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Indian Journal of Dermatology, Venereology and Leprology, Vol. 71, No. 4, July-August, 2005, pp. 262-266 Studies An open randomized comparative study of oral itraconazole pulse and terbinafine pulse in the treatment of onychomycosis Mishra Minati, Panda P, Tripathy Satyabrata, Sengupta Sujata, Mishra Kaushik Department of Dermatology and Venereology, S.C.B.Medical College, Cuttack, Orissa Code Number: dv05087 ABSTRACT BACKGROUND: Onychomycosis is a recalcitrant disease of the nails caused by dermatophytes, yeasts, and molds.AIMS: To compare the clinical efficacy of oral itraconazole pulse therapy and oral terbinafine pulse therapy in onychomycosis. METHODS: A randomized single-blind clinical comparative study was undertaken on 120 patients of onychomycosis during the period March 1999-February 2002. Sixty patients were randomly assigned to receive oral itraconazole 100 mg, two capsules twice daily for seven days a month and the other group of sixty patients received oral terbinafine 250 mg, one tablet twice daily for seven days every month. Four such monthly pulses were administered for each drug. The patients were evaluated at 4-weekly intervals till sixteen weeks and then at 24, 36 and 48 weeks. RESULTS: We observed a clinical cure rate of 82% and mycological cure rate of 90% in the group of patients treated with itraconazole while the group with terbinafine showed clinical and mycological cure rates of 79% and 87% respectively. This difference was not statistically significant. CONCLUSIONS: Both oral itraconazole and terbinafine are effective in the treatment of onychomycosis when administered in the pulse dosage form. Terbinafine is more cost effective while itraconazole has a broader spectrum of antimycotic activity. Keywords: Onychomycosis, Dermatophytes, Yeasts, Mould, Pulse INTRODUCTION Onychomycosis is a chronic infection of the nail predominantly caused by anthropophilic dermatophytes and, to a lesser extent, by yeasts ( Candida spp.), and non-dermatophyte molds. It represents 30% of all mycotic infections of the skin.[1],[2] Although onychomycosis is not life threatening, the psychosocial and emotional effects due to the disease can be profound and it can have a significant negative impact on the quality of life of those affected.[3],[4] Several clinical types of onychomycosis have been recognized, i.e. distal and lateral subungual onychomycosis (DSLO), white superficial onychomycosis (WSO), proximal subungual onychomycosis (PSO), endonyx onychomycosis, and candidal onychomycosis. Total dystrophic onychomycosis refers to the most advanced form affecting the entire nail plate. [5],[6],[7]
MATERIALS AND METHODS This randomized, single-blind, longitudinal, clinical comparative study was undertaken in the Department of Skin and Venereal Diseases, S. C. B. Medical College, Cuttack, in collaboration with the Department of Microbiology, during the period March 1999-February 2002.All patients presenting to the dermatology O.P.D. with clinical features of fingernail or toenail onychomycosis (e.g. discoloration, thinning, crumbling or destruction of the nail plate; subungual debris; or onycholysis) were subjected to direct microscopical examination of nail material under potassium hydroxide (KOH) examination and culture in Sabouraud′s Dextrose agar (SDA). Patients with nail abnormalities due to associated skin disease or any systemic diseases like psoriasis, lichen planus, contact dermatitis, congenital nail dystrophy, malnutrition, iron deficiency, etc. were excluded from the study. We came across 645 patents clinically suggestive of onychomycosis during the period of two years. The patients were clearly explained about the nature of the study and a written consent was taken for their participation in the study. A baseline liver function test was done in all of them and those with hepatic dysfunction in the form of jaundice and/or elevated hepatic enzymes more than twice the normal values were excluded from the study. Other criteria for exclusion were pregnancy, lactation, concomitant therapy with drugs having a possible interaction with itraconazole, age<15 years or >60 years, and mycologically negative cases (both negative for KOH examination and culture on Sabouraud′s dextrose agar (SDA)). A total of 120 patients satisfied the above criteria and agreed to participate in the study. They were in the 15-60 year age group (72 males and 48 females) and were recruited into the study. All patients were assigned individual identification numbers and were divided randomly and equally into two groups (A and B) using a table of random numbers. Thus, two groups of 60 patients each with 36 men and 24 women in the age group 15-60 were created. Group A received oral itraconazole 200 mg (two capsules of Cap. Sporanoxγ 100 mg) twice daily for seven consecutive days every month while Group B received oral terbinafine 250 mg {Tab. Sebifinγ 250mg} twice daily for seven consecutive days every month. The total duration of treatment for both groups was 4 