efinaconazole and Foot-Dermatoses

Successful management of onychomycosis is a challenge because cure rates with most antifungals are relatively low and recurrence rates are high. A drug-based approach by treating the nail alone may not suffice. There are several host-related factors (age, sex, body mass index [BMI], and patient's quality of life), disease-related factors (disease severity, duration, and the number of toenails affected), and comorbidities (tinea pedis and diabetes) that may affect treatment efficacy. Here, we review the post hoc analyses of the phase III trials of efinaconazole 10% solution that have investigated the impact of these factors on topical therapy for toenail onychomycosis. The significant clinical variables that may affect the efficacy of efinaconazole include sex, BMI, disease severity, disease duration, and tinea pedis. As older patients may have slower toenail growth and more severe, longstanding disease compared with younger patients, they may require longer treatment duration, beyond the 48-week standard regimen. Treatment compliance may need to be discussed for an improved health outcome. Therefore, these prognostic factors need to be carefully evaluated, which may aid in formulating individualized therapy to maximize treatment success.

Topics: Administration, Topical; Antifungal Agents; Foot Dermatoses; Humans; Nails; Onychomycosis; Quality of Life; Treatment Outcome; Triazoles

The purpose of this article is to review the safety, efficacy, and role of efinaconazole and tavaborole in the treatment of onychomycosis.. Onychomycosis is a fungal infection of the nail caused by dermatophytes, yeasts, and nondermatophyte fungi. Distal and lateral subungual onychomycosis (DLSO) accounts for the majority of the cases. These infections cause structural damage to the nail which makes treatment difficult. Both oral and topical agents exist for the treatment of onychomycosis. Oral medications have generally been more effective, yet adverse effects and drug interactions limit their use in some patients. Food and Drug Administration (FDA)-approved agents in the United States for oral therapies include terbinafine, itraconazole, and griseofulvin. The only topical product available up to recently was ciclopirox.. This article will review efinaconazole and tavaborole, 2 new topical antifungal agents released in 2014.

Topics: Administration, Topical; Animals; Antifungal Agents; Boron Compounds; Bridged Bicyclo Compounds, Heterocyclic; Clinical Trials as Topic; Foot Dermatoses; Humans; Microbial Sensitivity Tests; Onychomycosis; Triazoles

The patient was a 73-year-old healthy female farmer who had been treated with terbinafine for 25.5 months by a primary physician. She exhibited a discoloration and thickening of the right big toenail. She had no concomitant paronychia. Direct microscopy revealed chlamydoconidia and hyphae, and periodic acid-Schiff stained nail specimen showed septate hyphae. On the basis of these morphological features and gene analysis, the final diagnosis was ungual hyalohyphomycosis caused by Fusarium proliferatum. Topical application of 10% efinaconazole solution cured the disease in 10 months.

Topics: Administration, Topical; Aged; Antifungal Agents; Female; Foot Dermatoses; Fusariosis; Fusarium; Humans; Hyphae; Naphthalenes; Onychomycosis; Terbinafine; Triazoles

Efinaconazole 10% topical solution is a new antifungal therapy for the topical treatment of mild to moderate toenail onychomycosis. In vitro and in vivo data have shown significant antifungal activity against dermatophytes, Candida spp. and nondermatophyte molds, and its mechanism of action is through inhibition of fungal lanosterol 14α-demethylase. In two parallel, double-blind, randomized, controlled, Phase III trials, complete cure rates were 17.8 and 15.2%, respectively, and mycological cure rates were 55.2 and 53.4%, respectively, for efinaconazole 10% topical solution, which were superior to vehicle, with minimal adverse events. This drug profile reviews the most recent basic science and clinical data for efinaconazole in the treatment of toenail onychomycosis.

Topics: Administration, Topical; Animals; Antifungal Agents; Foot Dermatoses; Humans; Onychomycosis; Triazoles

Although there are limited data available on gender as an outcome variable in the treatment of onychomycosis, differences in disease prevalence and impact in males versus females have been observed. This article provides a gender subgroup analysis based on results from recent studies evaluating the efficacy, safety, and tolerability of efinaconazole topical solution 10% in the treatment of onychomycosis. Data were collected from two 52-week, prospective, multicenter, randomized, double-blind studies of patients 
(age range, 18-70 years) randomized to receive either efinaconazole topical solution 10% or vehicle for treatment of onychomycosis. Results from this analysis indicated that once-daily application of efinaconazole topical solution 10% may provide a useful topical option for treatment of mild to moderate toenail onychomycosis, especially in female patients.

Topics: Administration, Topical; Adolescent; Adult; Aged; Antifungal Agents; Double-Blind Method; Female; Foot Dermatoses; Humans; Male; Middle Aged; Onychomycosis; Prospective Studies; Randomized Controlled Trials as Topic; Sex Factors; Treatment Outcome; Triazoles; Young Adult

Onychomycosis is a fungal infection of the nail apparatus that can be challenging to treat due to the modest efficacy of existing antifungal therapies and a high rate of relapse and recurrence.. To investigate the efficacy and safety of efinaconazole 10% solution in pooled Phase III clinical trial participants with mild to moderate onychomycosis.. Phase III clinical trials data from NCT01008033 and NCT01007708 were pooled. Efficacy analysis for the primary and secondary outcome variables was conducted using the mITT population and analysed using Cochran-Mantel-Haenszel tests. Subgroup analysis was conducted for prognostic factors that may affect drug efficacy. Safety analysis was conducted on all recipients of a single drug dose.. Efinaconazole 10% nail solution was superior to vehicle for all primary and secondary outcome measures assessed. Complete cure was 18.5% vs 4.7% P< 0.001 [mITT] and mycological cure was 56.3% vs 16.6%, P< 0.001 [mITT]. Complete or almost complete cure and treatment success were achieved in 27.7% and 47.2% compared to 7.9% and 18.2% with vehicle, respectively (P< 0.001 [mITT]). In all subgroups, efinaconazole 10% solution had statistically higher cures rates compared to vehicle. Higher complete cure rates were observed in women and individuals with mild disease (≤33% involvement), but not in any other subgroup assessed. Treatment associated adverse events in the efinaconazole 10% solution group were similar to vehicle and limited to local site reactions (2%).. The findings from this pooled analysis suggest that efinaconazole 10% solution may become the preferred topical agent for mild to moderate onychomycosis.

