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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.

Read more at Wikipedia.org

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Voriconazole versus itraconazole for fungal prophylaxis after lung transplantation
From CHEST, 10/1/05 by John H. Sherner

PURPOSE: Aspergillus and other fungal infections are common causes of morbidity and mortality in lung transplant recipients. Most patients receive prophylaxis against fungal infections, but the optimal regimen has not been defined. The purpose of this study was to assess the efficacy of voriconazole as fungal prophylaxis.

METHODS: We retrospectively reviewed data from 56 lung transplant recipients. Group A (n = 23) consisted of patients who underwent transplantation after the introduction of voriconazole prophylaxis. Group B (n=23) consisted of patients transplanted immediately prior to the introduction of voriconazole, in whom itraconazole was used as prophylaxis. Both groups received inhaled amphotericin B during their initial hospitalization adn continued oral antifungal prophylaxis until one year post-transplantation. The primary endpoint was positive BAL fungal cultures during the first year. We also assessed clinical events related to aspergillus and overall mortality.

RESULTS: The incidence of patients with positive bronchial cultures for aspergillus at 1 year was 5/28 (18%) in the group A and 10/28 (36%) in group B (p = 0.134, ns). At the time of recovery of aspergillus, 4/5 (80%) patients in group A were actually receiving voriconazole, versus 90% (9/10) in group B receiving itraconazole. The incidence of patients with positive bronchial cultures for candida was 0 in group A versus 50% (14/28) in group B (p = < 0.0001). At one year, there was one clinical aspergillus event in each group, non-fatal in group A and fatal in group B. There was an additional fatal aspergillus event in group B at month 25, as well as an episode of scedosporium sepsis at month 13.

CONCLUSION: In our lung transplant population, the use of voriconazole results in decreased airway colonization with aspergillus and candida.

CLINICAL IMPLICATIONS: These findings suggest that voriconazole is effective antifungal prophylaxis for lung transplant recipients. The overall low rate of clinically significant fungal events do not allow any further conclusions to be drawn.

DISCLOSURE: John Sherner, None.

John H. Sherner MD * Scott Barnett PhD Shahzad Ahmad MD Nelson Burton MD Mary Schmidt MD Steven Nathan MD Walter Reed Army Medical Center, Washington, DC

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