Efficacy and safety of terbinafine 1% solution in the treatment of interdigital tinea pedis and tinea corporis or tinea cruris.

Two randomized, double-blind, vehicle-controlled, multicenter studies assessed the efficacy and safety of a new terbinafine 1% solution for the treatment of interdigital tinea pedis and tinea corporis or tinea cruris (tinea corporis/cruris). Patients with interdigital tinea pedis applied terbinafine 1% solution or vehicle twice daily for 1 week with 7 weeks of follow-up (N = 153), and patients with tinea corporis/cruris applied terbinafine 1% solution or vehicle once daily for 1 week with 3 weeks of follow-up (N = 66). Efficacy was assessed mycologically and clinically at the end of treatment and throughout follow-up. In the tinea pedis study, 66% of patients were effectively treated with terbinafine compared with 4% of the group treated by vehicle (P < .001; Mantel-Haenszel test). In the tinea corporis/cruris study, treatment was effective in 65% of the terbinafine group compared with 8% of the vehicle group (P < .001). There were no significant differences in the frequency of cutaneous adverse events between the 2 groups in either study. We conclude that one week of therapy with terbinafine 1% solution is highly effective, superior to vehicle, and safe for use in superficial fungal infections.

Prevalence of male pattern hair loss in 18-49 year old men.

BACKGROUND: Previous studies investigating the prevalence of male pattern hair loss (MPHL) typically used biased samples of men recruited from clinical populations which may limit generalizability of findings to broader populations. OBJECTIVE: To obtain an updated and improved estimate of the occurrence of MPHL in healthy men residing in the community. METHODS: Community-based sample of healthy men aged 18-49 years participated in a study investigating the effects of MPHL. Participants completed a brief questionnaire self reporting degree of hair loss, general health-related quality of life (HRQL) and hair-loss-specific measures. A trained observer also rated each participant using standardized classification for MPHL. RESULTS: The proportion of men with moderate to extensive hair loss (type III or greater) was 42%. The proportion of men with moderate to extensive hair loss increased with increasing age, ranging from 16% for men 18-29 years of age to 53% of men 40-49. Twelve percent of the men were classified as having predominantly frontal baldness (type A variants). CONCLUSIONS: MPHL, especially frontal baldness, may be more common than previously reported.

Ketoconazole 2% shampoo in the treatment of tinea versicolor: a multicenter, randomized, double-blind, placebo-controlled trial.

BACKGROUND: Tinea versicolor is a common superficial fungal infection caused by a lipophilic yeast. This chronically recurring opportunistic infection is especially prevalent in tropical and semitropical regions. The topical short-term application of ketoconazole 2% shampoo may provide effective and safe therapy for tinea versicolor. OBJECTIVE: The purpose of this study was to evaluate the efficacy and safety of a single application (1 day) versus three daily applications (3 days) of ketoconazole 2% shampoo versus placebo shampoo in the treatment of mycologically confirmed tinea versicolor. METHODS: Three hundred twelve patients were included in the primary analyses for this 31-day study. Global evaluation scores were measured on days 10 and 31 with a 5-point scale (1 = healed to 5 = worsening), and a cellophane tape test was done at baseline and days 3, 10, and 31. Efficacy was assessed by clinical response, defined as both a global evaluation score of 1 (healed) and a negative cellophane tape test on day 31. Signs and symptoms of tinea versicolor (scaling, itching, erythema, hypopigmentation, hyperpigmentation) also were evaluated at baseline, day 10, and day 31 with a 4-point scale (0 = absent to 3 = severe). RESULTS: Both regimens of ketoconazole shampoo were significantly (P < .001) more effective than placebo for rate of clinical response, global evaluation scores, and mycologic outcomes (cellophane tape test). The clinical response rates at day 31 were 73%, 69%, and 5% for the 3-day ketoconazole, 1-day ketoconazole, and placebo groups, respectively. The difference in the efficacy of the two ketoconazole treatment regimens was not statistically significant. There were no significant differences between any of the treatment groups in the number of patients who experienced adverse events. No serious adverse events occurred and no patient withdrew from the trial prematurely because of an adverse event. CONCLUSION: Ketoconazole 2% shampoo, used as a single application or daily for 3 days, is safe and highly effective in the treatment of tinea versicolor.