Topics: Administration, Topical; Aged; Antifungal Agents; Clinical Trials, Phase III as Topic; Female; Foot Dermatoses; Humans; Male; Middle Aged; Onychomycosis; Pharmaceutical Solutions; Randomized Controlled Trials as Topic; Severity of Illness Index; Treatment Outcome; Triazoles

Toenail onychomycosis is a common disease with limited treatment options; treatment failure and relapse are frequently encountered. Many patients experience long-standing disease affecting multiple toenails, with substantial discomfort and pain. Although some patients might prefer a topical therapy, efficacy with ciclopirox nail lacquer has been disappointing.. Efinaconazole topical solution, 10% is the first topical triazole antifungal agent specifically developed for the treatment of onychomycosis. This paper reviews the preclinical and clinical data on efinaconazole topical solution, 10%.. Efinaconazole has a broad spectrum of antifungal activity in vitro and is more potent than ciclopirox against common onychomycosis pathogens. It has a more optimal keratin affinity than ciclopirox, and it exhibits significantly greater in vivo activity owing to its superior nail penetration. Mycologic cure rates at week 52 were 55.2% (study 1) and 53.4% (study 2) with efinaconazole topical solution, 10% compared with 16.8% and 16.9%, respectively, with vehicle (P<.001 for both). In addition, efinaconazole is well tolerated.. Efinaconazole topical solution, 10% may likely become a preferred topical agent for the management of mild-to-moderate onychomycosis.

Topics: Administration, Topical; Antifungal Agents; Foot Dermatoses; Humans; Onychomycosis; Triazoles

Topics: Administration, Cutaneous; Adolescent; Antifungal Agents; Child; Female; Foot Dermatoses; Humans; Male; Onychomycosis; Solutions; Treatment Outcome; Triazoles

Onychomycosis, a difficult-to-treat fungal nail infection, is more prevalent in the elderly. Efinaconazole 10% topical solution is a firstline therapy for onychomycosis, based on phase III trials of 12-month treatment; the slow growth of onychomycotic nails suggests a longer treatment period may increase efficacy. This is the first efficacy and safety data for a 24-month duration of efinaconazole 10% topical solution treatment for onychomycosis. Enrolled patients (N = 101) with mild to moderate distal lateral subungual onychomycosis applied efinaconazole to all affected toenails once daily for 18-24 months. Efficacy and safety were evaluated at months 6, 12, 18, and 24 (M6, M12, M18, and M24). The study is ongoing; to date, 47 patients have completed to M24. Mycological cure (MC) was 60.0% at M12, increasing to 74.2% at M24; effective cure (MC and ≤10% clinical involvement of the target toenail) was 17.8% at M12, rising to 19.4% at M24. Mild to moderate application site reactions were the only efinaconazole-related adverse events in 8 patients (7.9%). Increased age, increased severity of onychomycosis, and the presence of mixed infections (dermatophyte plus non-dermatophyte moulds) may drive a need for longer treatment durations. Although the data are interim, there is a trend of increasing efficacy beyond M12 use, without increased safety risk, even in patients >70 years of age.

Topics: Administration, Cutaneous; Aged; Antifungal Agents; Drug Administration Schedule; Female; Foot Dermatoses; Humans; Male; Middle Aged; Onychomycosis; Treatment Outcome; Triazoles

Onychomycosis is especially common among diabetic patients. The purpose of this study was to investigate the efficacy of 10% efinaconazole solution among diabetic subjects, without restriction by nail plate involvement or glycemic control. Forty subjects were enrolled, with 36 reaching their final 50-week follow-up visit. Mycological cure was attained by 21 subjects (58.33%); 8 subjects (20%) attained either clinical cure (0% clinical involvement) or treatment success (≤10% clinical involvement). Glycemic control did not affect clinical outcome. The medication was well tolerated, with 4 local adverse events and no significant adverse events. The medication may represent a useful option for diabetic patients.

Topics: Administration, Topical; Adult; Aged; Antifungal Agents; Blood Glucose; Diabetes Complications; Female; Foot Dermatoses; Humans; Male; Middle Aged; Onychomycosis; Treatment Outcome; Triazoles

Onychomycosis is a difficult to treat condition whose prevalence is increasing. Until recently, there was no FDA approved antifungal agent for the treatment of onychomycosis in children. Although systemic antifungal agents are effective, their use is restricted by the potential adverse events and drug-drug interactions. There is evidence regarding the safety and efficacy of topical antifungal agents for pediatric onychomycosis. We have summarized the results of a recently published study using efinaconazole topical solution 10% to treat onychomycosis in children and discuss management of pediatric onychomycosis. In a multicenter, open-label phase 4 study, efinaconazole 10% solution was applied topically once daily in children aged 6 to 16 years with mild to severe, culture positive, distal and lateral subungual onychomycosis. Treatment was for 48 weeks with a follow-up at week 52. Pharmacokinetics was performed in a subset of patients. There were 62 patients enrolled in the study. At week 52, the efficacy was mycological cure rate 65% and complete cure rate 40%. All treatment-emergent adverse events (TEAE) were mild to moderate in severity with none resulting in study discontinuation. The only treatment-related TEAE was ingrown toenail. Efinaconazole was detected at low levels in plasma. Efinaconazole topical solution 10% is effective and safe in treating onychomycosis in children age 6 to 16 years and was recently FDA-approved for this indication. The on-label use of other topical agents, tavaborole solution 5% and ciclopirox nail lacquer solution 8% is reviewed. We also briefly discuss the use of oral agents, terbinafine, itraconazole, and fluconazole in pediatric onychomycosis.

