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ADVERSE DRUG REACTIONS

Adverse Effects of Voriconazole: Analysis of the French Pharmacovigilance Database

Resident, Department of Medical Pharmacology and Toxicology, Lapeyronie Hospital, Montpellier, France

Hélène Peyrière, PharmD PhD

Lecturer in Clinical Pharmacy, Department of Medical Pharmacology and Toxicology, Lapeyronie Hospital

Marylène Cociglio, PharmD PhD

Lecturer in Clinical Pharmacology, Department of Medical Pharmacology and Toxicology, Lapeyronie Hospital

Samira Djezzar, MD

Clinical Specialist, Pharmacovigilance Centre, Fernand Widal Hospital, Paris, France

Sylvie Hansel, PharmD PhD

Professor in Clinical Pharmacy, Department of Pharmacy, Lapeyronie Hospital

Jean-Pierre Blayac, MD PhD

Professor in Clinical Pharmacology, Department of Medical Pharmacology and Toxicology, Lapeyronie Hospital

Dominique Hillaire-Buys, MD PhD

Lecturer in Clinical Pharmacology, Department of Medical Pharmacology and Toxicology, Lapeyronie Hospital

for the Network of the French Pharmacovigilance Centers

Reprints: Dr. Peyrière, Service de Pharmacologie Médicale et Toxicologie, Hôpital Lapeyronie, 371 avenue du Doyen Gaston Giraud, 34295 Montpellier Cedex 5, France, fax 33-4-67-33-67-51, h-peyriere{at}chu-montpellier.fr

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 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.

Key Words: adverse drug effects, pharmacovigilance, voriconazole

Published Online, April 24, 2007. www.theannals.com, DOI 10.1345/aph.1H671