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The use of voriconazole and itraconazole increases the risk of hepatotoxicity

To assess the tolerability and safety profile of liver function of the most common systemic antifungals used to treat invasive fungal infections, a systematic review and meta-analysis of randomized controlled trials was conducted by scientists in Taiwan and the United States. The results of the analysis were published in the March issue of Antimicrobial agents and chemotherapy.

Two experts independently developed study selection criteria published between 1989 and August 31, 2009, assessing the quality of the studies and extracting the necessary data.

39 studies were identified with a total number of patients including more than 8,000. The frequency of treatment discontinuation due to the development of adverse drug reactions and the occurrence of liver damage varied considerably depending on the antifungal treatment used.

The combined risk of discontinuation due to the development of adverse drug reactions was highest for itraconazole (18.8%), amphotericin B (13.4%) and voriconazole (9.5% ), and minimal for caspofungin (3.8%). micafungin (3.6%) and fluconazole (2.2%). It was found that in 1.5% of patients, treatment with itraconazole was discontinued due to the development of hepatotoxicity.

In addition, in 19.7% of patients receiving voriconazole and in 17.4% of patients treated with itraconazole, serum liver enzyme levels increased, which did not require discontinuation of treatment, against 2.0 to 9.3% of patients in which fluconazole and echinocandins have been used. When stratified into empirical and etiotropic antifungal treatment groups, the results were comparable.

Manifestations of hepatotoxicity, possibly associated with the use of antifungal drugs, could also be affected by factors such as the administration of drugs to patients at high risk of liver damage and the increased likelihood of these injuries due to prolonged treatment.