Topics: Administration, Topical; Adolescent; Antifungal Agents; Child; Foot Dermatoses; Humans; Multicenter Studies as Topic; Onychomycosis; Triazoles

Pediatric onychomycosis management is challenging as there are limited treatment options. The objective of this study was to evaluate efinaconazole 10% topical solution in children with onychomycosis.. This phase 4, multicenter, open-label study (NCT02812771) evaluated safety, pharmacokinetics (PK), and efficacy of efinaconazole 10% topical solution in pediatric participants (6-16 years). Efinaconazole was administered once daily for 48 weeks, with a 4-week posttreatment follow up. Participants had culture-positive, mild-to-severe distal lateral subungual onychomycosis affecting at least 20% of at least 1 great toenail. The PK subset included participants 12-16 years with moderate-to-severe onychomycosis affecting at least 50% of each great toenail and onychomycosis in at least 4 additional toenails.. Of 62 enrolled participants, 60 were included in the safety population and 17 in the PK population. Efinaconazole 10% topical solution was well tolerated. The concentration-time profiles for efinaconazole and its major metabolite were relatively stable, with only minor fluctuations during the 24-hour dosing interval. Systemic exposure to efinaconazole was low. By week 52, 65.0% of participants achieved mycologic cure, with a 36.7% mycologic cure rate observed as early as week 12. A total of 40.0% of participants achieved complete cure, 50.0% achieved clinical efficacy, and 88.3% achieved fungal cure by week 52.. Efinaconazole was safe and efficacious in pediatric participants with mild-to-severe onychomycosis, with improved mycologic cure and complete cure rates compared with adults from two 52-week studies. J Drugs Dermatol. 2020;19(9):867-872. doi:10.36849/JDD.2020.5401.

Topics: Administration, Topical; Adolescent; Antifungal Agents; Area Under Curve; Child; Female; Follow-Up Studies; Foot Dermatoses; Fungi; Humans; Male; Onychomycosis; Severity of Illness Index; Solutions; Treatment Outcome; Triazoles

Onychomycosis is a common but difficult to treat nail disorder. Treatment strategies thus far have included oral and topical antifungals, surgical treatment and recently lasers have emerged as a therapeutic modality.. The objective of this study was to assess whether efinaconazole together with laser would result in greater clinical and mycologic cure and lower rate of relapse compared to efinaconazole alone.. Thirty subjects were randomized to either self-apply efinaconazole 10% once daily for 48 weeks, or follow the same treatment plan but also receive six treatments with a 1064 nm Nd: YAG laser every 4 weeks. The primary endpoint was to assess the proportion of subjects who achieved complete cure at week 52.. The combination therapy group showed significantly quicker mycological cure at the 48- and 52-week follow-up.. Both efinaconazole and combination with laser were efficacious treatment, but the combination therapy leads to quicker resolution with fewer rate of relapse.

Topics: Administration, Topical; Adult; Aged; Antifungal Agents; Combined Modality Therapy; Female; Follow-Up Studies; Foot Dermatoses; Humans; Laser Therapy; Lasers, Solid-State; Male; Middle Aged; Onychomycosis; Patient Satisfaction; Photography; Statistics, Nonparametric; Treatment Outcome; Triazoles

We evaluated the efficacy of efinaconazole 10% topical solution in long-term use, for up to 72 weeks, for onychomycosis, including severe cases. Among 605 participants, 219 patients diagnosed as having onychomycosis were evaluated for the efficacy of efinaconazole. The treatment success rate (<10% clinical involvement of the target toenail) at the final assessment time point was 56.6%, the complete cure rate was 31.1% and the mycological cure rate was 61.6%, all of which increased over time, demonstrating that continuous application contributed to the improvement of cure rate. Even in severe cases, reduction of the affected nail area was observed, showing the potential efficacy of the treatment. Responses to a quality of life questionnaire among patients with onychomycosis, OnyCOE-t, suggested that efinaconazole treatment improved the patients' quality of life. The incidence of adverse drug reaction in the patients eligible for the assessment was 6.3%, and this developed only in the administration site in all cases. No systemic adverse event was observed. In addition, no increase in the incidence of adverse drug reaction due to long-term use was found. Efinaconazole therapy was proved to exhibit excellent balance between efficacy and safety, and thus may serve as a useful treatment option for onychomycosis.

Topics: Administration, Topical; Aged; Antifungal Agents; Drug-Related Side Effects and Adverse Reactions; Female; Foot Dermatoses; Humans; Incidence; Long-Term Care; Male; Middle Aged; Onychomycosis; Quality of Life; Severity of Illness Index; Time Factors; Treatment Outcome; Triazoles

