Based upon review of the available literature, it is recommended that clinicians consider the affordable and highly effective topical agents terbinafine and butenafine as first-line therapy for patients with uncomplicated epidermal tinea infections. While also highly effective, naftifine should be considered a second-line treatment due to its prescription-only availability and increased cost. The topical azoles clotrimazole and miconazole are marginally less effective than the allylamines, but are widely available and inexpensive. The prescription drug ciclopirox is slightly superior to the azoles, but its expense and availability make it a less desirable choice for most patients. Tolnaftate is cheap and widely available, but its relative inferiority to other topical agents limits its use in treatment of tinea infections. Tolnaftate may have some utility as a prophylactic against epidermal tinea infections in susceptible individuals.46
For patients with complicated epidermal tinea infections as described above, or for those with confirmed infection and treatment failure using topical agents, oral antifungal medications should be used. Terbinafine and itraconazole are both highly effective and safe in treating tinea infections. Despite their relatively high cost, either of these agents may be considered first-line therapies. Fluconazole has been evaluated in limited trials, but data at this time are insufficient to recommend that it be considered a first-line agent in treatment of epidermal tinea infection.
Griseofulvin may be considered a second-line agent as it has been shown to be clearly less efficacious than either terbinafine or itraconazole. Oral ketoconazole has a limited role in the treatment of tinea infections. It has demonstrated efficacy equivalent to or slightly superior to griseofulvin, but its association with potentially severe liver injury makes it a very problematic choice.
Adverse reactions
As with any systemic medication, adverse effects may occur with oral antifungal agents. Oral antifungal agents are generally considered safe in the treatment of skin dermatophytoses. In systemic review of trials of oral antifungal agents in the treatment of tinea pedis, the most commonly identified adverse events were gastrointestinal complaints such as diarrhea or nausea, headaches, and skin complaints.33
Of particular note, ketoconazole has been repeatedly related to potentially serious hepatotoxicity, especially when used in longer duration of treatment.47 One large cohort study found the incident rate of acute liver injury to be 134.1 per 100,000 person-months among ketoconazole users, compared with 10.4 and 2.5 for itraconazole and terbinafine, respectively.48 Accordingly, baseline and monthly laboratory studies are advised when using ketoconazole.49
Serious complications associated with the use of topical antifungal agents are rare. As with any topical medication, local irritation and dermatitis may occur.
Correspondence Brian Thomas, MD, NOLF-IB, Bldg 184, Box 357140, San Diego, Ca 92135. E-mail: brian.c.thomas@navy.mil.
