What Is New in Fungal Pharmacotherapeutics?
April 2014 | Volume 13 | Issue 4 | Original Article | 389 | Copyright © April 2014
Ethan T. Routt MD,a Shelbi C. Jim On MD,a Joshua A. Zeichner MD,a and Leon H. Kircik MDb,c,d
aIcahn School of Medicine at Mount Sinai, New York, NY bDepartment of Dermatology, Indiana University School of Medicine, Indianapolis, IN cPhysicians Skin Care, PLLC, Louisville, KY dDepartment of Dermatology, Mount Sinai School of Medicine, New York, NY
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. J Drugs Dermatol.
Superficial cutaneous mycoses (SCM) are frequently encountered skin infections affecting 20-25% of the population worldwide.1 SCM are typically categorized by the location of fungal infection and further subdivided by its causative dermatophyte. Current therapies include an array of systemic and topical agents. Successful therapeutic outcomes are limited by patient non-adherence, medication side effects, potential drug interactions, antifungal resistance and disease recurrence. In the following, we will review several new and emerging pharmacotherapeutics for onychomycosis and tinea pedis.
Onychomycosis is a fungal infection of the nail unit (eg, nail plate, nail bed, and periungal tissue). Dermatophytes, yeasts, and nondermatophyte molds are common etiologic agents. Four onychomycosis variants exist: distal subungual onychomycosis, white superficial onychomycosis, proximal subungual onychomycosis, and candida onychomycosis. The dermatophyte Trichophyton rubrum is responsible for up to 90% of infections, followed by Trichophyton mentagrophytes.2 Less common pathogenic organisms include other dermatophytes, eg, Trichophyton tonsurans, Microsporum canis, and Epidermophyton Floccosum; yeasts, eg, Candida albicans and Candida parapsilosis; and molds, eg, Acremonium spp, Fusarium spp, Aspergillus, and Scytalidium spp.1
Approximately 10-12% of the US population3 suffers from onychomycosis and its incidence increases with advanced age. While most patients are asymptomatic, those who seek medical attention suffer from pain, paronychia, and interference with normal function.4
Several therapeutic options exist for onychomycosis, however it continues to be a challenge to clear and maintain. The primary endpoint in clinical trials evaluating onychomycosis treatment is the “complete cure,” defined as a negative fungal culture and potassium hydroxide (KOH) prep, as well as restoring the normal appearance of the nail. “Mycologic cure,” on the other hand, refers to onychomycotic nails, which are not 100% anatomically clear, but yield a negative fungal culture. Current systemic therapies include fluconazole, itraconazole, and terbinafine, while topically ciclopirox nail lacquer may be used.5
New Therapies for Onychomycosis
Itraconazole 200 mg single daily dose received FDA approval in April 2010 for the treatment of onychomycosis caused by T. rubrum or T. mentagrophytes in non-immunocompromised patients. Itraconazole is an azole antifungal agent with antifungal activity through cytochrome P450-dependent synthesis of ergosterol resulting in the disruption of fungal cell membrane and associated enzyme systems. The efficacy of the 200 mg single daily dose of itraconazole is comparable to two 100 mg itraconazole QD6 (Table 1).