Pulse itraconazole vs. continuous terbinafine for the treatment of dermatophyte toenail onychomycosis in patients with diabetes mellitus

BACKGROUND: Oral terbinafine and oral itraconazole are two of the most common agents used for the treatment of toenail dermatophyte onychomycosis. Despite the fact that diabetic patients are more likely to have onychomycosis than normal individuals are, there is little research into the efficacy of standard oral regimens of terbinafine and itraconazole for onychomycosis in the diabetic population. STUDY DESIGN: We present a prospective, randomized, single-blind, parallel group, comparator-controlled, multi-centre study designed to assess the efficacy of the pulse itraconazole (200 mg twice daily, 1 week on, 3 weeks off, for 12 weeks) vs. continuous terbinafine (250 mg once daily for 12 weeks) oral therapies in the treatment of dermatophyte toenail distal and lateral subungual onychomycosis (DLSO) in the diabetic population. EFFICACY PARAMETERS: Primary efficacy measures included mycological cure rate (negative KOH and culture) and effective cure (mycological cure plus nail plate involvement of 10% or less) at Week 48. RESULTS: At Week 48, mycological cure was attained by 88.2% (30 of 34) and 79.3% (23 of 29) of patients in the itraconazole and terbinafine groups, respectively (P not significant). Effective cure (mycological cure with 相似文献   

Efficacy of itraconazole, terbinafine, fluconazole, griseofulvin and ketoconazole in the treatment of Scopulariopsis brevicaulis causing onychomycosis of the toes

BACKGROUND: Scopulariopsis brevicaulis is a common non-dermatophyte mould that can cause onychomycosis. OBJECTIVE: To evaluate the efficacy and safety of the oral antifungal agents griseofulvin, ketoconazole, itraconazole, fluconazole and terbinafine in the treatment of S. brevicaulis. PATIENTS AND METHODS: In a prospective, comparative, parallel-group, single-blinded, randomized, non-industry-sponsored study, patients with toe onychomycosis caused by S. brevicaulis sp. were randomized and treated with one of 5 oral antifungal agents, i.e. griseofulvin, ketoconazole, itraconazole (pulse), fluconazole or terbinafine. The treatment regimens were: griseofulvin 600 mg twice daily for 12 months, ketoconazole 200 mg daily for 4 months, itraconazole pulse therapy given for 3 pulses, with each pulse consisting of 200 mg twice daily for 1 week with 3 weeks off between successive pulses, terbinafine 250 mg daily for 12 weeks and fluconazole 150 mg daily for 12 weeks. RESULTS: There were 59 patients (48 males, 11 females, mean age 35.6 years, range 25-53 years). All patients had clinical evidence of distal and lateral onychomycosis, with moderate to severe disease of the target nail. Between the treatment groups there was no significant difference in the mean age of the patients or the mean area of involvement with onychomycosis at baseline. The efficacy parameters were clinical cure (CC) and mycological cure (MC). At month 12 after the start of treatment, the response was: griseofulvin, CC 3/11, MC 0/11, CC + MC 0/11; ketoconazole, CC 10/12, MC 8/12, CC + MC 8/12; itraconazole, CC 12/12, MC 12/12, CC + MC 12/12; terbinafine, CC 12/12, MC 11/12, CC + MC 11/12, and fluconazole, CC 8/12, MC 8/12, CC + MC 8/12. Adverse effects consisted of: griseofulvin, gastro-intestinal symptoms, allergic reaction, photodermatitis, hepatic and renal dysfunction in 11 patients with discontinuation of treatment in 3 patients; ketoconazole, hepatic dysfunction but no symptomatic changes in 2 patients; itraconazole, nausea and vomiting in 2 patients; terbinafine, taste disturbance in 2 patients, nausea in 3 patients, and fluconazole, severe gastro-intestinal events in 5 patients. None of the patients receiving ketoconazole, itraconazole, terbinafine or fluconazole discontinued treatment. CONCLUSIONS: Itraconazole and terbinafine demonstrate efficacy against some cases of S. brevicaulis toe onychomycosis. These agents also appear to be safe in the course of therapy for toe onychomycosis. Griseofulvin is ineffective against toe onychomycosis caused by S. brevicaulis. Ketoconazole is not recommended for toe onychomycosis given its potential for adverse effects, particularly with the availability of the newer antifungal agents.     

