Efficacy and Safety of Terbinafine Hydrochloride 1% Cream vs. Sertaconazole Nitrate 2% Cream in Tinea Corporis and Tinea Cruris - A Comparative Therapeutic Trial

Efficacy and Safety of Terbinafine Hydrochloride 1% Cream vs. Sertacon...
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3827518/?report=printable
Indian J Dermatol. 2013 Nov-Dec; 58(6): 457460. doi: 10.4103/0019-5154.119958
PMCID: PMC3827518
Efficacy and Safety of Terbinafine Hydrochloride 1% Cream vs. Sertaconazole Nitrate 2% Cream in Tinea Corporis and Tinea Cruris: A Comparative Therapeutic Trial
SV Choudhary, S Bisati, AL Singh, and S Koley1
From the Department of Dermatology, Jawaharlal Nehru Medical College, Sawangi, Wardha, Maharashtra, India 1Department of Dermatology, B.S Medical College, Bankura, India Address for correspondence: Dr. Sanjiv V. Choudhary, 28, Modern Nagpur Society, Chatrapati Nagar, Nagpur - 440 015, India. E-mail: sanjiv_choudhary26@yahoo.com Received May 2012; Accepted October 2012. Copyright : Indian Journal of Dermatology This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Context:
To the best of our knowledge, till date no study comparing the efficacy and safety of terbinafine hydrochloride 1% cream and sertaconazole nitrate 2% cream has been done in localized tinea corporis and tinea cruris.
Aims:
This clinical trial was carried out to study and compare the efficacy of topical terbinafine hydrochloride 1% cream and sertaconazole nitrate 2% cream in localized tinea corporis and tinea cruris and to know the adverse effects of these antifungal creams.
Settings and Design:
In this prospective, single blind, randomized control trial with two arms, patient were randomized into two groups Group A (treatment with terbinafine cream) and Group B (treatment with sertaconazole cream). A total of 38 patients were enrolled for the study, 20 patients in group A and 18 patients in group B. But five patients of group A and three patients of group B were lost for follow-ups. Therefore sample size was of 30 patients with 15 patients in group A and group B each.
Materials and Methods:
Patients in group A and B were treated with twice daily topical 1% terbinafine hydrochloride and 2% sertaconazole nitrate cream respectively for a total duration of three weeks. Clinical improvement in signs and symptoms of each clinical parameter, namely itching, erythema, papules, pustules, vesicles, and scaling were graded weekly and clinical cure was assessed. KOH mount and culture was done weekly up to 3 weeks to access mycological cure. Fungal culture was done on Sabouraud's dextrose agar with chloramphenicol and cycloheximide.
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Statistical Analysis Used:
Statistical analysis was done using students paired and unpaired t-tests from the data obtained.
Results:
Comparison between Group A and Group B for complete cure (clinical and mycological) showed that at the end of 3 weeks both terbinafine and sertaconazole groups had 100% complete cure. When the two groups were compared for complete cure, at the end of 1st and 2nd week, statistically non-significant results were observed (P = 0.461 and P = 0.679 respectively). However, at the end of 2nd week, complete cure rate for terbinafine was 80% as compared to 73.35% for sertaconazole with no statistical significance. In both Group A and Group B, clinically significant local side effects like erythema, swelling, stinging sensation, or increased itching were not noticed. A majority of our patients in both the group showed Trichophyton rubrum followed by Trichophyton mentagrophytes growth on culture. In Group A, 11 patients showed growth of T. rubrum, 2 patients showed growth of T. mentagrophytes, and 1 patient had only KOH test positive. In Group B, 10 patients revealed growth of T. rubrum, followed by growth of T. mentagrophytes in 3 and Microsporum canis in 2 patients. The therapeutic response is more or less same in infection with different species.
Conclusions:
The newer fungistatic drug sertaconazole nitrate 2% cream was as effective as terbinafine hydrochloride 1% cream which is one of the fungicidal drugs, though terbinafine hydrochloride 1% cream has higher rates of complete cure at the end of 2 weeks as compared to sertaconazole nitrate 2% cream. Both the drugs showed good tolerability with no adverse effects. Keywords: Dermatophytosis, sertaconazole nitrate 2% cream, terbinafine hydrochloride 1% cream
Introduction
What was known? Clinical trials regarding efficacy of terbinafine hydrochloride 1% cream and sertaconazole nitrate 2% cream in localized dermatophytosis were available in comparison with other topical antifungal drugs or placebo. But comparative studies between these two drugs in localized tinea corporis and cruris were lacking.