Onychomycosis is a common disease that remains a difficult disorder to treat despite the introduction of new topical agents; and not all patients are cured. Clinical experience leads us to suggest a number of host-related factors can affect the chance of cure, but studies supporting these observations are currently lacking. Although many studies, particularly on topical agents, rely on severity classification when selecting patients for inclusion, a pilot study was unable to demonstrate any prognostic value of the extension of nail involvement. In addition, no universal severity classification exists, and most studies do not report prognostic factors.. To investigate the efficacy of efinaconazole topical solution, 10% in patients with mild-to-moderate onychomycosis and determine the impact of baseline severity on treatment outcome.. Post hoc pooled analysis of two identical, multicenter, randomized, double-blind, vehicle-controlled studies in 1655 patients aged 18-70 years with a clinical and mycological diagnosis of mild-to-moderate dermatophyte toenail onychomycosis (20-50% clinical involvement). Patients were randomized (3:1) to efinaconazole 10% solution or vehicle, once-daily for 48 weeks, with 4-week post treatment follow-up. Efficacy criteria included clear nail (0% target nail plate involvement), almost clear nail (≤5% target nail plate involvement), and clinical treatment success (≤10% target nail plate involvement) at week 52. For the post hoc analysis, patients were classified as mild (20%-29% nail involvement), moderate (30%-39%), and moderately severe (40%-50%) at baseline.. Overall, 25%, 23%, and 52% of patients had mild, moderate, or moderately severe disease at baseline. Baseline nail involvement did not appear to predict treatment outcomes. The proportion of patients with mild disease who had a clear nail progressively reduced by week 36 (58%) and week 48 (41%), and even further by week 52 (37%). Of the 237 patients treated with efinaconazole who were 'clear' at week 52, 37%, 24%, and 39% had mild, moderate or moderately severe disease respectively at baseline. The majority of patients (N=634) saw at least a 50% improvement in their target toenail by week 52. Almost half of these patients (N=312, 49.2%) were moderately severe at baseline.. This post hoc analysis supports previous data showing good efficacy of efinaconazole in mild onychomycosis. The relative contribution to overall efficacy results at week 52 of patients with moderate or moderately severe disease was unexpected for a topical therapy, and warrants further study, especially as they represent the majority of patients enrolled in the two studies. It is possible that comparable efficacy can be achieved in these more severe patients with longer treatment courses, or follow-up. J Drugs Dermatol. 2018;17(2):175-178.

Topics: Administration, Topical; Adolescent; Adult; Aged; Antifungal Agents; Double-Blind Method; Female; Foot Dermatoses; Humans; Male; Middle Aged; Onychomycosis; Prognosis; Severity of Illness Index; Treatment Outcome; Triazoles; Young Adult

Topics: Administration, Topical; Antifungal Agents; Boron Compounds; Bridged Bicyclo Compounds, Heterocyclic; Cost-Benefit Analysis; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Costs; Female; Follow-Up Studies; Foot Dermatoses; Humans; Male; Onychomycosis; Risk Assessment; Treatment Outcome; Triazoles

Although a completely normal nail would be the ideal outcome when treating onychomycosis, this is not always achievable and long treatment courses or patient expectations can impact patient adherence.. We analyzed cure rates from a number of subpopulations derived from the two pivotal phase III studies with efinaconazole topical solution (10%) to provide some insights into clinically meaningful treatment outcomes and support for effective long-term management programs.. Efinaconazole affords greater efficacy in milder disease, female patients, and those patients whose disease is relatively recent and confined to the great toenail, following 48 weeks' treatment. With longer treatment courses, similar results may be achieved in other subpopulations. Clinically meaningful results (a 40% improvement in the involvement of the diseased nail) were achieved with efinaconazole within six months in half the patients treated, and in over 90% of patients by study end. A greater proportion of female patients achieved clinically meaningful results at six months, although treatment success did not seem to be influenced by baseline disease severity.. The majority of patients treated with efinaconazole could expect to see clinically meaningful results within six months.

J Drugs Dermatol. 2016;15(10):1260-1266.

Topics: Administration, Topical; Adolescent; Adult; Aged; Antifungal Agents; Double-Blind Method; Female; Follow-Up Studies; Foot Dermatoses; Humans; Male; Middle Aged; Onychomycosis; Treatment Outcome; Triazoles; Young Adult

To evaluate efficacy of efinaconazole topical solution, 10% in onychomycosis patients with early and long-standing disease.. An analysis of 1655 patients, aged 18-70 years, randomized to receive efinaconazole topical solution, 10% or vehicle from two identical multicenter, double-blind, vehicle-controlled 48-week studies evaluating safety and efficacy. The primary end point was complete cure rate (0% clinical involvement of target toenail, and both negative potassium hydroxide examination and fungal culture) at Week 52. Three groups were compared: those with early disease (<1year), patients with a baseline disease of 1-5 years, and those with long-standing onychomycosis (>5years).. The majority of patients had long-standing disease; were older, male and white. While nail involvement of the target toenail did not differ noticeably amongst the three groups, the number of nails involved did increase progressively with disease duration. Differences were seen in terms of infecting pathogens in early disease that might have important treatment implications. Efinaconazole was more effective in treating early disease, however more than 40% of patients with long-standing disease were considered treatment successes.. A period of 52 weeks may be too brief to evaluate a clinical cure in onychomycosis.. Treatment of onychomycosis early to avoid disease progression to other toenails is important. Once daily efinaconazole topical solution, 10% is particularly effective in these patients.

Topics: Administration, Topical; Adult; Antifungal Agents; Disease Progression; Double-Blind Method; Female; Foot Dermatoses; Humans; Male; Middle Aged; Onychomycosis; Prospective Studies; Time Factors; Treatment Outcome; Triazoles

