Posaconazole is a new
drug in the
triazole class that has recently been investigated in pivotal Phase III clinical trials. Its antifungal activity is based on the inhibition of the fungal
ergosterol synthesis. As demonstrated in vitro,
posaconazole exhibits fungicidal activity against Aspergillus spp., Candida spp. and zygomycetes. Currently,
posaconazole is only available as an oral
suspension. Food consumption affects the bioavailability of
posaconazole, while the exposure to
posaconazole increases in a dose-proportional manner with a saturation of absorption occurring with a daily dose over 800 mg.
Posaconazole is well tolerated without an increase in risk of any treatment-related adverse events during prolonged treatment for 6 or more months (n = 108).
Posaconazole has been recently approved by the US FDA and other regulatory bodies for the treatment of oropharyngeal
candidiasis, and the prophylaxis of invasive Aspergillus and
Candida infections in severely immunocompromised patients. As demonstrated in two pivotal Phase III trials,
posaconazole prophylaxis of
invasive fungal infection in patients severely immunocompromised by
graft-versus-host disease (n = 600) or
neutropenia (n = 602) is superior to
fluconazole and/or
itraconazole prophylaxis. Significantly more patients who received
posaconazole, instead of
fluconazole, as treatment for oropharyngeal
candidiasis sustained clinical success after the treatment was stopped. Preliminary data from a subgroup analysis (n = 24) of two
salvage therapy trials for
invasive fungal infections, as well as single case reports and series and in vitro studies, suggest that
posaconazole might be an attractive oral treatment alternative for
zygomycosis.