Dermatophytoses is a superficial fungal infection of keratinized tissue, caused by keratinophilic fungi called dermatophytes. Dermatophytoses is commonly called as tinea. Tinea corporis and tinea cruris is the dermatophytoses of glabrous skin and groin, respectively. Many topical antifungals of different groups are available for the treatment of dermatophytoses such as azole derivatives, allylamines, benzylamines, morpholine, etc., Systemic drugs, such as terbinafine and itraconazole, are currently used for the treatment of severe and chronic dermatophytosis.[1] Topical antifungal drugs are effective in localized infections. Topical antifungal therapy based on the use of imidazoles, such as clotrimazole, miconazole, and ketoconazole, is most commonly used.[2] Sertaconazole is a newer topical antifungal agent which belongs to the imidazole class of antifungals. Like other azoles, sertaconazole inhibits the synthesis of ergosterol, an essential component of fungal cell walls resulting in disruption of mycelial growth and replication. However, at higher concentrations, sertaconazole binds directly to non-sterol lipids in the fungal cell wall, which leads to increased permeability and subsequent lysis of the mycelium. Thus, depending on concentration,
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sertaconazole may exhibit both fungistatic and fungicidal activities.[3] Terbinafine hydrochloride is one of the fungicidal allylamine groups of drugs with broad spectrum of antifungal activity. It interferes with fungal sterol biosynthesis at an early stage. It also inhibits squalene epoxidation, leading to intracellular accumulation of toxic squalene responsible for fungal cell death.[4] There is paucity of clinical studies regarding the clinical efficacy of newer antifungal like sertaconazole in treatment of tinea corporis and tinea cruris. As per our knowledge, there is not a single study available at present comparing the clinical efficacy of topical terbinafine and sertaconazole cream in treatment of tinea corporis and tinea cruris. With this background the present trial was carried out to study and compare the efficacy of topical terbinafine hydrochloride 1%, a fungicidal agent and sertaconazole nitrate 2% cream, a fungistatic agent in localized tinea corporis and tinea cruris and to study the adverse effects of these antifungal creams.
Materials and Methods

This randomized control trial with two arms, to compare the clinical efficacy and side effects of topical terbinafine hydrochloride 1% and sertaconazole nitrate 2% cream in the treatment of localized (<20% involvement) tinea corporis and tinea cruris, was conducted in the department of Dermatology, Acharya Vinoba Bhave Rural Hospital, Sawangi, Wardha during the period from Nov 2010 to Oct 2011. Patients were randomized into two groups: Group A (treatment with terbinafine cream) and Group B (treatment with sertaconazole cream). A total of 38 patients were enrolled for the study, 20 patients in group A and 18 patients in group B. But five patients of group A and three patients of group B were lost for follow-ups. Therefore, the sample size was of 30 patients with 15 patients in group A and group B each. Patients in group A and B were treated with topical 1% terbinafine hydrochloride and 2% sertaconazole nitrate cream, respectively. The inclusion criteria included untreated patients of dermatophytosis of all age groups, involvement of less than 20% of body surface area, and patients whose diagnosis was confirmed by KOH mount. Exclusion criteria's were the patients of resolving dermatophytoses, patients already on topical and systemic antifungal treatment, involvement of more than 20% body surface area, pregnant and lactating females, and patients with immunosuppressive disease or on immunosuppressive drugs. Diagnosis was made on clinical and mycological (KOH and culture) grounds. All the patients had similar demographic features with regards to age (ranged in age between 16 and 35 years in both the groups), sex (Group A: male = 11 and female = 4, Group B: male = 12 and female = 3) and duration of disease (6 months to one year in both the groups). To ensure regular follow up of patients, they were provided with topical medications weekly by us for 3 weeks. Patients were advised to apply the cream twice daily on affected sites. They were recalled at the end of every week to note the efficacy and any adverse effects like local erythema, swelling, stinging sensation, or increased itching, for a total duration of 3 weeks. The patients were graded for improvement in signs and symptoms of each clinical parameter, namely itching, erythema, papules, pustules, vesicles and scaling, and overall improvement was graded as Grade I (25% improvement), Grade II (50% improvement), Grade III (75% improvement), and Grade IV (100% improvement). KOH mount and culture was done weekly up to 3 weeks to access mycological cure. Fungal culture was done on Sabouraud's dextrose agar with chloramphenicol and cycloheximide. It was possible to get sufficient scales at baseline and at the end of 1 week of treatment for mycological assessment but due to good treatment response there were hardly any scales to perform the
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mycological assessment at the end of 2 nd and 3rd weeks. We performed the mycological assessment with whatever scales available at the end of 2nd and 3rd week. Mycological cure was defined as negative KOH and culture. Complete cure was defined as mycological cure with complete absence of clinical signs and symptoms. Statistical analysis was done using Students paired and unpaired t-tests from the data obtained.
