Voriconazole for serious fungal infections

Abstract

Voriconazole is a new second generation triazole effective against a wide spectrum of fungal pathogens. A randomised, controlled trial has shown it to be superior to amphotericin B in invasive aspergillosis, and it is a potential alternative to amphotericin B in neutropenic sepsis and to fluconazole in oesophageal candidiasis. Early clinical reports and in vitro susceptibility data suggest that it may also be a valuable antifungal against fluconazole-resistant Candida species and certain emerging fungal pathogens, which cause infections that are often refractory to conventional therapies. There is limited evidence of azole cross-resistance of clinical importance. Voriconazole is available as intravenous and oral formulations and has excellent tissue penetration and a good safety profile, the main problems being transient visual impairment and hepatotoxicity in patients with liver disease. It is metabolised by cytochrome P-450 isoenzymes causing important drug interactions but, in contrast to amphotericin B, is safe in renal failure and rarely causes infusion-related reactions. This review outlines the pharmacology of voriconazole and focuses on its clinical applications and safety profile.