Voriconazole

Abstract

▴ Voriconazole, a broad-spectrum triazole antifungal agent, inhibits the cytochrome P450-dependent enzyme 14-α-sterol demethylase, thereby disrupting the fungal membrane and stopping fungal growth. The drug shows excellent in vitro activity against Aspergillus spp., including itraconazole- and amphotericin B-resistant A. fumigatus isolates. ▴ At 12 weeks, 52.8% of voriconazole recipients achieved a successful outcome (complete or partial response) versus 31.6% of amphotericin B recipients in a randomised, nonblind trial in 392 patients (aged ≥12 years) with invasive aspergillosis. Patients received intravenous voriconazole (6 mg/kg once every 12 hours on day 1, then 4 mg/kg once every 12 hours for ≥7 days; patients could then be switched to oral voriconazole 200mg once every 12 hours) or intravenous amphotericin B (1 to 1.5 mg/kg/day for ≥14 days). At the investigators’ discretion, those who failed to respond to or experienced toxicity with the initial randomised drug could be switched to other licensed antifungal therapy. ▴ Voriconazole was generally well tolerated. The most common treatment-related adverse events were transient visual disturbances (≈30% of patients) and skin rashes (6%). ▴ Voriconazole was generally better tolerated than amphotericin B; voriconazole recipients experienced significantly (p < 0.02 both comparisons) fewer treatment-related adverse events or serious adverse events. The incidence of visual disturbances was significantly (p < 0.001) higher with voriconazole than amphotericin B treatment.