Results
In group A (terbinafine hydrochloride 1%) complete cure was noted in 6.66%, 80%, and 100% patients at the end of 1st, 2nd, and 3 rd week of treatment, respectively. Significant P value (0.000) was observed if the results were compared between baseline to 1st week, baseline to 2nd week, 1st to 2nd week, and 1st to 3rd week but the results compared between 2nd and 3rd week were not statistically significant (P-0.082) [Table 1 and Figure 1ad]. In group B (sertaconazole nitrate 2%), not a single patient showed complete cure at the end of first week. 73.33% and 100% patients showed complete clinical cure at the end of 2nd and 3rd week of treatment. A significant P value (0.000) was observed if the results were compared between baseline to 1st week, baseline to 2nd week, 1st to 2nd week, and 1st to 3rd week. A statistically significant P value (0.041) was also observed when the results were compared between 2nd and 3 rd week [Table 2 and Figure 2a-d.] A comparison between Group A and Group B for complete cure showed that at the end of 3 weeks both terbinafine and sertaconazole groups had 100% complete cure. When the two groups were compared for complete cure, at the end of 1st and 2nd week, statistically non-significant results were observed (P = 0.461 and P = 0.679, respectively). However, at the end of 2nd week, complete cure rate for terbinafine was 80% as compared to 73.35% for sertaconazole with no statistical significance [ Table 3 and Figure 1]. In both Group A and Group B, clinically significant side effects like local erythema, swelling, stinging sensation, or increased itching were not noticed. A majority of our patients in both the group showed Trichophyton rubrum followed by T. mentagrophytes growth on culture. In Group A, 11 patients showed growth of T. rubrum, 2 patients showed growth of T. mentagrophytes, and 1 patient had only KOH test positive. In Group B, 10 patients revealed growth of T. rubrum, followed by growth of T. mentagrophytes in 3 and Microsporum canis in two patients. The therapeutic response is more or less same in infection with different species.
Discussion
Individually in both terbinafine and sertaconazole groups, a statistically significant difference in complete cure was observed if the results were compared between baseline to 1st week, baseline to 2nd week, 1st to 2nd week, and 1st to 3rd week. But in the sertaconazole group, a statistically significant difference in complete cure was also observed when the results between 2nd and 3rd week was compared, which was not observed in terbinafine group. These observations indicate that 2 weeks of treatment with terbinafine hydrochloride 1% cream is sufficient as compared to 3 weeks of sertaconazole nitrate 2% cream. On comparison between these two groups, it was observed that sertaconazole nitrate 2% cream was as effective as terbinafine hydrochloride 1% at the end of 1st, 2nd and 3 rd week, though terbinafine 1% cream showed higher rates of complete cure at the end of 2 weeks. No clinically significant side effects like local erythema, swelling, stinging sensation, or increased itching were seen in both the groups.
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Bonifaz et al.[5] in their comparative study between terbinafine 1% gel vs ketocanazole 2% cream in tinea cruris and corporis used terbinafine 1% gel once daily for 1 week and observed a clinical and mycological overall evaluation in 72% of patients receiving terbinafine emulsion gel. In our study, we used terbinafine 1% cream twice daily for 3 weeks and attained complete cure rates of 80% and 100% at the end of 2 and 3 weeks, respectively. Millikan[6] in his study on efficacy and tolerability of terbinafine in the treatment of tinea cruris used terbinafine 1% cream twice daily for 2 weeks and observed that therapy was effective in 67% of terbinafine treated patients as compared to 11% in the placebo group. Greer et al.[7] in their study of treatment of tinea cruris with topical terbinafine, clinical results combined with evaluation of mycological tests at the end of therapy showed terbinafine to be rapid and significantly more effective in treatment of tinea cruris than placebo (78% vs 18% cure rate respectively) which is comparable to our study. No significant adverse effects occurred during terbinafine treatment. In a study done by Sharma et al.[8] on the efficacy and tolerability of sertaconazole nitrate 2% cream vs miconazole 1% cream in patients with cutaneous dermatophytosis, sertaconazole nitrate 2% cream was used twice daily for 2 weeks and they observed that 62.3% patients had a complete clinical cure. Sertaconazole was well tolerated without clinically significant side effects. In our study, complete cure rates of 73.33% at the end of 2nd week was seen. But we continued the treatment for another 1 week and observed complete cure rate (100%) at the end of the 3 rd week. Esso et al.[9] in their study of sertaconazole in the treatment of paediatric patients with cutaneous dermatophyte infections used 2% sertaconazole once daily for a period of 2 weeks and observed that clinical cure was achieved in 75% and 100% patients after 2 and 4 weeks, respectively. No local adverse effects were observed in their study. In our study, complete cure rates of 73.33% at the end of 2nd week was seen with application of sertaconazole cream twice daily for 2 weeks. Esso et al.[9] achieved 75% cure rate with only once daily application of sertaconazole at the end of 2 weeks as compared to twice daily application in our study which could be explained on the basis that in paediatric age group percutaneous absorption is more due to thinner skin as compared to adults. To the best of our knowledge, till date no study comparing the efficacy and safety of terbinafine hydrochloride 1% cream and sertaconazole nitrate 2% cream has been done. Our study showed that the newer fungistatic drug sertaconazole nitrate 2% cream is as effective as terbinafine hydrochloride 1% cream which is one of the fungicidal drugs, though terbinafine hydrochloride 1% cream has higher rates of complete cure at the end of 2 weeks as compared to sertaconazole nitrate 2% cream. Both the drugs showed good tolerability with no adverse effects. In conclusion, further similar studies need to be carried out to support our observation.