Transungual nail penetrance has traditionally been considered to be the only route of delivery for topical antifungals in onychomycosis. Subungual penetrance may be an alternate route of delivery.. To evaluate the ability of efinaconazole vehicle solution to reach the site of toenail onychomycosis through application to the hyponychium or hyponychium and dorsal nail surface, and assess the impact of the air gap between the nail plate and nail bed.. Twenty-three participants with moderate to severe, mycologically-confirmed onychomycosis were enrolled (mean age, 48.5 years). Two separate applications of vehicle solution containing fluorescein for visualization were applied at the hyponychium or hyponychium and dorsal nail surface. Affected nails were later clipped to allow examination of the nail bed and further examination of the ventral surface of the nail. Spread of formulation was assessed under visible and UV light conditions by photographing target toenails after vehicle application and after nail clipping.. There was a positive correlation between the size of the air gap and degree of affected nail involvement (R2=0.064). Assessments under both visible and UV light indicated that the vehicle had spread to the site of infection, with deposition of fluorescein wherever vehicle had reached, irrespective of application methodology or size of air gap. Nail clippings also indicated absorption into the ventral surface of the nail plate.. The relative contributions of subungual versus transungual application of drug to the nail plate to the efficacy of efinaconazole topical solution, 10% in treating onychomycosis were not assessed.. This study suggests that the low surface tension vehicle developed for efinaconazole topical solution, 10% can reach the site of infection by application to the hyponychium, dorsal or ventral nail surface and nail folds. This multidirectional approach to drug delivery at the site of fungal infection may contribute to the magnitude of efficacy seen in clinical trials.

Topics: Administration, Cutaneous; Adult; Aged; Air; Antifungal Agents; Female; Fluorescein; Foot Dermatoses; Humans; Male; Middle Aged; Nails; Onychomycosis; Pharmaceutical Vehicles; Severity of Illness Index; Triazoles

To identify those patients who are more likely to achieve treatment success with efinaconazole topical solution 10% based on clinical improvement and mycological status during treatment.. A subgroup analysis of patients, aged 18 to 70 years, randomized to receive efinaconazole topical solution 10% or vehicle from 2 identical multicenter, double-blind, vehicle-controlled 48-week studies evaluating safety and efficacy. The primary end point, complete cure rate (0% clinical involvement of target toenail, and both negative potassium hydroxide examination and fungal culture) at week 52 was evaluated based on mycologic cure at week 24, and the degree of clinical improvement in nail involvement at week 12.. Over a quarter (25.1%) of patients treated with efinaconazole topical solution 10% who could demonstrate at least 10% improvement in affected nail involvement by week 12 progressed to complete cures at week 52. Similarly, 21.7% of patients who demonstrated mycologic cure at week 24 achieved complete cures at week 52.. Early clinical improvement and mycologic clearance may help to predict treatment success with efinaconazole topical solution 10%.

Topics: Administration, Cutaneous; Adolescent; Adult; Aged; Antifungal Agents; Double-Blind Method; Female; Foot Dermatoses; Humans; Male; Middle Aged; Onychomycosis; Prognosis; Severity of Illness Index; Treatment Outcome; Triazoles; Young Adult

To evaluate efficacy, safety, and tolerability efinaconazole topical solution, 10% in diabetic patients with onychomycosis.. A post-hoc analysis of 112 patients, aged 29-70 years, randomized to receive efinaconazole topical solution, 10% or vehicle from two identical multicenter, double-blind, vehicle-controlled 48-week studies evaluating safety and efficacy. The primary end point was complete cure rate (0% clinical involvement of target toenail, and both negative potassium hydroxide examination and fungal culture) at week 52.. Mycologic cure rates (OC) were significantly greater with efinaconazole (56.5% and 56.3% in diabetic and non-diabetic patients respectively) compared to vehicle (P=0.016 and P<0.001, respectively). The primary end point, complete cure, was also greater for efinaconazole (13.0% and 18.8%, respectively vs 3.7% and 4.7%). Treatment success (percent affected target toenail ≤10%) for efinaconazole was 40.8% and 47.7%, respectively vs 18.5% and 18.2% with vehicle. There was no statistically significant difference between the diabetic and non-diabetic populations for any efficacy endpoint. Adverse events associated with efinaconazole were local site reactions and clinically similar to vehicle.. Once daily efinaconazole topical solution, 10% may provide a useful topical option in the treatment of diabetic patients with onychomycosis.

Topics: Administration, Topical; Adult; Aged; Antifungal Agents; Diabetes Mellitus; Double-Blind Method; Female; Foot Dermatoses; Humans; Male; Middle Aged; Onychomycosis; Treatment Outcome; Triazoles

Effective transungual delivery of topical antifungal agents in onychomycosis has been hampered by poor nail permeation. To be effective they must have antifungal efficacy, and effectively permeate through the dense keratinized nail plate to the site of infection in the nail bed and nail matrix. The therapeutic efficacy of efinaconazole topical solution, 10% has been established in two phase 3 clinical trials in distal lateral subungual onychomycosis.. To investigate the transungual delivery of efinaconazole in onychomycosis patients and its fungicidal activity in the toenail.. Concentrations of efinaconazole were determined as part of a multi-center, open label study in forty onychomycosis patients following repeated application of efinaconazole topical solution, 5% and 10% to the toenails over 28 days, with a 2-week follow-up. Fungicidal activity against T. rubrum in the ventral layer of human nails was determined using an in vitro human nail infection model (ChubTur®).. Efinaconazole concentrations in the nail were four orders of magnitude higher than MIC values of efinaconazole against dermatophytes. Further, nail drug concentrations were not influenced by the presence of disease or nail thickness, and maintained at high antifungal levels post-treatment. Efinaconazole was effective in reducing fungal viability, suggesting that sufficient amounts of efinaconazole were being delivered into the ventral layer of the nail plate.
. Effective transungual delivery of efinaconazole was demonstrated. The high efinaconazole concentrations in patient toenails and fungicidal activity in vitro potentially contribute to the clinical efficacy reported in phase 3 studies.

