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 Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 7  |  Issue : 1  |  Page : 10-15

Efficacy of daily oral terbinafine versus pulse fluconazole therapy in the treatment of tinea corporis, tinea cruris, and tinea faciei: A comparative study


Department of Dermatology, MGM Medical College & Hospital, MGM Medical College & Hospital, Navi Mumbai, Maharashtra, India

Date of Submission20-Apr-2020
Date of Acceptance01-May-2020
Date of Web Publication06-Jun-2020

Correspondence Address:
Dr. Shylaja Someshwar
Department of Dermatology, MGM Medical College & Hospital, Kamothe, Navi Mumbai 410209, Maharashtra.
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mgmj.MGMJ_30_20

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  Abstract 

Introduction: Both terbinafine and fluconazole are effective systemic drugs for dermatophytosis. They can be used intermittently as pulse doses or as daily doses for the treatment of the same. Aim: The aim of this study was to assess the efficacy and safety of 1 week twice a day therapy of terbinafine and to compare it with that of a daily 2-week course of terbinafine and weekly pulse fluconazole therapy. The adverse effects and relapse rates after the completion of therapy were assessed. Materials and Methods: A study was conducted with 90 patients divided into three Groups A, B, and C. Patients were assessed at 2 and 4 weeks of starting treatment and 6 weeks following the completion of treatment. Adverse effects if any were noted. Clinical scores were calculated, and skin scraping for potassium hydroxide (KOH) examination was done. Clinical improvement was assessed. A mycological cure is defined as a negative KOH examination. Results: There was a significant decrease in clinical scores before treatment and at 2 and 4 weeks of visits. The highest clinical cure rates were attained in Group A (80%), followed by Group B (73.33%) and Group C (63.3%). Mycological cure rate at 4 weeks was highest in Group A (93.3%), followed by Group B (86.7%) and Group C (83.3%). This difference in clinical and mycological cure rates in the three groups was not found to be statistically significant. Of the patients who had responded to treatment at 4 weeks, the clinical and mycological cure was maintained in 96.4% individuals in Group A, 96.1% in Group B, and 88% in Group C at 6 weeks. Thus, the highest number of recurrences was seen in Group C, followed by Group B and Group A. All the three treatment regimens were well tolerated. Side effects were seen in 17 patients. They were mild and predominantly gastrointestinal. Conclusion: All three drugs in different regimens were found to be equally efficacious in the treatment of dermatophytic infections in our center.

Keywords: Dermatophytosis, fluconazole, griseofulvin, terbinafine


How to cite this article:
Salunke P, Someshwar S, Bhobe M. Efficacy of daily oral terbinafine versus pulse fluconazole therapy in the treatment of tinea corporis, tinea cruris, and tinea faciei: A comparative study. MGM J Med Sci 2020;7:10-5

How to cite this URL:
Salunke P, Someshwar S, Bhobe M. Efficacy of daily oral terbinafine versus pulse fluconazole therapy in the treatment of tinea corporis, tinea cruris, and tinea faciei: A comparative study. MGM J Med Sci [serial online] 2020 [cited 2021 Oct 21];7:10-5. Available from: http://www.mgmjms.com/text.asp?2020/7/1/10/286105




  Introduction Top


Dermatophytosis refers to the superficial dermatophyte infection of the glabrous skin. It occurs most commonly with organisms of the genera Trichophyton, Microsporum, and Epidermophyton. Tinea corporis includes infection of the glabrous skin excluding scalp, beard, face, hands, feet, and groin. Tinea cruris includes infection of the genital, pubic, perineal, and perianal areas.[1] Although cases of localized dermatophytosis may respond to topical agents alone, systemic antifungal therapy may sometimes be needed in cases with more extensive involvement. Oral agents approved for tinea corporis, tinea cruris, tinea pedis, and onychomycosis, include griseofulvin, ketoconazole, terbinafine, and itraconazole. Fluconazole, itraconazole, and terbinafine have all been shown to reach effective and persistent levels in stratum corneum. The use of ketoconazole is limited due to hepatotoxicity. Griseofulvin rapidly clears from the stratum corneum as it is not keratinophilic and therefore carries a risk of relapse.[1] Studies with terbinafine have shown that high stratum corneum concentrations of 10–100 times that of the minimum inhibitory concentration (MIC) for most dermatophytes are maintained even at 7 weeks after a 1-week treatment course is stopped.[2]

