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   

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.     

Itraconazole pulse therapy for onychomycosis and dermatomycoses: An overview

Background: Itraconazole is a broad-spectrum antifungal agent that has been used to treat dermatomycosis and onychomycosis using continuous therapy. More recently the drug has been used as pulse dosing. Objective: Our purpose was to review the studies in which itraconazole pulse therapy (PT) has been administered in the management of dermatomycoses. Results: For tinea pedis and manuum, the recommended dosage is itraconazole 200 mg twice daily for 1 week (n = 220). A clinical response and mycologic cure rate of 90% ± 4% and 76% ± 6%, respectively, has been obtained. For tinea corporis/cruris, itraconazole 200 mg/day for 1 week (n = 354) resulted in a clinical response and mycologic cure rate of 90% ± 4% and 77% ± 6%, respectively. When three pulses of itraconazole are used to treat toenail onychomycosis (n = 1389), the clinical cure rate, clinical response, and mycologic cure rate at follow-up 12 months after the start of therapy were 58% ± 10%, 82% ± 3%, and 77% ± 5%, respectively. With two pulses for onychomycosis of the fingernails, the clinical cure rate, clinical response, and mycologic cure rate at follow-up, 9 months after the start of therapy, were 78% ± 10%, 89% ± 6%, and 87% ± 8%, respectively. Conclusion: Itraconazole PT is effective and safe in the treatment of tinea pedis/manuum, tinea corporis/cruris, and onychomycosis. (J Am Acad Dermatol 1997;37:969-74.)     

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.     

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.     

Combination of pulse therapy with terbinafine tablets and topical terbinafine cream for the treatment of dermatophyte onychomycosis: a pilot study

We performed a pilot study to assess the safety and efficacy of pulse therapy with terbinafine tablets in 66 patients with dermatophyte onychomycosis. One pulse consisted of oral terbinafine tablets (500 mg/day) given for 1 week followed by a 3-week interval. Topical 1% terbinafine cream was applied daily. The number of pulses was determined by the extent of improvement in the affected nails and by the patient's requests, up to a maximum of six pulses. Efficacy was assessed based on both clinical and mycological examinations 1 year after treatment initiation. We observed a complete cure in 51 patients (77.3%), marked improvement in five patients (7.6%), improvement in five patients (7.6%) and slight improvement in one patient (1.5%). Four patients (6.0%) showed no change. In the patients who were completely cured, the average number of pulses used was 3.7 +/- 1.4 pulses and the treatment duration was 3.3 +/- 1.6 months. Nine patients experienced adverse effects, consisting of gastrointestinal disturbance (eight patients) and drug-induced eruption (one patient). There were no abnormal findings in the laboratory tests, including liver function tests. In summary, terbinafine pulse therapy in combination with topical application of terbinafine cream appeared safe and effective in this pilot study.     

Itraconazole for the treatment of onychomycosis

Background The broad spectrum of activity of itraconazole in vitro manifests itself clinically with the drug being effective for the treatment of onychomycosis caused by dermatophytes, Candida and some non-dermatophyte molds. The pharmacokinetics of itraconazole in the nail results in drug remaining at therapeutic levels for 6–9 months after completion of therapy.
Methods An overview of studies where continuous or pulse itraconazole therapy has been used in the treatment of fingernail and toenail onychomycosis.
Results Following continuous therapy at 200 mg/day for 3 months for toenail onychomycosis ( n = 1741), the rates of clinical cure, clinical response and mycologic cure were: (meta-average ± 95% standard error (SE)), 52 ± 9%, 86 ± 2%, and 74 ± 3%, respectively, at follow-up 12 months following start of therapy. In fingernail onychomycosis ( n = 211), the duration of therapy was 6 weeks and the corresponding efficacy rates at follow-up, 9 months after start of therapy, were meta-average (± S.E.) 82 ± 5%, 90 ± 2%, and 86 ± 3%, respectively. In toenail onychomycosis treated with 3 pulses of therapy ( n = 1389), the clinical response, clinical cure and mycologic cure were observed in meta-average (± S.E.) 58 ± 10%, 82 ± 3%, and 77 ± 5% patients, respectively, at follow-up 12 months after the start of therapy. In fingernail onychomycosis treated with 2 pulses of therapy ( n = 210), at follow-up 9 months after the start of therapy, the corresponding efficacy rates were meta-average (± S.E.) 78 ± 10%, 89 ± 6%, and 87 ± 8%, respectively.
Conclusions Both the continuous and pulse therapy regimens are safe with few adverse effects. Compared to continuous therapy, the pulse regimen has an improved adverse-effects profile, is more cost-effective, and is preferred by many patients.     

