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Dermatophytes

Dermatophytes are molds that infect keratinized tissues including skin, hair, and nails. Whereas 40 dermatophyte species are known to infect humans, only about 15 of these are common causes of disease. These organisms belong to three genera, Microsporum, Trichophyton, and Epidermophyton. Because these fungi have such similar infectivity, morphology, and pathogenicity, they are often categorized according to the clinical syndrome and the preferred anatomic site with which they are associated, such as tinea capitis, tinea pedis, etc.

Itraconazole 100 mg Capsules (Sporanox)

Like other azoles, it interferes with the cytochrome P-450-dependent enzyme, 14a-demethylase. This leads to 14-methylsterol accumulation and ergosterol depletion in fungal cells and this results in alterations in a number of membrane-associated cell functions. Itraconazole has a broad spectrum of action including Aspergillus species, Blastomyces dermatitidis, Candida species, Coccidioides immitis, Cryptococcus neoformans, Histoplasma capsulatum, Paracoccidioides brasiliensis, Scedosporium apiospermum and Sporothrix schenckii.

Use and Administration of Itraconazole 100 mg (Sporanox)

Itraconazole can be used to treat various superficial fungal infections, including the dermatophytoses, pityriasis versicolor, and mucosal and cutaneous forms of candidosis. It is also effective in patients with subcutaneous infections, such as chromoblastomycosis, sporotrichosis and certain forms of phaeohyphomycosis.

Pharmacokinetics of Itraconazole 100 mg Capsules (Sporanox)

Absorption of itraconazole from the gastrointestinal tract is incomplete (about 55%), but is improved if the drug is given with food. Oral administration of a single 100-mg capsule will produce peak serum concentrations of between 0.1 and 0.2mg/l about 2-4 h later. Higher concentrations are obtained after repeated dosing, but there is marked variation between individuals. As with ketoconazole, there is a disproportionate increase in blood levels with increasing dosage.

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Itraconazole is a triazole antifungal drug. It is used orally to treat oropharyngeal and vulvovaginal candidiasis, pityriasis versicolor, dermatophytoses unresponsive to topical treatment, and systemic infections, including aspergillosis, blastomycosis, chromoblastomycosis, cocci-dioidomycosis, cryptococcosis, histoplasmosis, paracocci-dioidomycosis, and sporotrichosis.

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Itraconazole increases the risk of skeletal muscle toxicity of some statins by increasing their serum concentrations, but not all statins are equally affected. Concomitant use of atorvastatin, lovastatin, and simvastatin with itraconazole should be avoided or the doses should be reduced; fluvastatin and pravastatin have much less potential than other statins for clinically significant interactions with itraconazole and other CYP3A4 inhibitors; the effects of cerivastatin are intermediate. In a randomized, open, three-way, crossover study, 18 healthy subjects took single doses of cerivastatin 0.8 mg, atorvastatin 20 mg, or pravastatin 40 mg without or with itraconazole 200 mg.

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The effect of the combination of itraconazole with amphotericin on liver enzyme activities has been studied retrospectively in 20 patients with hematological malignancies or chronic lung disease complicated by fungal infection or colonization. They took itraconazole 200-600 mg/day for a median of 143 (range 44 days. Nine had no abnormal liver function tests, including periods of high concentrations of itraconazole (over 5000 µg/ml) and its active hydroxylated metabolite; only one had received concomitant amphotericin. All of the 11 patients with liver function abnormalities had received concomitant amphotericin.

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The safety, tolerability, and pharmacokinetics of itraconazole and its active metabolite hydroxyitraconazole after administration of itraconazole solution in hydroxy-propyl-P-cyclodextrin have been investigated in a multi-center study in 26 infants and children aged 6 months to 12 years with mucosal candidiasis or at risk of invasive fungal disease. There was a trend to lower minimum plasma concentrations in children aged 6 months to 2 years. The systemic absorption of the solubilizer hydro-xypropyl-P-cyclodextrin was less than 1%.

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Pleural and subsequent pericardial effusion developed in a woman treated with itraconazole 200 mg bd for a localized pulmonary infection with Aspergillus fumigatus. After more than 9 weeks of treatment she developed a pericardial effusion, which necessitated drainage. Itraconazole was withdrawn. Six weeks later, and 2 weeks after the resumption of itraconazole, she developed signs of pulmonary edema and cardiac enlargement.