Topics: Administration, Topical; Adult; Aged; Antifungal Agents; Drug Delivery Systems; Female; Follow-Up Studies; Foot Dermatoses; Humans; In Vitro Techniques; Male; Microbial Sensitivity Tests; Middle Aged; Nails; Onychomycosis; Permeability; Triazoles; Trichophyton

To evaluate the ability of efinaconazole vehicle to reach the site of toenail onychomycosis by spreading through the subungual space between the nail plate and nail bed. Lacquer-based vehicles are primarily limited to application on the nail plate and dependent on nail plate permeation.. 11 patients (mean age 48.5 years) were entered with clinically determined onychomycosis. Presence of fungal infection was confirmed by KOH testing in eight patients. Two separate applications of vehicle (with fluorescein incorporated for better visualization) were applied at the hyponychium, avoiding application to the exterior nail plate surface. Affected nails were later clipped to allow examination of the nail bed and further examination of the underside of the nail. Spread of formulation was assessed under visible and UV light conditions by photographing target toenails after vehicle application, and after nail clipping.. Assessments under both visible and UV light indicated that the vehicle had spread into the subungual space, with deposition of flourescein wherever vehicle had reached, including in the nail bed. Nail clippings also indicated deposition to the underside of the nail plate.. The relative contributions of spreading into the subungual space, or permeation through the nail plate to the efficacy of efinaconazole topical solution, 10% in treating onychomycosis were not assessed.. This study suggests that the vehicle developed for efinaconazole topical solution, 10%, when applied at the hyponychium, spreads into the subungual space between the nail plate and nail bed, reaching the site of infection.

Topics: Administration, Topical; Antifungal Agents; Female; Foot Dermatoses; Humans; Male; Middle Aged; Nails; Onychomycosis; Permeability; Treatment Outcome; Triazoles

Onychomycosis is a common nail infection, often resulting in nail plate damage and deformity. Topical lacquer treatments have negligible efficacy. Oral treatments, although more efficacious, are limited by drug interactions and potential hepatotoxicity.. We investigated the safety and efficacy of efinaconazole 10% solution (efinaconazole), the first triazole antifungal developed for distal lateral subungual onychomycosis.. Two identical, multicenter, randomized, double-blind, vehicle-controlled studies were conducted in patients with toenail distal lateral subungual onychomycosis (20%-50% clinical involvement [study 1: N = 870, study 2: N = 785]). Patients were randomized (3:1) to efinaconazole or vehicle, once daily for 48 weeks, with 4-week posttreatment follow-up. Debridement was not performed. The primary end point was complete cure rate (0% clinical involvement of target toenail, and both negative potassium hydroxide examination and fungal culture) at week 52.. Mycologic cure rates were significantly greater with efinaconazole (study 1: 55.2%, study 2: 53.4%) compared with vehicle (P < .001). The primary end point, complete cure, was also significantly greater for efinaconazole (study 1: 17.8% vs 3.3%, study 2: 15.2% vs 5.5%, P < .001). Treatment success (percent affected target toenail [0%-≤10%]) for efinaconazole ranged from 21.3% to 44.8% in study 1 and from 17.9% to 40.2% in study 2, compared with 5.6% to 16.8% and 7.0% to 15.4%, respectively, with vehicle. Adverse events associated with efinaconazole were local site reactions (2%) and clinically similar to vehicle.. A period of 52 weeks may be too brief to evaluate a clinical cure in onychomycosis.. Once daily topical efinaconazole appears to be a viable alternative to oral treatment options for onychomycosis.

Topics: Adolescent; Adult; Aged; Antifungal Agents; Double-Blind Method; Female; Foot Dermatoses; Humans; Male; Middle Aged; Onychomycosis; Triazoles; Young Adult

Topics: Administration, Topical; Antifungal Agents; Foot Dermatoses; Humans; Onychomycosis; Talaromyces; Triazoles

Toenail onychomycosis is a common condition that is equally challenging for podiatrists and patients. This case study documents a 26-year-old woman with bilateral total dystrophic onychomycosis of at least 5 years' duration. She had previously failed to respond to treatment with ciclopirox nail lacquer 8% and, despite hiding her condition with nail polish, was suffering from embarrassment, distress, and low self-esteem. At initial consultation, 100% of both great toenails was affected. After discussion of all treatment options, the patient opted for topical efinaconazole 10% solution, once daily for 48 weeks. Significant improvement was noted at the first (4-week) assessment period. This improvement was maintained through each subsequent virtual consultation, and complete cure was seen at a 30-week follow-up visit. To the author's knowledge, this is the first published report on the use of efinaconazole in total dystrophic onychomycosis. It suggests that the product may be effective in patients with even the most severe and treatment-recalcitrant disease, who are unwilling or unable to tolerate systemic antifungal therapy.

Topics: Administration, Topical; Adult; Antifungal Agents; Coronavirus; Female; Foot Dermatoses; Humans; Onychomycosis; Treatment Outcome; Triazoles

We report a case of contact dermatitis caused by both efinaconazole, a topical triazole antifungal drug, and luliconazole, a topical imidazole antifungal drug. Positive patch test reactions were observed with efinaconazole and luliconazole. A patch test with lanoconazole also elicited a positive reaction. We hypothesized that structural similarity between luliconazole and lanoconazole led to cross-reaction, and that the dithiolane ring common to both drugs or the structure of the vinyl imidazole with a dithiolane ring could be the antigenic determinant. Since efinaconazole and luliconazole have no common structures, patients could be sensitized to both drugs separately. The antigenic determinant of efinaconazole is unknown. However, the chemical formula of ravuconazole, an oral triazole antifungal drug, is similar to that of efinaconazole. Clinicians should carefully consider potential cross-reactivity between these drugs.