What is new? The newer fungistatic drug sertaconazole nitrate 2% cream is as effective as the fungicidal, terbinafine hydrochloride 1% cream in localized tinea corporis and cruris. Both the drugs showed good tolerability with no adverse effects.
Footnotes
Source of Support: Nil Conflict of Interest: Nil.
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References
1. Niewerth M, Korting HC. The use of systemic antimycotics in dermatotherapy. Eur J Dermatol. 2000;10:15560. [PubMed: 10694319] 2. Suschka S, Fladung B, Merk HF. Clinical comparison of the efficacy and tolerability of once daily canesten with twice daily nizoral (clotrimazole1% cream vs. ketoconazole 2% cream) during a 28-day topical treatment of interdigital tinea pedis. Mycoses. 2002;45:916. [PubMed: 12000508] 3. Croxtall JD, Plosker GL. Sertaconazole: A review of its use in the management of superficial mycoses in dermatology and gynaecology. Drugs. 2009;69:33959. [PubMed: 19275277] 4. Ryder NS. Terbinafine: Mode of action and properties of the squalene epoxidase inhibition. Br J Dermatol. 1992;126:27. [PubMed: 1543672] 5. Bonifaz A, Sal A. Comparative study between terbinafine 1% emulsion-gel versus ketoconazole 2% cream in tinea cruris and tinea corporis. Eur J Dermatol. 2000;10:1079. [PubMed: 10694308] 6. Millikan LE. Efficacy and tolerability of topical terbinafine in the treatment of tinea cruris. J Am Acad Dermatol. 1990;23:7959. [PubMed: 2229526] 7. Greer DL, Jolly HW. Treatment of tinea cruris with topical terbinafine. J Am Acad Dermatol. 1990;23:8004. [PubMed: 2229527] 8. Sharma A, Saple DG, Surjushe A, Rao GR, Kura M, Ghosh S, et al. Efficacy and tolerability of sertaconazole nitrate 2% cream vs. miconazole in patients with cutaneous dermatophytosis. Mycoses. 2011;54:21722. [PubMed: 19925567] 9. Esso DV, Fajo G, Losada I, Vilallonga M, Casanovas JM, Clanxet J, et al. Sertaconazole in the treatment of pediatric patients with cutaneous dermatophyte infections. Clin Therap. 1995;17:2649. [PubMed: 7614526]
Figures and Tables
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Table 1
Weekly comparison of complete cure among patients of terbinafine hydrochloride (A) Group
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Figure 1(a-d)
(a) Terbinafine group - Baseline lesion of tinea cruris. (b) Terbinafine group - Grade 3 (>75% improvement) at the end of 1 st week. (c) Terbinafine group - Grade 4 (100% improvement) at the end of 2nd week. (d) Terbinafine group Grade 4 (100% improvement) at the end of 3rd week
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Table 2
Weekly comparison of complete cure among patients of sertaconazole nitrate (B) Group
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Figure 2
(a) Sertaconazole group - Baseline lesion of tinea cruris. (b) Sertaconazole group - Grade 2 (>50% improvement) at the end of 1 st week. (c) Sertaconazole group - Grade 3 (>75% improvement) at the end of 2nd week. (d) group - Grade 4 (100% improvement) at the end of 3rd week.
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Table 3
Weekly comparison of complete cure between terbinafine (A) Group and sertaconazole (B) Group
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Figure 1
Bar diagram of weekly comparison between terbinafine hydrochloride (a) group and sertaconazole nitrate (b) group
Articles from Indian Journal of Dermatology are provided here courtesy of Medknow Publications
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Efficacy and Safety of Terbinafine Hydrochloride 1% Cream vs. Sertaconazole Nitrate 2% Cream in Tinea Corporis and Tinea Cruris - A Comparative Therapeutic Trial

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Efficacy and Safety of Terbinafine Hydrochloride 1% Cream vs. Sertaconazole Nitrate 2% Cream in Tinea Corporis and Tinea Cruris - A Comparative Therapeutic Trial

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Indian J Dermatol. 2013 Nov-Dec; 58(6): 457460. doi: 10.4103/0019-5154.119958