The use of an intermittent terbinafine regimen for the treatment of dermatophyte toenail onychomycosis

Objective  To compare the efficacy and safety of intermittent terbinafine with standard courses of terbinafine and itraconazole for dermatophyte toenail onychomycosis.
Design  Data from a Canadian study of continuous terbinafine (CTERB) and intermittent itraconazole (III) was compared to an intermittent terbinafine regimen (TOT) using similar protocol to the randomized study.
Interventions  Terbinafine 250 mg/day for 4 weeks followed by 4 weeks of no terbinafine and then an additional 4 weeks of terbinafine 250 mg/day (TOT); terbinafine 250 mg/day for 12 weeks (CTERB); itraconazole pulse of 200 mg twice daily for 7 days on, 21 days off, three pulses given (III).
Results  At 72 weeks, mycological cure rates (negative KOH and culture) were 36 of 43 (83.7%), 25 of 32 (78.1%), and 17 of 30 (56.7%), for the TOT, CTERB, and III groups, respectively ( P =  0.01 for TOT vs. III). Effective cure rates (simultaneous mycological cure and ≤10% nail plate involvement) were 34 of 43 (79.1%), 21 of 32 (65.6%), and 11 of 30 (36.7%), respectively ( P <  0.001 for TOT vs. III; P =  0.02 for CTERB vs. III). No significant differences in effective and mycological cure rates were noted between the two terbinafine groups. Adverse events reported were similar to those reported in the respective package inserts. Most adverse events were mild to moderate, transient, and did not require interruption of the drug regimens. No serious adverse events were reported.
Conclusions  A TOT intermittent terbinafine regimen provided similar efficacy and safety to the gold standard continuous terbinafine regimen and better effective cure rates than pulse itraconazole therapy.

Conflicts of interest

None declared     

Long-term effectiveness of treatment with terbinafine vs itraconazole in onychomycosis: a 5-year blinded prospective follow-up study

OBJECTIVE: To examine long-term cure and relapse rates after treatment with continuous terbinafine and intermittent itraconazole in onychomycosis. DESIGN: Long-term prospective follow-up study. SETTING: Three centers in Iceland. SUBJECTS: The study population comprised 151 patients aged 18 to 75 years with a clinical and mycological diagnosis of dermatophyte toenail onychomycosis. INTERVENTIONS: In a double-blind, double-dummy study, patients were randomized to receive either terbinafine (250 mg/d) for 12 or 16 weeks or itraconazole (400 mg/d) for 1 week in every 4 for 12 or 16 weeks (first intervention). Patients who did not achieve clinical cure at month 18 or experienced relapse or reinfection were offered an additional course of terbinafine (second intervention). MAIN OUTCOME MEASURES: The primary efficacy criterion was mycological cure, defined as negative results on microscopy and culture at the end of follow-up and no requirement of second intervention treatment. Secondary efficacy criteria included clinical cure without second intervention treatment and mycological and clinical relapse rates. RESULTS: Median duration of follow-up was 54 months. At the end of the study, mycological cure without second intervention treatment was found in 34 (46%) of the 74 terbinafine-treated subjects and 10 (13%) of the 77 itraconazole-treated subjects (P<.001). Mycological and clinical relapse rates were significantly higher in itraconazole vs terbinafine-treated patients (53% vs 23% and 48% vs 21%, respectively). Of the 72 patients who received subsequent terbinafine treatment, 63 (88%) achieved mycological cure and 55 (76%) achieved clinical cure. CONCLUSION: In the treatment of onychomycosis, continuous terbinafine provided superior long-term mycological and clinical efficacy and lower rates of mycological and clinical relapse compared with intermittent itraconazole.     

Randomized double-blind comparison of short-term itraconazole and terbinafine therapy for toenail onychomycosis.