Amorolfine and itraconazole combination for severe toenail onychomycosis; results of an open randomized trial in Spain

Objective In an open, randomized, clinical study of toenail onychomycosis with matrix area involvement, two alternative regimens of topical amorolfine/oral itraconazole therapy were compared with itraconazole monotherapy.
Patients/Methods A total of 131 patients were randomized to treatment. Patients in the combination groups were treated with amorolfine 5% nail lacquer (Loceryl®, Galderma Laboratories) once weekly for 24 weeks and 200 mg itraconazole once daily for 6 weeks (Group AI-6) or 12 weeks (Group AI-12). A control group received itraconazole monotherapy for 12 weeks (Group I-12). Strict inclusion criteria specified that subjects had to have onychomycosis of the toenails with matrix area involvement and/or > 80% total nail surface involvement. Mycological evaluations using both microscopic examination and culture of nail samples were performed at weeks 12 and 24. A stringent assessment of outcome at study end combined the results of mycological and clinical outcomes into a global cure rate. Safety was also assessed.
Results At week 12, mycological cure was attained in 42 of 45 patients (93·3%) in group AI-6, 29 of 35 patients (82·9%) in group AI-12, and 14 of 34 patients in group I-12. The difference between both combination groups and the control group were significant ( P  < 0·001). The global cure rate at week 24 was 83·7% (36 patients) in group AI-6, 93·9% (31 patients) in group AI-12, and 68·8% (22 patients) in group I-12. The difference between the AI-12 group and itraconazole monotherapy was significant ( P  < 0·05).
Conclusions These results indicate that amorolfine combination therapy represents an improved treatment strategy for patients with severe onychomycosis.     

Terbinafine: a review of its use in onychomycosis in adults

Terbinafine, an orally and topically active antimycotic agent, inhibits the biosynthesis of the principal sterol in fungi, ergosterol, at the level of squalene epoxidase. Squalene epoxidase inhibition results in ergosterol-depleted fungal cell membranes (fungistatic effect) and the toxic accumulation of intracellular squalene (fungicidal effect). Terbinafine has demonstrated excellent fungicidal activity against the dermatophytes and variable activity against yeasts and non-dermatophyte molds in vitro. Following oral administration, terbinafine is rapidly absorbed and widely distributed to body tissues including the poorly perfused nail matrix. Nail terbinafine concentrations are detected within 1 week after starting therapy and persist for at least 30 weeks after the completion of treatment. Randomized, double-blind trials showed oral terbinafine 250 mg/day for 12 or 16 weeks was more efficacious than itraconazole, fluconazole and griseofulvin in dermatophyte onychomycosis of the toenails. In particular, at 72 weeks' follow-up, the multicenter, multinational, L.I.ON. (Lamisil vs Itraconazole in ONychomycosis) study found that mycologic cure rates (76 vs 38% of patients after 12 weeks' treatment; 81 vs 49% of recipients after 16 weeks' therapy) and complete cure rates were approximately twice as high after terbinafine treatment than after itraconazole (3 or 4 cycles of 400 mg/day for 1 week repeated every 4 weeks) in patients with toenail mycosis. Furthermore, the L.I.ON. Icelandic Extension study demonstrated that terbinafine was more clinically effective than intermittent itraconazole to a statistically significant extent at 5-year follow-up. Terbinafine produced a superior complete cure rate (35 vs 14%), mycologic cure rate (46 vs 13%) and clinical cure rate (42 vs 18%) to that of itraconazole. The mycologic and clinical relapse rates were 23% and 21% in the terbinafine group, respectively, compared with 53% and 48% in the itraconazole group. In comparative clinical trials, oral terbinafine had a better tolerability profile than griseofulvin and a comparable profile to that of itraconazole or fluconazole. Post marketing surveillance confirmed terbinafine's good tolerability profile. Adverse events were experienced by 10.5% of terbinafine recipients, with gastrointestinal complaints being the most common. Unlike the azoles, terbinafine has a low potential for drug-drug interactions. Most pharmacoeconomic evaluations have shown that the greater clinical effectiveness of oral terbinafine in dermatophyte onychomycosis translates into a cost-effectiveness ratio superior to that of itraconazole, fluconazole and griseofulvin. CONCLUSION: Oral terbinafine has demonstrated greater effectiveness than itraconazole, fluconazole and griseofulvin in randomized trials involving patients with onychomycosis caused by dermatophytes. The drug is generally well tolerated and has a low potential for drug interactions. Therefore, terbinafine is the treatment of choice for dermatophyte onychomycosis.     

