Search Results (31)

Onychomycosis is a common nail disease that manifests with varying severity and frequency in specific patient populations, warranting a personalized treatment approach. Novel topical antifungals, such as efinaconazole 10% approved for use in North America and Japan, offer a safe treatment option for many of these patients, though real-world use requires special considerations. In this scoping review, a literature search was conducted in October 2025 using PubMed, Embase (Ovid), the Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science (Core Collection). In children and adolescents (≥6 years), efinaconazole 10% has shown higher efficacy rates than in adults, possibly attributed to less nail trauma, thinner nail plates, and faster nail growth. In the elderly, a mycological response can precede visual nail improvements, which may require extending treatment beyond the standard 48-week regimen, along with intermittent maintenance therapies. Although antifungal resistance is a concern, dermatophytes—including terbinafine-resistant strains—have generally shown high susceptibility to efinaconazole. In diabetic individuals, onychomycosis should be treated promptly to prevent secondary complications. Efinaconazole 10% showed similar efficacy in this population, regardless of glycemic control. In historically underserved populations, efinaconazole 10% showed no significant difference in efficacy for Latino/Hispanic patients, though further research is needed. Overall, efinaconazole 10% solution was well-tolerated across patient groups, with application-site reactions occurring without systemic sequalae. Healthcare providers are advised to check for concomitant tinea pedis, which increases the risk of relapse or re-infection, and advise patients on nail polish use, which may degrade after topical antifungal application. A shared decision-making framework can help improve treatment compliance and patient satisfaction. Full article

Background: Onychomycosis responds poorly to topical therapy, and efinaconazole (EFN) has low aqueous solubility. Methods: This study aimed to develop a 10% w/w EFN self-nanoemulsifying system (SNEDDS) with improved solubility, permeation, antifungal activity, and stability. Excipients were screened by EFN saturation solubility. An MCT oil/Solutol HS 15/Labrafil M2125 CS SNEDDS (5/75/20, w/w) was optimized via a pseudo-ternary diagram. Characterization included droplet size, PDI, and zeta potential, morphology, and drug–excipient compatibility. Solubility was measured across pH. Permeation of EFN SNEDDS vs. EFN suspension was tested by Franz diffusion cells. Antifungal activity against Trichophyton rubrum and Trichophyton mentagrophytes was assessed by paper-disc diffusion, and hyphal damage on human nails was examined by SEM. Stability was studied for six months under room, accelerated, and stress conditions. Results: The optimized SNEDDS formed sub-50 nm droplets with low polydispersity and favourable zeta potential. Solubility was maintained across pH, and cumulative permeation increased 13.6-fold versus suspension. Paper-disc assays showed larger inhibition zones at lower EFN doses. SEM on human nails revealed marked hyphal destruction. TEM confirmed spherical nanoemulsion droplets. FT-IR showed no new peaks, supporting compatibility. Particle size, PDI, zeta potential, and drug content remained stable over six months under all storage conditions. Conclusions: A 10% w/w EFN SNEDDS enhanced solubility, transungual permeation, and antifungal efficacy while maintaining robust stability, supporting its potential as an ethanol-free therapy for onychomycosis. Full article

Onychomycosis is a prevalent and clinically relevant complication among individuals with diabetes. It is associated with an elevated risk of secondary fungal and bacterial infections, foot ulceration, and, in advanced cases, amputation. Factors contributing to the increased prevalence of onychomycosis in this population include age, peripheral vascular disease, poor glycemic control, neuropathy, suboptimal foot hygiene, and nail trauma. While dermatophytes are the most common pathogens, diabetic patients are more prone to mixed infections involving Candida species with varying antifungal susceptibility profiles, necessitating accurate identification to guide therapy. Prompt diagnosis and early intervention are important to prevent complications. Systemic antifungals such as terbinafine and itraconazole are considered first-line therapies, particularly for moderate to severe onychomycosis. However, drug interactions, renal, hepatic, and metabolic comorbidities may necessitate individualized treatment plans. For patients with mild to moderate disease, or contraindications to oral therapy, topical agents such as efinaconazole or tavaborole offer viable alternatives. Adjunctive measures, including education on foot hygiene, prompt treatment of tinea pedis, and environmental sanitization, are important in preventing recurrence and reinfection. This review summarizes the epidemiology, diagnosis, and treatment considerations for onychomycosis in diabetic patients, emphasizing the need for individualized care to improve outcomes in this high-risk population. Full article