months. The cost of therapy was borne by the patients. The drugs were bought by the physician and dispensed to the patients in unmarked packets containing the entire dosage for seven days every month for four months. The patients were evaluated at the start of the therapy and thereafter at 4-week (or monthly) intervals for 4 months, followed by evaluation at weeks 24, 36, and 48. During these visits, they were assessed for growth of a normal and healthy appearing nail plate and asked for any adverse effects of the drugs. In addition, microscopic examination of nail material under KOH examination and culture of nail material in SDA was done at 16 weeks and 48 weeks. A liver function test was done twice for all patients at 6-month intervals from the start of therapy. Clinical cure was defined as replacement of greater than 70% of the mycotic nail bed and plate by normal and healthy appearing nail bed and plate, while any growth less than this was considered as treatment failure. Mycological cure was defined as negative microscopy under KOH examination and a negative culture in SDA at the end of the follow up period. At the end of the study, the results were compiled, tabulated and analyzed using suitable statistical tools like percentages and chi-square tests. [Table - 1] RESULTS In the itraconazole group (Group A), we observed fingernail involvement in 21.7%, toenail involvement in 30% and both fingernail and toenail involvement in 48.3% of the cases. In the terbinafine group (Group B), the corresponding figures were 26.7% for fingernail, 30% for toenail and 43.3% for both fingernail and toenail involvement. In either group, the maximum number of patients belonged to the age group 31-45 (45% in Group A and 47% in Group B). We observed associated dermatophyte infection of other sites in 19 (31.6%) patients (11, tinea pedis; 4, tinea manuum; 2, tinea cruris; and 2, tinea corporis) in Group A and in 15 (25%) patients (8, tinea corporis) in Group B. In both groups, the commonest associated dermatophyte infection was tinea pedis.
DISCUSSION Successful treatment of onychomycosis has been a challenge for dermatologists. Traditional agents like griseofulvin have a narrow spectrum, require a longer duration of therapy, and have a high relapse rate.[18],[21] Ketoconazole, although much more effective,[20],[21] carries risk of hepatotoxicity, that limits its widespread use. The agents most commonly used for the treatment of onychomycosis are fluconazole, itraconazole and terbinafine. These newer anti-fungal agents have better pharmacokinetic profiles, like prompt penetration of the nail and nail bed, persistence in the nail for months even after stopping therapy, and fewer adverse reactions.[9],[10],[14]Itraconazole is a highly lipophilic triazole antimycotic. It has a spectrum of action against dermatophytes, yeasts, molds, dimorphic and dematiaceous fungi. It acts by inhibiting the enzyme 14-demethylase, a microsomal cytochrome P-450 enzyme in the fungal membrane (thus blocking the conversion of lanosterol to ergosterol, which is an important constituent of fungal cell membrane) leading to arrest of fungal growth. It reaches the distal end of the nail within two weeks of starting therapy and persists in the nail plate for 9-12 months. It is equally effective for the treatment of onychomycosis in the form of daily therapy as well as pulse therapy. Terbinafine belongs to a newer family of antifungals, the allylamines. It acts by inhibiting the enzyme squalene epoxidase, blocking the biosynthesis of ergosterol. It is primarily effective against dermatophytes, and is less effective against yeasts, molds, and dimorphic fungi. Terbinafine reaches the nail plate by diffusion from both the matrix and the nail bed. It has been detected in the nail plate for 30-36 weeks after stopping therapy. Although conventionally given in a daily dose, pulse therapy with terbinafine for the treatment of onychomycosis is a viable option .Our study shows that pulse therapy with terbinafine 250 mg twice daily for 7 days a month is comparable to itraconazole pulse therapy of 200 mg twice daily and is significantly more cost effective for the treatment of onychomycosis. Both the agents achieved similar cure rates for dermatophytes, but itraconazole was more effective in nail infections caused by molds and candida. Both the agents were relatively free of major adverse effects when administered in the pulse dosage. CONCLUSION Terbinafine pulse therapy is as effective as itraconazole pulse therapy in treating onychomycosis (due to dermatophytes? If the difference in the cure rates for non-dermatophytes was significant with itraconazole this needs to be mentioned in the concluding paragraph) but significantly cheaper, ensuring that patients are more likely to complete the therapy.REFERENCES
Copyright 2005 - Indian Journal of Dermatology, Venereology and Leprology The following images related to this document are available:Photo images[dv05087t3.jpg] [dv05087t1.jpg] [dv05087t2.jpg] |
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