Fluconazole has been shown to attain in vitro MICs for most pathogens involved in superficial cutaneous mycoses, and therapeutic levels of the drug have been noted 1 week after treatment.[3] These studies support the notion that fluconazole and terbinafine may be used short term or even in pulse regimens for treating many of these infections. Hence, newer cost-effective pulse regimen with a well-tolerated antifungal agent is desirable. The fungicidal action of terbinafine combined with improved pharmacokinetics makes it an ideal drug for short-term therapy.[4] Our study was undertaken to assess the efficacy and safety of 1 week twice a day therapy of terbinafine and to compare it with that of a daily 2-week course of terbinafine and weekly pulse fluconazole therapy. Topical treatment with a fungicidal agent such as terbinafine helps in improving patient compliance by reducing the duration of therapy. Relapse rates after completion of therapy were also assessed.


  Materials and methods Top


The study design was approved by the institutional ethics review committee (IERC). Written informed consent was obtained from each subject before enrolling in the study. The study was conducted in the outpatient department of a tertiary care center situated in the periphery of Mumbai, the capital of Maharashtra state in India. A total of 90 patients of >18 years with a clinical diagnosis of tinea corporis, tinea cruris, and tinea faciei, attending the outpatient department with >5% body surface area involvement and a positive skin scraping for potassium hydroxide (KOH) [Figure 1], were screened. The study was conducted over a period of 1 year from September 2011 to August 2012. All patients were subjected to skin scraping for KOH mount, fasting and postprandial blood sugar testing, liver function test, renal function test, and human immunodeficiency viruses (HIV) enzyme-linked immunosorbent assay (ELISA). Symptoms and signs of erythema, scaling, and pruritus were scored on a scale of 0–3.0 (nil), 1 (mild), 2 (moderate), and 3 (severe), and a combined clinical score was calculated.
Figure 1: KOH examination ×40 showing branched septate hyphae and spores

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Patients with a combined clinical score of at least 5 were included in the study. Those with tinea capitis, tinea manuum, tinea pedis, and onychomycosis were excluded from the study. Pregnant and lactating women and patients with a known history or clinical evidence of severe cardiac, pulmonary, gastrointestinal, renal, hepatic, or neurological disease, and uncontrolled diabetes mellitus were also excluded. Immunosuppressed individuals, patients with deranged liver and renal function tests and an increase in blood sugar levels, and patients who have been on immunosuppressant in the previous 6 weeks were also not included. Patients who are on concurrent treatment with rifampicin, phenytoin, digoxin, oral anticoagulants, or H2-receptor antagonists were excluded.

Patients with prior treatment with systemic antifungal agents in the preceding 1 month, itraconazole in the preceding 6 months of treatment with topical antifungals and steroids in the preceding 2 weeks, and patients with a history of hypersensitivity to azoles or allylamine antifungals were excluded too.

Study design and procedure

A single observer open comparative study where the subjects were randomly divided into three groups; each group containing 30 patients according to computer-generated randomized numbers was to receive the following treatments:

  • A—Terbinafine 250mg once daily for 2 weeks


  • B—Terbinafine 250mg twice daily for 1 week


  • C—Fluconazole 150mg weekly for 4 weeks


The lesion identified was evaluated for the following signs and symptoms: erythema, scaling, pustules, vesiculation, maceration, papules, and pruritus. Signs and symptoms were scored on a scale of 0–3 as follows: 0 = none, 1 = mild, 2 = moderate, and 3 = severe. Individual scores were added, and the total score was reported. The patients were assessed at 2 and 4 weeks after starting treatment and at 6 weeks after the completion of treatment, and adverse effects if any were recorded. Skin scraping for the KOH examination was collected at each visit. The efficacy of the treatment was assessed according to the decrease in clinical score and rates of KOH smear negativity. The clinical cure is defined as a complete clearing of all signs and symptoms, that is, a clinical score of 0. Mycological treatment was assessed on the basis of KOH smear negativity. Liver and renal function tests were repeated at the end of 6 weeks after the completion of treatment.

