tavaborole and efinaconazole

Onychomycosis is a fungal nail infection caused by dermatophytes, nondermatophytes, and yeast, and is the most common nail disorder seen in clinical practice. It is an important problem because it may cause local pain, paresthesias, difficulties performing activities of daily living, and impair social interactions. The epidemiology, risk factors, and clinical presentation and diagnosis of onychomycosis were discussed in the first article in this continuing medical education series. In this article, we review the prognosis and response to onychomycosis treatment, medications for onychomycosis that have been approved by the US Food and Drug Administration, and off-label therapies and devices. Methods to prevent onychomycosis recurrences and emerging therapies are also described.

Topics: Antifungal Agents; Boron Compounds; Bridged Bicyclo Compounds, Heterocyclic; Ciclopirox; Fluconazole; Humans; Itraconazole; Laser Therapy; Nanoparticles; Onychomycosis; Photochemotherapy; Plasma Gases; Prognosis; Pulse Therapy, Drug; Risk Factors; Secondary Prevention; Severity of Illness Index; Terbinafine; 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

Fungal diseases of the nail bed (onychomycosis) and epidermis are recurrent illnesses in the elderly and immunocompromised patients, which have few efficacious treatment options. Current treatment options for onychomycosis are limited to topical agents, laser treatment, and oral antifungals. Previous generations of topical agents were not efficacious, owing to poor penetration of the nail bed. Oral antifungal drugs, such as itraconazole, terbinafine, and fluconazole, not only give better response rates but also inhibit a host of CYP450 enzymes. Oral antifungals can exacerbate drug-drug interactions for patients taking other medications concurrently. Newer topical agents might recognize improved efficacy and provide therapeutic alternatives when the use of oral antifungal agents is contraindicated. Recently, the Food and Drug Administration (FDA) approved efinaconazole and tavaborole for the treatment of onychomycosis. Additionally, the FDA approved luliconazole for the treatment of tinea pedis, tinea cruris, and tinea corporis. This review examines the mechanism of action, spectrum of activity, pharmacokinetics, and clinical trials data and considers the place in therapy for these 3 new antimycotic agents.

Topics: Administration, Topical; Animals; Antifungal Agents; Arthrodermataceae; Boron Compounds; Bridged Bicyclo Compounds, Heterocyclic; Dermatomycoses; Humans; Imidazoles; Microbial Sensitivity Tests; Randomized Controlled Trials as Topic; Treatment Outcome; Triazoles

Onychomycosis is a common and difficult-to-treat fungal infection of the nail unit that gradually leads to dystrophic changes of the nail plate and nail bed. If untreated, infection progresses and may lead to discomfort, reduced quality of life, and risk of complications in patients with comorbid conditions (eg, diabetes, human immunodeficiency virus, peripheral vascular disease). Onychomycosis treatments are designed to eradicate causative pathogens (most commonly Trichophyton rubrum and Trichophyton mentagrophytes), restore healthy nails, and prevent recurrence or spread of infection. Given the deep-seated nature of most cases of onychomycosis, an effective antifungal agent needs to achieve and maintain sufficient drug concentrations throughout the nail unit for the duration of healthy nail in-growth. Oral antifungal drugs are the most effective available therapy and are generally well tolerated, but may be limited by safety concerns and the potential for drug-drug interactions (DDIs). Thus, treating physicians and pharmacists must be cognizant of a patient's current medications; indeed, it may not be feasible to treat onychomycosis in patients with diabetes, heart disease, or depression because of the risk for DDIs. Current topical therapy is not associated with risk of DDIs. Tavaborole and efinaconazole, two recently approved topical agents, have demonstrated good nail penetration and high negative culture rates in clinical trials of patients with onychomycosis. This article provides the treating physician and pharmacist with information on the safety and effectiveness of current oral (allylamine, azole) and topical (ciclopirox, efinaconazole, tavaborole) treatment to aid in making informed treatment decisions based on the unique characteristics (medication history, comorbidities, nature of onychomycosis) of each patient.

Topics: Administration, Oral; Administration, Topical; Antifungal Agents; Boron Compounds; Bridged Bicyclo Compounds, Heterocyclic; Chemical and Drug Induced Liver Injury; Ciclopirox; Cytochrome P-450 CYP2D6 Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Drug Interactions; Humans; Itraconazole; Naphthalenes; Onychomycosis; Pyridones; Terbinafine; Triazoles

Onychomycosis is an often overlooked and/or undertreated disease. This may be in part due to an under appreciation among both physicians and patients of its impact on quality of life and the potential for significant complications, from tinea corporis and cruris, to bacterial superinfection. Some health care providers are unaware of the effective low-risk treatments currently available. Changing demographic characteristics such as the relative aging of the population; the increasing prevalence of diabetes and peripheral vascular disease, and widespread iatrogenic immunosuppression; and changes in lifestyle practices such as earlier and greater participation in sports, are likely to lead to an increased prevalence of onychomycosis in both adults and children. Two topical onychomycosis treatments, efinaconazole 10% solution, and tavaborole 5% solution were recently approved by the FDA. This article reviews the state of knowledge and describes, briefly, these new treatment options.

