Adverse Effects of Voriconazole: Analysis of the French Pharmacovigilance Database

Abstract

Background: The most common adverse effects of voriconazole reported during clinical trials were disturbances of vision (30% of pts.), skin rashes (17.3%), and elevations in hepatic enzymes level (~10% of pts.; varying with enzymes). However, postmarketing data concerning safety of voriconazole are limited. Objective: To describe voriconazole adverse drug effects (ADEs) after 4 years of the drug's availability in France and determine their occurrence. Methods: All cases of ADEs including voriconazole reported to the French Pharmacovigilance Database between 2002 and 2005 were analyzed. For each case, the following data were recorded; age, sex, indication, concomitant disease, concomitant medications, and ADE description. Causality link between voriconazole and ADEs was performed using the Naranjo probability scale. Results: A total of 227 ADE cases were reported in 178 adults and 9 children (<12 y), with 66% occurring in males. The patients' median age was 49.6 (2–80) years. ADEs included liver function test abnormalities (23%), visual disturbances (18%), skin rashes (17%), neurologic disturbances (14%), cardiovascular events (10%), hematologic disorders (8%), and renal disturbances (4%). Other less commonly identified ADEs included headache, nausea, vomiting, and diarrhea. Drug–drug interactions were observed in 7 cases. According to the Naranjo criteria, 84% of ADEs were classified as possible, 7% as probable, 5% as highly probable, and 4% as doubtful. Conclusions: Most AOEs found in this study are well documented in the literature, except for cardiac complications, which are rarely reported. Few ADEs related to drug interactions were observed; however, due to the extensive metabolism of voriconazole by cytochrome P450 isoenzymes, clinicians should be aware of potential interactions between voriconazole and other drugs metabolized through this pathway.