Itraconazole (Sporanox)

Requires gastric acidity for absorption and should not be taken with antacids and is best taken after meals.

90-100% effective in the treatment of sporotrichosis.

Active in vitro and in vivo for Aspergillus fumigatus, Candida spp., Cryptococcus neoformans, Trichophyton spp., and the dimorphic fungi (Blastomyces dermatitidis, Histoplasma capsulatum, Coccidioides spp., Paracoccidioides brasiliensis, Penicillium marneffei, and Sporothrix schenckii).

Indicated for treatment of non-CNS-invasive aspergillosis[ and increases response rates when added to steroid-treated patients with allergic bronchopulmonary aspergillosis.

Itraconazole capsules are the treatment of choice for indolent cases of blastomycosis and histoplasmosis, nonmeningeal forms of coccidioidomycosis, and paracoccidioidomycosis.

The capsule form is also useful for the treatment of sporotrichosis and penicilliosis marneffei and the various dermatophytoses, including onychomycosis of the toenail and fingernail

HIV patients with histoplasmosis should receive lifelong maintenance therapy.

It has no place in the therapy of cryptococcosis, mainly due to poor CNS penetration and high incidence of relapse.

Intravenous itraconazole has been approved for use in persistently febrile neutropenic patients when a fungal etiology is suspected.

Oral itraconazole solution is indicated for the therapy of oropharyngeal and esophageal candidiasis.

Ottawa onazole suspension prevents invasive fungal infections when used for prophylaxis in patients with hematological malignancies and can be a reasonable alternative to fluconazole in this setting.

Side effects include nausea, epigastric pain, hypercholesterolemia, and hypertriglyceridemia.

Water insoluble, and its bioavailability is variable after oral ingestion.

Best absorbed with food.

The oral solution generally achieves higher bioavailability than the capsule.

Unpredictable bioavailability of the oral solution is seen in bone marrow transplants and human immunodeficiency virus (HIV) patients.

After absorption, itraconazole is found in equal amounts in plasma as native drug and the hydroxy-itraconazole metabolite.

Metabolized in the liver and is a substrate and strong inhibitor of CYP3A4.

Elimination half-time is ∼30 to 40 hours after both oral and intravenous administration, and steady-state concentration is reached after 4 days of treatment.

Does not penetrate the CSF.

Patients with creatinine clearance of less than 30 mL/min should not be treated with intravenous itraconazole.

Causes nausea and vomiting, and these symptoms are dose dependent.

Dividing the dose increases tolerance.

Other adverse events include AST/ALT (alanine aminotransferase) elevation, hypokalemia, and rash.

Hypokalemia can be severe, especially in high doses (> 400 mg daily) and accompanied by hypertension and dependent edema.

The oral solution is generally less well tolerated due to the presence of cyclodextrin, which can cause diarrhea and gastrointestinal discomfort, possibly due to osmotic effect.

Serious hepatotoxicity can lead to liver failure but is rare.

Heart failure is caused by a direct negative inotropic effect.

Intravenous itraconazole can cause chemical phlebitis.

Use in pregnancy and lactation is contraindicated (class C).

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