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   

Prognostic factors for cure following treatment of onychomycosis

Objective To examine if host baseline factors and week 24 mycology results are associated with mycological and clinical cure in patients with onychomycosis treated with oral terbinafine. Design Open pilot study to determine prognostic factors in the treatment of onychomycosis. Setting Outpatient dermatology clinic. Patients A total of 199 patients from the Icelandic arm of a trial comparing continuous terbinafine with intermittent terbinafine in onychomycosis were recruited for additional observation. Main outcome measures Mycological, clinical and complete cure of the target toenail 72 weeks after treatment was initiated. Results Patients with matrix involvement or slow nail growth were less likely to reach mycological, clinical and complete cure. Lateral involvement affected complete and mycological cure rates negatively. Patients with a dermatophytoma were less likely to reach mycological cure. Patients with a history of prior infection, men and older patients were less likely to reach clinical cure. Positive culture at 24 weeks affected mycological and clinical cure at 72 weeks negatively. Limitations Only patients treated with terbinafine were considered. Conclusions Several host‐related factors at baseline and positive culture at 24 weeks had negative effects on cure of onychomycosis 72 weeks after treatment was initiated. This finding merits a large study on prognostic outcome factors in onychomycosis.     

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.     

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.     

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。     

Prediction of outcome in the treatment of onychomycosis

Patients with toenail onychomycosis remain a therapeutic challenge despite the introduction of new systemic therapies. Around 20% of patients remain uncured even with optimal oral therapy, but the reasons for treatment failure are unclear. Thus far there are no data to suggest that treatment failures can be identified on the basis of their presenting features or progress during treatment. In a series of patients, we have attempted to identify clinical parameters that determine the patient response to 12 weeks of oral terbinafine for confirmed dermatophyte onychomycosis. As part of a dose-defining randomized multicentre study, 35 patients were followed for 48 weeks. The unaffected nail length, growth rate, hyperkeratosis, onycholysis and presence of a dermatophytoma were assessed prospectively. To confirm our findings, at the end of the study period we analysed retrospectively photographs that had been taken regularly throughout the trial. The average degree of hyperkeratosis was less severe in the group achieving a disease-free nail, meaning clinical and mycological cure. For mycological cure alone, no predictive factors could be identified.     

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.     

A META-ANALYSIS COMPARING EFFICACY OF CONTINUOUS TERBINAFINE WITH INTERMITTENT ITRACONAZOLE FOR TOENAIL ONYCHOMYCOSIS

Background:

Toenail onychomycosis is a challenge for clinicians to treat. While both Itraconazole and terbinafine have proven to be effective against onychomycosis, very little is known about their comparative efficacy in achieving mycological and clinical cure.

Aim:

The purpose of this meta-analysis is to compare the efficacy of continuous terbinafine with intermittent itraconazole in the treatment of toenail onychomycosis.

Material and Methods:

all RCTs comparing continuous terbinafine with intermittent itraconazole were identified from PUBMED and BIDS electronic database.

Results:

analysis of total eight trials including 1181 patients state that treatment with continuous terbinafine is more likely to produce mycological and clinical cure compared to intermittent itraconazole with odds ratio 2.3(95% CI, 1.7 to 3.0 P<0.0001)

Conclusion:

though both itraconazole and terbinafine are well tolerated and highly effective drugs, continuous terbinafine is more effective than intermittent itraconazole at achieving mycological cure of toenail onychomycosis     

Fifth toenail clinical response to systemic antifungal therapy is not a marker of successful therapy for other toenails with onychomycosis

BACKGROUND: Onychodystrophy is a major manifestation of onychomycosis. However, nail trauma may also result in onychodystrophy. The fifth toenail, due to its location, suffers repeated friction/pressure trauma from shoes. OBJECTIVE: To test the hypothesis that treatment failure of fifth toenail onychomycosis is not a marker of treatment failure of other toenails with onychomycosis. METHODS: Fifty patients who had fifth toenail deformity (with or without onychomycosis) and onychomycosis of the other toenails were treated with oral terbinafine, 250 mg/day, for 4 months. RESULTS: Forty-three patients completed the study. Before the study, 26/43 (61%) had callus lateral to the fifth toe (suggesting mechanical pressure in that area). Twenty-one/43 (49%) of the fifth toenails had onychomycosis. At the end of the treatment period, only 4/21 (19%) of the fifth toenails (with initial onychomycosis), compared with 12/21 (57%) of the other toenails, were completely cured (CC). Out of the whole group (n=43), the clinical cure rate of the fifth toenail was 4/43 (9%) and for the other toenails, 20/43 (47%) (P<0.05). The mycological cure rates were 11/21 (52%) for the fifth toenail and 25/43 (58%) for the other toenails. Callus lateral to the fifth toe was associated with a poor clinical result (P<0.01). CONCLUSIONS: Clinical improvement of the fifth toenail after systemic antifungal therapy is less favourable and does not correspond with the clinical cure of the other toenails, mostly because of mechanical factors. Therefore, patients should be told to adjust their expectations as to the visual results of their antifungal treatment.     