Once-weekly fluconazole (150, 300, or 450 mg) in the treatment of distal subungual onychomycosis of the toenail.

BACKGROUND: Onychomycosis is a prevalent infection of the nail caused primarily by dermatophytes. Fluconazole is active in vitro against the most common pathogens of onychomycosis, penetrates into the nail bed, and is clinically effective in the treatment of a wide variety of superficial fungal infections. OBJECTIVE: The purpose of this study was to compare the efficacy and safety of three different doses of fluconazole (150, 300, and 450 mg) given orally once weekly to that of placebo in the treatment of distal subungual onychomycosis of the toenail caused by dermatophytes. METHODS: In this multicenter, double-blind study, 362 patients with mycologically confirmed onychomycosis were randomized to treatment with fluconazole, 150, 300, or 450 mg once weekly, or placebo once weekly for a maximum of 12 months. To enter the study, patients were required to have at least 25% involvement of the target nail with at least 2 mm of healthy nail from the nail fold to the proximal onychomycotic border. Patients who were clinically cured or improved at the end of treatment were further evaluated over a 6 month follow-up period. At both the end of therapy and the end of follow-up, clinical success of the target nail was defined as reduction of the affected area to less than 25% or cure. RESULTS: At the end of therapy, 86% to 89% of patients in the fluconazole treatment groups were judged clinical successes as defined above compared with 8% of placebo-treated patients. Clinical cure (completely healthy nail) was achieved in 28% to 36% of fluconazole-treated patients compared with 3% of placebo-treated patients. Fluconazole demonstrated mycologic eradication rates of 47% to 62% at the end of therapy compared with 14% for placebo. The rates at the end of follow-up were very similar, indicating that eradication of the dermatophyte was maintained over the 6-month period. All efficacy measures for the fluconazole groups were significantly superior to placebo (p=0.0001); there were no significant differences between the fluconazole groups on these efficacy measures. The clinical relapse rate among cured patients over 6 months of follow-up was low at 4%. Fluconazole was well tolerated at all doses over the 12-month treatment period, with the incidence and severity of adverse events being similar between the fluconazole and placebo treatment groups. Mean time to clinical success in the fluconazole treatment groups was 6 to 7 months. This time frame may be used as a guideline for fluconazole treatment duration. CONCLUSION: The results of this study support the use of fluconazole in the treatment of distal subungual onychomycosis of the toenail caused by dermatophytes. Doses between 150 to 450 mg weekly for 6 months were clinically and mycologically effective as well as safe and well tolerated.

Once-weekly fluconazole (150, 300, or 450 mg) in the treatment of distal subungual onychomycosis of the fingernail.

