Friday, 11 October 2013

Cardiotoxicity of antifungal drugs

The treatment of fungal disease is significantly hampered by the unavailability of new antifungal drugs, and increasing resistance towards registered antifungals such as the triazoles. With the introduction of the echinocandin class of antifungals (Caspofungin (Merck) in 2001, followed shortly by Micafungin (Astellas) and Anidulafungin in 2005 and 2006 respectively), the situation has improved but not resolved. There is still a widespread shortfall of antifungal treatment options.

Of the drugs currently available, cardiotoxicity appears to be a side effect in some patients with pre-existing cardiac disease. Some traditional antifungal drugs, such as the polyene amphoteracin B (AmB) have been associated with reduced cardiac function. Other examples include itraconazole, which has been implicated in heart failure in some patients, and voriconazole, which has been linked with Torsades de pointes -- an electrical disturbance in the heart which, left untreated, can lead to fatal heart disease.

A study into echinocandin cardiotoxicity by Stover et al. (2013) has shown that rat hearts treated with Anidulafungin and Caspofungin display reduced function, including at doses similar to that in humans after administration. Notably, and interestingly, Micafungin was not associated with statistically significant changes in this study, which coincides with the fact that there are no adverse cardiac events noted with patients taking Micafungin. On the other hand, Caspofungin and Anidulafungin have both been reported, with the former being responsible for sudden cardiac death in one patient and the latter being responsible for a case of flash pulmonary oedema.

The current advice to clinicians at the moment is to monitor all patients with pre-existing cardiac disease who are on AmB or triazole antifungals. More research is needed into the potential cardiotoxicity of echinocandin drugs in patients with pre-existing cardiac disease.

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