Voriconazole: The Newest Triazole Antifungal Agent

Abstract

Fungal infections remain a significant cause of morbidity and mortality despite advances in medicine and the emergence of new antifungal agents (1). Immunocompromised patients are particularly at risk of developing these infections, with Candida and Aspergillus spp. being the mycoses most commonly identified (2). Patients who develop candidemia have a greater chance of prolonged hospitalization and have a mortality rate as high as 60%. In addition, the prevalence of Candida spp. that are resistant to triazole antifungal agents is increasing, making treatment options a concern. Aspergillosis carries a 100% mortality rate if left untreated (3). Although there are numerous treatment options, no broad-spectrum antifungal agents with an acceptable safety profile and with both intravenous and oral formulations are available at this time. Amphotericin B is currently the drug of choice for the treatment of systemic infections caused by Aspergillus and Candida spp. (2–4). However, the high incidence of toxicity associated with amphotericin B has limited its use in many patients. Lipid formulations of amphotericin B are better tolerated than conventional amphotericin B and have similar efficacy. However, these agents are costly and are generally reserved for second-line therapy in patients who did not respond to or could not tolerate conventional amphotericin B therapy. Caspofungin, an echinocandin antifungal agent, has in vitro activity against Aspergillus and Candida spp. However, due to a lack of clinical trials, it is generally reserved for aspergillosis that is refractory to other antifungal treatment. Fluconazole and itraconazole are triazole antifungal agents used in the treatment of fungal infections. They have both intravenous and oral formulations and favorable safety profiles. However, the triazoles' spectrum of activity is somewhat limited. Fluconazole is active mainly against Candida albicans and Cryptococcus neoformans. Itraconazole is most active against Aspergillus spp. and has greater activity than fluconazole against resistant strains of Candida spp. other than C. albicans (2). Voriconazole is the newest agent in the armamentarium against fungal infections. It is a triazole antifungal with a structure related to that of fluconazole and a spectrum of activity comparable to that of itraconazole. Voriconazole was approved by the Food and Drug Administration in May 2002 for the treatment of invasive aspergillosis and refractory infections of Scedosporium apiospermum and Fusarium spp. Studies have also shown it to be a promising agent for empiric treatment in febrile neutropenia.