Itraconazole

Itraconazole is an antifungal medication used to treat a variety of fungal infections, including those affecting the mouth, vagina, skin, and nails (both fingernails and toenails). It works by disrupting the fungal cell membrane, inhibiting fungal growth and aiding in the resolution of the infection. Approved by the FDA in 1992, itraconazole is effective against infections caused by Cryptococcus, Histoplasma, Aspergillus, and Blastomyces. While itraconazole has demonstrated effectiveness in treating paracoccidioidomycosis, coccidioidomycosis, and candidiasis, it is not approved by the FDA for these conditions.

BRAND NAMES:

Sporanox - Sporanox contains Itraconazole as the main active ingredient for 1ml oral solution contains 10mg itraconazole.

Tolsura - Tolsura available in capsules contains itraconazole 65 mg and 130mg.

MECHANISM OF ACTION:

Itraconazole have an active metabolite hydroxyitraconazole. Itraconazole inhibits ergosterol synthesis, which helps maintain the cell membrane in fungi. Lanosterol must undergo a 14 alpha-demethylation reaction to become ergosterol, which is catalyzed by fungal 14 alpha-demethylase. It blocks this reaction by interacting with the fungal 14 alpha-demethylase substrate–binding site. This impaired ergosterol synthesis leads to fungal membrane abnormalities that increase permeability and disrupt fungal cell membrane integrity, changing membrane-bound enzyme activity.

PHARMACOKINETICS:

Absorption: The bioavailability of itraconazole is significantly affected by food it will be enhanced when taken with food or acidic beverages. The absorption rate may be reduced in patients with achlorhydria or those using proton pump inhibitors, as itraconazole, requires an acidic environment for optimal absorption.

Distribution: It has a high volume of distribution and is highly protein bound approximately 99% primarily to albumin.

Metabolism: Itraconazole is primarily metabolized in the liver by cytochrome P450 ENZYMES. The drug’s metabolism produces active metabolites, such as hydroxyitraconazole, which also contribute to its antifungal activity.

Excretion: It is mainly excreted through feces, only a small amount being eliminated through the urine.

DOSAGE AND ADMINISTRATION:

The drug dosage is prescribed depending on the severity of the patient's health, and age.

For fungal infections, the prescribed dose is 200mg by mouth daily or twice daily. 200mg twice daily mostly prescribed for three days in life-threatening infections. The maximum dose is 600mg daily.
For oropharyngeal, 20ml orally for one to two weeks, alternately, 10ml dose orally twice daily for 2 to 4 weeks. In esophageal, 20ml orally twice daily for 14 to 21 days.
For treating Onychomycosis of the fingernails, the recommended dosage is 200mg orally twice daily for seven days, followed by 21 days off.
In treating Histoplasmosis, 200mg orally daily capsules, maximum dosage of 400mg per day. The dosage can be increased based on the therapeutic effects.
For treating invasive aspergillus, 20ml orally every 12 hours, alternatively 200 to 400mg daily capsules.
For treating Onychomycosis of the toenails, 200mg capsules each day for 2 weeks is prescribed. For treating blastomycosis, 200mg oral capsules maximum dose of 400mg per day are prescribed.

CONTRAINDICATIONS:

Itraconazole is contraindicated in patients with heart failure, liver impairment, or hypersensitivity to itraconazole or its components.

DRUG INTERACTIONS:

While taking itraconazole some medicines should be avoided as some drugs interact with the other drugs and cause severe adverse effects. Below are a few drugs that should be avoided while taking itraconazole.