Background: Fungal infections, particularly among immunocompromised individuals, present significant challenges due to rising incidence rates, treatment costs, and increasing resistance to antifungal agents. This study evaluates trends in antifungal use among Medicaid beneficiaries, focusing on prescribing patterns, costs, and pricing to optimize therapy. Methods: Using the national Medicaid outpatient pharmacy claims data collected by the US Center of Medicare and Medicaid Services, a retrospective drug utilization analysis was conducted for antifungal medications from 2009 to 2023. Antifungal medications were categorized based on therapeutic use. The study examined annual utilization, reimbursement, and pricing trends, along with the market share. Results: Overall Medicaid utilization of superficial fungal infections’ (SFIs’) medications increased from 3.95 million prescriptions in 2009 to 6.16 million in 2023. Nystatin was the most frequently utilized SFI agent, while fluconazole emerged as the most commonly prescribed agent for invasive fungal infections (IFIs). In 2022, a notable spike occurred in the number of prescriptions for both SFIs and IFIs. Medicaid’s total expenditure on SFI medications rose from USD 121.9 million in 2009 to USD 155 million in 2023, while spending on IFI medications fluctuated substantially, peaking at USD 156.8 million in 2022 before declining to USD 80.7 million in 2023. After being introduced to the market, efinaconazole became the most expensive SFI agent over the years. Isavuconazole, the latest approved IFI medication, demonstrated sustained utilization, reimbursement, and price increases. Conclusions: The substantial rise in antifungal utilization and spending underscores the growing financial burden on Medicaid, emphasizing the need for policy interventions to manage costs and generic drug substitution while ensuring equitable access to these essential treatments. However, this study is limited by the lack of clinical outcome data and information on off-label use. Additionally, reimbursement data may not accurately reflect actual drug prices. Full article

Background/Objectives: In an 18- to 24-month Treatment Phase with once-daily efinaconazole 10% solution, subjects with onychomycosis showed an increased rate of cure at Month 24 versus the phase III trials. In order to further improve efficacy, we initiated an extended intermittent efinaconazole Maintenance Phase with use 2–3 times weekly for an additional 24 months from Month 24 to Month 48. These are the first data presented for a 48-month efinaconazole use period. Methods: For patients completing 18–24 months of once-daily efinaconazole, the target great toenail from the Treatment Phase was graded as ‘Clinical Cure’ (≤10% affected area) or ‘No Clinical Cure’ (>10% affected area) at Month 24. Mycological and clinical outcomes were assessed every 4 months from Month 24 to Month 48. There were 35 patients who enrolled in the extension and continued intermittent efinaconazole use to Month 48. Patients with ‘Clinical Cure’ at M24 were reviewed for sustained cure at M48; patients with ‘No Clinical Cure’ were reviewed for development of ‘Cure’ at M48. All patients were reviewed at all visits for adverse events that may be related to efinaconazole use. Results: ‘Clinical Cure’ was found in 6 of 35 enrolled patients at Month 24, and clinical cure status was sustained to Month 48 with intermittent efinaconazole maintenance use. For 29 patients with ‘No Clinical Cure’, 3/29 achieved ‘Clinical Cure’ status at Month 48 with intermittent efinaconazole. Effective Cure and Complete Cure rates improved over the maintenance period to Month 48 in subjects without clinical cure at Month 24. Younger patients showed higher cure rates over the maintenance period, but age group cure differences did not reach statistical significance in this dataset, and 49% of the ≥70-year population had at least a 20% reduction in nail area with maintenance therapy to Month 48. There was only 1 case of possible efinaconazole application site reaction in the Intermittent Maintenance Period to Month 48; prolonged efinaconazole use to Month 48 does not appear to increase the risk of reaction. Efinaconazole use periods are associated with very low positive culture rates in this dataset, including typical contaminant organisms, suggesting efinaconazole presence in the nail plate is providing prophylactic therapy. Conclusions: Intermittent efinaconazole may provide suitable prophylaxis of onychomycosis relapse. Prolonged efinaconazole therapy to Month 48 appears to be safe for all ages and can continue to provide prophylaxis of onychomycosis with Intermittent Maintenance use beyond Month 24 to Month 48. Full article