BACKGROUND: Onychomycosis is a prevalent infection of the nail caused primarily by dermatophytes. Fluconazole is active in vitro against the most common pathogens, penetrates into the nail bed, and is clinically effective in the treatment of a wide variety of fungal infections. OBJECTIVE: The purpose of this study was to assess the safety and efficacy of oral fluconazole 150, 300, and 450 mg administered once weekly compared with placebo in the treatment of distal subungual onychomycosis of the fingernail caused by dermatophytes. METHODS: This was a multicenter, randomized, double-blind, placebo-controlled study enrolling 349 patients with onychomycosis of the fingernails. Clinical and mycologic efficacy as well as measures of safety were assessed monthly for a maximum of 9 months of treatment, with additional safety visits occurring at weeks 2 and 6. For inclusion, patients were required to have clinically and mycologically documented onychomycosis of the fingernail caused by dermatophytes with at least 25% involvement of the target fingernail. After end of therapy, patients with improved or cured fingernails entered a blinded 6-month follow-up without drug treatment during which efficacy was assessed every 2 months. Efficacy was assessed by clinical (visual) and mycologic (microscopic and culture) measures. Clinical measures included assessments of the percentage of target nail involvement, measurement of the distance from the nail fold to the proximal onychomycotic border, and signs and symptoms of onychomycosis. RESULTS: Fluconazole was significantly superior to placebo in eradicating clinical and mycologic symptoms of onychomycosis, both at the end of active treatment and at 6 months after treatment (p=0.0001 for all efficacy measures). At the end of therapy, 91% to 100% of patients in the fluconazole groups were judged clinical successes, defined as reduction of the affected area of the target nail to less than 25% or cure, compared with 8% for placebo. Clinical cure rates at end of therapy were 76%, 85%, and 90% for fluconazole 150, 300, and 450 mg, respectively, compared with 3% for placebo. These clinical success and cure rates were largely maintained or improved during follow-up. Clinical relapse in cured patients during the follow-up period was very low (1.5% to 3.3%). Fluconazole demonstrated mycologic eradication rates of 89% to 100% at the end of treatment and 90% to 99% at the end of follow-up; for placebo the rates were 8% and 12%, respectively. CONCLUSION: Fluconazole administered once weekly is safe and effective in eradicating distal subungual onychomycosis of the fingernail caused by dermatophytes.

Pharmacokinetics of three doses of once-weekly fluconazole (150, 300, and 450 mg) in distal subungual onychomycosis of the toenail.

BACKGROUND: Preliminary clinical data suggest that fluconazole is effective in the treatment of patients with onychomycosis. To design optimum dosage regimens, a better understanding of fluconazole's distribution into and elimination from nails is needed. OBJECTIVE: The purpose of this study was to determine plasma and toenail concentrations of fluconazole. METHODS: In this multicenter, randomized, double-blind investigation, fluconazole (150 mg, 300 mg, or 450 mg) or matching placebo was administered once a week for a maximum of 12 months to patients with onychomycosis of the toenail. A total of 151 subjects participated in the pharmacokinetic assessment. Blood samples and distal toenail clippings from both affected and healthy nails were obtained for fluconazole concentration determinations at baseline, at the 2-week visit, at each monthly visit until the end of treatment, and then at 2, 4, and 6 months (nail samples only at the latter two) after fluconazole was discontinued. RESULTS: Fluconazole was detected in healthy and affected nails at the 2-week assessment in nearly all subjects. The median time to reach steady-state fluconazole concentrations in healthy nails was 4 to 5 months in the three fluconazole dose groups. In affected nails, steady-state fluconazole concentrations were achieved more slowly, with a median time of 6 to 7 months. At the 8-month assessment, affected toenail fluconazole concentrations were higher than corresponding plasma fluconazole concentrations, with ratios of 1.31 to 1.50 in the three active treatment groups. Toenail concentrations of fluconazole declined slowly after treatment was discontinued, with elimination half-lives of 2.5, 2.4, and 3.7 months for the 150, 300, and 450 mg doses, respectively. Measurable fluconazole concentrations were still present in toenails at 6 months after treatment in most subjects. CONCLUSION: Fluconazole penetrates healthy and diseased nails rapidly, yielding detectable concentrations after two weekly doses. Once it penetrates nail, fluconazole persists for up to 6 months or longer after therapy is stopped. These favorable pharmacokinetic characteristics support a once-weekly fluconazole dosage regimen for the treatment of patients with onychomycosis.

Pharmacokinetics of three once-weekly dosages of fluconazole (150, 300, or 450 mg) in distal subungual onychomycosis of the fingernail.

