tavaborole and Foot-Dermatoses

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

Onychomycosis is a fungal nail infection that accounts for half of all nail diseases. Oral drugs on the market have adverse effects, while it is difficult for traditional topical drugs to penetrate the nail plate to reach the diseased nail bed. Tavaborole is a new drug that addresses the unmet needs of currently available treatments. Tavaborole (5%) is FDA approved for treating toenail onychomycosis and has shown antifungal activities against yeast, moulds and dermatophytes.. The objective of this article is to review the efficacy, pharmacokinetics, pharmacodynamics, and safety of tavaborole for treatment of toenail onychomycosis. Expert commentary: Tavaborole, with its unique mechanism, may be a good candidate for use in treating children with fungal infections, diabetic individuals, and treating mixed infections. Tavaborole may be paired with other therapies to potentially increase cure rates.

Topics: Administration, Topical; Animals; Antifungal Agents; Boron Compounds; Bridged Bicyclo Compounds, Heterocyclic; Child; Foot Dermatoses; Humans; Onychomycosis

Topics: Administration, Topical; Animals; Antifungal Agents; Boron Compounds; Bridged Bicyclo Compounds, Heterocyclic; Clinical Trials as Topic; Foot Dermatoses; Humans; Onychomycosis; Pharmaceutical Solutions

Tavaborole topical solution, 5% (tavaborole) is a novel, boron-based, antifungal pharmaceutical agent indicated for treatment of toenail onychomycosis due to the dermatophytes Trichophyton rubrum or Trichophyton mentagrophytes. In preclinical studies, tavaborole effectively penetrated through full-thickness, non-diseased cadaver fingernails, including those with up to four layers of nail polish. Limited systemic absorption was observed following topical application of tavaborole. In phase III clinical trials involving patients with distal subungual onychomycosis affecting 20-60% of a target great toenail, significantly more patients treated with tavaborole versus vehicle achieved completely clear nail with negative mycology following daily application for 48 weeks. Treatment-emergent adverse events reported by at least 1% of patients treated with tavaborole and at a greater frequency versus vehicle included ingrown toenail, exfoliation, erythema and dermatitis. Treatment discontinuations were uncommon. Results from preclinical studies and phase III clinical trials establish tavaborole as a safe and efficacious treatment for toenail onychomycosis.

Topics: Administration, Topical; Antifungal Agents; Boron Compounds; Bridged Bicyclo Compounds, Heterocyclic; Drug Interactions; Foot Dermatoses; Humans; Onychomycosis; Solutions

Onychomycosis is a fungal nail plate infection that has been increasing in prevalence. A variety of oral and topical anti-fungal agents are currently available but their use is limited by their adverse effect profile, drug-drug interactions, and limited efficacy. Therefore, there is a great need for newer anti-fungal agents. Tavaborole is one of these newer agents and was approved by the US Food and Drug Administration in July 2014 for the topical treatment of mild to moderate toenail onychomycosis. Tavaborole is a novel, boron-based anti-fungal agent with greater nail plate penetration than its predecessors, due to its smaller molecular weight. It has proven through several Phase II and III trials that it can be a safe and effective topical agent for the treatment of mild to moderate toenail onychomycosis without the need for debridement. In this paper, we review the landscape of topical and systemic treatment of onychomycosis, with particular attention to the pharmacokinetics, safety, and efficacy of topical tavaborole.

Topics: Administration, Topical; Antifungal Agents; Boron Compounds; Bridged Bicyclo Compounds, Heterocyclic; Drug Approval; Foot Dermatoses; Humans; Onychomycosis; United States; United States Food and Drug Administration

Onychomycosis is a stubborn fungal infection of the nails that can be difficult to effectively manage. One of the challenges with topical therapies is penetrating the nail plate to reach the site of infection. As the first antifungal in a boron-containing class of drugs with a novel mechanism of action, tavaborole is able to penetrate the nail plate more effectively than ciclopirox and amorolfine lacquers. In Phase II/III clinical trials, tavaborole was shown to be safe and clinically effective. Tavaborole 5% solution was approved by the US FDA for the treatment of toenail onychomycosis in July 2014 and is an important addition to the topical treatment arsenal against this stubborn infection.