Topics: Administration, Topical; Aged; Antifungal Agents; Dermatitis, Contact; Epitopes; Foot Dermatoses; Humans; Imidazoles; Male; Patch Tests; Triazoles

Onychomycosis is a chronic fungal infection of the nails and is commonly observed in adults, especially the elderly, those who are diabetic, have poor peripheral circulation, and are immunocompromised; however, onychomycosis in children is being reported more frequently, especially in older children. There could also be a genetic predisposition to developing onychomycosis. Given that onychomycosis is uncommon in children, it is important to confirm the diagnosis mycologically. Treatment of onychomycosis includes oral or topical antifungal agents. In North America, the available oral antifungal agents are terbinafine, itraconazole, and fluconazole; however, none of these agents are approved by Food and Drug Administration (FDA) for children with onychomycosis. Terbinafine is, however, approved for tinea capitis in children aged 4 years and older. In general, these oral agents have been found to be safe and effective for pediatric onychomycosis. The available topical agents are efinaconazole solution 10%, tavaborole solution 5%, and ciclopirox nail lacquer topical solution 8%. The former two are approved by the FDA for the treatment of pediatric onychomycosis in children aged 6 years and older, while the third one is approved in children over the age of 12 years who have onychomycosis. In a phase-IV, multicenter, open label study, efinaconazole solution 10% was administered to children aged 6-16 years with culture positive, mild-to-severe distal and lateral subungual onychomycosis affecting ≥20% of at least one great toenail. Treatment was for 48 weeks, with follow-up at week 52. Efinaconazole solution 10% was found to be safe and well tolerated in this pediatric population. By week 52, the mycological cure was 65%, and the complete cure was 40%. The topical agents could be an important addition to the armamentarium of therapies available to treat pediatric onychomycosis safely and effectively.

Topics: Administration, Topical; Adolescent; Adult; Aged; Antifungal Agents; Child; Foot Dermatoses; Humans; Onychomycosis; Terbinafine; Triazoles

Topics: Administration, Topical; Antifungal Agents; Drug Costs; Foot Dermatoses; Healthy Volunteers; Humans; Nails; Onychomycosis; Solutions; Triazoles; United States

We treated tinea unguium (onychomycosis caused by dermatophytes) patients with efinaconazole 10% solution. All patients with tinea unguium who tested positive for fungi in fingernails and toenails, regardless of age or severity, were eligible for the treatment. The number of patients was 106, consisting of 43 men and 63 women with a mean age of 66.7 years. The patients were treated with efinaconazole for a mean treatment duration of 38.1 weeks. Therapeutic efficacy was rated on a 5-point scale as follows: "cured", "markedly improved", "improved", "slightly improved" or "no change". A single nail was selected in each patient as the target nail. Selected nails were the big toenails with less than 50% involvement in 25 patients, the big toenails with 50% or more involvement in 52 patients, the fingernails in 10 patients and the second to fifth toenails in 19 patients with a mean treatment duration of 43.9, 38.1, 38.7 and 33.7 weeks, respectively. All groups showed an improvement in the percentage involvement from 30.6% to 9.8%, 77.6% to 35.7%, 82.7% to 17.6% and 80.3% to 15.5%, respectively (P < 0.01). The improvement rate (i.e. percentage of those rated as improved and better) was 76.0%, 65.4%, 80.0% and 89.5%, respectively. Efinaconazole 10% topical solution is beneficial for patients, regardless of age, severity or clinical type.

Topics: Administration, Topical; Aged; Aged, 80 and over; Antifungal Agents; Female; Foot Dermatoses; Hand Dermatoses; Humans; Male; Middle Aged; Onychomycosis; Photography; Treatment Outcome; Triazoles

We describe a case of a 23-year-old female patient with no apparent underlying diseases. She showed a discoloration of the proximal portion of the left big toenail with paronychia. Direct microscopy revealed septate hyphae with conidiophores, and a periodic acid-Schiff-stained nail specimen revealed septate hyphae branching at angles of approximately 45°. On the basis of phylogenetic analysis, we finally arrived at the diagnosis of ungual aspergillosis caused by Aspergillus subramanianii. After p.o. administration of terbinafine and topical application of 10% efinaconazole solution, the disease resolved in 6 months. A. subramanianii is one of the new species in the genus Aspergillus section Circumdati. Reported clinical isolates have been isolated from lung tissue, wounds and feet. This is the first documented case of onychomycosis caused by A. subramanianii. Onychomycosis due to Aspergillus species is uncommon. We summarized the reported cases of ungual aspergillosis in Japan.

Topics: Administration, Cutaneous; Administration, Oral; Adult; Antifungal Agents; Aspergillosis; Aspergillus; Female; Foot Dermatoses; Humans; Hyphae; Japan; Microscopy; Onychomycosis; Terbinafine; Triazoles; Young Adult

Onychomycosis is a common progressive fungal infection of the nail bed, matrix, or plate leading to destruction and deformity of the toenails and fingernails. The prevalence of onychomycosis is increasing in the United States, particularly in the growing population of Latino patients. In this study, we evaluated the efficacy and safety of efinaconazole solution 10% in Latino patients with onychomycosis. Once-daily application of efinaconazole solution 10% may be an effective topical option for treatment of onychomycosis in this patient population.

Topics: Administration, Topical; Antifungal Agents; Female; Foot Dermatoses; Hispanic or Latino; Humans; Male; Middle Aged; Onychomycosis; Randomized Controlled Trials as Topic; Treatment Outcome; Triazoles; United States

Topics: Administration, Topical; Aged; Antifungal Agents; Dermatitis, Allergic Contact; Foot Dermatoses; Humans; Male; Nail Diseases; Onychomycosis; Patch Tests; Triazoles

Topics: Administration, Topical; Aged; Antifungal Agents; Dermatitis, Allergic Contact; Foot Dermatoses; Humans; Male; Onychomycosis; Patch Tests; Triazoles

In 1996, oral terbinafine joined itraconazole and fluconazole on the short list of systemic medications that could be used to treat onychomycosis (although fluconazole was not approved for this indication by the US Food and Drug Administration [FDA], it was commonly used for this purpose). In 1999, ciclopirox was the first topical treatment to be FDA approved. The addition of the topical antifungal agents efinaconazole and tavaborole in 2014 expanded the roster of medications available to more effectively manage onychomycosis in a wide range of patients, including those for whom comorbid conditions, concomitant medications, or patient preference limited the use of systemic antifungals.

