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Posaconazole Better Than Fluconazole as Antifungal Prophylaxis
The extended-spectrum triazole posaconazole appears to be more effective than fluconazole as prophylaxis among patients at risk for invasive fungal infections, particularly those due to invasive aspergillosis, according to two international, phase III trials reported in the January 25th issue of The New England Journal of Medicine. Survival may also be better when posaconazole is used.
Dr. Andrew J. Ullmann, at the Johannes Gutenberg University in Mainz, Germany, and associates compared the two drugs between 1999 and 2003 as a prophylaxis among 600 patients with graft-versus-host disease after stem-cell transplantation and immunosuppressive therapy.
The patients were treated at 90 centers were randomized to receive posaconazole oral suspension (Noxafil, Schering-Plough) at a dose of 200 mg three times daily, or a fluconazole encapsulated tablet (Diflucan, Pfizer) 400 mg once daily. Subjects also took placebo treatments so that therapies appeared to match. Treatment lasted for up to 112 days.
The incidence of invasive fungal infection was 5.3% in the posaconazole group and 9.0% in the fluconazole group (p = 0.07). Most fungal infections were caused by invasive aspergillus, for which posaconazole was more effective (2.3% versus 7.0%, p = 0.006).
Posaconazole was also associated with fewer deaths due to invasive fungal infections (1% versus 4%, p = 0.046). Rates of treatment-related serious adverse events were similar (13% and 10%).
Posaconazole should be considered an option for prophylaxis in patients with severe graft-versus-host disease," Dr. Ullmann and his associates conclude.
A prospective trial, led by Dr. Oliver A. Cornely at the University of Cologne in Germany, compared prophylactic treatments among neutropenic patients with acute myelogenous leukemia or the myelodysplastic syndrome.
The study took place between 2002 and 2005 at 89 centers. Three hundred four patients were randomized to posaconazole; 240 patients were randomized to fluconazole; and 58 to itraconazole. Each drug was administered as an oral suspension: posaconazole (200 mg t.i.d.), fluconazole (400 mg q.d.) or itraconazole (Sporanox, Janssen, 200 mg b.i.d.).
During the 100-day period after randomization, invasive fungal infections occurred in 5% in the posaconazole group versus 11% in the fluconazole/itraconazole group (p = 0.003). Overall mortality during the same period was 14% and 21%, respectively (p = 0.04), while corresponding mortality rates due to fungal infection were 2% and 5% (p = 0.01).