Data analysis

The significance of the decrease in the clinical score and mycological cure rates at second and the fourth week was assessed by Wilcoxon signed-rank test. The clinical scores in all three groups were compared at 2 and 4 weeks with Kruskal–Wallis test, and the clinical scores in two groups at a time were compared by the Mann–Whitney U test.


  Results Top


A total of 128 patients were screened, of whom 90 patients fulfilled the inclusion criteria. They were randomly divided into three groups, each containing 30 patients. The mean age of patients in the study was 35.7 years. There was no significant difference in the age of the three groups by one-way analysis of variance (ANOVA) and by Kruskal–Wallis test. The male-to-female sex ratio was 8:1. The mean body surface area involved in patients was 7.8%. Most individuals, 81 patients in the study had 6%–10% body surface area involvement, two had 11%–15% body surface area involvement, and seven had 16%–20% body surface area involvement [Figure 2]. The most common clinical diagnosis was tinea corporis with tinea cruris (83.3%), followed by tinea corporis (22.2%) and tinea cruris (5.5%). Tinea cruris was relatively rare in the female population. Of the 10 females, 7 (70%) had tinea corporis and 3 (30%) had tinea corporis with cruris. None had isolated tinea cruris. Of the 80 males, 13 (16.25%) had a clinical diagnosis of tinea corporis, 5 (6.25%) had tinea cruris, and 90% had tinea corporis with tinea cruris [Figure 3].
Figure 2: Percentage body surface area involvement in study population

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,
Figure 3: Percentage wise clinical diagnosis in males and females

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The mean clinical score was 7.3. In Group A, the mean clinical score was 7.6. In Group B, the score was 7.7, and in Group C, the mean score was 6.7 [Figure 4]. There was a decrease in clinical scores before treatment and 2 and 4 weeks after treatment in all three treatment groups as calculated by Wilcoxon signed-rank test. Clinical treatment is defined by complete clearance of signs and symptoms, that is, a clinical score of 0 was attained in 16 patients at the end of 2 weeks. Thirty percent were diagnosed with tinea corporis with cruris, whereas none had tinea cruris alone. In the group receiving terbinafine 250mg daily for two weeks, the clinical cure rate was 80%, whereas the mycological cure rate was 93.3% at 4 weeks.
Figure 4: Mean clinical score in each treatment group

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In the group receiving 1 week twice a day dose of terbinafine, the clinical cure rate was 73.3% and mycological cure rate was 86.7% at 4 weeks. In the group receiving weekly doses of fluconazole, the clinical cure rate was 63.3%, whereas the mycological cure rate was 83.3% at 4 weeks [Figure 5]. There was a trend toward the highest cure rates with the group receiving 2-week terbinafine course. However, there was no statistically significant difference in the cure rates in the three treatment groups. Clinical cure at 6 weeks was maintained in 27 (90%) patients in Group A, 25 (83.3%) patients in Group B, and 22 (73.3%) patients in Group C [Figure 6]. The significance of the decrease in clinical scores in each group at 2 and 4 weeks was tested by Wilcoxon signed-rank test. Mycological cure was defined as no fungal filaments detectable on KOH examination of skin scrapings. Side effects were seen in 18.8% of patients. They were predominantly gastrointestinal and were seen in 16.7% of patients in either of the groups receiving terbinafine and in 20% of patients receiving fluconazole. One patient in the group receiving 1 week twice a day dose of terbinafine developed an urticarial rash [Table 1]. The liver and renal function tests done after completion of therapy were within normal limits. The relapse rates calculated at 6 weeks were highest in the group receiving fluconazole (12%), followed by the group receiving 1 week twice a day dose of terbinafine (3.84%), and by the one receiving 2-week therapy of terbinafine (3.57%).
Figure 5: Number of patients showing mycological cure at 4 weeks in each treatment group