Topics: Administration, Cutaneous; Administration, Oral; Antifungal Agents; Boron Compounds; Bridged Bicyclo Compounds, Heterocyclic; Ciclopirox; Clinical Trials as Topic; Clinical Trials, Phase III as Topic; Fluconazole; Foot Dermatoses; Humans; Itraconazole; Naphthalenes; Onychomycosis; Pyridones; Terbinafine; Treatment Outcome; Triazoles; United States

Topics: Administration, Cutaneous; Antifungal Agents; Boron Compounds; Bridged Bicyclo Compounds, Heterocyclic; Ciclopirox; Foot Dermatoses; Humans; Naphthalenes; Onychomycosis; Pyridones; Terbinafine; Treatment Outcome; Triazoles

Topics: Administration, Cutaneous; Antifungal Agents; Boron Compounds; Bridged Bicyclo Compounds, Heterocyclic; Ciclopirox; Drug Administration Schedule; Foot Dermatoses; Humans; Onychomycosis; Pyridones; Triazoles

Topics: Administration, Topical; Antifungal Agents; Boron Compounds; Bridged Bicyclo Compounds, Heterocyclic; Cost-Benefit Analysis; Drug Costs; Female; Foot Dermatoses; Humans; Male; Onychomycosis; Sensitivity and Specificity; Severity of Illness Index; Triazoles

Transungual drug delivery of antifungals is considered highly desirable to treat common nail disorders such as onychomycosis, due to localized effects, and improved adherence resulting from minimal systemic adverse events. However, the development of effective topical therapies has been hampered by poor nail penetration. An effective topical antifungal must permeate through, and under the dense keratinized nail plate to the site of infection in the nail bed and nail matrix. We present here the formulation development program to provide effective transungual and subungual delivery of efinaconazole, the first topical broad spectrum triazole specifically developed for onychomycosis treatment. We discuss the important aspects encompassing the formulation development program for efinaconazole topical solution, 10%, focusing on its solubility in a number of solvents, in vitro penetration through the nail, and in vivo efficacy. Efinaconazole topical solution, 10% is a stable, non-lacquer, antifungal with a unique combination of ingredients added to an alcohol-based formulation to provide low surface tension and good wetting properties. This low surface tension is believed to affect effective transungual delivery of efinaconazole and believed to provide a dual mode of delivery by accessing the nail bed by wicking into the space between the nail and nail plate.

Topics: Administration, Topical; Antifungal Agents; Chemistry, Pharmaceutical; Drug Delivery Systems; Foot Dermatoses; Humans; Nail Diseases; Nails; Onychomycosis; Permeability; Pharmaceutical Solutions; Solubility; Triazoles

Onychomycosis is a common fungal infection of the nail unit that results in discoloration, subungual debris, thickening, onycholysis, and often pain and impairment of mobility. Dermatophytomas are characterized by a thick fungal mass within and under the nail plate and are especially resistant to treatment. Here we report a case of a patient with a dermatophytoma who had failed oral terbinafine but was successfully treated with efinaconazole 10% topical solution.

Topics: Administration, Topical; Aged; Antifungal Agents; Foot Dermatoses; Humans; Male; Naphthalenes; Onychomycosis; Terbinafine; Tinea; Treatment Outcome; Triazoles

Topics: Antifungal Agents; Boron Compounds; Bridged Bicyclo Compounds, Heterocyclic; Ciclopirox; Debridement; Foot Dermatoses; Hand Dermatoses; Humans; Laser Therapy; Morpholines; Naphthalenes; Onychomycosis; Pyridones; Terbinafine; Triazoles

Onychomycosis, a common nail infection that often is associated with substantial patient distress, disability, and pain, is a challenge to manage successfully. This report presents the case of a 44-year-old man with moderate distallateral subungual onychomycosis (DLSO) of more than 5 years' duration and discusses effective treatment with efinaconazole solution 10%, a new topical antifungal, once daily for 48 weeks. At baseline, 50% of the great toenail was affected and laboratory test results were positive for Trichophyton rubrum. Mycologic cure was noted at week 36 with complete cure observed at the end of treatment (week 48). This case demonstrates for physicians that efinaconazole solution 10% is a promising new topical treatment of onychomycosis and emphasizes the importance of mycologic cure as an early indicator of treatment success.

Topics: Adult; Antifungal Agents; Foot Dermatoses; Humans; Male; Onychomycosis; Triazoles; Trichophyton

Toenail onychomycosis is a common disease with limited treatment options, as treatment failures and relapses frequently are encountered. Many patients experience long-term disease that affects multiple toenails and causes substantial discomfort and pain. Although many patients prefer topical therapies, treatment efficacy with ciclopirox and amorolfine lacquers has been disappointing. Efinaconazole solution 10% is a new triazole antifungal agent specifically developed for the treatment of onychomycosis. Efinaconazole has shown a broad spectrum of antifungal activity in vitro and is more potent than ciclopirox against common onychomycosis pathogens. It has lower keratin binding and quicker drug release from keratin than ciclopirox and amorolfine and exhibits remarkably greater in vivo activity. Efinaconazole has limited or no potential for drug interactions and a low resistance potential. Efinaconazole provides a viable alternative to oral therapy for the treatment of toenail onychomycosis.

Topics: Administration, Topical; Antifungal Agents; Foot Dermatoses; Humans; Onychomycosis; Recurrence; Triazoles