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Itraconazole

Itraconazole (marketed as Sporanox® by Janssen Pharmaceutica) is an antifungal agent that is prescribed to patients with fungal infections. The drug may be given orally or intravenously. more...

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Pharmacology

The mechanism of action of itraconazole is the same as the other azole antifungals: it inhibits cytochrome P450 oxidase mediated sysnthesis of ergosterol.

Indication

Itraconazole has a broader spectrum of activity than fluconazole (but not as broad as voriconazole or posaconazole). In particular, it is active against aspergillus, which fluconazole is not. It is also licenced for use in blastomycosis, histoplasmosis and onychomycosis.

Dosing

Itraconazole is available as capsules or as an oral solution. The dose is 200mg once a day, to 400mg in severe infection. There is an intravenous preparation available in the US, but not in the UK. In the UK, if an intravenous preparation is required, then an alternative antifungal drug should be used.

The main problem with the use of itraconazole is its poor absorption, especially when given in capsule form. The oral solution is much better absorbed and should always be used in preference to the capsule. The cyclodextrin contained in the oral solution can cause an osmotic diarrhoea, and if this is a problem, then half the dose can be given as oral solution and half as capsule in order to reduce the amount of cyclodextrin given. Itraconazole capsules should always be taken with food, as this improves absorption. Itraconazole oral solution should be taken an hour before food, or two hours after food (and likewise if a combination of capsules and oral solution are used). Itraconazole should be taken with orange juice or cola, as absorption is also improved by acid. Absorption of itraconazole is impaired when taken with an antacid, H₂-blocker or proton pump inhibitor.

In life-threatening situations, some doctors give an oral loading dose of 200mg three times a day for three days, before dropping down to the usual dose. Because itraconazole absorption is unreliable, blood levels should be monitored at least once a week in those patients who are being treated for life-threatening (or potentially life-threatening) fungal infections.

In intravenous dosing, four doses of itraconazole 200mg are given 12 hours apart, before changing the dose to once daily. There is no safety data for giving the intravenous preparation for more than 14 days continuously.

Adverse effects

Itraconazole is a relatively well tolerated drug (although not as well tolerated as fluconazole or voriconazole) and the range of adverse effects it produces is similar to the other azole antifungals.

Elevated alanine aminotransferase levels is found in 4% of people taking itraconazole
Congestive Heart Failure

The cyclodextrin that is used to make the syrup preparation can cause diarrhoea.

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Response to itraconazole in patients with mediastinal granuloma
From CHEST, 10/1/05 by Talaat A. Al Shuqairat

PURPOSE: Mediastinal Granuloma is an uncommon cause of a mediastinal mass. It is thought to be due to Histoplasma infection. Surgical resection is advocated to prevent the possible progression of mediastinal granuloma to fibrosing mediastinitis. Antifungals are also thought to be helpful. We evaluated the role of itraconazole in treatment of patients with mediastinal granuloma.

METHODS: We evaluated five patients with mediastinal granuloma who were seen in the pulmonary clinic at the University of Missouri-Columbia Hospital over the last three years. The patients were 30.6 [+ or -] 9.9 years of age, and 3 of them were females. The diagnosis of mediastinal granuloma was confirmed by biopsy in all patients. Three patients were treated with Itraconazole (200 mg once a day). One patient had surgical resection only, and another patient had resection followed by treatment with Itraconazole. Patients were followed up for at least four months. Fungal stains and cultures were negative for all patients. Two patients had positive Histoplasma antibodies.

RESULTS: Four months after starting therapy, patients receiving itraconazole alone were asymptomatic and they had almost total resolution of the mediastinal mass. The patient who had surgical resection did not have any recurrence on follow up. The patient who had resection followed by Itraconazole treatment had partial improvement. None of the patients treated with Itraconazole had liver function derangements. The most common side effect was diarrhea.

CONCLUSION: Despite lack of evidence for active Histoplasma infection, patients with mediastinal granuloma responded well to treatment with Itraconazole. The medication was effective, safe and well-tolerated. Itraconazole should be considered as the first line of treatment for mediastinal granuloma.

CLINICAL IMPLICATIONS: Patients who have Mediastinal Gransuloma, whether diagnosed by biopsy or clinically, may have no evidence of a previous Histoplasma infection. Such patients would still respond to Itraconazole treatment, without the need for surgical resection of the mass.

DISCLOSURE: Talaat Al Shuqairat, None.

Talaat A. Al Shuqairat MD * University of Missouri-Columbia, Columbia, MO

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