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Efficacy of a 1-week, twice-daily regimen of terbinafine 1% cream in the treatment of interdigital tinea pedis Results of placebo-controlled, double-blind, multicenter trials Brian Berman, M D , a Charles Ellis, MD, b James Leyden, MD, c Nicholas Lowe, MD, d Ronald Savin, MD, e Jerome Shupack, MD, f Matthew Stiller, MD, f Eduardo Tschen, MD,g Nardo Zaias, MD, h and Jay E. Birnbaum, PhD i Davis and Santa Monica, California; Ann Arbor,
Michigan," Philadelphia, Pennsylvania," New Haven, Connecticut," New York, New York," Albuquerque, New Mexico," Miami Beach, Florida," and East Hanover, New Jersey Background: Patients with tinea pedis often discontinue treatment before eradication of the fungus when their symptoms improve. The result is an incomplete cure/recurrence. Objective: Terbinafme, a topical fungicidal agent, was evaluated in double-blind, placebocontrolled trials ( 159 patients) for its ability to achieve cure and relief of symptoms in the same time frame, that is, before compliance wanes. Methods: MycoIogic characteristics (with potassiumhydroxide examination and culture) and clinical signs and symptoms were assessed at baseline, at the end of a 1-week, twice-daily treatment and at 1, 3, and 5 weeks after the completion of therapy. Results: Both terbinafme and vehicle provided early relief of symptoms. However, only terbinafine gave progressive mycologic improvement such that at 5 weeks after treatment, 88% of the patients receiving terbinafme had converted from positive to negative mycology compared with 23% of the patients treated with vehicle. Conclusion: The rapid and potent fungicidal action of terbinafine results in a high cure rate in interdigital tinea pedis with 1 week of treatment and may avoid failures caused by noncompliance. (J AM ACAD DERMATOL 1992;26:956-60.)
Terbinafme (Lamisil) is a new allylamine derivative with potent fungicidal activity against dermatophytes, molds, and certain dimorphic fungi. 1 Efficacy in tinea pedis has been demonstrated with 4 weeks application of terbinaflne 1% cream, z, 3 However, this drug has several attributes that suggest the possibility of a briefer course of therapy: high intrinsic activity, reflected by m e a n minimal From University of California, Davisa; University of Michigan Medical Centerb; the University ofPennsylvania Hospitale;Skin Research Foundation of California, Santa Monitor; Yale University School of Medicine, New HavenC; New York University Medical Centerr; University of New Mexico School of Medicine, Albuquerqueg; Greater Miami Skin and Laser Centerh; and Sandoz Research Institute, East Hanover) Sponsored by Sandoz Pharmaceuticals Corporation, East Hanover, N,J. Reprint requests: Jay E. Birnbaum, PhD, Director of Dermatology, Sandoz Research Institute, 59 Route 10, East Hanover, NJ 07936.
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inhibitory concentrations (MICs) against dermatophytes ranging from 0.001 to 0.01 #g/Ird4; a tendency to accumulate and persist in the stratum corneum, shown with systemic administrationS; and a fungicidal rather than a fungistatic mechanism. 6 Consequently, the drug concentration in the skin after a brief course of treatment m a y be more important than continued application. We report the results of a 1-week course of terbinafine in interdigital tinea pedis in two placebo-controlled, doubleblind, multicenter trials. MATERIAL AND METHODS
Male and female outpatients with interdigital tinea pedis, but in otherwise good health, were included. Patients with noninterdigital lesions (i.e., moccasintype tinea pedis) with concomitant yeast infections or bacterial infections of the foot or elsewhere, with concurrent onychomycosis of the toenails, with signs of sys-
Volume 26 Number 6 June 1992
temic fungal disease, or with a history of diabetes were excluded. The diagnosis of tinea pedis was established by both a positive potassium hydroxide (KOH) wet mount and a positive culture of a baseline specimen from a designated target lesion. The target lesion was also used to assess six clinical signs--fissuring, erythema, maceration, vesicles, desquamation, and exudation--and the symptoms of pruritus and burning/stinging. The severity of each sign and symptom was rated according to the following scale: 0 = none; 1 = mild; 2 = moderate; or 3 = severe. A baseline total score (maximum total: 8 X 3 = 24) for the target lesion of 6 or more including a score of 2 or more for at least erythema or a score 2 or more for each of two other signs was required for study admission. Patients were randomly assigned to the terbinafine or vehicle treatment groups. The assigned medication was applied to the target lesion as well as other fungal lesions of the feet twice daily, morning and evening, for 1 week. Mycologic respons e and signs and symptoms of the target lesionwere evaluated after 1, 2, 4, and 6 weeks. Overall severity of the disease (all lesionson both feet) at baseline and all subsequent visits was assessed with the same scoring system (0 to 3) used to evaluate clinical signs and symptoms. The overall severity score represents a clinicaUy integrated assessment of the disease with respect to all signs and symptoms combined. The distribution of scores, as well as the mean scores, was determined for both treatment groups. At weeks 4 and 6, the global clinical response of the disease (the improvement of all lesions on both feet) was assessed according to the following scale: clinical cure--complete improvement from baseline;marked improvement = ->75% improvement but less than complete improvement; moderate improvement = _>50% improvement but _