Cumulative meta-analysis of systemic antifungal agents for the treatment of onychomycosis

BACKGROUND: Onychomycosis is a common nail disease that is often chronic, difficult to eradicate, and has a tendency to recur. The most common oral therapies for dermatophyte toenail onychomycosis include terbinafine, itraconazole and fluconazole. OBJECTIVES: A cumulative meta-analysis of the randomized controlled trials (RCTs) for antimycotic agents was performed to determine whether the pooled estimate of the cure rates has remained consistent over the years. Furthermore, for each agent we compared the overall meta-analytical average of both mycological and clinical response rates of RCTs vs. open studies. METHODS: We searched MEDLINE (1966 to November 2002) for relevant studies evaluating the efficacy of the oral antifungal agents terbinafine, itraconazole (pulse or continuous), fluconazole and griseofulvin for treating dermatophyte toenail onychomycosis. Studies included in this meta-analysis required a standard accepted dosage regimen, treatment duration and follow-up period. To determine the cumulative meta-analytical average, studies were sequentially pooled by adding one study at a time according to the date of publication (i.e. earliest to the most recent). RESULTS: There were 36 studies included in the analyses. For RCTs the change in efficacy of mycological cure rates from the first trial to the overall cumulative meta-average for each drug comparator is as follows (with 95% confidence interval): terbinafine, 78 +/- 6% (n = 2 studies, 79 patients) to 76 +/- 3% (n = 18 studies, 993 patients) (P = 0.68); itraconazole pulse, 75 +/- 10% (n = 1 study, 20 patients) to 63 +/- 7% (n = 6 studies, 318 patients) (P = 0.25); itraconazole continuous, 63 +/- 5% (n = 1 study, 84 patients) to 59 +/- 5% (n = 7 studies, 1131 patients) (P = 0.47); fluconazole, 53 +/- 6% (n = 1 study, 72 patients) to 48 +/- 5% (n = 3 studies, 131 patients) (P = 0.50); and griseofulvin, 55 +/- 8% (n = 2 studies, 109 patients) to 60 +/- 6% (n = 3 studies, 167 patients) (P = 0.41). The cumulative meta-analytical average of mycological cure rates when comparing RCTs vs. open studies was: terbinafine, 76 +/- 3% (n = 18 studies, 993 patients) vs. 83 +/- 12% (n = 2 studies, 391 patients) (P = 0.0028); itraconazole pulse, 63 +/- 7% (n = 6 studies, 318 patients) vs. 84 +/- 9% (n = 3 studies, 194 patients) (P = 0.0001); and fluconazole, 48 +/- 5% (n = 3 studies, 131 patients) vs. 79 +/- 3% (n = 3 studies, 208 patients) (P = 0.0001). CONCLUSIONS: The cumulative meta-analysis of cure rates for RCTs suggests that over time, as new RCTs have been conducted, the efficacy rates have remained consistent. The efficacy rates of open studies are substantially higher compared with RCTs and may therefore overestimate cure rates.     

Evaluation of 6 weeks treatment of terbinafine in tinea unguium in a double-blind trial comparing 6 and 12 weeks therapy

