Voriconazole: in the treatment of invasive aspergillosis.
Voriconazole, a broad-spectrum triazole antifungal agent, inhibits the cytochrome P450-dependent enzyme 14-alpha-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 > or =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 > or =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 > or=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 (approximately 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.
Muijsers
Richard B R
RB
Adis International Limited, Mairangi Bay, Auckland, New Zealand.
Goa
Karen L
KL
Scott
Lesley J
LJ
D000284:Administration, Oral; D000818:Animals; D000935:Antifungal Agents / Q000493:pharmacokinetics* / Q000494:pharmacology* / Q000627:therapeutic use; D001228:Aspergillosis / Q000188:drug therapy*; D002986:Clinical Trials as Topic; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004347:Drug Interactions; D006801:Humans; D007275:Injections, Intravenous; D011743:Pyrimidines / Q000493:pharmacokinetics* / Q000494:pharmacology* / Q000627:therapeutic use; D014230:Triazoles / Q000493:pharmacokinetics* / Q000494:pharmacology* / Q000627:therapeutic use; D065819:Voriconazole
D000935:Antifungal Agents; D011743:Pyrimidines; D014230:Triazoles; D065819:Voriconazole