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Figure 6: (A) Tinea corporis (Group A), visit 1, clinical score: 6, KOH positive. (B) Tinea corporis (Group A), visit 4, clinical score: 0, KOH negative. (C) Tinea corporis (Group B), visit 1, clinical score: 6, KOH positive. (D) Tinea corporis (Group B), visit 4, clinical score: 0, KOH negative. (E) Tinea corporis (Group C), visit 1, clinical score: 0, KOH positive. (F) Tinea corporis (Group C), visit 3, clinical score: 0, KOH negative

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Table 1: Showing the side effects in patients on different regimens of antifungal therapy

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This study shows that therapy with 1 week twice a day dose of terbinafine is as effective as a 2-week course. Also, therapy with fluconazole is equally efficacious. Other studies support the idea that fluconazole and terbinafine may be used short term or even in pulse regimens for treating many of these infections. Side effects were seen in 18.8% of patients. They were predominantly gastrointestinal and were seen in 16.7% of patients in either of the groups receiving terbinafine and in 20% of patients receiving fluconazole. One patient in the group receiving 1 week twice a day dose of terbinafine developed an urticarial rash. The liver and renal function tests done after completion of therapy were within normal limits. Conventional oral antifungals of long duration are associated with toxicity and poor compliance. Hence newer cost-effective pulse regimen with the well-tolerated antifungal agent is desirable. Pulse regimens are also associated with greater patient compliance by reducing the treatment duration. Fluconazole has long been used as pulse therapy owing to its long half-life. The fungicidal action of terbinafine combined with improved pharmacokinetics makes it an ideal drug for the purpose.[4]


  Discussion Top


Dermatophytosis continues to be a worldwide problem, constituting a large bulk of cases attending the dermatology outpatient departments in tropical countries. It may occur as a protracted illness of the skin and its appendages lasting for more than a year with or without recurrences. It is often difficult to treat even in the absence of nail or hair infection.[5]

In this study, the male-to-female ratio was 8:1. This was higher than the sex ratios in other studies. The male-to-female ratio of 1.57:1 was seen in a study conducted in Gujarat.[6] A study conducted at Calicut showed a sex ratio of 2.06:1.[7] Sarma and Borthakur[8] have reported a sex ratio of 3:1 in a study conducted in northeast India. A higher incidence of dermatophytosis in males than that in females has been reported both in India and abroad.[9] Philpot[10] suggested that males may be more vulnerable to infection due to higher exposures in the army, schools, and sporting activities, and due to the type of shoes and socks they use. This is especially true for tinea cruris. Most cases in our study had a clinical diagnosis of tinea corporis with tinea cruris (75 of 90; 83.3%), 20 patients (22.2%) had only tinea corporis, and 5 (5.5%) patients had only tinea cruris. Tinea cruris was relatively more common among males. None of the females had isolated tinea cruris, whereas only 30% had tinea cruris with corporis. Most females (70%) had isolated tinea corporis. This is in contrast to the male population in which the most common clinical diagnosis was tinea corporis with cruris (90%), followed by isolated tinea corporis (16.25%) and isolated tinea cruris (5%).

The mean age of individuals was 35.7 years. Most of the individuals were in the 18–27 year age-group followed by a 38–47 year age-group. Mulay et al.[11] in a study has shown that the maximum numbers of cases were of tinea corporis, which formed 58.92%, and this was followed by tinea cruris, which formed 38.87% of the cases. The most common age-group affected was 20–29 years, and the males outnumbered the females.[11] The higher incidence in young males could be due to greater physical activity and increased sweating. The major clinical type was tinea corporis, followed by tinea cruris. In a study conducted at Calicut, history of contact with infected family members was seen in 16.6% and with nonfamily members in 2.6%. There was one case of conjugal transmission.[8] In our study, 20 patients, that is, 22% of patients gave a history of contact with infected family members. There was one case of conjugal transmission. Among the three groups, the group treated with terbinafine daily for 2 weeks, had the highest cure rates at 2 and 4 weeks. These high cure rates were maintained even at 6 weeks following the completion of treatment. A complete clinical cure was seen in 80%, and a mycological cure was seen in 93.3% of patients 4 weeks after the start of treatment. At 6 weeks following the completion of treatment, clinical and mycological cure was maintained in 96.4% of these individuals. Within the group treated with terbinafine 250mg twice daily for 1 week, the clinical cure rate at 4 weeks was 73.3%, and a mycological cure was seen in 86.7%. The clinical and mycological cure was maintained in 96.1% of patients in this group at 6 weeks following the completion of treatment.

