Itraconazole can treat many different fungal infections. Many of these fungal infections are rare; however, they can be detrimental to the immunocompromised. Itraconazole treats blastomycosis, histoplasmosis, and aspergillosis and has FDA approval as a treatment for these infections. However, itraconazole has also shown efficacy in treating paracoccidioidomycosis, coccidioidomycosis, and candidiasis, but it does not have approval from the FDA for these conditions.[1][2] In addition to treating infections, itraconazole can be used as prophylaxis in patients at risk of these systemic fungal infections. Some patient populations that frequently use itraconazole prophylaxis are patients with HIV, those receiving chemotherapy, or people who have had an organ transplant. Itraconazole offers excellent prophylaxis for these immunocompromised patients due to its broad-spectrum coverage, safety profile, and minimal fungal resistance.[3]

In addition to treating systemic infections, itraconazole can also treat superficial fungal infections like onychomycosis, which has FDA approval. However, the cure rate of onychomycosis with itraconazole therapy is only 63%.[4] Itraconazole can also be used to treat moderate to severe seborrheic dermatitis and other topical mycoses, although this use does not have FDA approval. Although itraconazole is an effective therapy for seborrheic dermatitis, antifungal shampoos, and topical steroids are first-line therapies. When treating seborrheic dermatitis, itraconazole administration occurs as a pulse therapy, which means large doses of the drug are administered intermittently to avoid side effects but achieve the drug’s therapeutic effects.[5]

Itraconazole is a broad spectrum anti-fungal agent. Itraconazole inhibits ergosterol synthesis, which helps to maintain the cell membrane in fungi. Lanosterol must undergo a 14 alpha-demethylation reaction, which is catalyzed by fungal cytochrome P450 to become ergosterol. Itraconazole blocks this reaction by interacting with the fungal cytochrome P450 substrate-binding site. This impaired ergosterol synthesis leads to fungal membrane abnormalities that increase permeability and changes membrane-bound enzyme activity.[6]

Itraconazole can be administered intravenously, in a capsule, or as an oral solution that allows administration of the drug in the inpatient or outpatient setting. The absorption of the itraconazole via the capsule is highly variable. This variability results from intestinal epithelial damage and varying gastric acid environments from person to person. However, the newer formulations of the drug, intravenous, and oral solution, which contain hydroxypropyl-beta-cyclodextrin, have shown better absorption and bioavailability.[1][3]

While itraconazole is a relatively safe medication, there are some adverse side effects with itraconazole use. Cardiotoxicity is a rare adverse effect. Itraconazole can decrease heart contractility and left ventricular ejection fraction.[7] The risk of cardiotoxicity increases with a dose greater than 400 mg/day. While most patients' heart function improves after discontinuing itraconazole, some patients require a transplant.[8] Another adverse effect is hepatotoxicity, which is often a reversible increase in aminotransferase levels. This side effect is minimizable with intermittent or short-term dosing. In patients already being treated for hypertension, itraconazole can cause resistant hypertension.[9] The most common adverse effects are gastrointestinal disturbances, such as nausea, mild diarrhea, vomiting, and abdominal pain. Researchers noted these side effects in 2 to 39% of patients that have used itraconazole.[2] When itraconazole administration is via the intravenous formulation, there is also a risk of injection site reactions, headache, and rash.

There are some contraindications for itraconazole use. The main one being heart failure or history of heart failure due to itraconazole’s potential cardiotoxic effects. Another contraindication is liver failure or disease because itraconazole can cause hepatotoxicity. Itraconazole is also contraindicated in pregnant patients. It has demonstrated teratogenic and embryotoxic effects in animal studies. In a systematic review, researchers found itraconazole to cause eye defects in babies whose mothers had exposure to the drug during pregnancy.[10]

Itraconazole also has the potential for many drug-drug interactions because it metabolized by cytochrome P450 3A4 in the liver, like many other drugs. For example, patients taking itraconazole and terfenadine, astemizole, or cisapride may have serious cardiac rhythm disturbances. Itraconazole can also prolong the sedative effects of medications such as midazolam and triazolam, which means clinicians should avoid this combination. Itraconazole can also enhance the effects of oral antidiabetic drugs, which can result in severe hypoglycemia. It is essential to consider drug-drug interactions when prescribing itraconazole, especially if the same cytochrome enzyme metabolizes the other drugs in the liver.[2]