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Hepatic Events Associated with Atomoxetine Treatment for Attention-Deficit Hyperactivity Disorder

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Abstract

Objective: This study describes and assesses potential hepatobiliary events related to atomoxetine therapy, as reported in clinical trials and as spontaneous adverse event reports post-launch in 2002.

Methods: Case reports that contained potential hepatobiliary events were identified by a computerized search of the Eli Lilly and Company atomoxetine spontaneous adverse events and clinical trials databases. All cases were reviewed by at least two company physicians, one with expertise in hepatology, to determine the relevance of the information in respect of potential liver toxicity.

Results: Of 7961 paediatric and adult patients treated with atomoxetine in clinical trials, 41 were identified as having hepatobiliary events requiring additional analysis. Most of these events were mild increases in ALT and AST levels. None of these cases met Hy’s rule criteria or progressed to liver failure. During the 4 years after market launch, 351 spontaneous reports of adverse events were related to the liver, of which 69 had other explanations unrelated to atomoxetine. Of the remaining 282 cases, 133 contained possible confounding factors (and were deemed to be possibly related), 146 presented too little information to assess, and three suggested atomoxetine as a probable cause of liver injuries. One of the three had a positive rechallenge. All three patients recovered after discontinuation of the drug.

Conclusions: Since the launch of atomoxetine therapy, three spontaneously reported cases of reversible drug-induced liver injury were deemed probably related to it. Atomoxetine should be discontinued in patients with jaundice or laboratory evidence of liver injury and should not be restarted.

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Acknowledgements

This work was supported by Eli Lilly and Company, Indianapolis, IN, USA. The authors contributed to the study concept and design; collection, analysis and interpretation of data; preparation of the manuscript; and decision to publish the data. Drs Bangs, Jin, Desaiah, Allen, Regev and Wernicke and Ms Zhang are employees of Eli Lilly and Company and own stock. Dr Holly Read is a former employee of Eli Lilly and Company and owns stock. Dr Read’s current affiliation is Abbott Laboratories.

The authors wish to thank the investigators for their role in the conduct of the trials that contributed data for this manuscript and also to thank the many patients who participated in the trials.

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Authors and Affiliations

  1. Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana, 46285, USA

    Mark E. Bangs, Ling Jin, Shuyu Zhang, Durisala Desaiah, Albert J. Allen, Holly A. Read, Arie Regev & Joachim F. Wernicke

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  1. Mark E. Bangs
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  2. Ling Jin
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  3. Shuyu Zhang
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  4. Durisala Desaiah
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  8. Joachim F. Wernicke
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Correspondence to Mark E. Bangs.

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Bangs, M.E., Jin, L., Zhang, S. et al. Hepatic Events Associated with Atomoxetine Treatment for Attention-Deficit Hyperactivity Disorder. Drug-Safety 31, 345–354 (2008). https://doi.org/10.2165/00002018-200831040-00008

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