BACKGROUND: Fluconazole has proven to be safe and effective for a variety of superficial and systemic fungal infections. Preliminary analysis of extensive Phase III studies suggests that it is very effective for the treatment of onychomycosis. Its pharmacokinetic properties, including low molecular weight and high water-solubility, suggest a unique ability to penetrate the nail. This feature is likely to account in part for fluconazole's effectiveness in the treatment of onychomycosis. OBJECTIVE: Determinations of plasma and fingernail concentrations of fluconazole were performed as part of a larger study comparing the safety and efficacy of once-weekly fluconazole (150, 300, and 450 mg) to placebo in the treatment of distal subungual onychomycosis of the fingernails caused by dermatophytes. The relationship between fluconazole concentrations and efficacy was also examined. METHODS: Pharmacokinetic studies were performed by means of plasma and fingernail samples from 133 patients, a subset of 349 patients participating in a double-blind, placebo-controlled clinical trial of fluconazole administered in once-weekly doses of 150, 300, or 450 mg until cure of onychomycosis or for a maximum of 9 months. Blood and fingernail samples for pharmacokinetic analysis were taken at baseline, at week 2, and at monthly intervals during the treatment phase of the study. Patients considered clinically cured or improved also participated in a 6-month follow-up study. During this phase, patients were monitored and samples taken every 2 months. RESULTS: Significant amounts of fluconazole were detected in the earliest fingernail samples taken (after 2 weeks of treatment). After two weekly doses, 30% to 33% of steady-state concentrations had been achieved in healthy nails and 22% to 29% in affected nails. Steady state was achieved in 3 to 5 months. Fluconazole concentration in nails as well as plasma followed dose-proportional pharmacokinetics. Nail:plasma ratios in affected nails were 0.4 to 0.6 at 2 weeks and 1.7 to 1.8 at 6 months. Fluconazole concentrations fell slowly after drug discontinuation and were still detectable 4 months after end of treatment. A statistically significant correlation was found between steady-state concentration and clinical and global outcomes. CONCLUSION: Fluconazole rapidly penetrates the fingernail, where it is retained at detectable levels for at least 4 months after drug discontinuation. A significant correlation exists between fluconazole concentration in the fingernails and clinical and global outcomes.

Oral terbinafine in the treatment of toenail onychomycosis: North American multicenter trial.

BACKGROUND: Onychomycosis is an increasing problem with limited therapeutic options. OBJECTIVE: We evaluated the safety and efficacy, of oral terbinafine, a new fungicidal antimycotic, in patients with toenail onychomycosis. METHODS: A North American multicenter, double-blind, placebo-controlled study evaluated the mycologic and clinical efficacy of oral terbinafine 250 mg/day for 12 or 24 weeks in 358 patients with toenail onychomycosis. RESULTS: A total of 74% of patients treated with 12 or 24 weeks of terbinafine achieved a successful clinical outcome. Approximately 11% of terbinafine responders showed evidence of relapse 18 of 21 months after cessation of treatment. Terbinafine was well tolerated; most adverse events were transient and mild to moderate in severity. CONCLUSION: The results of this study confirm that oral terbinafine is a safe and effective therapy for the treatment of onychomycosis.

Tretinoin emollient cream for photodamaged skin: results of 48-week, multicenter, double-blind studies.

BACKGROUND: The ability of topical tretinoin to improve certain signs of skin photodamage has been shown previously. OBJECTIVE: Our purpose was to assess the effectiveness of tretinoin emollient cream in maintaining or further improving photodamaged skin during extended use. METHODS: Photodamaged subjects who completed 24 weeks of once-daily use of tretinoin emollient cream 0.05% (n = 149) or 0.01% (n = 149) continued to use the same strength formulation in a 24-week double-blind extension. RESULTS: Maintenance of improvement or continued reduction in signs of photodamage was noted in both investigators' and subjects' evaluations of the 0.05% and 0.01% preparations; these results were confirmed by skin replica analyses. Cutaneous side effects were less common during the extension study than during the first 24 weeks of therapy. CONCLUSION: Both strengths of tretinoin emollient cream (0.05% and 0.01%) appeared safe and effective in the treatment of photodamaged skin during a 48-week treatment period.