Terbinafine (Lamisil) has been registered throughout the world for the treatment of finger and toenail onychomycosis. The recommended duration of treatment of toenail onychomycosis based on phase III studies is 12 weeks. This study was designed to determine: (i) if patients in whom the proximal part of the toenails was not affected respond as well after 6 weeks treatment as after 12 weeks treatment; (ii) to identify factors which may allow selection of patients for shorter treatment duration; and (iii) confirm that 6 weeks therapy is sufficient in fingernail mycosis. One hundred and forty-eight patients received 250 mg terbinafine daily for either 6 or 12 weeks in a double- blinded manner, and were followed until 48 weeks after start of therapy. Cure of the nail infection was defined as negative mycological tests (mycological cure) and progressive growth of normal nail (clinical cure). Mycological cure was recorded in 43 of 72 (59.7%) in the 6-week group and 55 of 76 (72.4%) in the 12-week group. In those who completed the study per protocol in the 6-week group. 34 of 61 (55.7%) were cured mycologically corresponding to 46 of 56 (82.1%) in the 12-week group. The overall clinical and mycological cure rates for the two groups were 28 of 61 (45.9%) and 33 of 56 (58.9%), respectively. In the small number of patients with associated fingernail infection, all were improved and six of eight (75.0%) were cured after a duration of treatment of 6 weeks. A priori risk factors for failure of cure could not be identified in either group. However, shorter duration of disease prior to treatment and no involvement of the big toenail was associated with a trend toward better responses in both groups. It can be concluded from this study that, in toenail mycosis without visible matrix involvement, 6 weeks treatment of terbinafine is generally not sufficient, whereas fingernail infections respond well to this short therapy.     

Itraconazole versus terbinafine (LAMISIL®): which is better for the treatment of onychomycosis?

Objectives To compare the efficacy, safely and tolerability of oral terbinafine with itraconazole in patients with toenail onychomycosis treated for 4 months. Setting Departments of dermatology of six universities and one private clinic. Design Double-blind double-dummy, multicentric, multinational, parallel-group therapeutic trial, involving 179 patients with toenail onychomycosis. Patients were randomly treated with either 200 mg/day oral itraconazole or 250 mg/day terbinafine for 4 months. After the 4th month both treatment groups received oral placebo for another 8 months. The total duration of the study was therefore 12 months. After the 12th month a final evaluation of efficacy was performed in 167 patients (85 on itraconazole and 82 on terbinafine) and a final evaluation of tolerability was performed in 175 patient. Results The dermatophytes identified at the initial visit were Trichophyton rubrum (82.1%), Trichophyton mentagrophytes (14%) and others (3.9%), The mycological cure rates at the end of the 4th and 12th months were 54.9% and 95.3% in the terbinafine group and 51.8% and 84.31% in the itraconazole group (the difference between the groups was. statistically significant at the 12th month, P < 0.04). Clinical cure was achieved by 8.5% and 9.4% of the patients in the terbinafine and itraconazole groups at the 4th month (not significant. NS) and these rates increased to 57.8% and 62.9%. respectively, at the 12th month (difference between groups NS, P > 0,05). A complete mycological cure associated with clinical improvement over 50%. was observed at the 4th month in 50% of the patients treated with terbinafine and 49.4% of the patients treated with itraconazole which was not statistically significant (NS). At the 12th month the rates increased to 95.4% with terbinafine and 75.7% with itraconazole (statistically significant. P < 0.001). Seven patients of the terbinafine group and 9 patients of the itraconazole group presented drug-related side effects (NS). Six patients (6.3%) discontinued the study due to adverse events in the itraconazole group hut no patient discontinued in the terbinafine group. At entry into the study all subjects in both groups presented normal values in liver function tests which remained unchanged throughout the study in the patients of the terbinafine group. One patient of the itraconazole group presented small increases in SGOT and SGPT associated with abdominal pain and nausea.     

Prognostic factors of mycological cure following treatment of onychomycosis with oral antifungal agents

BACKGROUND: There is considerable literature on the efficacy and safety of various drugs used in treating onychomycosis; however, little information is available regarding prognostic factors which may be associated with non-response to conventional treatment. OBJECTIVES: To identify parameters influencing mycological cure at 72 weeks following treatment of toenail onychomycosis with oral antifungal agents. METHODS: Univariate and multivariate logistic regression analysis from a randomized double-blind controlled trial including 496 patients with toenail onychomycosis caused by dermatophytes. RESULTS: Baseline parameters including patient's age, gender, weight, number of toenails involved, percentage of nail involvement, duration of infection, history of previous treatment were not associated with mycological cure. In the multivariate prognostic factor analysis based on factors assessed at week 12, positive mycological culture at 12 weeks [odds ratio (OR): 0.583; 95% confidence interval (CI): 0.370-0.918] was negatively associated with mycological cure at 72 weeks. Similarly, in the multivariate prognostic factor analysis based on factors assessed at week 24, positive direct microscopy at 24 weeks (OR: 0.373; 95% CI: 0.211-0.659) and mycological culture at 24 weeks (OR: 0.293; 95% CI: 0.168-0.513) were negatively associated with mycological cure at 72 weeks. CONCLUSIONS: Mycological culture at 12 and 24 weeks and direct microscopic examination at 24 weeks can help in early identification of patients failing to respond to conventional oral antifungal treatment.     