In a study that compared terbinafine with griseofulvin by Voravutinon et al.,[12] one cohort received oral terbinafine 125mg twice daily, and the other received oral griseofulvin 500mg/twice daily. Treatment continued for 6 weeks, and the results were comparable, with 77% of the terbinafine patients treated effectively compared with 82% of the griseofulvin cohort.

Farag et al.[13] studied tinea corporis and tinea cruris is an open-label fashion for 1 week with oral terbinafine at 250mg per day. There were a total of 22 patients, with 10 having tinea corporis, 10 having tinea cruris, and 2 having both. Patients were followed up for 6 weeks after the completion of treatment, at which time the lesions had resolved in all 22 patients. Furthermore, all patients were mycologically cured by the end of the follow-up period.[13] In another study, intermittent pulse terbinafine once in 3 days for 3 weeks achieved a cure rate of 91.3% with low relapse in tinea corporis and cruris.[2] With the group receiving fluconazole 150mg weekly for 4 weeks, clinical cure was attained in 63.3% of patients and a mycological cure was attained in 83.3% of patients. Clinical and mycological cure was maintained in 78.6% of individuals at 6 weeks following the completion of treatment. Another study done by Monteiro-Gei and Perera[14] examined the efficacy and safety of once-weekly fluconazole at a dose of 150mg for tinea corporis or tinea cruris. The authors found 95% cured overall, and they noted that 70% of patients required two doses for a cure, 20% of patients required three doses for a cure, and 10% required four doses. There were no adverse effects or significant laboratory abnormalities.[14]

Stary and Sarnow[15] studied fluconazole in the treatment of tinea corporis and tinea cruris in a single-center open-label study. One hundred patients with tinea corporis and tinea cruris were treated with fluconazole at 150mg once weekly for 2–4 weeks. Weekly doses were given when the weekly clinical and mycological examinations indicated that the disease was still present. There were follow-up assessments at weeks 1 and 3 after treatment. At the 3-week follow-up evaluation, the clinical cure was reported in 71% of patients. Of 60 patients who were cultured 1 week after their last dose of a drug, 83% were mycologically cured. The results of the mycological cure rate at the 3-week follow-up was not clear in this article.[15] In our study, clinical and mycological cure rates at 4 weeks were highest in the group treated with 2 weeks of terbinafine 250mg daily. Clinical and mycological cure rates were 80% and 93.3%, respectively. This was closely followed by the group receiving terbinafine 250mg twice daily for 1 week (clinical and mycological cure rates 73.3% and 86.7%, respectively). The lowest cure rates were in the group receiving fluconazole. Clinical and mycological cure rates were 63.3% and 83.3%, respectively.

The difference between the clinical and mycological cure rates in the three groups in this study was not found to be statistically significant. However, the group receiving 250 mg once daily terbinafine showed a marginally higher cure rates. Relapse rates at 6 weeks following the completion of treatment were highest in the group receiving fluconazole (12%), followed by the group receiving 1 week twice a day dose of terbinafine (3.8%) and the group receiving a daily dose of terbinafine for 2 weeks (3.57%). The side effects were mild and did not warrant discontinuation of therapy in either of the groups. They were predominantly gastrointestinal and were seen in five individuals in either group receiving terbinafine and six individuals in the group receiving fluconazole. One patient in the group receiving a 1-week pulse dose of terbinafine developed an urticarial rash. Side effects following oral administration of terbinafine 125mg twice daily include gastrointestinal symptoms (3%–4%), allergy (1%), and miscellaneous mild nonspecific symptoms (1%). No significant hematological, hepatic, or renal effects have been observed. On the basis of the drug’s fungicidal action and the early appearance of negative cultures in these studies, a short-duration therapy is predicted to be effective.[16]

In a study by Monteiro-Gei and Perera,[14] there were no adverse effects or significant laboratory abnormalities were noted with four weekly doses of fluconazole. In a study by Faergemann et al.,[17] 7.5% of individuals showed the treatment-related side effects. They concluded that fluconazole 150mg once weekly for 6 weeks is both clinically and mycologically effective in the treatment of tinea corporis and tinea cruris, and few side effects were reported.[17]


  Conclusion Top


Conventional oral antifungals of long duration are associated with toxicity and poor compliance. Hence, newer cost-effective pulse regimen with a well-tolerated antifungal agent is desirable. However, in our study, two different daily regimens of terbinafine and weekly pulse dose of fluconazole given for patients of tinea corporis, tinea cruris, and tinea faciei were found to be equally effective and with a similar side effect profile.