A randomized, placebo- and active-controlled, parallel-group, multicentre, investigator-blinded study of four treatment regimens of posaconazole in adults with toenail onychomycosis

Background Onychomycosis accounts for up to 50% of all onychopathies. Objectives To evaluate the efficacy of four posaconazole regimens compared with placebo in the treatment of toenail onychomycosis, to assess the safety and tolerability of posaconazole, and to estimate the relative efficacy of posaconazole against terbinafine. Methods A phase 2B, randomized, placebo‐ and active‐controlled, parallel‐group, multicentre, investigator‐blinded (double blind for placebo) study (ClinicalTrials.gov identifier: NCT00491764). Onychomycosis patients aged 18–75 years (n = 218) were randomized equally to one of six treatment regimens: posaconazole (oral suspension) 100, 200 or 400 mg once daily (24 weeks); posaconazole 400 mg once daily (12 weeks); terbinafine (tablets) 250 mg once daily (12 weeks); or placebo (24 weeks). The primary efficacy variable was complete cure (negative mycology and 0% nail involvement) at week 48. Results All posaconazole treatment arms had a significantly (P ≤ 0·012) greater proportion of patients with complete cure at week 48 compared with placebo. The proportions of patients with complete cure were numerically higher for posaconazole 200 mg/24 weeks (54·1%) and 400 mg/24 weeks (45·5%), but lower for 400 mg/12 weeks (20%) compared with terbinafine (37%; differences were not statistically significant). Posaconazole was well tolerated. Seven patients receiving posaconazole withdrew because of asymptomatic liver enzyme increases, as mandated by protocol discontinuation criteria. Conclusions The efficacy and favourable safety profile of posaconazole suggest a potential new treatment for onychomycosis. The availability of low‐cost generic terbinafine may limit posaconazole use to second‐line treatment of infections refractory to, or patients intolerant of, terbinafine, or nondermatophyte mould infections.     

Single-blind, randomized, prospective study on terbinafine and itraconazole for treatment of dermatophyte toenail onychomycosis in the elderly

BACKGROUND: The 2 most common agents used to treat dermatophyte onychomycosis of the toe are terbinafine (continuous) and itraconazole (pulse). Although comparative studies have been performed evaluating the efficacy of these 2 agents in adults, no such studies have been reported specifically in the elderly subset. OBJECTIVE: This prospective, randomized, single-blind, non--industry-sponsored, comparative study evaluated the efficacy and safety of terbinafine (continuous) and itraconazole (pulse) therapies in the treatment of dermatophyte onychomycosis of the toe in the elderly population. METHODS: Elderly patients (> or =60 years old) with dermatophyte onychomycosis of at least 1 great toe were randomly assigned to receive either terbinafine 250 mg/day for 12 weeks or itraconazole (pulse) 200 mg twice a day for 1 week, given for 3 pulses. At month 6 from the start of therapy, if there was less than 50% reduction in the affected nail plate area compared with baseline, or if there was less than 3 mm outgrowth of unaffected nail plate as measured in midline, then patients who had been administered terbinafine (continuous) therapy were given an extra 4 weeks of the drug (total of 16 weeks of therapy), and those who had received itraconazole (pulse) therapy were given an extra pulse (fourth pulse). Patients were evaluated at 1.5, 3, 6, 12, and 18 months from the start of therapy. The efficacy measures included mycologic cure rate and clinical efficacy (mycologic cure plus clinical cure or clinical improvement so that 10% or less of nail plate was clinically involved). RESULTS: There were 101 elderly patients enrolled in the study with 50 and 51 patients receiving terbinafine and itraconazole, respectively. The terbinafine group consisted of 28 men and 22 women, age (mean +/- standard error [SE]) 68.0 +/- 0.9 years, duration of onychomycosis (mean +/- SE) 18.2 +/- 1.4 years, number of nails involved (mean +/- SE) 5.5 +/- 0.5, and percent baseline nail plate area involved (mean +/- SE) 67.5% +/- 4.2%. The corresponding figures for the itraconazole (pulse) group were 24 men and 27 women, age (mean +/- SE) 68.8 +/- 0.8 years, duration of onychomycosis (mean +/- SE) 16.1 +/- 1.7 years, number of nails involved (mean +/- SE) 6.0 +/- 0.7, and percent baseline nail plate area involved (mean +/- SE) 74.9% +/- 3.8%, respectively, with no significant difference between the groups. At month 6, the number of patients that required an extra 4 weeks of terbinafine in the allylamine group or an extra itraconazole pulse in the triazole group was 13 of 50 and 23 of 51, respectively. The mycologic cure rate and clinical efficacy at 18 months from the start of therapy for the terbinafine group were 64.0% and 62.0%, respectively. The corresponding figures for the itraconazole (pulse) group were 62.7% and 60.8%, respectively, with no significant difference between the 2 groups. There were no dropouts during therapy. For both groups the drug appeared safe with no significant adverse events (AEs) or clinically significant laboratory abnormalities. All the AEs were mild and transient. There was high compliance with both regimens. CONCLUSIONS: In the elderly, for the treatment of dermatophyte toe onychomycosis, both terbinafine (continuous) and itraconazole (pulse) therapies are effective, safe, and associated with high compliance.     

