Itraconazole pulse therapy for onychomycosis and dermatomycoses: An overview☆,☆☆,★
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STATISTICS
The efficacy rates for the treatment of tinea pedis, tinea corporis/cruris, tinea versicolor, and onychomycosis were derived from studies performed worldwide using similar protocols. The results have been combined by means of the method of DerSimonian and Laird,8 and modified for single group analysis.9 This method results in a sample-size weighted average and a standard error for each feature. The 95% confidence interval (CI) is 1.96 × standard error.
TINEA PEDIS/MANUUM
Initially itraconazole 100 mg/day was given for 4 weeks, with a subsequent dose of 200 mg/day for 2 weeks.10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 Based on the pharmacokinetics, and because the palms and soles have a thicker stratum corneum, lack sebaceous glands, and have a slower turnover rate than glabrous skin, the dosage was increased to 400 mg/day while reducing the duration of therapy to 7 days.21, 22, 23 Because the drug remains in skin for at least 4 weeks after completion of
TINEA CORPORIS/CRURIS
In the earlier studies itraconazole 100 mg/day was used for 15 days.25, 26, 27, 28, 29 The pharmacokinetics of itraconazole led to a regimen of 200 mg/day for 1 week.30, 31 With itraconazole 100 mg/day for 2 weeks (n = 73), 2 to 4 weeks after the completion of therapy, pooled data from studies with similar protocols indicate CR and MC rate of meta-average (± SE) 91% ± 10% and 76% ± 6%, respectively.24, 25 With 200 mg/day for 1 week (n = 354) the CR and MC rate at follow-up were 90% ± 4% and 77%
ADVERSE EVENTS DURING TRIALS IN TINEA PEDIS AND TINEA CORPORIS/CRURIS
The following itraconazole dosage regimens have been analyzed: 200 mg/day for 1 week (n = 386), 400 mg/day for 1 week (n = 275), 100 mg/day for 2 weeks (n = 54), 100 mg/day for 4 weeks (n = 68), and placebo (n = 50).25 For the whole group the most common adverse events were (itraconazole vs placebo; attributable risk [AR]): headache 3.2% vs 6% (AR: −2.8%), somnolence 0.8% vs 0% (AR: 0.8%), fatigue 0.5% vs 0% (AR: 0.5%), dizziness 0.4% vs 0% (AR: 0.4%), abdominal pain 1.5% vs 0% (AR: 1.5%),
TINEA VERSICOLOR
One week of itraconazole 200 mg/day given for 7 days is effective in the treatment of pityriasis versicolor.32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42 The majority of Malassezia furfur strains are sensitive to itraconazole 0.1 μg/ml.38 The data from worldwide studies can be divided into two groups: patients (n = 135) treated with a total dosage less than 1000 mg, usually 100 mg/day for 7 days, and those treated with a cumulative dose equal to or exceeding 1000 mg (n = 351).36, 37 In the latter
SEBORRHEIC DERMATITIS
Itraconazole 200 mg/day given for 1 week is also effective in the treatment of seborrheic dermatitis with CR in 91% of patients (n = 100).24
FINGERNAIL AND TOENAIL ONYCHOMYCOSIS
De Doncker et al.4, 43 demonstrated that onychomycosis of the fingernails and toenails is effectively treated with two pulses and three pulses, respectively. Subsequently, studies performed worldwide have confirmed the efficacy of itraconazole PT in both fingernail and toenail onychomycosis.44, 45, 46, 47, 48, 49 When three pulses of itraconazole are used to treat dermatophyte toenail onychomycosis, pooled data (14 studies, 1389 patients) indicate a clinical cure (CC) rate, CR, and MC rate
ADVERSE EFFECTS WITH ITRACONAZOLE PT FOR ONYCHOMYCOSISSEBORRHEIC DERMATITIS
The spectrum of adverse effects observed is similar to that seen with the treatment of dermatomycoses.45, 50 The most common adverse effects were gastrointestinal disorders (abdominal pain, nausea, constipation, flatulence, diarrhea, dyspepsia), fatigue, rash, pruritus, and headache. On the basis of the pooled worldwide data (n = 2108) when PT was used to treat dermatophyte toenail onychomycosis, the adverse effects rate was 18.6%, with 17.9% for placebo.24 With PT the rate of elevation of LFTs
MONITORING DURING THERAPY
Itraconazole PT is well tolerated and the incidence of adverse effects is comparable to placebo therapy. In the international product monograph57 and the U.S. product monograph,58 there are no monitoring guidelines or requirements. Consideration may be given to performing pretherapy monitoring, especially when indicated by history. In addition, patients might benefit from being advised about potential adverse effects of therapy.
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Systemic Antifungal Agents
2020, Comprehensive Dermatologic Drug Therapy, Fourth EditionAcral manifestations of fungal infections
2017, Clinics in DermatologyCitation Excerpt :Systemic therapy is rarely required.3 Researchers have reported that itraconazole 2 × 200 mg daily for 1 week was very effective.12 Others have also reported that both itraconazole 100 mg for 4 weeks and 400 mg for 1 week treatment regimens were effective and well tolerated for the treatment of tinea manuum.13
Systemic antifungal agents
2012, Comprehensive Dermatologic Drug Therapy: Expert Consult - Online and PrintCutaneous drug reactions
2009, Weedon's Skin Pathology: Third EditionCombatting antifungal resistance: Paradigm shift in the diagnosis and management of onychomycosis and dermatomycosis
2023, Journal of the European Academy of Dermatology and Venereology
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From the Janssen Research Foundation, Beerse,a and the Division of Dermatology, Department of Medicine, Sunnybrook Health Science Center and the University of Toronto.b
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Reprints not available from the authors.
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