Topics: Anti-Infective Agents, Local; Antifungal Agents; Boron Compounds; Bridged Bicyclo Compounds, Heterocyclic; Humans; Onychomycosis; Pharmaceutical Solutions; Treatment Outcome; Triazoles

Topics: Acids, Carbocyclic; Benzoxazines; Boron Compounds; Bridged Bicyclo Compounds, Heterocyclic; Cephalosporins; Cyclopentanes; Drug Approval; Drug Combinations; Drug Therapy; Glucagon-Like Peptides; Guanidines; Humans; Imidazoles; Immunoglobulin Fc Fragments; Interferon-beta; Isoquinolines; Penicillanic Acid; Polyethylene Glycols; Pyridines; Quinuclidines; Recombinant Fusion Proteins; Tazobactam; Triazoles; United States; United States Food and Drug Administration

Approximately 20-25% of the population worldwide is affected by superficial cutaneous mycoses (SCM). SCM are cutaneous fungal infections with a wide array of systemic and topical treatment options. However, successful therapeutic outcomes are limited by patient non-adherence, medication side effects, potential drug interactions, antifungal resistance and disease recurrence. Advances in formulation technology have allowed for the development of more effective and safer therapies. In this article we will review several new and emerging pharmacotherapeutics for onychomycosis and tinea pedis.

Topics: Allylamine; Antifungal Agents; Boron Compounds; Bridged Bicyclo Compounds, Heterocyclic; Education, Medical, Continuing; Humans; Imidazoles; Itraconazole; Onychomycosis; Tinea Pedis; Triazoles

Onychomycosis is a common disease that remains difficult to treat despite the introduction of new topical agents. Clinical trials on efinaconazole and tavaborole included 48 weeks' daily treatment regimens with a 4-week follow-up. It has been suggested that either a longer treatment regimen or longer follow-up would lead to even better results, primarily due to the time taken for the diseased nail to grow out, especially in those patients with more severe disease.. To investigate the impact of a longer follow-up period on the efficacy of efinaconazole 10% topical solution in patients with moderate-to-severe onychomycosis.. &Single center, open-labeled study in 23 subjects aged 18-80 years with a clinical and mycological diagnosis of moderate-to-severe dermatophyte toenail onychomycosis (40-75% clinical involvement). Subjects were treated with efinaconazole 10% solution, once-daily for 48 weeks, with two 12-week post-treatment follow-ups (at week 60 and 72). Primary efficacy endpoint was complete cure rate (0% clinical involvement of target toenail, and both negative potassium hydroxide examination and fungal culture). Secondary endpoints included mycologic cure rates and treatment success (defined as those patients who had at least a 50% improvement in affected toenail from baseline).. Twenty-two subjects completed the study. Mean baseline age 59.4 years (range, 37-77), predominance of male subjects (73.9%). Median baseline severity 50% affected target toenail. At week 72, two subjects were complete cures and 56.5% of subjects achieved treatment success. There were no complete cures at week 48, but 39.1% achieved treatment success. Mycologic cure rates were 91.3% at week 48. Median percent affected target toenail reduced to 40%, and further to 25% (week 48 and 72, respectively). Treatment was well tolerated, with no adverse events related to medication.. This single-center phase 4 study supports previous data showing good efficacy and tolerability of efinaconazole in moderately severe onychomycosis. Continued reduction in disease severity post-treatment suggest that a longer follow-up of patients treated with efinaconazole would afford better efficacy results, as indicated by greater treatment success, and increase in number of subjects who became complete cures.

Topics: Administration, Cutaneous; Adolescent; Adult; Aged; Aged, 80 and over; Antifungal Agents; Boron Compounds; Bridged Bicyclo Compounds, Heterocyclic; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Male; Middle Aged; Onychomycosis; 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

Topical onychomycosis therapy is commonly prescribed due to its tolerability and low incidence of side effects. There are limited data on adverse events associated with the newer topical onychomycosis drugs. The objectives of this study is to classify the most common adverse reactions associated with ciclopirox 8% solution, efinaconazole 10% solution, and tavaborole 5% solution. The United States Food and Drug Administration Adverse Event Reporting (FAERS) database was analyzed for the most common adverse reactions associated with ciclopirox 8% solution, efinaconazole 10% solution, and tavaborole 5% solution. Google Trends was used to examine public interest in these drugs and these data were compared with yearly adverse events in the FAERS database. The most common adverse reactions associated with ciclopirox 8% solution, efinaconazole 10% solution, and tavaborole 5% solution were drug ineffectiveness. Application site erythema and nail discoloration were reported with all three medications. Increased Google searches for efinaconazole and tavaborole were associated with increased in reporting of adverse events to the FDA. Topical antifungals are safe alternatives for patients who have contraindications to oral medications. For improved efficacy, physicians should confirm the diagnosis of onychomycosis and choose appropriate candidates before starting topical therapy. Patients should be given clear instructions on drug usage and counseled about the more common side effects, including application site reactions and nail discoloration.

