Itraconazol

Itraconazole is a triazole antifungal medication used to treat a range of systemic and superficial fungal infections. It works by inhibiting fungal cytochrome P450 14α-demethylase, an enzyme involved in ergosterol synthesis, leading to disruption of the fungal cell membrane and growth arrest.

Itraconazole has activity against many pathogens, including Histoplasma, Blastomyces, Aspergillus, Sporothrix, and certain Candida species. It is used for systemic mycoses as well as dermatophyte infections and onychomycosis. Not all infections respond to itraconazole, and effectiveness depends on the organism and site of infection. Resistance can occur with prolonged exposure.

The drug is available in oral capsules, an oral solution, and an intravenous formulation. Absorption is influenced by the formulation and gastric conditions: capsules are typically taken with a meal to enhance absorption, while the solution has good bioavailability and may be taken without regard to meals in some regimens. Itraconazole is extensively metabolized in the liver by CYP3A4 and has a relatively long half-life, with tissue distribution that includes skin, nails, and other tissues.

Dosing is tailored to the infection and patient, generally ranging from 200 to 400 mg per day for adults. For onychomycosis, pulse regimens (for example, 200 mg twice daily for one week per month for several months) are sometimes used. Safety concerns include potential hepatotoxicity, gastrointestinal upset, and, with certain formulations, negative inotropic effects that can worsen heart failure. It is a strong inhibitor of CYP3A4 and has numerous drug interactions, including with statins, QT-prolonging agents, and CYP3A4 inducers. Caution is advised in pregnancy and lactation, and in patients with liver disease or congestive heart failure.

Itraconazole has been marketed since the 1990s under brand names such as Sporanox, Onmel, and Orungal.