Previous studies evaluating short-term itraconazole and terbinafine therapy for onychomycosis have varied in protocol and size; this double-blind study enabled a large-scale, standardized, direct comparison. Patients with toenail onychomycosis were randomized to itraconazole 200 mg daily (n = 146) or terbinafine 250 mg daily (n = 146) for 12 weeks, with a 36-week follow-up. Mycological cure rates at the follow-up end-point were significantly equivalent (61% with itraconazole vs. 67% with terbinafine). A similar proportion of patients in each group experienced adverse events during treatment (itraconazole, 22%; terbinafine, 23%). More patients receiving terbinafine stopped treatment permanently because of treatment-related adverse events (8% vs. 1%).     

Therapeutic efficacy and safety of one-week intermittent therapy with itraconazole for onychomycosis in a Chinese patient population.

OBJECTIVE: To evaluate the efficacy and safety of a 1-week intermittent itraconazole dosing schedule for onychomycosis. METHODS: In this multicenter, open-label study, 646 patients received itraconazole 200 mg twice daily for 1 week/month, followed by 3 weeks without therapy. Patients with fingernail infections received 2 treatment cycles, patients with toenail or combined toenail and fingernail infections received 3 cycles. Efficacy was evaluated at week 9 (2-month regimen), week 13 (3-month regimen) and 3, 6 or 9 (toenails only) months after completion of therapy. RESULTS: Clinical and mycologic cure rates for fingernails were greater than 90% 6 months after completion of 2 treatment cycles. Clinical and mycologic cure rates for toenails were 84 and 98%, respectively, 9 months after completion of 3 cycles. Treatment was well tolerated; adverse events (mostly mild) occurred in 4.6% of patients. CONCLUSION: A 1-week intermittent itraconazole dosing regimen is a safe and effective treatment for onychomycosis.     

伊曲康唑间歇冲击治疗趾甲真菌病疗效和血清及甲中药物水平临床研究

目的:研究伊曲康唑间歇冲击疗法治疗趾甲真菌病(甲母质未受累)的疗效和在血清及甲中药物水平的变化。方法:41例趾甲真菌病患者应用伊曲康唑连续3个冲击治疗,第52周进行最终疗效评价;采用高压液相色谱仪(HPLC)法对其中15例趾甲真菌病患者进行了血清及甲中药物测定。结果:每次冲击后4周,血清中均未测得伊曲康唑;甲组织中伊曲康唑水平较高,在8或12周时达到高峰,停药后,伊曲康唑仍能以较高的水平在甲中储留36周;同一时间点,指甲和趾甲中的药物水平相似(P>0.05)。在第52周时,趾甲真菌病的临床治愈率为66.7％,临床有效率为79.5％,真菌学清除率为64.1％。结论:伊曲康唑口服吸收后从血液迅速向甲组织分布,停药后仍以较高水平储留在甲组织中并持续存在36周以上。     

Long-term outcomes in the treatment of toenail onychomycosis

Most clinical studies in subjects with toenail onychomycosis end with a final assessment at 48–52 weeks. This fails to take full account of the physiology of toenail growth, as toenails can take up to 12–18 months to grow out fully. Accurate assessment of long-term outcomes therefore requires follow-up of at least 2 years after completion of the study. We have evaluated long-term outcomes of treatment in the patients whom we contributed to two multicentre studies of oral therapy for toenail onychomycosis caused by dermatophyte infection. In the first, a dose-finding study for terbinafine (Lamisil^®), the high rates of mycological and clinical cure achieved by terbinafine at week 48 were maintained more than 2 years after completion of the study. In the second, a comparative study between terbinafine and itraconazole (Sporanox^®), the excellent mycological and clinical cure rates achieved by terbinafine at week 48 were again maintained more than 2 years after completion of the study. By contrast, the failure and relapse rates seen with itraconazole were much higher. Other studies undertaken in recent years have confirmed these positive findings with respect to terbinafine, and have demonstrated its superiority over itraconazole in maintaining mycological and clinical cure over long periods. These long-term benefits of terbinafine probably relate to its primarily fungicidal action against dermatophytes, compared to the fungistatic action of itraconazole and other triazole agents. Future clinical studies should therefore incorporate at least 2 years' follow-up.     