特比萘芬合用地巴唑治疗甲真菌病的随机双盲对照研究

目的 观察特比萘芬与地巴唑联合治疗甲真菌病的疗效。方法 甲真菌病患者随机分组,治疗组口服特比萘芬250mg每日1次,同时口服地巴唑10mg每日3次;对照组口服特比萘芬250mg每日1次,同时口服安慰剂。治疗组指甲真菌病疗程为6周,趾甲疗程为8周;对照组指甲真菌病疗程为8周,趾甲疗程为10周。观察2种方法的疗效。结果 治疗后第24周随访,治疗组54例痊愈率为70.4%(38/54例),有效率为83.3%(45/54例);对照组51例痊愈率为66.7%(34/51例),有效率为80.4%(41/51例),两组比较差异均无显著性(P>0.05)。结论 特比萘芬与血管扩张剂联合治疗甲真80.4%(41/51例),两组比较差异均无显著菌病能缩短疗程,且无明显不良反应。     

A multicentre, randomized, controlled study of the efficacy, safety and cost-effectiveness of a combination therapy with amorolfine nail lacquer and oral terbinafine compared with oral terbinafine alone for the treatment of onychomycosis with matrix involvement

BACKGROUND: Onychomycosis is common, accounting for up to 50% of all nail disorders. Toenail onychomycosis can cause nail deformity, embarrassment, pain and walking difficulties. Some populations, such as individuals with diabetes, are at higher risk for developing secondary complications such as infections. Treatment takes many months and therapeutic choices can increase clinical effectiveness, lower toxicity and minimize healthcare costs. OBJECTIVES: Based on the results of a previous pilot study, the objective of the present study was to show, in a larger population, the enhanced efficacy of a combination of amorolfine nail lacquer and oral terbinafine in the treatment of onychomycosis with matrix involvement. In addition, a cost-effectiveness analysis was performed. METHODS: In this multicentre, randomized, open-label, parallel group study, patients were randomized to receive either a combination of amorolfine hydrochloride 5% nail lacquer once weekly for 12 months plus terbinafine 250 mg once daily for 3 months (AT group) or terbinafine alone once daily for 3 months (T group). The study duration was 18 months including a 6-month treatment-free phase following the 12-month active treatment phase for the AT group and a 15-month treatment-free phase following the 3-month active treatment phase for the T group. The primary efficacy criterion was overall response, dichotomized into success or failure, success being the combination of clinical cure and negative mycology at month 18. This criterion was used as the effectiveness measure in the pharmacoeconomic analysis, conducted from a payer perspective. RESULTS: In total, 249 patients were included into the study: 120 in the AT group and 129 in the T group. A significantly higher success rate was observed for patients in the AT group relative to those in the T group at 18 months (59.2% vs. 45.0%; P = 0.03). Both treatment regimens were safe and well tolerated. Treatment cost per cured patient was lower for the combination than for terbinafine alone in all countries. CONCLUSIONS: Study results confirmed that, in the treatment of dermatophytic toenail onychomycosis with matrix involvement, amorolfine nail lacquer in combination with oral terbinafine enhances clinical efficacy and is more cost-effective than terbinafine alone.     

Onychomykose durch Trichophyton rubrum und Sekundärinfektion durch Aspergillus versicolor bei einer 12-jährigen Patientin

Case report

A 12-year-old with a functional circulatory disturbance had toe nail onychomycosis caused by Trichophyton rubrum. There were no other underlying diseases.

