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A Surveillance Method for the Early Identification of Idiosyncratic Adverse Drug Reactions

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Abstract

Background: Pemoline is a CNS stimulant that was introduced in 1975 in the US and was used to treat children with attention deficit hyperactivity disorder. Pemoline was withdrawn from the market 30 years later because of fatal hepatotoxicity associated with its use.

Objective: To create a system that will estimate the potential association between a serious adverse event and a medication early in its marketing cycle. Method: All case reports of acute liver failure associated with pemoline and reported to the US FDA from 1975 through 1999 were reviewed. All published articles on pemoline-induced hepatotoxicity were reviewed, and the Naranjo adverse drug reaction probability scale was applied. The incidence rate of idiopathic acute liver failure was estimated from the published literature. The data were analyzed using Fisher’s Exact test and relative risks (RR) were calculated.

Results: As early as 1978, there was a significant signal indicating that pemoline was associated with acute liver failure, with an RR of 24.08 (95% CI 4.67, 124.10; p < 0.05). With an increased number of cases, the significance of the association had been steadily increased.

Conclusion: This method enables researchers, clinicians, drug companies and regulators to identify uncommon adverse drug reactions, caused mostly by new medications, earlier than they currently are in the course of marketing and thus quantify serious adverse events.

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Notes

  1. 1The use of trade names is for product identification purposes only and does not imply endorsement.

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Acknowledgements

This study was supported by The Ivey Chair in Molecular Toxicology, University of Western Ontario and Jonathan’s Alert, The Hospital for Sick Children, Toronto. No sources of funding were used in the preparation of this article.

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 Medicine, Schulich School of Medicine & Dentistry, The University of Western Ontario, London, Ontario, Canada

    Fatma A. Etwel, Michael J. Rieder &  Gideon Koren

  2. Department of Physiology & Pharmacology, Schulich School of Medicine & Dentistry, The University of Western Ontario, Toronto, Ontario, Canada

    Fatma A. Etwel, Michael J. Rieder, John R. Bend &  Gideon Koren

  3. Department of Paediatrics, Schulich School of Medicine & Dentistry, The University of Western Ontario, London, Ontario, Canada

    Michael J. Rieder, John R. Bend &  Gideon Koren

  4. Department of Pathology, Schulich School of Medicine & Dentistry, The University of Western Ontario, London, Ontario, Canada

    John R. Bend

  5. The Hospital for Sick Children, Toronto, Ontario, Canada

    Gideon Koren

Authors
  1. Fatma A. Etwel
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  2. Michael J. Rieder
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  3. John R. Bend
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  4. Gideon Koren
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Correspondence to Gideon Koren.

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Etwel, F.A., Rieder, M.J., Bend, J.R. et al. A Surveillance Method for the Early Identification of Idiosyncratic Adverse Drug Reactions. Drug-Safety 31, 169–180 (2008). https://doi.org/10.2165/00002018-200831020-00006

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  • DOI: https://doi.org/10.2165/00002018-200831020-00006

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