Pharmacoeconomic assessment of ciclopirox topical solution, 8%, oral terbinafine, and oral itraconazole for onychomycosis

Most pharmacoeconomic data available for antifungal agents are based on US or European cost parameters. Similar data have not been reported in a Canadian health care system. A pharmacoeconomic analysis was performed considering the costs of drug acquisition and medical management, which were representative of the Canadian health care system, for each of the therapies approved for use in toenail onychomycosis in Canada: continuous oral terbinafine, oral pulse itraconazole, and topical ciclopirox 8% nail lacquer. A survey of provincial fee schedules was conducted to determine the representative costs of parameters relating to onychomycosis treatment, such as consultation visit cost, return visit cost, mycology testing, liver function testing, and complete blood count analysis. Manufacturers' costs were used to calculate representative drug acquisition costs. Meta-analysis was used to determine the average mycologic cure rates of each therapy, and the medical literature was consulted to determine the relapse rates for each therapy. Ciclopirox nail lacquer had the lowest drug acquisition costs compared with continuous terbinafine and pulse itraconazole ($197.89 vs $311.39 and $323.40, respectively). Using the pharmacoeconomic model with three 1-year treatment phases, in which failures or relapses were re-treated with the primary drug, the expected cost per patient was $601.52 with ciclopirox nail lacquer, $746.72 with oral terbinafine, and $938.42 with itraconazole. The main analysis assumed that two bottles of ciclopirox nail lacquer were required per treatment. The cost for the ciclopirox lacquer exceeded continuous terbinafine but remained lower than pulse itraconazole when three bottles of ciclopirox nail lacquer were considered in the calculation of cost per mycological cure. A variety of relapse rates were tested, and ciclopirox using two or fewer bottles remained cost-effective compared with continuous terbinafine or pulse itraconazole, regardless of the relapse rate. Where three bottles are required, the cost-effectiveness of ciclopirox nail lacquer is less than that of continuous terbinafine but more cost-effective than that of pulse itraconazole.     

Itraconazole pulse therapy is effective in the treatment of Majocchi's granuloma: a clinical and pharmacokinetic evaluation and implications for possible effectiveness in tinea capitis

Majocchi's granuloma is a folliculitic and perifolliculitic dermatophyte infection of the dermis, a site that is not generally colonized by fungi in immunocompetent individuals. Topical agents are usually ineffective therapeutically because of the deep location of the infection. The objective of this study was to determine the effectiveness of oral itraconazole. We also examined the pharmacokinetics of the drug in scalp hair during pulse therapy. This information would then be useful in determining the efficacy of itraconazole administered by means of intermittent pulse dosing in the treatment of tinea capitis. Seven patients (age range 25–75 years) were treated up to three times with itraconazole pulse therapy, 200 mg twice daily for 1 week, with 2 weeks off between pulses. Samples of scalp hair and plasma were also obtained to determine the pharmacokinetics of the drug at these two sites. All seven patients responded to therapy, clinical and mycological cure being achieved after one pulse (one patient), two pulses (three patients), or three pulses (three patients, each with toenail onychomycosis); none relapsed over a 6–18-month follow-up period. In all six patients who received two or more pulses of itraconazole, almost complete cure was observed before the second pulse, with full resolution within 2 weeks of its completion. Itraconazole was also detected in the hair after 1 week, and at concentrations 2.6-fold and 3.4-fold higher, respectively, after the second and third pulses. After the discontinuation of therapy, itraconazole was then detectable in the hair for 9 months, at least in a female patient who did not have her hair cut. Two pulses of oral itraconazole therapy thus appear to be effective in the treatment of Majocchi's granuloma, and it is possible that one pulse may be sufficient in some patients. These data suggest that itraconazole pulse therapy should be effective in the treatment of tinea capitis.     

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.     