Background: This systematic review reports on treatments for onychomycosis in patients with diabetes and the drug interactions with other drugs in regard to the complicated diabetic patient profile. Methods: The recommendations in the preferred reporting items for systematic reviews and meta-analysis (PRISMA) checklist were applied and the included studies were evaluated using the Consolidated Standards of Reporting Trials (CONSORT) statement and the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement. Searches were conducted in November 2023, using the PubMed (Medline), Scopus, Cochrane Library, and Web of Science databases; studies on antifungal treatments for onychomycosis in patients with diabetes were included. Two authors performed the study selection and data extraction, and any discrepancies between the two reviewers were resolved through discussions with a third reviewer. This review was registered in PROSPERO (CRD42023442107). Results: The systematic review included 10 studies that met the selection criteria. Mycological cures for mild to moderate onychomycosis were: Ageratina pichinchensis (8.6%), 8% ciclopirox (8.6% 24 weeks and 54.3% 48 weeks), 10% efinaconazole (56.5–58.33%), terbinafine (73–76.6%), itraconazole (88.2%), and laser therapy (43.8%). No serious adverse effects or drug interactions were observed because patients with major complications, such as peripheral vascular disease, diabetic neuropathy, liver and renal dysfunction, poorly controlled diabetes, and severe onychomycosis, were excluded. Conclusions: The antifungal treatments described in the included studies are safe for patients with well-controlled diabetes, but there are currently no studies involving patients with diabetes and multiple complications, such as diabetic foot syndrome or severe onychomycosis. Thus, further research is needed in terms of this patient profile. Full article

Background: Recently, an increasing number of resistant-to-terbinafine dermatophytosis cases have been reported. Thus, identifying an alternative antifungal agent that possesses broad-spectrum activity, including against resistant strains, is needed. Methods: We compared the antifungal activity of efinaconazole with that of fluconazole, itraconazole, and terbinafine against clinical isolates of dermatophytes, Candida, and molds using in vitro assays. Minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) of each antifungal agent were quantified and compared. Susceptible and resistant clinical isolates of Trichophyton mentagrophytes (n = 16), Trichophyton rubrum (n = 43), Trichophyton tonsurans (n = 18), Trichophyton violaceum (n = 4), Candida albicans (n = 55), Candida auris (n = 30), Fusarium spp, Scedosporium spp, and Scopulariopsis spp (n = 15 for each) were tested. Results: Efinaconazole was the most active antifungal agent tested against dermatophytes, with MIC50 and MIC90 (concentrations that inhibited 50% and 90% of strains tested, respectively) values of 0.002 and 0.03 mg/mL, respectively. Fluconazole, itraconazole, and terbinafine showed MIC₅₀ and MIC₉₀ values of 1 and 8 mg/mL, 0.03 and 0.25 mg/mL, and 0.03 and 16 mg/mL, respectively. Against Candida isolates, efinaconazole MIC₅₀ and MIC₉₀ values were 0.016 and 0.25 mg/mL, respectively, whereas fluconazole, itraconazole, and terbinafine had MIC₅₀ and MIC₉₀ values of 1 and 16 mg/mL, 0.25 and 0.5 mg/mL, and 2 and 8 mg/mL, respectively. Against various mold species, efinaconazole MIC values ranged from 0.016 to 2 mg/mL versus 0.5 to greater than 64 mg/mL for the comparators. Conclusions: Efinaconazole showed superior potent activity against a broad panel of susceptible and resistant dermatophyte, Candida, and mold isolates. (J Am Podiatr Med Assoc 114(5), 2024; doi:10.7547/22-132) Full article