A randomized trial of amorolfine 5% solution nail lacquer combined with oral terbinafine compared with terbinafine alone in the treatment of dermatophytic toenail onychomycoses affecting the matrix region

In view of recent advances in the development of antifungal agents, this study examined the possible synergy of two new antifungal agents, terbinafine and amorolfine. The study compared two different courses of terbinafine treatment combined with amorolfine 5% solution nail lacquer. Terbinafine was given orally for 6 (AT6 group) or 12 weeks (AT12 group) and amorolfine nail lacquer applied weekly for 15 months. A control group received terbinafine alone for 12 weeks. This was a randomized, prospective, open study of severe dermatophyte toenail onychomycosis with matrix region involvement. Nail samples were taken before the start of the study, at inclusion and at the visits at 6 weeks, 3, 9, 15 and 18 months. To assess the value of such combined therapy we chose an early parameter as the principal outcome variable, which was the result of mycological examination, including direct microscopy and culture, at 3 months (allowing a margin of 15 days). The secondary parameters of success were the mycological results at the later visits, clinical evaluation and a combined mycological-clinical response. Safety and tolerance were also assessed. Adverse events were recorded and liver function tests were performed monthly during the terbinafine treatment. Of the 147 patients included in the trial, 121 attended the 3-month visit, within a time limit of 15 days of 3 months after the beginning of treatment: 40 in the AT6 group, 40 in the AT12 group and 41 in the control group. In all, 32 of 121 patients (26. 4%) had negative mycological results on direct microscopy and culture: 14 of 40 (35.0%) in the AT6 group, 11 of 40 (27.5%) in the AT12 group and seven of 41 (17.1%) in the control group. The cure rate for the global (mycological and clinical cure) response measured at 18 months in 145 patients was 44.0% (22 patients) in the AT6 group, 72.3% (34 patients) in the AT12 group and 37.5% (18 patients) in the terbinafine group. These results suggest that the combination of amorolfine and terbinafine may be of value in the treatment of severe onychomycosis. At the same time a pilot pharmacoeconomic analysis was performed demonstrating a better cost per cure ratio for the patients receiving combination treatment.     

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.     

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.     

Onychomycosis: current treatment and future challenges

Onychomycosis is a fungal infection of the nails, more often of the toenails. It is a common condition, with an estimated overall prevalence of 3–10% in European populations. Dermatophytes, especially Trichophyton rubrum and Trichophyton mentagrophytes , are the usual pathogens. Some 50% of infected patients fail to seek medical advice. Medically confirmed onychomycosis should be treated. This recommendation is based on several disease-specific considerations: cosmetic and functional disability, lack of spontaneous remission, impairment of health and wellbeing in elderly patients and the need to reduce contamination in communal bathing places. Current treatments for onychomycosis include oral antifungal agents such as terbinafine (Lamisil^®) and itraconazole (Sporanox^®). They offer significantly improved rates of cure, shorter treatment regimens and a lower level of adverse events than was previously the case. Comparative studies have shown that terbinafine is more effective than griseofulvin, fluconazole or itraconazole in the treatment of this condition, providing a cure rate of 70–80% and an excellent tolerability profile. Terbinafine is also the most cost-effective agent. However, several problems remain that will provide future challenges in the treatment of onychomycosis, not least the consistent treatment failure rate of 20%. In many of these cases, surgery may need to precede drug therapy in order to maximise the prospects of clinical and mycological cure. In addition, duration of treatment also needs to be more closely adjusted to the individual case by prior identification of severity and extent of toenail infection, and combined oral and topical therapy also requires further investigation.     

Terbinafine in the treatment of onychomycosis: a review of its efficacy in high-risk populations and in patients with nondermatophyte infections

