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Voriconazole: in the treatment of invasive aspergillosis
Richard B R Muijsers1, Karen L Goa, Lesley J Scott
1Adis International Limited, Mairangi Bay, Auckland, New Zealand.
Abstract:
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.
Insights
Voriconazole demonstrates superior efficacy in treating invasive aspergillosis compared to amphotericin B, with a higher success rate and better overall tolerability, despite causing more visual disturbances.
Area of Science:
- Mycology
- Pharmacology
- Infectious Diseases
Background:
- Invasive aspergillosis is a serious fungal infection.
- Voriconazole is a broad-spectrum triazole antifungal.
- Resistance to existing antifungals necessitates new treatment options.
Purpose of the Study:
- To compare the efficacy and safety of voriconazole versus amphotericin B for invasive aspergillosis.
- To evaluate treatment outcomes and adverse events in patients with invasive aspergillosis.
Main Methods:
- A randomized, nonblind trial involving 392 patients aged 12 years or older with invasive aspergillosis.
- Patients received either intravenous voriconazole or intravenous amphotericin B.
- Treatment regimens included dose adjustments and potential switching to oral voriconazole or other therapies.
Main Results:
- Voriconazole achieved a successful outcome in 52.8% of patients at 12 weeks, compared to 31.6% for amphotericin B.
- Voriconazole was generally better tolerated, with significantly fewer treatment-related adverse events and serious adverse events.
- Common adverse events for voriconazole included transient visual disturbances (30%) and skin rashes (6%).
- Visual disturbances were significantly more frequent with voriconazole than amphotericin B.
Conclusions:
- Voriconazole is an effective and generally well-tolerated treatment for invasive aspergillosis.
- Voriconazole offers a significant advantage over amphotericin B in terms of treatment success and tolerability.
- Clinicians should be aware of the potential for visual disturbances with voriconazole therapy.