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Efficacy of a 1-week, twice-daily regimen of terbinafine 1% cream in the treatment of interdigital tinea pedis Results of placebo-controlled, double-blind, multicenter trials Brian Berman, M D , a Charles Ellis, MD, b James Leyden, MD, c Nicholas Lowe, MD, d Ronald Savin, MD, e Jerome Shupack, MD, f Matthew Stiller, MD, f Eduardo Tschen, MD,g Nardo Zaias, MD, h and Jay E. Birnbaum, PhD i Davis and Santa Monica, California; Ann Arbor,
Michigan," Philadelphia, Pennsylvania," New Haven, Connecticut," New York, New York," Albuquerque, New Mexico," Miami Beach, Florida," and East Hanover, New Jersey Background: Patients with tinea pedis often discontinue treatment before eradication of the fungus when their symptoms improve. The result is an incomplete cure/recurrence. Objective: Terbinafme, a topical fungicidal agent, was evaluated in double-blind, placebocontrolled trials ( 159 patients) for its ability to achieve cure and relief of symptoms in the same time frame, that is, before compliance wanes. Methods: MycoIogic characteristics (with potassiumhydroxide examination and culture) and clinical signs and symptoms were assessed at baseline, at the end of a 1-week, twice-daily treatment and at 1, 3, and 5 weeks after the completion of therapy. Results: Both terbinafme and vehicle provided early relief of symptoms. However, only terbinafine gave progressive mycologic improvement such that at 5 weeks after treatment, 88% of the patients receiving terbinafme had converted from positive to negative mycology compared with 23% of the patients treated with vehicle. Conclusion: The rapid and potent fungicidal action of terbinafine results in a high cure rate in interdigital tinea pedis with 1 week of treatment and may avoid failures caused by noncompliance. (J AM ACAD DERMATOL 1992;26:956-60.)
Terbinafme (Lamisil) is a new allylamine derivative with potent fungicidal activity against dermatophytes, molds, and certain dimorphic fungi. 1 Efficacy in tinea pedis has been demonstrated with 4 weeks application of terbinaflne 1% cream, z, 3 However, this drug has several attributes that suggest the possibility of a briefer course of therapy: high intrinsic activity, reflected by m e a n minimal From University of California, Davisa; University of Michigan Medical Centerb; the University ofPennsylvania Hospitale;Skin Research Foundation of California, Santa Monitor; Yale University School of Medicine, New HavenC; New York University Medical Centerr; University of New Mexico School of Medicine, Albuquerqueg; Greater Miami Skin and Laser Centerh; and Sandoz Research Institute, East Hanover) Sponsored by Sandoz Pharmaceuticals Corporation, East Hanover, N,J. Reprint requests: Jay E. Birnbaum, PhD, Director of Dermatology, Sandoz Research Institute, 59 Route 10, East Hanover, NJ 07936.
14/1/36380 956
inhibitory concentrations (MICs) against dermatophytes ranging from 0.001 to 0.01 #g/Ird4; a tendency to accumulate and persist in the stratum corneum, shown with systemic administrationS; and a fungicidal rather than a fungistatic mechanism. 6 Consequently, the drug concentration in the skin after a brief course of treatment m a y be more important than continued application. We report the results of a 1-week course of terbinafine in interdigital tinea pedis in two placebo-controlled, doubleblind, multicenter trials. MATERIAL AND METHODS
Male and female outpatients with interdigital tinea pedis, but in otherwise good health, were included. Patients with noninterdigital lesions (i.e., moccasintype tinea pedis) with concomitant yeast infections or bacterial infections of the foot or elsewhere, with concurrent onychomycosis of the toenails, with signs of sys-
Volume 26 Number 6 June 1992
temic fungal disease, or with a history of diabetes were excluded. The diagnosis of tinea pedis was established by both a positive potassium hydroxide (KOH) wet mount and a positive culture of a baseline specimen from a designated target lesion. The target lesion was also used to assess six clinical signs--fissuring, erythema, maceration, vesicles, desquamation, and exudation--and the symptoms of pruritus and burning/stinging. The severity of each sign and symptom was rated according to the following scale: 0 = none; 1 = mild; 2 = moderate; or 3 = severe. A baseline total score (maximum total: 8 X 3 = 24) for the target lesion of 6 or more including a score of 2 or more for at least erythema or a score 2 or more for each of two other signs was required for study admission. Patients were randomly assigned to the terbinafine or vehicle treatment groups. The assigned medication was applied to the target lesion as well as other fungal lesions of the feet twice daily, morning and evening, for 1 week. Mycologic respons e and signs and symptoms of the target lesionwere evaluated after 1, 2, 4, and 6 weeks. Overall severity of the disease (all lesionson both feet) at baseline and all subsequent visits was assessed with the same scoring system (0 to 3) used to evaluate clinical signs and symptoms. The overall severity score represents a clinicaUy integrated assessment of the disease with respect to all signs and symptoms combined. The distribution of scores, as well as the mean scores, was determined for both treatment groups. At weeks 4 and 6, the global clinical response of the disease (the improvement of all lesions on both feet) was assessed according to the following scale: clinical cure--complete improvement from baseline;marked improvement = ->75% improvement but less than complete improvement; moderate improvement = _>50% improvement but _
