Original article

Flutrimazole shampoo 1% versus ketoconazole shampoo 2% in the treatment of pityriasis versicolor. A randomised double-blind comparative trial
D. Rigopoulos,1 S. Gregoriou,1 G. Kontochristopoulos,2 A. Ifantides3 and A. Katsambas1
1 3

Department of Dermatology, University of Athens, A Sygros Hospital, Athens, 22nd Department of Dermatology, A Sygros Hospital, Athens and Biopathologist, Private Practice, Athens, Greece

Summary

Flutrimazole is an imidazole derivative that has been proven to be efcient in supercial skin fungal infections. The aim of this randomised double-blind study was to compare for the rst time, the efciency and safety of utrimazole 1% shampoo versus ketoconazole 2% shampoo in the treatment of tinea versicolor. Study population consisted of 60 patients with pityriasis versicolor diagnosed clinically and through direct microscopy and culture. Patients were randomly assigned to two groups: one instructed to apply utrimazole shampoo 1% and one instructed to apply ketoconazole shampoo 2% both on head and body for 14 days. Patients were re-evaluated 14 days after the end of treatment clinically and through direct microscopy and culture. Twenty-one of 26 patients (80.8%) in the ketoconazole and 22 of 29 patients (75.9%) in the utrimazole group had both visual healing and negative mycological evaluation. Comparison of the response between the two groups with the Yates corrected chisquare was found statistically not signicant (v2 0.19, d.f. 1, P 0.91). None of the patients in the two groups reported any adverse effects. Fourteen (53%) patients in the ketoconazole group and 23 (79%) in the utrimazole group assessed the shampoos as cosmetically acceptable regarding texture, smell and foam properties. Flutrimazole shampoo 1% appears to present efcacy comparable with ketoconazole 2% in the treatment of tinea versicolor.

Key words: utrimazole, ketoconazole, pityriasis versicolor, therapy.

Introduction
Pityriasis versicolor is a supercial fungal infection caused by lipophilic yeast of Malassezia species. The disease is very common throughout the world affecting mainly young adults of both sexes. Classical treatment includes agents such as propylene glycol, zinc pyrithione, selenium sulde, ciclopiroxolamine and imidazole derivatives.1
Correspondence: Dimitris Rigopoulos MD, PhD, Asst Professor of Dematology, Andreas Syngros Hospital, 5 Ionos Dragoumi str, 16121 Athens, Greece. Tel.: +2107265194. Fax: +2107211122. E-mail: drigop@hol.gr Accepted for publication 8 November 2006

Flutrimazole is an azole derivative that has been proven to be efcient when applied in cream formulation in supercial skin fungal infections.2 The aim of this randomised double-blind study was to compare for the rst time, the efciency and safety of utrimazole 1% shampoo versus ketoconazole 2% shampoo in the treatment of tinea versicolor.

Subjects and methods

Study population consisted of 60 patients with pityriasis versicolor diagnosed clinically, after uorescence examination of involved areas under Woods light, and through direct microscopy and culture. Skin scrapings from lesional and perilesional skin were examined with KOH 10% and strippings taken by Scotch tape were

2007 The Authors Journal Compilation 2007 Blackwell Publishing Ltd Mycoses (2007), 50, 193195

doi:10.1111/j.0933-7407.2006.01352.x

D. Rigopoulos et al.

cultured in Petri dishes with Dixon medium.3 Patients were excluded from the study, if they had serious concurrent diseases, other fungal infections or eye problems that could be irritated by the shampoo. The patients included in the study had not used any topical or systemic antifungal agent for the past month and gave informed written consent. Patients were randomly assigned by a computer to one of two groups. Patients in Group A were instructed to apply utrimazole shampoo 1% and patients in Group B ketoconazole shampoo 2%, on both head and body and leave it for 5 min (conrmed by timers) before rinsing. The formula of the utrimazole shampoo was: utrimazole gel 1% mgw/v, polysorbate 20, capryly/ capryl glucoside 60%, cocamidopropyl betaine 30%, acrylate/steareth-20methacrylate copolymer, 30% diazolinidyl urea, dimethicone propyl pg-betaine 30%, sodium hydroxide, essence puried water (manufactured by Olvos Science, Athens, Greece). The formula of the ketoconazole shampoo was: ketoconazole 2%, sodium lauryl sulphate, disodium monolauryl ether sulphosuccinate, coconut fatty acid diethanolamide, laurdimonium hydrolised animal collagen, macrogol 120 methyl glucose dioleate, concentrated hydrochloric acid, imidurea, perfume bouquet, erythrosine, sodium hydroxide, sodium chloride, water puried (Fungoral 2% Janssen-Cilag, Athens, Greece). Both products came in identical containers. Patients repeated the procedure every day for 14 days. The classical treatment duration of 14 days was preferred against the ultra short treatment of 3 days because of the better established response rates. Clinical and laboratorial re-evaluation through culture and direct microscopy took place 14 days after the end of treatment. Investigators assessing the clinical outcome were blinded concerning the therapeutical agent used. A patient was considered to show positive response if all visual evidence/symptoms

of fungal disease had disappeared (scaling and itching) with the exception of hypopigmentation and direct microscopy and culture were negative on day 28. Patients were also asked to report any adverse events and cosmetically evaluate the shampoo. A statistical analysis between the two groups was performed by using t-test for age, sex and duration of the disease and Yates corrected chi-square for the efcacy of the two shampoos.