Introduction: Efinaconazole 10% topical solution labeling for onychomycosis describes phase III trials of 12 months of treatment; the slow growth of onychomycotic nails suggests a longer treatment period may increase efficacy. We present here the first evaluation of extended use of efinaconazole 10% topical solution for up to 24 months. Materials and Methods: Enrolled patients (n = 101) had one target great toenail with mild to moderate distal lateral subungual onychomycosis and applied efinaconazole 10% topical solution to all affected toenails once daily for 18 months (EFN18) or 24 months (EFN24). Efficacy and safety were evaluated at each visit by visual review and mycology sampling. Results: Regarding the target toenail for patients treated for 24 months (EFN24), mycological cure (negative microscopy and culture) was 66.0% at Month 12, increasing to 71.7% at Month 24; effective cure (mycological cure and ≤10% affected nail) was 13.2% at Month 12, rising to 22.6% at Month 24. Mild to moderate application site reactions (symptoms of erythema/scaling) were the only efinaconazole-related reactions, in eight patients (7.9%). No systemic efinaconazole events or drug interactions were found. Patients aged 70 years or more had similar efficacy to younger patients at all time periods and did not show any increased treatment risks. Thinner nails exhibited better clearance versus thicker nails. A higher proportion of patients with Trichophyton mentagrophytes complex infection experienced application site reactions (35.7%), and a higher effective cure was found at Month 24 versus T. rubrum patients. Conclusion: There is a trend of increasing mycological cure and effective cure beyond Month 12 to Month 24, without an increased safety risk. The enrolled population in this trial was significantly older than in the phase III trials, with a greater degree of onychomycosis severity; however, increased age did not appear to reduce the chance of efficacy to Month 24 in this study. Our data suggest that lack of ability to clear nail dystrophy remains a significant problem for patients, rather than any lack of efinaconazole action over long-term treatment periods. Full article

Background: Dermatophytoma, also described as a longitudinal streak/spike, is a form of onychomycosis that presents as yellow/white streaks or patches in the subungual space, with dense fungal masses encased in biofilm. This scoping review of the literature was conducted to address a general lack of information about the epidemiology, pathophysiology, and treatment of dermatophytomas in onychomycosis. Methods: A search was performed in the PubMed and Embase databases for the terms “longitudinal spike” or “dermatophytoma.” Outcomes of interest were definition, prevalence, methods used for diagnosis, treatments, and treatment efficacy. Inclusion and exclusion of search results required agreement between two independent reviewers. Results: Of a total of 51 records, 37 were included. Two reports provided the first unique definitions/ clinical features of dermatophytomas. Overall, many descriptions were found, but one conclusive definition was lacking. Prevalence data were limited and inconsistent. The most frequently mentioned diagnostic techniques were clinical assessment, potassium hydroxide/microscopy, and fungal culture/mycology. Oral terbinafine and topical efinaconazole 10% were the most frequently mentioned treatments, followed by topical luliconazole 5% and other oral treatments (itraconazole, fluconazole, fosravuconazole). In studies with five or more patients without nail excision, cure rates were highest with efinaconazole 10%, which ranged from 41% to 100% depending on the clinical and/or mycologic assessment evaluated. Other drugs with greater than or equal to 50% cure rates were topical luliconazole 5% (50%), oral fosravuconazole (57%), and oral terbinafine (67%). In studies that combined oral terbinafine treatment with nail excision using surgical or chemical (40% urea) methods, cure rates ranged from 50% to 100%. Conclusions: There is little published information regarding dermatophytomas in onychomycosis. More clinical research and physician education are needed. Although dermatophytomas have historically been considered difficult to treat, the efficacy data gathered in this scoping review have demonstrated that newer topical treatments are effective, as are oral antifungals in combination with chemical or surgical methods. Full article