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Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Kannan P, Janaki C, Selvi GS. Prevalence of dermatophytes and other fungal agents isolated from clinical samples. Indian J Med Microbiol 2006;24:212-5.  Back to cited text no. 1
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2.
Lesher JL Jr. Oral therapy of common superficial fungal infections of the skin. J Am Acad Dermatol 1999;40:S31-4.  Back to cited text no. 2
    
3.
Gupta AK, Chaudhry M, Elewski B. Tinea corporis, tinea cruris, tinea nigra, and piedra. Dermatol Clin 2003;21:395-400, v.  Back to cited text no. 3
    
4.
Rand S. Overview: The treatment of dermatophytosis. J Am Acad Dermatol 2000;43:S104-12.  Back to cited text no. 4
    
5.
Kaaman T. The clinical significance of cutaneous reactions to trichophytin in dermatophytosis. Acta DermVenereol 1978;58:139-43.  Back to cited text no. 5
    
6.
Singh S, Beena PM. Profile of dermatophyte infections in Baroda. Indian J Dermatol Venereol Leprol 2003;69:281-3.  Back to cited text no. 6
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Bindu V, Pavitran K. Clinico-mycological study of dermatophytes in Calicut. Indian J Dermatol Venerol Leprol 2002;68:259-61.  Back to cited text no. 7
    
8.
Sarma S, Borthakur AK. A clinico-epidemiological study of dermatophytoses in northeast India. Indian J Dermatol Venereol Leprol 2007;73:427-8.  Back to cited text no. 8
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9.
Kanwar AJ, Mamta, Chander J. Superficial fungal infections. In: Valia RG, Valia AR, editors. IADVL Textbook and Atlas of Dermatology. 2nd ed. Mumbai, India: Bhalani Publishing House; 2001. p. 215-58.  Back to cited text no. 9
    
10.
Philpot CM. Some aspects of the epidemiology of tinea. Mycopathologia 1977;62:3-13.  Back to cited text no. 10
    
11.
Mulay DN, Ahuja BB, Garg AK. A study on the ecology and treatment of dermatophytosis in Delhi. Indian J Dermatol Venereol 1970;36:215-20.  Back to cited text no. 11
    
12.
Voravutinon V. Oral treatment of tinea corporis and tinea cruris with terbinafine and griseofulvin: A randomized double blind comparative study. J Med Assoc Thai 1993;76:388-93.  Back to cited text no. 12
    
13.
Farag A, Taha M, Halim S. One-week therapy with oral terbinafine in cases of tinea cruris/corporis. Br J Dermatol 1994;131:684-6.  Back to cited text no. 13
    
14.
Montero-Gei F, Perera A. Therapy with fluconazole for tinea corporis, tinea cruris, and tinea pedis. Clin Infect Dis 1992;14:S77-81.  Back to cited text no. 14
    
15.
Stary A, Sarnow E. Fluconazole in the treatment of tinea corporis and tinea cruris. Dermatology 1998;196:237-41.  Back to cited text no. 15
    
16.
Villars V, Jones TC. Clinical efficacy and tolerability of terbinafine (lamisil)—A new topical and systemic fungicidal drug for treatment of dermatomycoses. Clin Exp Dermatol 1989;14:124-7.  Back to cited text no. 16
    
17.
Faergemann J, Mörk NJ, Haglund A, Odegård T. A multicentre (double-blind) comparative study to assess the safety and efficacy of fluconazole and griseofulvin in the treatment of tinea corporis and tinea cruris. Br J Dermatol 1997;136:575-7.  Back to cited text no. 17
    


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