Adverse effects of voriconazole: analysis of the French Pharmacovigilance Database.
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 (approximately 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 ADEs 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.
Eiden
Céline
C
Department of Medical Pharmacology and Toxicology, Lapeyronie Hospital, Montpellier, France.
Peyrière
Hélène
H
Cociglio
Marylène
M
Djezzar
Samira
S
Hansel
Sylvie
S
Blayac
Jean-Pierre
JP
Hillaire-Buys
Dominique
D
D000293:Adolescent; D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems / Q000706:statistics & numerical data*; D000368:Aged; D000369:Aged, 80 and over; D000935:Antifungal Agents / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D004347:Drug Interactions; D005260:Female; D005602:France; D006801:Humans; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D011743:Pyrimidines / Q000009:adverse effects*; D012871:Skin Diseases / Q000139:chemically induced; D014230:Triazoles / Q000009:adverse effects*; D014786:Vision Disorders / Q000139:chemically induced; D065819:Voriconazole
D000935:Antifungal Agents; D011743:Pyrimidines; D014230:Triazoles; D065819:Voriconazole