TRACON-Q 200 CAPSULES

Indications

• Fungal infections
• Tinea corporis
• Tinea cruris
• Onychomycosis
• Aspergillosis
• Histoplasmosis
• Systemic candidiasis

Mechanism of action

Itraconazole mediates its antifungal activity by inhibiting 14α-demethylase, a fungal cytochrome P450 enzyme that converts lanosterol to ergosterol, a vital component of fungal cell membranes. The azole nitrogen atoms in itraconazole's structure form a complex with the active site of this enzyme, impeding its function. This results in the accumulation of lanosterol and 14-methylated sterols, increasing the permeability of the fungal cell membrane and leading to cell death. Other proposed mechanisms include the inhibition of cytochrome c oxidative and peroxidative enzymes, further disrupting fungal cell membranes.

Pharmacodynamics

Itraconazole is an antifungal agent that inhibits cell growth and promotes cell death of fungi. It exhibits in vitro activity against various fungi, including _Blastomyces dermatitidis_, _Histoplasma capsulatum_, _Histoplasma duboisii_, _Aspergillus flavus_, _Aspergillus fumigatus_, and _Trichophyton_ species. Its effectiveness depends on the specific fungal strain and the site of infection.

Pharmacokinetics

Itraconazole is well-absorbed when taken orally, with absorption enhanced by the presence of food. It has a large volume of distribution, indicating extensive tissue binding. The drug undergoes hepatic metabolism primarily through cytochrome P450 enzymes, particularly CYP3A4, and is eliminated via the feces and urine. Itraconazole has a long half-life, allowing for once-daily dosing in many cases. Plasma concentrations can be affected by various drug interactions, necessitating careful monitoring.

Adverse effects

• Hepatic necrosis
• Dizziness
• Syncope
• Confusion
• Nausea
• Vomiting
• Headache
• Abdominal pain
• Rash
• Allergic reactions

Interactions

• carbamazepine+itraconazole: Moderate (decreases efficacy)
• itraconazole+anti-androgens: Moderate (increases exposure)
• itraconazole+darolutamide: Moderate (increases exposure)
• fosphenytoin+itraconazole: Unknown (decreases exposure)
• phenobarbital+itraconazole: Unknown (decreases concentration)
• phenytoin+itraconazole: Unknown (decreases exposure)
• primidone+itraconazole: Unknown (decreases concentration)
• itraconazole+aliskiren: Unknown (increases exposure)
• cobicistat+itraconazole: Unknown (increases exposure)
• itraconazole+coumarins: Unknown (increases anticoagulant effect)

Precautions

• Monitor liver function during high doses or extended courses
• Discontinue if signs or symptoms of hepatic disease occur
• Caution advised for patients regarding driving and skilled tasks due to potential effects

Pregnancy

Use during pregnancy only if the potential benefit justifies the potential risk to the fetus. Consult relevant guidelines for detailed information.

Breast-feeding

Precaution is advised; it is unknown if itraconazole is excreted in human milk. Consult relevant guidelines for detailed information.

Storage

Store in a refrigerator (2–8°C) and consult product literature for specific storage recommendations.

Formulations

• 100 mg capsules
• 200 mg capsules
• Powder for solution for infusion

Mechanism of action

Itraconazole mediates its antifungal activity by inhibiting 14α-demethylase, a fungal cytochrome P450 enzyme that converts lanosterol to ergosterol, a vital component of fungal cell membranes. The azole nitrogen atoms in the chemical structure of itraconazole form a complex with the active site, or the haem iron, of the fungal enzyme to impede its function. The accumulation of lanosterol and 14-methylated sterols results in increased permeability of the fungal cell membrane, and modified membrane-bound enzyme activity, and dysregulated chitin synthesis. Other proposed mechanisms of action of itraconazole include the inhibition of fungal cytochrome c oxidative and peroxidative enzymes that also lead to the disruption of fungal cell membranes. In vitro studies have demonstrated that itraconazole inhibits the cytochrome P450-dependent synthesis of ergosterol, which is a vital component of fungal cell membranes.

Pharmacodynamics

Itraconazole is an antifungal agent that inhibits cell growth and promotes cell death of fungi. It exhibits in vitro activity against _Blastomyces dermatitidis_, _Histoplasma capsulatum_, _Histoplasma duboisii_, _Aspergillus flavus_, _Aspergillus fumigatus_, and _Trichophyton_ species.