Results
Fifty-ve patients (26 for the ketoconazole and 29 for the utrimazole group) returned for the follow-up visit. Demographics of all patients and duration of the disease in the two groups are presented in Table 1. There were no statistically signicant differences regarding age, sex and duration of the disease for the patients in the two groups. Twenty-one patients (80.8%) in the ketoconazole and 22 (75.9%) in the utrimazole group had both clinical response and negative mycological evaluation. When considering only clinical response, cure rates on day 28 were 88% (23 of 26) and 86% (25 of 29), respectively (Table 2). Comparison of response between the two groups with the Yates corrected chi-square was found statistically not signicant (v2 0.19, d.f. 1, P 0.91). None of the patients reported any adverse effect. Fourteen (53%) patients in the ketoconazole group and 23 (79%) in the utrimazole group assessed the shampoos as cosmetically acceptable regarding texture, smell and foam properties.

Discussion
Flutrimazole shares the mode of action of other imidazole- or triazole-containing antifungals, i.e. inhibition of fungal lanosterol 14 a-demethylase, as it strongly

Table 1 Demographic data and duration of disease for the patients in both groups at baseline Sex (male/female) Flutrimazole Ketoconazole P-value 14/15 14/12 >0.05 Age (years; mean SD) 32.8 7.4 30.5 9.2 >0.05 Duration (months; mean SD) 5.2 4.7 5.9 5.1 >0.05

Table 2 Clinical cure of scaling and itching but excluding hypopigmentation, negative direct microscopy examination and negative culture results in the two groups on day 28 Clinical response Flutrimazole Ketoconazole 25/29, 86.2% 23/26, 88.5% Negative KOH examination 22/29, 75.9% 22/26, 84.6% Negative culture 22/29, 75.9% 21/26, 80.8% Clinical and mycological cure 22/29, 75.9% 21/26, 80.8%

Comparison of response between the two groups with the Yates corrected chi-square was found statistically not signicant (v2 0.19, d.f. 1, P 0.91).

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2007 The Authors Journal Compilation 2007 Blackwell Publishing Ltd Mycoses (2007), 50, 193195

Flutrimazole 1% shampoo in pityriasis versicolor

inhibits ergosterol biosynthesis in a cell-free homogenate of Candida albicans, with an IC50 value of 0.071 lmol l)1. It displays potent broad-spectrum in vitro activity against dermatophytes, lamentous fungi and yeast, saprophytic and pathogenic to animals and humans (minimum inhibitory concentration, MIC: 0.0255.0 lg ml)1).2 Studies have shown that the activity of utrimazole is comparable with that of clotrimazole and ketoconazole and markedly higher than that of bifonazole.46 Although utrimazoles antifungal properties have been well established, no formal study exists on the agents efcacy regarding the treatment of pityriasis versicolor in human patients. In vitro testing against 23 isolates of Malassezia furfur from guinea-pigs has shown that ketoconazole presents stronger inhibitory activity than utrimazole (geometric mean MIC: 0.51 lg ml)1 vs. 16 lg ml)1).7 In animal experiments involving three consecutive days of topical treatments, bifonazole 1% cream, clotrimazole 1% cream, utrimazole 1% and 2% creams, ketoconazole 2% cream and shampoo and miconazole 2% cream all reduced M. furfur dermatitis lesion severity below that of untreated control animals.8 In the patient population under study, there was no signicant difference in the cure rates between the ketoconazole and utrimazole groups suggesting that excellent outcome can be achieved with either agent. Moreover, the utrimazole shampoo formulation seems to exhibit antifungal activity comparable with the ketoconazole shampoo formulation available for decades. None of the patients in the two groups reported any adverse effects, conrming the reported low incidence of allergic contact reactions after imidazole topical application, despite their widespread use.8 In addition to the utrimazole shampoo formulation sharing the well established safety prole of the utrimazole cream formulation,9 more users attributed to the product an acceptable cosmetic prole than its ketoconazole counterpart. In conclusion, utrimazole 1% appears to present efcacy comparable with ketoconazole 2% in the treatment of pityriasis versicolor. Taking into account the better tolerability of the shampoo formulation, a

factor important for patients compliance, we believe that utrimazole shampoo 1% should be considered as an excellent alternative therapy for the management of tinea versicolor.

References
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