Topics: Administration, Cutaneous; Antifungal Agents; Boron Compounds; Bridged Bicyclo Compounds, Heterocyclic; Clinical Trials as Topic; Drug Compounding; Foot Dermatoses; Humans; Onychomycosis

Onychomycosis is a challenging nail disease that is difficult to treat due to the thickness and impermeability of the nail plate. At present, systemic agents are the first-line of treatment for this type of infection; however, topical treatment is recommended in milder cases (<50% involvement) or when oral treatment is contraindicated. Effective topical treatments capable of penetrating the nail plate and reaching the site of infection continue to be sought. Tavaborole, the first member of a new class of boron-containing antifungals, is a lightweight, water-soluble topical nail solution for the treatment of toenail onychomycosis. Tavaborole has a unique mechanism of action against fungal organisms and retains antifungal properties in the presence of keratin. Tavaborole 5.0% nail solution has shown a favourable safety and efficacy profile in Phase II/III clinical trials and is currently under review for licensing in the US by the US Food and Drug Administration.

Topics: Adult; Antifungal Agents; Boron Compounds; Bridged Bicyclo Compounds, Heterocyclic; Clinical Trials as Topic; Foot Dermatoses; Humans; Onychomycosis

Onychomycosis is a fungal infection of the fingernails and toenails that results in thickening, discoloration, splitting of the nails and lifting of the nail from the nail bed. The disease is caused by dermatophytes and has a high incidence within the general population, especially among older individuals. Present treatment options include both oral and topical drugs, with oral therapies giving better outcomes; however, neither of these treatment options provides high cure rates that are durable. The difficulty in treating onychomycosis results from the deep-seated nature of the infection within the nail unit (nail plate, nail bed and surrounding tissue) and the inability of drugs to effectively reach all sites. Ongoing drug development activities have focused on novel delivery technologies to facilitate penetration of existing antifungal drugs through the nail plate and on the discovery of inherently penetrable antifungals. AN-2690 represents an oxaborole antifungal that is designed to penetrate the nail plate and is showing promising results in clinical trials.

Topics: Administration, Topical; Animals; Antifungal Agents; Boron Compounds; Bridged Bicyclo Compounds, Heterocyclic; Foot Dermatoses; Hand Dermatoses; Humans; Onychomycosis

Background: This study was designed to evaluate the safety, tolerability, pharmacokinetics (PK), and efficacy of tavaborole in pediatric patients.\ Study Design: In this open-label, single-arm study, pediatric patients (aged 6 to <17 years) with distal subungual onychomycosis affecting ≥20% of the target great toenail applied tavaborole once daily to all affected toenails (2 drops/great toenail, 1 drop/other toenail) for 48 weeks. In addition, a maximal-use subgroup (aged 12 to <17 years) applied tavaborole to all 10 toenails and ≤2 mm of surrounding skin for the first 28 days.\ \ Results: Treatment-emergent adverse events (TEAEs) were reported by 55.6% of patients; the most frequently reported (≥5% of patients) were nasopharyngitis, contusion, sinusitis, and vomiting. Most TEAEs and local treatment reactions (LTRs) were mild or moderate and considered unrelated to treatment. There was 1 serious AE (severe appendicitis, considered unrelated to treatment) and there were no deaths, discontinuations because of AEs, or dose adjustments because of AEs. The most frequently reported LTRs were erythema and scaling. The incidence of LTRs diminished over time. Tavaborole was absorbed systemically, and plasma concentrations were measurable. The PK parameters determined in this study under maximal-use conditions indicate that steady state was achieved within the study period. For efficacy, 8.5% of patients achieved complete cure (clear nail and negative mycology [negative fungal culture and negative potassium hydroxide wet mount]) at week 52, and 14.9% achieved complete/almost complete cure at week 52 (clear or almost clear nail [≤5% dystrophic or discolored distal toenail plate] and negative mycology).\ \ Conclusion: Tavaborole was well tolerated in this pediatric population, and safety, PK, and efficacy profiles were comparable with those in adults.\ \ Trial registration: ClinicalTrials.gov identifier: NCT03405818\ \ J Drugs Dermatol. 2019;18(2):190-195.

