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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.

Background: As the use of the newer oral antifungal agents for the treatment of superficial fungal infections becomes more widespread, the issue of safety surrounding their use is becoming an increasingly important consideration. Itraconazole is effective and well tolerated, with most side effects being minor and reversible. The most common adverse events are gastrointestinal upset, headache, and transient skin reaction. There have also been rare reports of hepatitis., Objective: To assess the hepatic safety of pulse and continuous itraconazole in the treatment of onychomycosis., Methods: An analysis was performed on all itraconazole clinical trials sponsored by Janssen Research Foundation in the treatment of onychomycosis, where there was an assessment of laboratory safety. A review of the published literature was also undertaken to assess the hepatic safety of itraconazole in common practice., Results: The data indicate that itraconazole pulse treatment is safe, with no significant differences in the number of code 4 abnormalities (baseline value is in the normal range and at least two values, or the last testing in the observation period, exceed twice the upper limit of normal) in the liver function parameters studied: alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, and total bilirubin. The incidence of all the code 4 abnormalities was below 2%. In the literature there are reports of symptomatic hepatitis with itraconazole continuous therapy but no published report of symptomatic hepatotoxicity using the pulse regimen., Conclusions: Itraconazole pulse therapy for onychomycosis appears to be safe, especially from the perspective of potential liver damage. In the itraconazole package insert liver function tests are recommended for patients receiving continuous itraconazole for periods of time exceeding 1 month. There is no such monitoring requirement for the pulse regimen unless the patient has a history of underlying hepatic disease, the liver function tests are abnormal at baseline, or at any time that there is the development of signs or symptoms suggestive of liver dysfunction.

Tinea capitis is the most common pediatric fungal infection, usually affecting school-age children. It is caused by a dermatophyte from the genus Trichophyton or Microsporum. The predominant pathogens vary according to geographic location. Infection rates are higher in urban regions, especially those with overcrowded living conditions. In the United States, the incidence is highest among African-American children and appears to be significantly lower among Asian Americans. Tinea capitis may persist into adulthood, especially in females with Trichophyton tonsurans infection. Tinea capitis also has been reported in neonates, infants, and elderly patients.

Onychomycosis in children is often accompanied by tinea pedis and a family history of onychomycosis. The prevalence of onychomycosis in children is substantially lower than that of adults; therefore it is important to confirm the clinical diagnosis. The most common presentation of onychomycosis is the distal and lateral subungual type. The organism most commonly isolated in North America is Trichophyton rubrum. Oral antifungal therapy is required, especially when the onychomycosis is of moderate to severe intensity, with nail matrix involvement. The new oral antifungal agents itraconazole, terbinafine, and fluconazole are being increasingly used for the treatment of onychomycosis. Review of the literature suggests that these agents are effective and safe in managing onychomycosis in children. The short duration of therapy required with these drugs should help improve compliance. The data suggest that the new oral antifungal agents have a role in the treatment of onychomycosis in children. Further experience will help us better position these drugs when evaluating the management of onychomycosis in children.

Superficial cutaneous and mucosal Candida infections are common and widely affect both the immunocompromised as well as the immunocompetent populations. Common infections may include Candida paronychia, cutaneous candidiasis, oral candidiasis, vulvovaginal candidiasis, and Candida onychomycosis. Although C albicans has been considered to be the most common pathogen, other Candida species have emerged as potential causes of certain infections. Currently, a variety of antifungal agents is available to treat these infections. They include fluconazole, ketoconazole, and itraconazole. These agents have been widely used to treat fungal infections, including superficial and systemic candidiasis. However, some concerns exist regarding safety associated with long-term use of ketoconazole, and emerging issues of Candida resistance to fluconazole in some patient subsets have been reported. Itraconazole has proven efficacy in treating cutaneous and mucosal Candida infections. Additionally, studies have demonstrated that itraconazole may have increased efficacy and an excellent safety profile when administered in a pulse-dose, or intermittent fashion, for superficial mycotic infections. Itraconazole is an effective agent that warrants consideration when selecting treatment for Candida infections.

Terbinafine is an allylamine antifungal agent widely used to treat dermatophyte onychomycosis and dermatomycoses. We report 10 severe cutaneous adverse reactions associated with terbinafine therapy which required discontinuation of the antifungal agent: erythema multiforme (five patients), erythroderma (one), severe urticaria (one), pityriasis rosea (one) and worsening of pre-existing psoriasis (two patients). The spectrum of cutaneous adverse effects associated with terbinafine therapy is reviewed. Patients should be counselled about discontinuing terbinafine at the onset of a cutaneous eruption and about seeking medical advice about further management.

Terbinafine is an allylamine antifungal agent first launched in the USA in May 1996 with an estimated 7.5 million individuals worldwide having used the drug. Given orally it is effective for the treatment of dermatophyte infections and is prescribed predominantly for the superficial mycoses. Adverse effects have been reported in 46.7% of patients receiving the oral drug (compared with 29.2% receiving placebo, the attributable risk to terbinafine being 17.5%). Thus, oral terbinafine is associated with the rare development of symptomatic idiosyncratic hepatobiliary dysfunction (1:45,000-1:54,000) and we now describe three patients who developed this disorder whilst taking the medication. The hepatitis produced has the features of both hepatocellular necrosis (with elevations of hepatic enzyme concentrations) and cholestatic injury (with elevations of alkaline phosphatase and cholesterol levels), the latency period between the start of medication and the development of liver injury being approximately 4-6 weeks. The US terbinafine product monograph recommends that serum hepatic enzymes should be assessed in individuals receiving terbinafine for more than 6 weeks, as a result of which some physicians monitor these values at baseline and at 4-6 weeks.

Onychomycosis is one of the most stubborn superficial mycoses. With few exceptions, oral antifungal therapy is needed to achieve resolution. Before oral itraconazole, fluconazole, and terbinafine hydrochloride became available, physicians had to rely on prolonged therapy with griseofulvin or oral ketoconazole. Of the newer oral agents, itraconazole appears to have the broadest spectrum of action, with therapeutic activity against dermatophytes, yeasts, and some nondermatophyte molds. Tissue pharmacokinetics accounts for significantly greater efficacy and much shorter treatment courses for fungal infections of the skin and nails. In general, oral itraconazole, fluconazole, and terbinafine are very well tolerated. The newer oral agents offer improved efficacy over griseofulvin and ketoconazole for onychomycosis and dry tinea pedis.

A 40-year-old woman had a 10-year history of dermatophyte-related toenail onychomycosis (tinea unguium) and dry-type tinea pedis, which had failed to respond to previous therapy with topical antifungal agents or oral griseofulvin. The patient was successfully treated with four cycles of intermittent itraconazole therapy (that is, 400 mg/d for 1 week per month for 4 months). At the end of this time, the tinea pedis had resolved and the onychomycosis improved significantly after four cycles were completed. Twelve months after the onset of therapy, both conditions had resolved completely according to both clinical and mycologic criteria. Itraconazole was well tolerated, with no side effects reported. These observations suggest that itraconazole intermittent dosing is a highly effective therapy for the treatment of onychomycosis caused by dermatophyte organisms, because it provides a high cure rate after only a short course of therapy.