Therapy and outcome

Oral therapy with terbinafine 125  mg once weekly in addition to ciclopirox nail lacquer was ineffective. Two years later the disease worsened and A. versicolor was found in pure culture. A preparation of 10?% terbinafine HCl in a 20% urea ointment (Onychomal®) applied daily for 4 weeks, then once weekly resulted in complete cure after 7 months.     

特比萘芬间歇疗法治疗老年人甲真菌病的疗效和安全性评价

目的探讨特比萘芬间歇疗法在治疗老年人甲真菌病中的疗效和安全性。方法采用随机双盲方法,将老年人甲真菌病患者分为2组。特比萘芬间歇疗法组:特比萘芬250mg,1次/d,连续4周,停药4周,再予连续4周;特比萘芬持续疗法组:特比萘芬250mg,次1/d,连续12周。在服药后第12周、24周、36周、48周、72周进行回访,观察疗效和不良反应。结果在72周时,特比萘芬间歇疗法组与持续疗法组的临床有效率为79.17%和81.82%;真菌清除率为83.33%和90.91%。在不同的观察时间,两组的临床有效率和真菌清除率相比较,差异均无统计学意义(P均>0.05)。结论在治疗老年人甲真菌病中,特比萘芬间歇疗法可以达到与特比萘芬持续疗法类似的疗效和安全性。     

Canadian perspectives on antifungal treatment for onychomycosis

Onychomycosis is a common nail disease caused by dermatophytes, yeasts, and nondermatophyte molds affecting approximately 6.5% of the Canadian population. Approved therapies for onychomycosis in Canada are terbinafine 250 mg once daily for 6 to 12 weeks; itraconazole 200 mg twice daily given for two to three pulses (one pulse = 200 mg daily for 1 week, with 3 weeks off the drug before the next pulse); and ciclopirox nail lacquer 8% used once daily for up to 48 weeks. These medications can be used for dermatophyte onychomycosis of toenails or fingernails. Liver enzyme monitoring should be performed when prescribing the oral medications. Ciclopirox is one of the newest antifungal agents and is the only topical therapy specifically indicated for onychomycosis in Canada. Topical therapy for onychomycosis provides an advantage over oral treatment in safety and cost, giving ciclopirox wide potential for use. It remains to be seen what future role ciclopirox will have in the Canadian onychomycosis spectrum.     

The successful treatment of Trichophyton rubrum nail bed (distal subungual) onychomycosis with intermittent pulse-dosed terbinafine

BACKGROUND: The standard treatment of Trichophyton rubrum nail bed onychomycosis (or distal subungual onychomycosis [DSO]) with daily terbinafine for 12 weeks involves treating for a fixed period shorter than the time required for complete replacement of the nail bed and overlying nail plate by normal growth. The same total amount of terbinafine pulse-dosed for approximately 12 months would treat the patient until normal replacement of the mycotic nail bed has occurred.OBJECTIVES: To determine the effectiveness of intermittent administration of oral terbinafine (250 mg/d for 7 consecutive days every 2-4 months) to cure DSO and to determine the maximum effective treatment interval. DESIGN: A prospective, nonrandomized, open study of sequential groups of office patients. SETTING: A private dermatology practice. METHODS: A sequence of 4 groups of office patients with DSO (n = 10-20 each) were treated with pulse-dosed terbinafine for 7 consecutive days at intervals of 2, 3, and 4 months, respectively. In each group, treatment was continued until the distally advancing new nail bed and nail had completely removed the mycotic defect or failure of fungistasis was detected. MAIN OUTCOME MEASUREMENT: Results were determined by monthly evaluation. Cure was noted as complete replacement of the mycotic nail bed and overlying nail plate (ascertained by monthly metric measurements of the mycosis-free nail bed and overlying nail place distal to the proximal nail fold). Treatment failure was noted when the mycosis-free proximal portion of the nail bed failed to increase in correspondence with the distally directed movement of the nail bed and overlying nail. RESULTS: Thirty-nine (93%) of the 42 patients in the first 3 groups were cured (95% binomial confidence interval, 67%-100%) with no evidence of decrease in efficacy. However, the group of patients who received the 7-day pulse treatment every 4 months experienced significantly more failures (P<.01), and cures dropped to 10 of 17 cases. CONCLUSION: Terbinafine is an effective treatment for DSO when pulse-dosed for 7 days every 3 months but not every 4 months.     

