol, which is a vital component of
fungal cell membranes. It is postulated, but not proven, that the therapeutic
effect of ketoconazole in tinea (pityriasis) versicolor is due to the reduction
of Pityrosporum orbiculare (Malassezia furfur) and that the
therapeutic effect in dandruff is due to the reduction of Pityrosporum ovale.
Support for the therapeutic effect in tinea versicolor comes from a three-arm,
parallel, double-blind, placebo controlled study in patients who had moderately
severe tinea Â (pityriasis) versicolor. Successful response rates in the primary
efficacy population for each of both three-day and single-day regimens of
ketoconazole 2% shampoo were statistically significantly greater (73% and 69%,
respectively) than a placebo regimen (5%). There had been mycological
confirmation of fungal disease in all cases at baseline. Mycological clearing
rates were 84% and 78%, respectively, for the three-day and one-day regimens of
the 2% shampoo and 11% in the placebo regimen. While the differences in the
rates of successful response between either of the two active treatments and
placebo were statistically significant, the difference between the two active
regimens was not.
NIZORAL® (ketoconazole) is a broad spectrum synthetic
antifungal agent which inhibits the growth of the following common
dermatophytes and yeasts by altering the permeability of the cell membrane:
dermatophytes: Trichophyton rubrum, T. mentagrophytes, T. tonsurans, Microsporum
canis, M. audouini, M. gypseum and Epidermophyton floccosum;
yeasts: Candida albicans, C. tropicalis, Pityrosporum ovale (Malassezia
ovale) and Pityrosporum orbiculare (M. furfur). Development
of resistance by these microorganisms to ketoconazole has not been reported.