BACKGROUND: The prevalence of onychomycosis is higher in certain high-risk populations, such as the immunocompromised, diabetics and human immunodeficiency virus (HIV)-positive patients. These patients can also develop onychomycosis due to nondermatophyte fungi. Although the efficacy of terbinafine is well demonstrated in the treatment of conventional dermatophyte nail infection, there are few data on the efficacy of terbinafine in high-risk patient groups or in nondermatophyte fungi, which can be difficult to treat. OBJECTIVES: To review previously published data regarding the safety and efficacy of terbinafine in special patient populations, such as those with diabetes mellitus or HIV infection, those receiving immunosuppressive therapy, and patients with onychomycosis due to nondermatophyte fungi. METHODS: A Medline literature search up to October 2002 was performed in order to identify relevant studies. Pertinent abstracts presented at international meetings were also included. Cure rates (per-protocol and intention-to-treat) were extracted or calculated. All available safety data were also collated. RESULTS: Terbinafine was highly effective and well tolerated in patients with diabetes mellitus. Mycological cure rates of 62-78% were achieved in three studies, which is comparable with the efficacy in nondiabetic populations. Mycological cure rates of 64-91% were achieved in subsets of diabetic patients with Candida-positive nail cultures. The efficacy of terbinafine in patients receiving immunosuppressive therapy was also similar to that reported in immunocompetent patients. Levels of ciclosporin in the blood clearly decreased, with little clinical consequence; however, consideration should be given to the monitoring of ciclosporin levels in patients concomitantly receiving immunosuppressive therapy and terbinafine. Two small studies reported that terbinafine was also effective in treating onychomycosis in HIV-positive patients. Terbinafine was also effective and well tolerated in the treatment of nondermatophyte onychomycosis. CONCLUSIONS: This review suggests that terbinafine is a safe and effective treatment for onychomycosis in high-risk populations. However, the majority of these studies only included small numbers of patients and larger clinical trials are needed, especially in patients with HIV infection.     

Terbinafine in the treatment of dermatophyte toenail onychomycosis: a meta‐analysis of efficacy for continuous and intermittent regimens

Objective To compare mycological and complete cures of terbinafine continuous and intermittent regimens in the treatment of toenail onychomycosis. Methods The PubMed database was searched using the terms “terbinafine”, “onychomycosis”, “continuous” and “pulse(d)” or “intermittent”. The inclusion criteria were head‐to‐head comparison of terbinafine pulse and continuous regimens for dermatophyte toenail infections. Risk ratios were calculated for intention‐to‐treat and evaluable patient analyses, when possible. Pooled estimates for total and subgroup analyses were calculated using a random effect model, Mantel‐Haenszel method and their probabilities were calculated with z‐statistics. Results Nine studies from eight publications were included. Two continuous regimens and four intermittent regimens were investigated. A pooled risk ratio of 0.87 was obtained for intention‐to‐treat (95% CI: 0.79–0.96, P = 0.004, n = 6) and evaluable patient (95% CI: 0.80–0.96, P = 0.003, n = 8) analyses of mycological cure, favouring continuous terbinafine. For complete cure, pooled risk ratios of 0.97 (95% CI: 0.77–1.23, P = 0.82, n = 7) for intention‐to‐treat and 0.93 (95% CI: 0.76–1.13, P = 0.44, n = 9) for evaluable patient analyses showed equality of the two regimens. The pulse regimen that demonstrated consistently comparable results to the continuous terbinafine regimen was two pulses of terbinafine 250 mg/day for 4 weeks on/4 weeks off. Conclusions Meta‐analysis of published studies of toenail onychomycosis showed that a continuous terbinafine regimen is generally significantly superior to a pulsed terbinafine regimen for mycological cure. In contrast, some pulse terbinafine regimens were as effective as continuous terbinafine regimens for complete cure.     

Topical antifungal treatment prevents recurrence of toenail onychomycosis following cure

Recurrence rates are high for onychomycosis, with prophylactic topical antifungal use proposed to counter recurrence. Although this is a reasonable action for many clinicians, few studies have been conducted on the efficacy of topical prophylaxis. A retrospective chart review (2010–2015) was conducted in patients receiving oral terbinafine or itraconazole for toenail onychomycosis. Following complete cure, a topical antifungal (amorolfine, bifonazole, ciclopirox olamine, or terbinafine spray) was used weekly as prophylaxis. Recurrence was recorded along with patient characteristics including demographics and concomitant medical conditions. Data from 320 patients were collected. Recurrence was significantly lower in patients receiving topical antifungal prophylaxis than in no prophylactic treatment following oral terbinafine (p < .001), but not itraconazole (p = .185). Regardless of oral treatment, the use of topical antifungals as prophylaxis (p < .001) decreased, and the number of affected toenails (p = .048) and family history of fungal infections (p < .001) increased the likelihood that recurrence would occur. This study supports the use of topical antifungal medications as prophylactic treatment to help prevent recurrence of toenail onychomycosis and suggests that those with a family history of fungal infections should be closely monitored.