Toenail onychomycosis is more effectively treated with oral medications than with topical therapy. Griseofulvin was the initial oral choice, but it must be taken for a long time to be effective. Newer medications that work faster, including azoles and allylamines, are much more expensive. Crawford and associates reviewed data on the clinical effectiveness of oral treatment of toenail onychomycosis.

Comparative and placebo-controlled studies looked at itraconazole, terbinafine, griseofulvin, ketoconazole, and fluconazole. Itraconazole and terbinafine have been demonstrated to be more effective than placebo in two direct-comparison trials (itraconazole in a dosage of 200 mg per day and terbinafine in a dosage of 250 mg per day) lasting almost 12 months, demonstrating a risk difference in favor of terbinafine. Further studies showed no advantage in higher or longer dosing regimens. Intermittent dosing schedules with itraconazole provided cure rates similar to those of continuous treatment.

Studies comparing griseofulvin with itraconazole (at least 500 mg per day compared with 100 mg per day, respectively) and griseofulvin with ketoconazole (500 to 1,000 mg per day compared with 200 mg per day, respectively) have demonstrated low and not significantly different cure rates. Terbinafine (250 mg per day) has been found to be more effective than griseofulvin (1,000 mg per day). Fluconazole has a higher cure rate when compared with placebo, with the highest cure rate following the longest course of treatment (nine months) and accompanying the highest dosage regimen (450 mg per week). Trichophyton rubrum was the most commonly identified fungus in the studies. Adverse effects were similar for all treatments in which they were recorded. Measurements of clinical success varied greatly among studies, and most of the studies were sponsored by manufacturing pharmaceutical companies, making comparisons difficult.

The authors conclude that a pooled analysis of cure rates taken around 12 months demonstrated that terbinafine (250 mg per day) was more effective than itraconazole (400 mg per day) in curing toenail fungal infection. Intermittent regimens of itraconazole appear to have cure rates similar to those of continuous administration. The cure rates appear similar among itraconazole and griseofulvin, and itraconazole and ketoconazole. Fluconazole provides a modest cure rate.

In an editorial in the same issue, Epstein states that variations in definition of cure among studies cause problems in comparisons of treatment efficacies. Because of the decreased efficacy of griseofulvin, ketoconazole, and fluconazole in the treatment of onychomycosis, he notes that further studies of these drugs are no longer appropriate.