A double-blind, randomized study comparing itraconazole pulse therapy with continuous dosing for the treatment of toe–nail onychomycosis

Abstract

In this multicentre, double-blind, parallel group study, we evaluated the efficacy and safety of continuous treatment with itraconazole, 200 mg daily for 3 months, in comparison with itraconazole pulse therapy, 400 mg daily 1 week per month for 3 months, in the treatment of toe-nail onychomycosis. The study included 129 patients with distal subungual onychomycosis of the toe-nails, confirmed by microscopy and positive for dermatophyte culture; 65 received continuous treatment and 64 received pulse therapy. Patients were followed up for 9 months after treatment. After 12 months, there were 62 evaluable patients in the continuous group and 59 evaluable patients in the pulse group. The clinical response (i.e. the size of the affected area and the progress of the infection) and mycological cure (i.e. negative results on microscopy and culture) were the main outcome measures. A clinical response was defined as a cure or a marked improvement. Clinical response rates were 69%, in the continuous group, and 81% in the pulse group at month 12; the corresponding mycological cure rates were 66 and 69%. A better improvement in signs and symptoms was noted in the pulse group. Six patients were withdrawn from treatment because of adverse events, not all of which were thought to be drug-related. There were no clinically relevant laboratory abnormalities. We conclude that both regimens are effective, safe and well tolerated. The superiority of one treatment over the other was not established, but the results tended to favour pulse therapy. Equivalence testing confirmed that pulse therapy was at least equivalent to continuous treatment.

Oral Treatments for Toenail Onychomycosis

“…Havu et al 21 found that the cure rate was not significantly different between 3 months of continuous treatment with itraconazole (200 mg/d) and an intermittent (1 week of treatment in every 4 [1:4]) regimen of 400 mg/d (N=121). De Doncker et al 20 evaluated 2 different intermittent schedules of itraconazole of 3 and 4 months (400 mg/d; 1:4 weeks) and found that the cure rates at 24 weeks were 64% for patients who received the shorter treatment and 72% for those who received 4 months of treatment.…”

“…De Donker et al, 20 1996 Infected nail length (percentages), onycholysis, and subungual hyperkeratosis Incomplete Havu et al, 21 1997…”

Onychomycosis - epidemiology, diagnosis and management

“…1). [11] However, the worldwide prevalence of onychomycosis is increasing. In one study that evaluated the prevalence and risk factors of onychomycosis in individuals representing different strata of population in New Delhi the prevalence of onychomycosis was conÞ rmed in 45% of the analysed patients.…”

Is This the Right Drug or the Dose for the Management of Onychomycosis?

“…Pulse therapy with itraconazole embodies dosing for 1 week (pulse) per month for a set number of months [17]. The instances of regimens that have been investigated for safety and efficacy in randomized trials included a three and a four pulse regimen with doses of 200 mg of itraconazole twice daily [18,19] and a two pulse regimen with 200 mg of itraconazole twice daily [17,[20][21][22]. Data from clinical practice and clinical trials indicate that the 1-week pulse regimen of itraconazole is well tolerated and associated with a favorable safety profile [23].…”