The efficacy of topical antifungal therapy in onychomycosis has been hindered by the failure of the antimycotic to permeate the nail plate. This research aims to design and develop a transungual system for the effective delivery of efinaconazole utilizing constant voltage iontophoresis. Seven prototype drug-loaded hydrogel formulations (E1–E7) were prepared to assess the influence of solvent (ethanol) and cosolvent (Labrasol^®) on transungual delivery. Optimization was performed to evaluate the effect of three independent variables; voltage, solvent-to-cosolvent ratio, and penetration enhancer (PEG 400) concentration on critical quality attributes (CQAs), such as drug permeation and loading into the nail. The selected hydrogel product was characterized for pharmaceutical properties, efinaconazole release from the nail, and antifungal activity. Preliminary data indicates ethanol, Labrasol^®, and voltage influence the transungual delivery of efinaconazole. Optimization design indicates a significant impact by applied voltage (p-0.0001) and enhancer concentration (p-0.0004) on the CQAs. Excellent correlation between selected independent variables and CQAs was confirmed by the high desirability value (0.9427). A significant (p < 0.0001) enhancement in the permeation (~78.59 µg/cm²) and drug loading (3.24 µg/mg) was noticed in the optimized transungual delivery with 10.5 V. FTIR spectral data indicates no interaction between the drug and excipients, while the DSC thermograms confirmed the amorphous state of the drug in the formulation. Iontophoresis produces a drug depot in the nail that releases above the minimum inhibitory concentration level for an extended period, potentially reducing the need for frequent topical treatment. Antifungal studies further substantiate the release data and have shown remarkable inhibition of Trichophyton mentagrophyte. Overall, the promising results obtained here demonstrate the prospective of this non-invasive method for the effective transungual delivery of efinaconazole, which could improve the treatment of onychomycosis. Full article

Fusarium are uncommon but important pathogenic organisms; they cause non-dermatophyte mould (NDM) onychomycosis. Patients typically respond poorly to treatment owing to Fusarium’s native resistance to multiple antifungal drugs. However, epidemiological data for Fusarium onychomycosis are lacking in Taiwan. We retrospectively reviewed the data of 84 patients with positive Fusarium nail sample cultures at Chang Gung Memorial Hospital, Linkou Branch between 2014 and 2020. We aimed to investigate the clinical presentations, microscopic and pathological characteristics, antifungal susceptibility, and species diversity of Fusarium in patients with Fusarium onychomycosis. We enrolled 29 patients using the six-parameter criteria for NDM onychomycosis to determine the clinical significance of Fusarium in these patients. All isolates were subjected to species identification by sequences and molecular phylogeny. A total of 47 Fusarium strains belonging to 13 species in four different Fusarium species complexes (with Fusarium keratoplasticum predominating) were isolated from 29 patients. Six types of histopathology findings were specific to Fusarium onychomycosis, which may be useful for differentiating dermatophytes from NDMs. The results of drug susceptibility testing showed high variation among species complexes, and efinaconazole, lanoconazole, and luliconazole showed excellent in vitro activity for the most part. This study’s primary limitation was its single-centre retrospective design. Our study showed a high diversity of Fusarium species in diseased nails. Fusarium onychomycosis has clinical and pathological features distinct from those of dermatophyte onychomycosis. Thus, careful diagnosis and proper pathogen identification are essential in the management of NDM onychomycosis caused by Fusarium sp. Full article

Onychomycosis is a common nail disease caused by fungi. The primary pathogens are dermatophytes; however, yeasts, non-dermatophyte moulds, and mixed fungal populations may also contribute to the development of a recalcitrant condition, usually accompanied by difficulties in everyday life and severe emotional stress. Treatment failure and relapse of the infection are the most frequent problems, though new issues have become the new challenges in the therapeutic approach to onychomycosis. Resistance to antifungals, an increasing number of comorbidities, and polydrug use among the ageing population are imperatives that impose a shift to safer drugs. Topical antifungals are considered less toxic and minimally interact with other drugs. The development of new topical drugs for onychomycosis is driven by the unmet need for effective agents with prolonged post-treatment disease-free time and a lack of systemic impact on the patients’ health. Efinaconazole, Tavaborole, and Luliconazole have been added to physicians’ weaponry during the last decade, though launched on the market of a limited number of countries. The pipeline is either developing new products (e.g., ME-1111 and NP213) with an appealing combination of pharmacokinetic, efficacy, and safety properties or reformulating old, well-known drugs (Terbinafine and Amphotericin B) by using new excipients as penetration enhancers. Full article

