Itraconazole (Sporanox)

Itraconazole (Sporanox) is an anti-fungal drug. It works by inhibiting the synthesis of ergosterol, a main component in the fungal cell membrane. It is related to ketoconazole (Nizoral) and fluconazole (Diflucan).

Itraconazole is an approved treatment for several HIV-related fungal infections. It is a first-line treatment for candidiasis (thrush) in the mouth, throat or vagina, and for fungal infections of the toes such as tinea and onychomycosis.

It is also an approved treatment for systemic histoplasmosis, cryptococcosis, and aspergillosis, where other treatments are in appropriate or ineffective. For people with impaired immune function who have been treated for a fungal infection, itraconazole may be used as maintenance therapy to prevent relapses.

There are three formulations of itraconazole: capsules, solution and a formulation for intravenous infusion. It requires the stomach to be acidic for it to be properly absorbed, so it should not be taken at the same time as antacids or drugs that include an antacid such as the tablet form of ddI (didanosine, Videx). Two to three times as much drug is absorbed when it is taken with food compared with when taken on an empty stomach.

Itraconazole solution is licensed in the United Kingdom for treating oral and oesophageal candidiasis. For optimal absorption it should be taken without food. The liquid should be swished around the mouth and swallowed. The mouth must not be rinsed with water afterwards. The standard dose is 200mg per day for one week. If this is not sufficient, it can be continued for a second week. The dose and duration of treatment may be doubled when treating fluconazole-resistant Candida strains.

Side-effects include diarrhoea, nausea, vomiting and abdominal pain, but these rarely require treatment to be stopped in people taking doses up to 400mg per day. Itraconazole can also rarely cause clinically important, even fatal hepatitis. It is therefore important that liver functions are regularly monitored. There have also been reports of an increased risk of heart failure, although this is rare.

Itraconazole is metabolised by the CYP3A4 enzyme, so it interacts with a large number of other medications. Taking any protease inhibitor, except for nelfinavir (Viracept) at the same time as itraconazole can increase itraconazole levels, putting patients at risk of side-effects.^{1 2} A dose reduction of itraconazole may be required. In contrast, non-nucleoside reverse transcriptase inhibitors (NNRTIs) are expected to reduce itraconazole levels, although these interactions have not been studied.

Itraconazole should be used with caution by patients taking other drugs that are metabolised by the same pathway.