Drug Safety 2006; 29 (12): 1163-1172 ORIGINAL RESEARCH ARTICLE 0114-5916/06/0012-1163/$39.95/0  2006 Adis Data Information BV. All rights reserved. Fluvastatin and Hepatic Reactions A Signal From Spontaneous Reporting in Italy Anita Conforti, 1 Lara Magro, 1 Ugo Moretti, 1 Stefania Scotto, 2 Domenico Motola, 3 Francesco Salvo, 4 Barbara Ros 5 and Roberto Leone 1 1 Clinical Pharmacology Unit, Reference Centre for Education and Communication within the WHO Programme for International Drug Monitoring, University of Verona, Verona, Italy 2 Lombardy Centre of Pharmacovigilance, Milan, Italy 3 Department of Pharmacology, Interuniversity Research Centre for Pharmacoepidemiology, University of Bologna, Bologna, Italy 4 Department of Clinical and Experimental Medicine and Pharmacology, Section of Pharmacology, University of Messina, Messina, Italy 5 Pharmaceutical Service of Friuli Venezia Giulia Health Department, Trieste, Italy Background: Signal detection is a crucial element in recognising new adverse Abstract drug reactions (ADRs) as soon as possible. HMG-CoA reductase inhibitors (‘statins’), the most potent cholesterol-lowering drugs, are generally well tolerated but can occasionally lead to liver toxicity. Pre- and postmarketing studies on statins revealed an incidence of 0.1–3% elevation in hepatic transaminase levels. However, these elevations are asymptomatic, reversible, dose related or probably due to other causes. Postmarketing studies clearly showed the lack of evidence of hepatotoxicity from statins, apart from some isolated case reports of serious hepatic damage described in the literature. It is still unclear whether serious hepatic reactions are dose related and more frequent than the expected rate in the general population. Objective: In this study, the hypothesis that fluvastatin could cause serious liver injuries more than the other statins is investigated, in the light of a quantitative and qualitative signal analysis, drug consumption data and evidence from the litera- ture. Methods: The Italian Interregional Group of Pharmacovigilance (Gruppo Interre- gionale di Farmacovigilanza; GIF) is an example of signal detection within the Italian spontaneous ADR reporting system. The GIF database holds reports of suspected ADRs submitted by five Italian pharmacovigilance regional centres. In the GIF database, all reports of suspected ADRs are classified according to the WHO criteria for causality assessment. The reactions are coded according to the WHO Adverse Reaction Terminology and classified as serious or non-serious events on the basis of the WHO Critical Term List. Every 6 months the GIF database is analysed to extract potential signals through a qualitative case-by-case analysis and using a quantitative methodology called proportional reporting ratio (PRR). This methodology permitted us to identify the potential signal ‘fluvastatin and hepatic reactions’. Results: At 31 December 2004, the GIF database contained 35 757 reports with an annual reporting rate of 170 reports per million inhabitants. We found a total of