Sustained improvement in photodamaged skin with reduced tretinoin emollient cream treatment regimen: effect of once-weekly and three-times-weekly applications.

BACKGROUND: Previous studies have documented reversal of long-term photodamage with once-daily applications of topical tretinoin. OBJECTIVE: Our purpose was to assess the effectiveness of tretinoin emollient cream in maintaining improvement in photodamage with a reduced frequency of applications. METHODS: A total of 126 subjects who completed 48 weeks of once-daily treatment with tretinoin emollient cream 0.05% were enrolled for an additional 24 weeks of tretinoin once weekly, three times weekly, or no therapy. RESULTS: The clinical improvement observed during 48 weeks of once-daily treatment was sustained with three-times weekly applications and to a lesser extent with once-weekly dosing, whereas effects tended to regress in subjects off therapy. The overall incidence of adverse events in the skin and subcutaneous tissues appeared to vary with dose frequency. CONCLUSION: After 48 weeks of once-daily treatment, the continued use of tretinoin emollient cream 0.05% at a dose of three times per week maintains and, in some cases, may further enhance improvement in photodamage. Discontinuation of therapy results in some reversal of beneficial effects.

Aggressive acne treatment: as simple as one, two, three?

Too often acne treatment focuses on diminishing lesions without considering what an active patient really wants: completely clear skin. In addition to benzoyl peroxide cleansing and topical acne medication, a three-tier approach of oral agents often achieves clear skin regardless of the severity of acne. Tetracycline is the first line of treatment, followed by minocycline if the first drug is not effective. If these two antibiotics fail to clear the acne, isotretinoin can be highly effective - but patients need to know that the drug produces birth defects in almost all women who take the drug while pregnant.

Psychological effects of androgenetic alopecia on women: comparisons with balding men and with female control subjects.

BACKGROUND: Several studies have examined the psychological impact of androgenetic alopecia on men but scientific evidence is absent regarding its effects on women. OBJECTIVE: Our purpose was to determine the psychosocial sequelae of androgenetic alopecia in women and, comparatively, in men. METHODS: Subjects were newly referred patients with androgenetic alopecia (96 women and 60 men) and 56 female control patients. Subjects completed standardized questionnaires to assess their psychological reactions to their respective conditions and to measure body image, personality, and adjustment. RESULTS: Androgenetic alopecia clearly was a stressful experience for both sexes, but substantially more distressing for women. Relative to control subjects, women with androgenetic alopecia possessed a more negative body image and a pattern of less adaptive functioning. Specific correlates of the adversity of patients' hair-loss experiences were identified. CONCLUSION: The results confirm the psychologically detrimental effects of androgenetic alopecia, especially on women. The implications for patient care are discussed.

Minoxidil. Update on its clinical role.

The study and common use of minoxidil have legitimized research in common baldness. Prior to this time, with rare exception, the field was dominated by charlatans and "snake oil merchants." Minoxidil has opened the door to scientific inquiry and allowed support of serious laboratory investigation. Minoxidil is the first "generation" of hair-growing agents. We hope that succeeding generations will fulfill our wildest tonsorial dreams.

Inocoterone and acne. The effect of a topical antiandrogen: results of a multicenter clinical trial.

BACKGROUND AND METHODS: Because acne is androgen dependent, antiandrogen therapy might improve the condition. Inocoterone acetate (RU 882) is a nonsteroidal antiandrogen that binds to the androgen receptor and has antiandrogenic activity in animal models. To test its topical effect on acne, 126 male subjects with facial acne completed a 16-week, multi-center, double-blind study in which the twice-daily application of a 10% solution of inocoterone was compared with vehicle solution. Baseline and monthly examinations included acne lesion counts and general and endocrine laboratory tests. RESULTS: Inflammatory papules and pustules showed greater reduction in the inocoterone-treated subjects than in the subjects treated with vehicle. This difference achieved statistical significance by week 12 (24% reduction vs 10%) and week 16 (26% reduction vs 13%) and, with longitudinal analysis, throughout the course of the study. Global assessments and changes in comedo counts and sebum excretion rates were not significantly different between the groups. No serious adverse reactions were encountered. CONCLUSIONS: In this double-blind study of 126 male subjects with acne, a topical solution of the antiandrogen inocoterone, compared with vehicle, produced a modest but statistically significant reduction in the number of inflammatory acne lesions.