Therapeutic Options for the Treatment of Tinea Capitis Caused by Trichophyton Species: Griseofulvin Versus the New Oral Antifungal Agents, Terbinafine, Itraconazole, and Fluconazole

Tinea capitis is a relatively common fungal infection of childhood. Griseofulvin has been the mainstay of management. However, newer oral antifungal agents are being used more frequently. A multicenter, prospective, randomized, single-blinded, non-industry-sponsored study was conducted in centers in Canada and South Africa to determine the relative efficacy and safety of griseofulvin, terbinafine, itraconazole, and fluconazole in the treatment of tinea capitis caused by Trichophyton species. The regimens for treating tinea capitis were griseofulvin microsize 20 mg/kg/day x 6 weeks, terbinafine [> 40 kg, one 250 mg tablet; 20-40 kg, 125 mg (half of a 250 mg tablet); < 20 kg, 62.5 mg (one-quarter of a 250 mg tablet)] x 2-3 weeks, itraconazole 5 mg/kg/day x 2-3 weeks, and fluconazole 6 mg/kg/day x 2-3 weeks. Patients were asked to return at weeks 4, 8, and 12 from the start of the study. Griseofulvin was administered for 6 weeks and the final evaluation was at week 12. Terbinafine, itraconazole, and fluconazole were administered for 2 weeks and the patient evaluated 4 weeks from the start of therapy. At this time, if clinically indicated, one extra week of therapy was given. There were 200 patients randomized to four treatment groups (50 in each group). At the final evaluation at week 12, the number of evaluable patients were griseofulvin, 46; terbinafine, 48; itraconazole, 46; and fluconazole, 46. Patients who discontinued therapy or were lost to follow-up were griseofulvin, 1/3; itraconazole, 0/4; terbinafine, 0/4; and fluconazole, 0/4. The causative organisms were Trichophyton tonsurans and T. violaceum species. Patients were regarded as effectively treated at week 12 if there was mycologic cure and either clinical cure or only a few residual symptoms. Effective treatment was recorded in, intention to treat, griseofulvin (46 of 50, 92.0%), terbinafine (47 of 50, 94.0%), itraconazole (43 of 50, 86.0%), and fluconazole (42 of 50, 84.0%) (p=0.33). Adverse effects were reported only in the griseofulvin group (gastrointestinal effects in six patients). Discontinuation from therapy due to adverse effects occurred only in the griseofulvin group (nausea in one patient). For the treatment of tinea capitis caused by the Trichophyton species, in this study, griseofulvin given for 6 weeks is similar in efficacy to terbinafine, itraconazole, and fluconazole given for 2-3 weeks. Each of the agents has a favorable adverse-effects profile.     

Single-blind, randomized, prospective study of sequential itraconazole and terbinafine pulse compared with terbinafine pulse for the treatment of toenail onychomycosis

OBJECTIVE: Efficacy and safety of sequential pulse therapy with itraconazole and terbinafine were compared with pulse terbinafine alone in the treatment of toenail onychomycosis. METHODS: This was a 72-week prospective, single-blind, randomized, multicenter, comparative, parallel group, nonindustry-sponsored trial. A total of 190 patients were recruited from 3 outpatient dermatology offices in North America. Patients were at least 18 years old and had a clinical and mycologic diagnosis of dermatophyte toenail onychomycosis. Patients were randomly assigned to receive sequential pulse therapy (IIT) with 2 pulses of itraconazole followed by 1 or 2 pulses of terbinafine (itraconazole pulse is 200 mg twice daily for 1 week and terbinafine pulse is 250 mg twice daily for 1 week) versus 3 or 4 pulses of terbinafine (TTT). Main outcome measures at week 72 evaluated mycologic cure rate (negative light microscopy and culture), clinical cure (nail appears completely or totally normal), complete cure (clinical and mycologic cure), and effective therapy (mycologic cure and clinical response with at least 5 mm of new, uninvolved nail growth). RESULTS: At week 72, in the IIT versus TTT groups, the mycologic cure rate was 54 of 75 (72.0%) versus 44 of 90 (48.9%), clinical cure rate was 42 of 75 (56.0%) versus 35 of 90 (38.9%), effective therapy 49 of 75 (65.3%) versus 41 of 90 (45.6%), and complete cure 39 of 75 (52.0%) versus 29 of 90 (32.2%), respectively. Both regimens were well tolerated with no new adverse effects being identified. The rate of permanent discontinuation of therapy because of adverse effects was 2 of 81 (2.5%) with IIT and 2 of 95 (2.1%) with TTT. Each of the adverse effects normalized over time. The number of patients who reported an adverse effect in the 2 groups was 12 of 81 (14.8%) versus 22 of 95 (23.2%), respectively. All these adverse effects were reversible and mild to moderate in severity. CONCLUSION: Sequential pulse therapy with itraconazole and terbinafine is effective and safe for the treatment of dermatophyte toenail onychomycosis.     