Topics: Administration, Topical; Adverse Drug Reaction Reporting Systems; Antifungal Agents; Boron Compounds; Bridged Bicyclo Compounds, Heterocyclic; Ciclopirox; Erythema; Humans; Nails; Onychomycosis; Pigmentation; Retrospective Studies; Solutions; Treatment Failure; Triazoles; United States; United States Food and Drug Administration

Topics: Administration, Topical; Antifungal Agents; Boron Compounds; Bridged Bicyclo Compounds, Heterocyclic; Ciclopirox; Humans; Medication Adherence; Onychomycosis; Patient Education as Topic; Triazoles

There currently are 3 topical agents approved by the US Food and Drug Administration (FDA) to treat onychomycosis: tavaborole, efinaconazole, and ciclopirox. The phase 3 clinical trial designs for these treatments and their notable differences make it difficult for clinicians to interpret the data into clinical practice. For example, the primary end point predominantly used to assess efficacy in all the trials is complete cure, defined as no involvement of the nail plus mycologic cure; also, a notable number of patients fail to achieve a complete cure despite clear improvement in the nail. Despite close similarities in the end points and overall design of the clinical trials used for these agents, differences in design are notable, including the age range of participants, the range of mycotic nail involvement, the presence/absence of tinea pedis, and the nail trimming/debridement protocols used. The differences in clinical trial designs for the 3 FDA-approved topical agents and the lack of head-to-head studies makes efficacy interpretation and comparison inappropriate. This article reviews the phase 3 clinical trials that led to FDA approval of these agents, focusing on their similarities and differences.

Topics: Administration, Cutaneous; Antifungal Agents; Boron Compounds; Bridged Bicyclo Compounds, Heterocyclic; Ciclopirox; Clinical Trials, Phase III as Topic; Drug Approval; Humans; Onychomycosis; Pyridones; Research Design; Treatment Outcome; Triazoles; United States

Patients with onychomycosis may mask infected nails with polish. Tavaborole topical solution, 5% is a boron-based, small-molecule pharmaceutical approved for the treatment of toenail onychomycosis caused by Trichophyton rubrum and Trichophyton mentagrophytes; efinaconazole topical solution, 10% is approved for the same indication. Nail polish appearance after application of tavaborole (dropper) or efinaconazole (brush); respective applicator appearance; presence of color transfer from respective applicators; and color transfer to remaining solutions after dosing of polished nails were evaluated.. Twelve ex vivo human cadaver fingernails were cleaned, polished with two coats of L'Oréal® Nail Color, Devil Wears Red #420, and mounted on floral foam. Nails were treated with tavaborole or efinaconazole solutions once daily for 7 days. Dropper and brush applicators were applied to white watercolor paper immediately after dosing to evaluate color transfer from polished nails. On day 7, remaining solutions were transferred to clear glass vials to evaluate color transfer from applicators to solutions. Nails, applicators, and papers were photographed daily following application; remaining solutions were photographed after 7 days of dosing.. Tavaborole-treated polished nails showed no polish discoloration, and tavaborole applicators did not change in appearance during treatment. No color transfer from polished nails was evident to applicator, paper, or remaining solution. Efinaconazole-treated polished nails showed substantial polish changes after the first day of treatment, with polish appearance and discoloration progressively worsening over 7 days of treatment. Color transfer from nails was evident to applicator, paper, and remaining solution.. Daily dropper application of tavaborole to ex vivo polished nails did not alter polish appearance. Brush application of efinaconazole produced visible changes in polish appearance and color transfer to applicators, paper, and remaining solution. Tavaborole topical solution, 5% may not alter nail polish appearance; the impact of nail polish on tavaborole clinical efficacy has not been evaluated.

Topics: Antifungal Agents; Boron Compounds; Bridged Bicyclo Compounds, Heterocyclic; Humans; Nails; Onychomycosis; 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

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

Topics: Antifungal Agents; Attention Deficit Disorder with Hyperactivity; Boron Compounds; Botulinum Toxins, Type A; Bridged Bicyclo Compounds, Heterocyclic; Brimonidine Tartrate; Depression; Dermatitis, Atopic; Food Hypersensitivity; Humans; Immunologic Factors; Ivermectin; Phosphodiesterase Inhibitors; Phototherapy; Piperidines; Protein Kinase Inhibitors; Pyrimidines; Pyrroles; Quinoxalines; Skin Diseases; Societies, Medical; Thalidomide; Triazoles; United States