Itraconazole pulse therapy for the treatment of Candida onychomycosis

In this open label, multicentre trial, 44 patients with clinical and mycological evidence of Candida onychomycosis were treated with itraconazole pulse therapy. Onychomycosis of the toes alone and concomitant disease involving the fingers and toes was treated with three pulses, and onychomycosis of the fingers alone with two pulses. Final evaluation for patients with finger and toe onychomycosis was at 6-9 months and 9-12 months, respectively. There were 29 patients with toe onychomycosis (C. albicans, 27; C. glabrata, one; Candida species, one), 12 patients with finger onychomycosis (C. albicans, two; C. glabrata, one) and three patients had combined toe and finger onychomycosis (C. albicans, two; C. guillermondii, one). In the patients with toe onychomycosis mycological cure was observed in 29 of 32 patients (90.6%). There was complete cure [mycological cure (negative culture and KOH at endpoint evaluation) with clinical cure] or marked improvement (mycological cure with 75% or greater decrease in area of involvement of target nail compared with pretherapy) in 24 of 32 patients (75.0%). All 12 patients with finger onychomycosis alone due to Candida species achieved a mycological cure (100%). In this group of patients complete cure or marked improvement was observed in 11 of 12 patients (91.7%). Itraconazole pulse therapy was well tolerated and no serious adverse events were reported in the patients treated with this triazole. In conclusion, itraconazole pulse therapy is an effective and safe treatment for both finger and toe onychomycosis associated with Candida.     

A meta-analysis comparing long-term recurrences of toenail onychomycosis after successful treatment with terbinafine versus itraconazole

Abstract As the most frequently used systemic antifungal agents for onychomycosis, terbinafine and itraconazole have both proved to have the conditions of recurrence in various degrees during follow-up period after end of therapy; very little is known about their comparative recurrences after long-term follow-up. We conducted a meta-analysis of available trials to compare the long-term recurrences of toenail onychomycosis after successful treatment with terbinafine versus itraconazole. Meta-analysis was performed by the Review Manager version 5.0.25. Risk ratio and 95% confidence intervals were calculated by the fixed effect model. Five trials and total 251 eligible patients were included in this meta-analysis. The combined risk ratio of the meta-analysis comparing terbinafine with itraconazole for mycological recurrence rate was 0.44 (95% CI 0.29-0.66), which suggests that itraconazole therapy is more likely to produce mycological recurrence compared with terbinafine therapy.     

四种抗真菌药物治疗甲癣疗效比较的文献系统复习

目的比较特比萘芬与伊曲康唑、氟康唑、灰黄霉素治疗甲癣疗效的差异。方法检索Medline文献数据库,查找所有比较特比萘芬与伊曲康唑、氟康唑、灰黄霉素治疗甲癣的双盲随机对照试验的文献,找出这4种药物治疗甲癣的真菌学治愈率并对其进行汇总,得出合并后真菌学治愈率的比值比(OR)及其95%可信区间(CI)。结果①有6篇比较特比萘芬与伊曲康唑、1篇特比萘芬与氟康唑、2篇特比萘芬与灰黄霉素治疗甲癣的双盲随机对照试验文献被纳入。②特比萘芬250mg/d连续疗法优于伊曲康唑400mg/d冲击疗法[OR=5.01,95%CI(3.42～7.33)]和伊曲康唑200mg/d连续疗法[OR=2.58,95%CI(1.91～3.49)]。特比萘芬的疗效亦优于氟康唑(P<0.001)和灰黄霉素[OR=3.46,95%CI(1.89～6.31)]。结论特比萘芬治疗甲癣的疗效优于伊曲康唑、氟康唑和灰黄霉素。     

Long-term results in patients with onychomycosis treated with terbinafine or itraconazole

BACKGROUND: Previously, a double-blind, randomized, multicentre study (LION study) compared the efficacy of continuous terbinafine 250 mg daily for 3 or 4 months with itraconazole pulse therapy 400 mg daily for 3 or 4 months. At the end of the study at week 72 terbinafine proved to be more effective. OBJECTIVES: To perform a 4-year follow-up of the Finnish participants in this study. METHODS: Patients were re-examined clinically and mycologically. RESULTS: Complete clinical and mycological cure with terbinafine for 4 months was 78% compared with 35% with terbinafine for 3 months, 24% with itraconazole for 4 months and 28% with itraconazole for 3 months. CONCLUSIONS: These results suggest that the initial treatment for onychomycosis should be a 4-month continuous course of terbinafine.