Topics: Administration, Topical; Adolescent; Antifungal Agents; Boron Compounds; Bridged Bicyclo Compounds, Heterocyclic; Child; Drug Compounding; Female; Foot Dermatoses; Humans; Male; Onychomycosis; Pharmaceutical Solutions; Treatment Outcome

The role of topical antifungal agents in the long-term management of toenail onychomycosis is not well established. The current study evaluated durability of clinical benefit of tavaborole topical solution, 5%, for the treatment of toenail onychomycosis.. We conducted a pooled analysis of 8-week, post-study follow-up (PSFU) data from two phase 3, randomized controlled trials in a subset of patients who experienced complete or almost clear nail (CN) at the end of treatment (week 52); 48 weeks of treatment with once-daily tavaborole compared with placebo in adults with distal subungual onychomycosis was evaluated at week 60. Complete cure (completely CN plus negative mycology) of the target great toenail and treatment success (<10% nail involvement plus negative mycology) were evaluated at week 52 versus week 60.. Of the 62 patients who completed the PSFU, complete cure was higher in the tavaborole-treated group versus the vehicle control group (28.6% vs. 7.7%). Additionally, treatment success was 53.1% for the tavaborole group versus 23.1% in the vehicle group. Small sample size entering the PSFU limited robust statistical analysis.. Tavaborole topical solution, 5%, appears to provide durable clinical benefit, making it an attractive long-term treatment option for dermatophyte-associated onychomycosis of the toenail.

Topics: Administration, Topical; Adult; Aged; Antifungal Agents; Boron Compounds; Bridged Bicyclo Compounds, Heterocyclic; Double-Blind Method; Drug Administration Schedule; Female; Follow-Up Studies; Foot Dermatoses; Humans; Hypertension; Male; Middle Aged; Onychomycosis; Placebo Effect; Treatment Outcome

Women with onychomycosis may suffer more effects on their quality of life than men. There is limited female-specific data on the treatment of onychomycosis. Tavaborole is a topical treatment option for onychomycosis. This post-hoc study evaluated the nail plates of women using data from the tavaborole 5% Phase III studies at baseline and end of study for the areas of healthy nail and infected nail. Over 52 weeks (48-week treatment, 4-week follow up), women treated with tavaborole had an average 32% increase in healthy nail and 21% decrease in infected nail. Patients with baseline infection involving >50% of the nail plate had an average increase in percentage of unaffected nail surface area of 81% and a corresponding 51% decrease in infected nail. These analyses suggest that patients with the greatest toenail involvement at baseline had greater overall improvements than those who were less affected. This evaluation provides additional clinical guidance for treating women with onychomycosis using tavaborole. J Drugs Dermatol. 2018;17(2):168-172.

Topics: Administration, Topical; Adult; Aged; Aged, 80 and over; Antifungal Agents; Boron Compounds; Bridged Bicyclo Compounds, Heterocyclic; Female; Foot Dermatoses; Humans; Middle Aged; Onychomycosis; Treatment Outcome; Young Adult

Dermatophytoma is a little-known, difficult to treat fungal infection that complicates onychomycosis. First described by Roberts and Evans in the late 1990's, dermatophytoma presents as a dense concentration of fungal hyphae within or under the nail plate and is generally white or yellow/brown in color, and linear (streaks) or round (patches) in shape; primary etiologic organisms are dermatophytes. Oral antifungals have limited success in treating dermatophytoma owing to difficulties accessing and penetrating what is hypothesized to be a fungal biofilm. In this respect, dermatophytoma is generally treated with a combination therapy approach, often including both surgical and pharmacologic intervention for improved outcomes. A post-hoc assessment of Phase II tavaborole onychomycosis studies was conducted in order to assess the prevalence of dermatophytoma and outcomes in patients treated with topical tavaborole. Of the 366 subjects enrolled in the Phase II onychomycosis studies, we identified 102 cases of dermatophytoma; 21 of 86 (24.4%) subjects treated with tavaborole were able to achieve complete resolution of dermatophytoma by day 180, while no subjects on vehicle obtained resolution. Similarly, 23 of 86 subjects (26.7%) treated with tavaborole solution had complete resolution of dermatophytoma by day 360, while only 1 of 16 subjects (6.3%) on vehicle obtained resolution. Moreover, 13 of 19 subjects (68.4%) treated with tavaborole solution were able to sustain resolution, while only 6 of 19 (31.6%) had reoccurrence, of dermatophytoma during the 180-day washout period (day 360). We present 5 cases of dermatophytoma identified in Phase II trials that responded in a positive manner following treatment with tavaborole solution for onychomycosis of the great toenail. Although not representative of all subject outcomes, these findings provide insight into the use of topical tavaborole for dermatophytoma, a condition previously thought to respond only to oral or combination therapy.

