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Hepatic adverse drug reactions: a case/non-case study in Italy

  • Pharmacoepidemiology and Prescription
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Objective

Adverse drug reactions (ADRs) can involve all tissues and organs. Liver injuries are considered among the most serious and are a cause for concern among physicians and patients. To assess the extent of drug-induced liver injuries in Italy we compared the number of cases of hepatic ADRs with reports of all other drug-related reactions present in the same database.

Methods

Spontaneous reports from six Italian Regions collected from January 1990 to May 2005 were analysed. Adverse reactions were classified according to WHO Adverse Reaction Terminology for causality assessment, and only those with “certain”, “probable” or “possible” causality assessment were included. Association between drugs and hepatic ADRs was assessed using the case/non case method, calculating the ADR reporting odds ratio (ROR) as a measure of disproportionality.

Results

On May 2005, the database contained 35,767 ADR reports, of which 11,829 were excluded because they were unclassifiable or unlikely in terms of causality assessment. Therefore, the analysis was carried out on 23,938 reports, of which 1,069 concerned hepatic ADRs (cases) and 22,869 concerned non-cases. The proportion of serious ADRs was about 40% in the overall database, and about 74% among cases. The drug classes with the highest number of cases were statins (ROR = 2.9, 95% CI 2.4–3.5), antiplatelet agents (ROR = 3.5; 95% CI 2.6–4.6), NSAIDs (ROR = 2.9; 95% CI 2.1–3.9) and macrolides (ROR = 1.7; 95% CI 1.2–2.3).

Conclusion

Hepatic adverse drug reactions remain a serious concern for several drugs widely used in clinical practice. Monitoring hepatic enzymes on a monthly basis for the first 6 months of treatment has been suggested for patients taking medications known to be hepatotoxic. A better knowledge of the epidemiology and mechanisms of hepatic ADRs may contribute to minimising their occurrence.

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Acknowledgements

We are very grateful to the Pharmaceutical Departments of Emilia Romagna, Friuli Venezia Giulia, Lombardia, Provincia Autonoma di Trento, Sicilia, and Veneto Regions, and their local Health Districts, for collecting the adverse reaction forms. We would also like to thank Chiara Biagi PharmD, who actively participated in this research when preparing her graduate thesis at the Department of Pharmacology, University of Bologna. The authors have no conflicts of interest that are directly relevant to the content of this study.

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Authors and Affiliations

  1. Department of Pharmacology and Interuniversity Research Centre for Pharmacoepidemiology, University of Bologna, Via Irnerio, 48, 40126, Bologna, Italy

    Domenico Motola, Antonio Vargiu, Alberto Vaccheri & Nicola Montanaro

  2. Clinical Pharmacology Unit, Department of Medicine and Public Health, University of Verona, Verona, Italy

    Roberto Leone, Ilaria Meneghelli & Gianpaolo Velo

  3. Lombardy Centre of Pharmacovigilance, Milan, Italy

    Alfredo Cocci & Mauro Venegoni

  4. Department of Clinical and Experimental Medicine and Pharmacology, Section of Pharmacology, University of Messina, Messina, Italy

    Francesco Salvo & Paola Maria Cutroneo

  5. Pharmaceutical Service of Friuli Venezia Giulia Health Department, Trieste, Italy

    Barbara Ros

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  1. Domenico Motola
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  2. Antonio Vargiu
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  3. Roberto Leone
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  4. Alfredo Cocci
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  5. Francesco Salvo
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  6. Barbara Ros
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  7. Ilaria Meneghelli
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  10. Alberto Vaccheri
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  11. Gianpaolo Velo
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  12. Nicola Montanaro
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Correspondence to Nicola Montanaro.

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Motola, D., Vargiu, A., Leone, R. et al. Hepatic adverse drug reactions: a case/non-case study in Italy. Eur J Clin Pharmacol 63, 73–79 (2007). https://doi.org/10.1007/s00228-006-0222-z

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  • DOI: https://doi.org/10.1007/s00228-006-0222-z

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