Itraconazole in the Treatment of Onychomycosis: A Double-Blind Comparison with Miconazole

Abstract

Background: In recent years, itraconazole pulse therapy for onychomycosis has been developed [three 1-week pulses with itraconazole 400 (2 × 200) mg daily every month]. This has proved an effective and safe regimen which requires only 50% of the medication used for continuous dosing schedules. Parallel to the development of the new dosage schedule, additional studies were conducted to further document the safety and efficacy of itraconazole 200 mg once daily for 3 months to treat onychomycosis. Objective: To compare the safety of itraconazole 200 mg once daily for 3 months, with or without itraconazole 200 mg once weekly for a further 3 months, with that of miconazole cream twice daily for 6 months, in the treatment of onychomycosis. Treatment efficacy was compared as a secondary objective. Methods: In this multicenter, double-blind study, patients were randomized to receive itraconazole 200 mg once daily for 3 months followed by either itraconazole 200 mg once weekly for 3 months (ITR-ITR group, n = 599) or oral placebo once weekly for 3 months (ITR-PLAC group, n = 613), or to receive miconazole cream twice daily for 6 months (MIC-MIC group, n = 396). The primary variable was elevation of alanine aminotransferase (ALT) concentration above 50 U/l. Results: Overall incidence of elevation of ALT concentration above 50 U/l, adverse events and rate of withdrawal because of adverse events were low and similar in the three treatment groups. Efficacy was significantly greater in the ITR groups than the MIC-MIC group. Conclusion: Itraconazole and miconazole were well tolerated and had no significant effect on liver function, but itraconazole was significantly more effective.

A practical application of onychomycosis cure – combining patient, physician and regulatory body perspectives

“…Clinical cure defined as 100% clear nail or 0% nail plate involvement is infrequently reported in oral, topical and laser‐based trials (36–38% of studies) (Table ) . A completely clear nail may not actually be possible in all patients as nail dystrophy and/or matrix damage caused by onychomycosis may be permanent .…”

Oral Treatments for Toenail Onychomycosis

“…Sometimes deviations occurred when undefined clinical cure data were presented. 13,31,37,39 In most reports the reverse was true: authors stated their intention to evaluate the effect of the drug of interest on certain clinical signs and symptoms but failed to present separate data for them. Instead, an estimate of "clinical success" was made without explicit reference to any individual clinical feature.…”

Toenail onychomycosis: current and future treatment options

“…Despite this improvement, cure rates with topical monotherapy remain lower than those with systemic antifungal therapy. Table 2 summarizes major studies evaluating topical antifungal treatments for toenail onychomycosis (26,28,29,57–66).…”

“…Although some of these agents have been researched in large randomized multicenter trials, many other topical therapies have been investigated in nonrandomized and unblinded studies with poorly defined entry criteria and outcome measures. Other topical therapies include bifonazole urea (28,71,72), miconazole (63,64), tioconazole (62,63,73), topical ketoconazole (74), tolnaftate ointment (27), Melaleuca alternifolia (tea tree) oil (65,66), vitamin E (75), and oil of bitter orange (76).…”