J Drugs Dermatol. 2018;17(3):347-354.

Topics: Administration, Topical; Adult; Antifungal Agents; Boron Compounds; Bridged Bicyclo Compounds, Heterocyclic; Double-Blind Method; Female; Foot Dermatoses; Humans; Male; Middle Aged; Onychomycosis; Treatment Outcome

Toenail onychomycosis is a chronic fungal infection that often requires prolonged treatment in order to effectively manage pathogenic organisms and obtain a clear nail. Traditionally, certain clinical features of onychomycosis, including the presence of substantial lateral disease, focal fungal masses, yellow/brown streaks, and extensive nail involvement (ie, >50%), indicate a poor treatment prognosis and have proven difficult-to-treat with oral or traditional topical therapies. Owing to the novel features of topical tavaborole, we sought to understand the potential utility of tavaborole in difficult-to-treat onychomycosis. A blinded, post-hoc assessment of Phase III trials was conducted, focusing on initial presentation, midpoint assessment (24 weeks), and final outcomes (52 weeks) in subjects identified as having difficult-to-treat onychomycosis and treated for 48 weeks with once-daily application of either tavaborole 5% solution or vehicle. Our post-hoc analysis identified 84 difficult-to-treat cases (tavaborole 5%; n=60; vehicle, n=24) in subjects with toenail onychomycosis due to Trichophyton rubrum or Trichophyton mentagrophytes. No subjects identified as difficult-to-treat and treated with vehicle achieved a complete cure, while 6 subjects treated with tavaborole 5% attained a completely clear nail and negative mycology. Similarly, 7 subjects treated with tavaborole 5% solution achieved an almost complete cure (≤10% involvement and negative mycology) while 1 subject on vehicle achieved an almost complete cure. We present a case series of 4 patients, of varying age and difficult-to-treat clinical features, which responded positively to tavaborole 5% solution. Three of the subjects achieved complete cure after being treated with tavaborole 5%, with one additional subject (an 88-year-old female) achieving an almost complete clear nail by treatment end. The outcomes presented here may not be reflective of patients that may present with these clinical characteristics. Additional investigations would be useful in order to assess the value of topical tavaborole 5% solution in difficult-to-treat clinical presentations of onychomycosis.

J Drugs Dermatol. 2017;16(10):1016-1021.

Topics: Administration, Topical; Adult; Aged, 80 and over; Antifungal Agents; Boron Compounds; Bridged Bicyclo Compounds, Heterocyclic; Double-Blind Method; Female; Foot Dermatoses; Humans; Male; Onychomycosis; Treatment Outcome

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

Onychomycosis, a fungal nail infection, can impact quality of life.. We sought to evaluate the efficacy and safety of tavaborole topical solution, 5% for treatment of toenail onychomycosis.. In 2 phase-III trials, adults with distal subungual onychomycosis affecting 20% to 60% of a target great toenail were randomized 2:1 to tavaborole or vehicle once daily for 48 weeks. The primary end point was complete cure of the target great toenail (completely clear nail with negative mycology) at week 52. Secondary end points included completely or almost clear nail, negative mycology, completely or almost clear nail plus negative mycology, and safety.. Rates of negative mycology (31.1%-35.9% vs 7.2%-12.2%) and complete cure (6.5% and 9.1% vs 0.5% and 1.5%) significantly favored tavaborole versus vehicle (P ≤ .001). Completely or almost clear nail rates also significantly favored tavaborole versus vehicle (26.1%-27.5% vs 9.3%-14.6%; P < .001). Rates of completely or almost clear nail plus negative mycology (15.3%-17.9% vs 1.5%-3.9%) were significantly greater for tavaborole versus vehicle (P < .001). Application-site reactions with tavaborole included exfoliation (2.7%), erythema (1.6%), and dermatitis (1.3%).. Duration of follow-up is a limitation.. Tavaborole demonstrates a favorable benefit-risk profile in treatment of toenail onychomycosis.