特比萘芬治疗糖尿病患者甲真菌病疗效和对血糖水平的影响

目的:评价特比萘芬连续疗法治疗糖尿病患者甲真菌病的有效性、安全性、耐受性和对患者血糖水平的影响。方法:90例糖尿病甲真菌病患者口服特比萘芬250mg,每日1次,指甲癣患者连续口服12周,趾甲癣患者连续口服16周;停药第24周观察最终疗效和血糖水平。结果:在第36周时,指甲真菌病的临床治愈率84.8%,有效率90.9%,真菌学治愈率93.9%;第40周时,趾甲真菌病的临床治愈率78.9%,有效率87.7%,真菌学治愈率89.5%;治疗前后空腹血糖和糖化血红蛋白水平无显著性差异。结论:特比萘芬治疗糖尿病患者甲真菌病有效、安全,耐受性良好;对患者血糖水平无明显影响。     

Treatment of tinea imbricata: a randomized clinical trial using griseofulvin, terbinafine, itraconazole and fluconazole

BACKGROUND: Griseofulvin has been the mainstay of treatment for tinea imbricata (TI) for decades; however, there have been few reports of efficacy of newer antifungals in the treatment of this condition. Many patients with TI have several obstacles to treatment due to their remote geographical locations and the primitive nature of their societies. OBJECTIVES: The aim of this study was to compare the efficacy of itraconazole, terbinafine and fluconazole with that of griseofulvin after 4 weeks of therapy. METHODS: Patients aged 12-76 years with the clinical diagnosis of TI were randomly assigned to one of four treatment groups: griseofulvin 500 mg twice daily for 4 weeks, terbinafine 250 mg daily for 4 weeks, itraconazole 200 mg twice daily for 1 week or fluconazole 200 mg once weekly for 4 weeks. Disease activity was monitored weekly. Laboratory measurements included monitoring complete blood count and liver function enzymes. Fifty-nine patients were included in the efficacy analysis: 13 in the fluconazole group, 15 in the griseofulvin group, 12 in the terbinafine group and 19 in the itraconazole group. RESULTS: Significant remission was achieved in the terbinafine and griseofulvin groups, lasting up to 8 weeks after cessation of therapy. The fluconazole group experienced no significant remission, and remission was of short duration in the itraconazole group. No adverse events were reported, and non-compliance with medications or follow-up was the only reason for removal from the study. CONCLUSIONS: Griseofulvin and terbinafine are effective in the treatment of TI. The decision of whether to treat at all and which medication to choose depends greatly on the extent of involvement, the social situation, and the availability of resources such as laboratory testing and follow-up.     

Long-term efficacy of antifungals in toenail onychomycosis: a critical review

BACKGROUND: Modern antifungal drugs achieve high mycological and clinical cure rates in onychomycosis of the toes, but little is known about the long-term evolution of the treated patients. OBJECTIVES: The aim of this review was to analyse the therapeutic results recorded more than 1 year after initiation of therapy. METHODS: We used two endpoints for the analysis: EP1 (the number of patients with negative mycology after follow-up, divided by the number of patients included at day 0, including all patients lost to follow-up), and EP2 (the number of patients with negative mycology after follow-up divided by the number of patients with negative mycology at week 48). Clinical cure rate (EPclin) was the number of patients clinically cured or with minimal residual lesions divided by the number of patients included at day 0. RESULTS: From a Medline search we identified 17 studies providing results beyond 48 weeks. Ketoconazole 200 mg d(-1) up to 1 year resulted in EP1 of 11% at 18 months, and EP2 of 43%. Griseofulvin 1 g d(-1) for 1 year allowed an EP1 of 43% at 18 months, and EP2 of 71%. The mean EP1 after fluconazole once weekly up to 1 year was 49% at 18 months, and EP2 was 91%. With itraconazole 200 mg d(-1) or 400 mg d(-1) for 1 week each month for 3-4 months, EP1 was 37% at 18 months, and 53% at 2 years; EP2 was 76% at 4 years. Terbinafine 250 mg d(-1) for 12-16 weeks achieved an EP1 of 62% at 18 months, 72% at 2 years, and 60% at 4 years; EP2 was 80% at 18 months, 81% at 2 years, and 71% at 4 years. In the only study planned to compare the long-term efficacy of terbinafine and itraconazole, EP1 at 18 months was significantly higher with continuous terbinafine than with intermittent itraconazole (66% vs. 37%, P < 0.001). The clinical cure rates were 21% at 60 weeks and 37% at 72 weeks with fluconazole. EPclin was 27% at 18 months and 35% at 2 years with itraconazole. EPclin was 48% at 18 months, 69% at 2 years and 50% at 4 years with terbinafine. CONCLUSIONS: Considering the stringency of the criteria we used, this critical review suggests that the long-term efficacy achieved with terbinafine is superior to that obtained with griseofulvin, ketoconazole, fluconazole or itraconazole.     

