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   

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.     

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.     

Liver failure and transplantation after itraconazole treatment for toenail onychomycosis

Three weeks after completing a 4-pulse course of itraconazole for toenail onychomycosis, a 25-year-old woman patient developed severe liver crisis and required an emergency liver transplant. We report the case and discuss the use of itraconazole in onychomycosis and dermatomycoses.     

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.     

Efficacy and safety of terbinafine for nondermatophyte and mixed nondermatophyte and dermatophyte toenail onychomycosis

Ninety-seven healthy male and female subjects, 18–70 years of age, entered a randomized, double-blind, placebo-controlled, multicenter study conducted over a 24-week treatment period and a 72-week follow-up (study week 96) period without treatment.
Subjects   received: (1) terbinafine 250 mg for 12 weeks followed by placebo for 12 weeks; (2) terbinafine 250 mg for 24 weeks; or (3) placebo for 24 weeks.
Clinical and mycologic evaluations of a target toenail were performed before, during, and after the treatment period. Evaluations consisted of measurements of nail growth, unaffected nail length, and estimated percentage of nail involvement. Cultures and KOH microscopy were used for mycologic evaluations.
The primary efficacy variable was effective treatment, defined as negative mycology and either no nail involvement or at least 5 mm of new unaffected nail growth at 48 weeks. Complete cure, the secondary variable, was defined as negative mycology and zero nail involvement at 48 weeks. Overall efficacy was assessed after 12, 18, and 24 weeks of therapy and every 6 weeks up to week 48 by both investigator and subject using a five-point scale (excellent, very good, good, fair, and poor).
Adverse events were assessed after 4, 8, 12, 18, and 24 weeks of treatment and after a 6-week follow-up period with no treatment. Adverse events were graded by severity (mild, moderate, or severe) and relationship to the study drug (not related, remote or unlikely, possibly, probably, or definitely).     

Long-term follow up of patients with toenail onychomycosis after treatment with terbinafine

The long-term outcome of 111 patients treated with oral terbinafine for toenail onychomycosis with a novel treatment protocol was assessed a median of 138 weeks alter entry into the trial. All but three patients had either one or two 12 week courses of terbinafine 250 mg daily. 01 the 77 evaluable patients, 72.7% were still classified as responders (i.e. negative mycological culture and at least 3 mm olnew unaffected nail growth) on reassessment. The present study shows that a favourable long-term outcome can be achieved in patients who have been treated with at least one 12 week course of terbinafine.     

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。     

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     

Randomized controlled trial comparing photodynamic therapy based on methylene blue dye and fluconazole for toenail onychomycosis

Photodynamic therapy (PDT) is a medical modality that uses a combination of visible light and a photosensitive compound in the presence of oxygen. It is widely used to treat non‐melanoma skin cancer; other indications are being investigated, especially onychomycosis. Eighty patients with toenail onychomycosis were enrolled and completed this randomized, parallel, placebo‐controlled study. For 24 weeks, 40 patients (Group A) were treated with one placebo capsule per week and sessions of 2% methylene blue aqueous solution irradiated with light emission diode device (MBLED/PDT) with 18 J/cm²; and another 40 patients (Group B) were treated with 300 mg oral fluconazole per week and sessions of placebo PDT (haematoxylin‐diluted 1 : 10). The use of MBLED/PDT consisted of sessions with an interval of 15 days between each session for 6 months. Microbiological and clinical cure was assessed at 1 and 12 months posttreatment. Group A (MBLED/PDT) patients showed a significant response (p < 0.002) compared with Group B (fluconazole), especially in patients who required nail abrasion (p < 0.001). The MBLED/PDT is safe, effective, and well tolerated; it promotes a favorable outcome with good patient adherence and may be considered as a practical and feasible treatment option for toenail onychomycosis.