Topics: Administration, Topical; Adolescent; Adult; Aged; Aged, 80 and over; Antifungal Agents; Boron Compounds; Bridged Bicyclo Compounds, Heterocyclic; Double-Blind Method; Female; Foot Dermatoses; Humans; Male; Middle Aged; Onychomycosis; Young Adult

To assess the potential efficacy, safety, and optimal dosing concentration of tavaborole, a novel, boron-based pharmaceutical agent with broad-spectrum antifungal activity, for the treatment of onychomycosis of the toenail due to dermatophytes.. One double-blind, randomized, vehicle-controlled study (study 1) and two open-label studies (studies 2 and 3) examined the efficacy, safety, and optimal dosing concentration of tavaborole topical solution applied once daily or three times weekly for 180 days at concentrations of 1.0%, 2.5%, 5.0%, or 7.5%. Patient cohort 3 of study 2 received open-label tavaborole 5.0% once daily for 360 days. All three studies assessed day 180 treatment success, defined as complete or partial clinical evidence of clear nail growth plus negative fungal culture.. A total of 336 patients were included in the intent-to-treat (ITT) or modified ITT populations and efficacy analyses across the 3 studies. In study 1, treatment success rates at day 180 were higher with tavaborole 2.5%, 5.0%, and 7.5% vs vehicle (27%, 26%, and 32% vs 14%, respectively; slope P=0.030). In cohort 3 of study 2, 7% of patients achieved treatment success with tavaborole 5.0% at day 360. Negative culture rates at day 180 in study 1 were numerically higher for tavaborole 2.5%, 5.0%, and 7.5% vs vehicle (slope P=0.046). Application-site reactions of general irritation, erythema, scaling, and stinging/burning were most common with tavaborole 7.5%, were generally mild to moderate, and resolved with treatment discontinuation and/or a reduction in dosing frequency. No systemic safety concerns were observed.. Tavaborole solution demonstrated favorable efficacy and safety in phase 2 clinical studies. Based on these findings, tavaborole topical solution, 5% was further investigated in larger, more definitive phase 3 studies. Results from these completed phase 3 studies will provide additional evidence regarding the safety and efficacy of tavaborole in the treatment of toenail onychomycosis.

Topics: Administration, Topical; Adolescent; Adult; Aged; Antifungal Agents; Boron; Boron Compounds; Bridged Bicyclo Compounds, Heterocyclic; Cohort Studies; Dose-Response Relationship, Drug; Double-Blind Method; Erythema; Female; Foot Dermatoses; Humans; Male; Middle Aged; Onychomycosis; Treatment Outcome; Young Adult

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

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

Tavaborole is a novel, low-molecular weight oxaborole antifungal drug under development by Anacor Pharmaceuticals Inc. for the topical treatment of onychomycosis of the toenail. The drug has received its first global approval for this indication in the US. This article summarizes the milestones in the development of tavaborole leading to this first approval for onychomycosis of the toenails.

Topics: Administration, Topical; Antifungal Agents; Boron Compounds; Bridged Bicyclo Compounds, Heterocyclic; Drug Approval; Drug Design; Foot Dermatoses; Humans; Onychomycosis; United States; United States Food and Drug Administration

Systemic antifungal treatments are believed to be more effective than topicals for the treatment of onychomycosis; however, they are associated with more risks of adverse events. Tavaborole is the first member of a new class of antifungals that has been developed as a new topical nail solution for the treatment of toenail onychomycosis caused by dermatophytes. During Phase I-III clinical trials, tavaborole 5.0% nail solution showed a favorable safety and efficacy profile. Tavaborole 5.0% received US FDA market approval on 8 July 2014.

Topics: Antifungal Agents; Boron Compounds; Bridged Bicyclo Compounds, Heterocyclic; Drug Evaluation; Foot Dermatoses; Humans; Microbial Sensitivity Tests; Onychomycosis