Therapeutic Efficacy and Safety of One-Week Intermittent Therapy with Itraconazole for Onychomycosis in a Chinese Patient Population

Abstract

Objective: To evaluate the efficacy and safety of a 1-week intermittent itraconazole dosing schedule for onychomycosis. Methods: In this multicenter, open-label study, 646 patients received itraconazole 200 mg twice daily for 1 week/month, followed by 3 weeks without therapy. Patients with fingernail infections received 2 treatment cycles, patients with toenail or combined toenail and fingernail infections received 3 cycles. Efficacy was evaluated at week 9 (2-month regimen), week 13 (3-month regimen) and 3, 6 or 9 (toenails only) months after completion of therapy. Results: Clinical and mycologic cure rates for fingernails were greater than 90% 6 months after completion of 2 treatment cycles. Clinical and mycologic cure rates for toenails were 84 and 98%, respectively, 9 months after completion of 3 cycles. Treatment was well tolerated; adverse events (mostly mild) occurred in 4.6% of patients. Conclusion: A 1-week intermittent itraconazole dosing regimen is a safe and effective treatment for onychomycosis.

Itraconazole and Fluconazole and Certain Rare, Serious Adverse Events

“…We identified 15 patients with potentially drug-induced serious illness and sent for their medical records (13) and death certificates (2). After review of records, we identified two newly diagnosed adverse liver events, one of which was serious and required hospitalization, and two adverse blood disorders for which a drug etiology could not be ruled out.…”

Pharmacoeconomic analysis of the new oral antifungal agents used to treat toenail onychomycosis in the USA

“…1,2 Until the mid-1990s the agents used to treat onychomycosis in the US were griseofulvin and ketoconazole 3 . Of the newer oral antifungal agents available for the treatment of onycho- 11 Double-blind, randomized, comparative 1000 12 months 59/72 (81.9) Walsøe et al 12 Double-blind, comparative 500 6 months 0/10 (0) ITRACONAZOLE (continuous) Arenas et al 13 Open 24 Open 400 mg ϫ 1 week 3 pulses 41/50 (82.0) Canadian package insert 25 Double-blind, randomized placebo-controlled 400 mg ϫ 1 week 3 pulses 48/78 (61.5) Evans et al 26 Double-blind, randomized comparative 400 mg ϫ 1 week 3 or 4 pulses 41/107 (38.3) Ginter et al 27 Open 400 mg ϫ 1 week 3 or 4 pulses 152/197 (77.0) Haneke et al 28 Open 400 mg ϫ 1 week 3 or 4 pulses 465/567 (82.0) Haneke et al 29 Double-blind, randomized comparative 200 3 months 400/540 (74.0) Havu et al 19 Double-blind, randomized comparative 400 mg ϫ 1 week 3 pulses 41/59 (69.5) Kejda 30 Open, randomized 400 mg ϫ 1 week 3 pulses 20/26 (75.0) Negroni et al 31 Open 400 mg ϫ 1 week 3 or 4 pulses 83/117 (71.0) Svejgaard et al 32 Double-blind, randomized comparative 400 mg ϫ 1 week 3 pulses 74/158 (47.0) Tosti et al 33 Open, randomized comparative 400 mg ϫ 1 week 4 pulses 15/20 (75.0) Wang et al 34 Open 400 mg ϫ 1 week 3 pulses 105/107 (98.1) TERBINAFINE (Continuous) Alpsoy et al 35 Open, randomized comparative 250 mg/day 3 months 19/24 (79.2) Arenas et al 13 Open 16 Double-blind, randomized comparative 250 mg/day 3 months 73/109 (67.0) Evans et al 26 Double-blind, randomized comparative 250 mg/day 3 or 4 months 81/107 (75.7) Faergemann et al 10 Double-blind, randomized comparative 250 mg/day 4 months 36/43 (83.7) Goodfield et al 37 Double-blind, randomized placebo-controlled 250 mg/day 3 months 37/45 (82.2) Havu et al 38 Double-blind, randomized comparative 250 mg/day 3 months 41/46 (89.1) Honeymann et al 20 Double-blind, randomized comparative 250 mg/day 4 months 78/82 (95.3) Kejda 30 Open, randomized 250 mg/day 3 months 19/25 (76.0) Negroni et al 31 Open 250 mg/day 3 months 60/111 (53.1) Svejgaard et al 39 Double-blind, randomized comparative 250 mg/day 3 months 19/48 (39.6) Svejgaard et a...…”

Comparison of efficacy criteria across onychomycosis trials: need for standardization

“…Forty‐four studies are included in this analysis 5–48 . The efficacy parameter used predominantly to determine the effectiveness of treatment is mycologic cure, defined by most studies as “negative culture and negative microscopy.” There are variations of this definition, where mycologic cure is defined as either negative culture or negative microscopy alone 5–7 .…”

“…The most common definitions of clinical response are “cured or markedly improved.” Less common definitions include: “clinical cure or improvement sufficient to reduce the affected area of the target nail to < 25%,” 8,9 “patients with 90% to 100% clear nail,” 7 and “cured, markedly improved, improved and not improved.” 19 In some studies, clinical response has been “monitored by observance of the outgrowth of a scratch mark placed at the border between infected and normal areas.” 20,21 In another study, clinical response has been defined as the “per cent of patients achieving more than 4 mm outgrowth of normal nail and the sum of clinical signs and symptoms scores including onycholysis, hypenkeratosis, brittleness and paronychial inflamation,” 22 while other studies have used “mycologic cure and at least 5 mm of new clear toenail growth.” 23,24 Clinical response has also been reported as clinical efficacy, clinical success, and effective therapy.…”