Topical tretinoin for treatment of photodamaged skin. A multicenter study.

The clinical and histologic effects of a new emollient cream formulation of topical tretinoin at concentrations of 0.05% and 0.01% were examined in 251 subjects with mild to moderate photodamaged facial skin in a randomized, double-blind, vehicle-controlled, multicenter study. Seventy-nine percent of the subjects who received 0.05% tretinoin for 24 weeks showed overall improvement in photodamaged skin compared with improvement in 48% of the vehicle-treated control subjects. Significant reductions were found in fine wrinkling, mottled hyperpigmentation, roughness, and laxity after 0.05% tretinoin therapy when compared with controls. In addition, histologic changes of increased epidermal thickness, decreased melanin content, and stratum corneum compaction provide independent evidence supporting clinical improvement. Side effects of erythema, peeling, and stinging were usually mild and well tolerated.

Treatment of chronic tinea pedis (athlete's foot type) with topical terbinafine.

Twenty-seven patients with chronic tinea pedis, athlete's foot type, were enrolled in a randomized, double-blind trial of topical treatment with terbinafine 1% cream versus its vehicle (placebo). Patients were examined weekly during 4 weeks of twice-daily treatment and at follow-up 2 weeks after the conclusion of therapy. No adverse events were reported in either treatment group. Drug efficacy was evaluated in 22 patients, of whom nine (41%) were treated with terbinafine and 13 (59%) with placebo. Analysis of combined mycologic and clinical results showed that terbinafine was significantly more effective than placebo at the end of therapy (78% vs zero) and at the 2-week follow-up (89% vs zero) (p less than or equal to 0.001 at both intervals.

Treatment of chronic moccasin-type tinea pedis with terbinafine: a double-blind, placebo-controlled trial.

Terbinafine is an orally and topically active fungicidal drug of the allylamine series. Its oral efficacy at 125 mg taken twice daily was evaluated in a randomized, double-blind, placebo-controlled study in moccasin-type tinea pedis. The study was conducted simultaneously in two centers and consisted of 41 evaluable cases (23 terbinafine, 18 placebo). Mycologic cure and near to complete clearing of signs and symptoms were obtained in 59% of the terbinafine-treated patients after 6 weeks of treatment and in 65% at 2 weeks after treatment. Corresponding efficacy for placebo-treated patients was zero at both evaluations. Side effects in both groups were minimal. We conclude that terbinafine is well tolerated and highly effective in moccasin-type tinea pedis.

Oral terbinafine versus griseofulvin in the treatment of moccasin-type tinea pedis.

The safety and effectiveness of oral terbinafine, 125 mg twice daily, and griseofulvin, 250 mg twice daily, in patients with moccasin-type tinea pedis were examined in a double-blind randomized trial. At the end of the 6-week treatment period, both a clinical and mycologic cure or a mycologic cure with minimal signs of infection was noted in 12 (75%) of the 16 terbinafine-treated patients compared with only 3 (27%) of the 12 patients treated with griseofulvin. The overall response rate 2 weeks after the completion of treatment was 88% in the terbinafine-treated group and 45% in the griseofulvin-treated group. When contacted again 6 to 15 months after completion of the study, 94% of the terbinafine-treated patients reported sustained clearing of tinea pedis, and 88% of those with nail involvement at the time of treatment reported improvement. In contrast, tinea pedis remained cured in only 30% of the patients who had received griseofulvin, and onychomycosis improved in only 14%.