Posaconazole is also an attractive agent for use as prophylaxis in patients at high risk for invasive fungal infections due to its potent activity against Aspergillus species and availability as an oral formulation. Prospective clinical trials have demonstrated that posaconazole is effective in preventing invasive fungal infections and reducing fungal related mortality in high-risk patients. In a randomized multicenter study posaconazole prophylaxsis was compared to fluconazole or itraconazole in patients with neutropenia secondary to chemotherapy for acute myelogenous leukemia or myelodysplastic syndrome (41). Significantly fewer invasive fungal infections were observed in patients randomized to posaconazole (5%) compared to those who received fluconazole or itraconazole (11%; P = 0.003) within 100 days following randomization. This difference was primarily due to a lower incidence of invasive aspergillosis in the posaconazole group (1% vs. 7%, respectively; P < 0.001; Fig. 2B). A second prophylaxis study compared posaconazole to fluconazole in allogeneic stem cell transplant patients with graft-versus-host disease who were receiving immunosuppressive therapy (42). Similar rates of invasive fungal infections were observed in the posaconazole recipients compared to those randomized to fluconazole (5.3% vs. 9%; P = 0.07). However, posaconazole was superior to fluconazole in preventing proven or probable invasive aspergillosis (1% vs. 5.9%; P = 0.001). Adverse events related to study drug were similar between prophylaxis groups in both studies.
However, variable trough concentrations were reported in patients who received posaconazole (coefficients of variation ranging between 57% and 68%), raising concerns about the bioavailability of this agent.
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