itraconazole

Itraconazole is an azole antifungal used to treat a wide range of fungal infections. It inhibits fungal cytochrome P450 14α-demethylase, blocking the conversion of lanosterol to ergosterol and thereby disrupting fungal cell membrane synthesis and growth.

Spectrum and indications: It is active against many Candida species, Aspergillus, several dimorphic fungi such as Histoplasma and Blastomyces, dermatophytes, and other fungi. It is used for mucosal and disseminated candidiasis, histoplasmosis, blastomycosis, sporotrichosis, onychomycosis, and other dermatophytic infections. It is available in oral capsule, oral solution, and intravenous forms.

Pharmacokinetics and safety: Absorption is variable and influenced by formulation and gastric pH; the oral solution is well absorbed, while capsules require acidity and are often taken with meals for better absorption. Itraconazole is extensively metabolized by CYP3A4 and inhibits this enzyme, leading to numerous drug interactions. It is highly protein-bound and, because of hepatic metabolism, hepatic impairment can markedly increase exposure. It is not primarily renally excreted.

Adverse effects and cautions: Common adverse effects include nausea, abdominal pain, and headache; serious hepatotoxicity and heart failure have been reported. Use with caution in patients with heart failure or reduced ventricular function. It has many drug interactions with statins, certain antiarrhythmics, calcineurin inhibitors, and HIV protease inhibitors. Pregnancy should be avoided unless benefits outweigh risks (pregnancy category C). Dosing is infection-specific and should follow guidelines, with monitoring of liver function and drug interactions.