Background: Onychomycosis is the most common nail disease seen in clinical practice. Medication safety, severity of disease, comorbidities, concomitant medications, patient age, and cost are all important considerations when treating onychomycosis. Because cost may affect treatment decisions, we sought to analyze Medicaid formulary coverage of onychomycosis antifungals. Methods: Public state Medicaid formularies were searched for coverage of US Food and Drug Administration–approved onychomycosis medications and off-label oral fluconazole. Total drug cost for a single great toenail was calculated using the National Average Drug Acquisition Cost. Pearson correlation coefficients were calculated to compare coverage and cost, mycologic cure rate, and complete cure rate. Results: Oral terbinafine and off-label fluconazole were widely covered for onychomycosis treatment. There was poor coverage of oral itraconazole and topical ciclopirox, and there was no coverage of topical efinaconazole and tavaborole without step-edits or prior authorization. There was a significant negative correlation between medication coverage and cost (r = 20.758; P = .040). There was no correlation between medication coverage and mycologic (r = 0.548; P = .339) and complete (r = 0.768; P = .130) cure rates. Conclusions: There is poor Medicaid coverage of antifungals for the treatment of onychomycosis, with step-edits and prior authorization based on cost rather than treatment safety and efficacy. We recommend involving podiatrists and dermatologists in developing criteria for insurance approval of onychomycosis treatments. Full article

Dermatophytomas are characterized as a hyperkeratotic fungal mass in the subungual space, showing as dense white or yellow, typically in longitudinal streaks or patches. Masses can be visualized by traditional microscopy or histology. Newer technologies such as dermoscopy and optical coherence tomography also provide visual features for dermatophytoma diagnosis. The density of fungal mass, and lack of adherence to the nail structures, as well as possible biofilm development, may play a role in the reduction in drug penetration and subsequent lack of efficacy with traditional oral therapies such as terbinafine and itraconazole. A combination of drug treatment with mechanical or chemical debridement/avulsion has been recommended to increase efficacy. The topical antifungal solutions such as tavaborole, efinaconazole, and luliconazole may reach the dermatophytoma by both the transungual and subungual routes, due to low affinity for keratin and low surface tension. Current data indicates these topicals may provide efficacy for dermatophytoma treatment without debridement/avulsion. Similarly, fosravuconazole (F-RVCZ) has an improved pharmacological profile versus ravuconazole and may be an improved treatment option versus traditional oral therapies. The availability of improved treatments for dermatophytomas is crucial, as resistance to traditional therapies is on the increase. Full article

As regulatory and technical landscapes for pharmaceutical formulation development are rapidly evolving, a risk-management approach using multivariate analysis is highly essential for designing a product with requisite critical quality attributes (CQA). Efinaconazole, a newly approved poorly water-soluble antifungal triazole drug has poor permeability. Spanlastics, new-generation surfactant nanovesicles, being fluidic, help improve the permeability of drugs. Therefore, we optimized efinaconazole spanlastics using the concepts of Formulation-by-Design (FbD) and explored the feasibility of transungual delivery for the management of onychomycosis. Using the Ishikawa fishbone diagram, the risk factors that may have an impact on the CQA of efinaconazole spanlastic vesicles were identified. Application of the Plackett–Burman experimental design facilitated the screening of eight different formulation and process parameters influencing particle size, transmittance, relative deformability, zeta potential, entrapment efficiency, and dissolution efficiency. With the help of Pareto charts, the three most significant factors were identified, viz., vesicle builder (Span), edge activator (Tween), and mixing time. The levels of these three critical variables were optimized by FbD to reduce the particle size and maximize the transparency, relative deformability, encapsulation efficiency, and dissolution efficiency of efinaconazole spanlastic nanovesicles. Bayesian and Lenth’s analysis and mathematical modeling of the experimental data helped to quantify the critical formulation attributes required for getting the formulation with optimum quality features. The optimized efinaconazole-loaded spanlastic vesicles had a particle size of 197 nm, transparency of 91%, relative deformability of 12.5 min, and dissolution efficiency of 81.23%. The spanlastic formulation was incorporated into a gel and explored ex vivo for transungual delivery. This explorative study provides an example of the application of principles of risk management, statistical multivariate analysis, and the FbD approach in developing efinaconazole spanlastic nanovesicles. Full article