Terbinafine (Lamisil) treatment of toenail onychomycosis in patients with insulin-dependent and non-insulin-dependent diabetes mellitus: a multicentre trial

BACKGROUND: Diabetes mellitus (DM) affects an estimated 175 million people world-wide. Approximately one-third of patients with DM have toenail onychomycosis. OBJECTIVES: To determine the efficacy and safety of terbinafine treatment of toenail onychomycosis in patients with DM receiving insulin and/or oral antidiabetic agents. Special interest was focused on potential drug interactions with oral hypoglycaemic substances. METHODS: In a multicentre trial, patients suffering from insulin-dependent DM (IDDM) or non- insulin-dependent DM (NIDDM) with toenail onychomycosis were treated for 12 weeks with oral terbinafine 250 mg daily and followed up to 48 weeks. In addition to clinical, mycological and laboratory investigations, blood glucose levels were monitored. RESULTS: At the end of the trial (week 48), a mycological cure rate of 73% was achieved. The rates of clinical cure and complete cure (mycological cure plus clinical cure) were 57% and 48%, respectively. There was no statistically significant difference between the NIDDM and IDDM groups with respect to the cure rates (P > 0.05). No hypoglycaemic episode was reported and none of the patients had hypoglycaemia during the treatment phase. CONCLUSIONS: With excellent cure rates and a good tolerability profile, terbinafine should continue to be a drug of choice for the treatment of toenail onychomycosis in the rising number of NIDDM patients receiving multiple medication.     

An open randomized comparative study of oral itraconazole pulse and terbinafine pulse in the treatment of onychomycosis

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.     

The prevalence, aetiological agents and therapy of onychomycosis in patients with psoriasis: a prospective controlled trial

BACKGROUND: Nail involvement morphologically resembling onychomycosis frequently accompanies psoriatic lesions. The role of psoriasis as a predisposing factor for onychomycosis and the possible influence of psoriasis on responsiveness of onychomycosis to treatment are controversial. AIM: To investigate the frequency of onychomycosis, the aetiological agents responsible for it, and the efficacy of terbinafine 250 mg/day in patients with psoriasis compared with controls in order to reveal the role of psoriatic process on fungal growth. METHODS: Over a 1-year period, 168 patients with psoriasis and 164 nonpsoriatic controls were recruited. In the case of clinically suspected of fungal infection, further mycological investigations were performed. Systemic terbinafine therapy 250 mg daily for 12 weeks was administered to the patients with onychomycosis. Patients were followed up clinically and mycologically for 24 weeks. RESULTS: Onychomycosis was diagnosed in 22 patients with psoriasis (13.1% of the psoriasis group, which constituted 28.6% of patients with suspicion of onychomycosis) and 13 controls (7.9% of control group; 40.6% of controls with suspicion of onychomycosis). The prevalence rates of onychomycosis were similar in both groups. The most commonly isolated fungi were dermatophytes in the psoriasis group and nondermatophytic moulds in controls. Dermatophytes were more common in psoriatic than control nails (P = 0.02). All patients in each group were cured at the end of the therapy. CONCLUSION: It seems that nail psoriasis constitutes a risk factor not for onychomycosis, but specifically for dermatophytic nail infections. Because of the similar therapeutic results in each group, different antifungal treatment protocols may not be needed in psoriasis. However, to confirm this, new comprehensive studies are necessary.