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Telithromycin Use and Spontaneous Reports of Hepatotoxicity

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Abstract

Background and objective: Recent reports have described cases of telithromycin-related hepatotoxicity. The objective of this study is to quantify the effect of telithromycin use on the risk of hepatotoxicity.

Methods: We conducted a spontaneous-report case-control study of hepatotoxicity in telithromycin recipients using reports from the US FDA Adverse Event Reporting System. Reports from between 1 January 2005 and 30 June 2005 were examined. Cases included reports of patients with abnormal liver function tests, hepatocellular damage and hepatic impairment, while patients with reported conditions with similar reporting probabilities were considered as controls. The primary outcome measure of the analysis was the reporting odds ratio (ROR) evaluating the a priori hypothesis that telithromycin use confers an elevated risk of hepatotoxicity relative to other agents.

Results: A total of 2219 cases and 20 667 controls were identified. We estimated an ROR for hepatotoxicity associated with telithromycin compared with other agents of 1.82 (95% CI 1.12, 2.96) after controlling for age and gender, approximating an 82% excess risk in users of telithromycin relative to users of other agents.

Conclusions: This analysis is the first to specifically quantify the effect of telithromycin on the risk of hepatotoxicity. Telithromycin use may increase the risk of hepatotoxicity by >80%. Biases inherent in spontaneous reports include under-reporting of events and differential or time-varying reporting due to enhanced clinician awareness. Future studies should employ alternative data sources because of the inherent limitations of passive surveillance systems.

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Acknowledgements

This work was supported by an institutional postdoctoral training grant (T32) from the Agency for Health Care Research and Quality (Dr Dore). The funding source played no role in the design, conduct or reporting of this study.

Dr Dore receives consultancy fees from Pfizer Inc. for work independent of Brown Medical School. This arrangement with Pfizer played no role in the design, conduct or reporting of this study. Dr Lapane was the principal investigator and has received a grant from Pfizer Inc., which was used entirely to train doctoral students interested in pharmacoepidemiology. Mrs DiBello has no conflicts of interest that are directly relevant to the content of this article. No other individuals contributed to this study.

These data were presented in abstract form (poster) at the International Conference on Pharmacoepidemiology (ICPE), Lisbon, Portugal; August 2006.

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Authors and Affiliations

  1. Department of Community Health, Brown Medical School, Providence, Rhode Island, USA

    David D. Dore, Julia R. DiBello & Kate L. Lapane

  2. Department of Community Health, Box G-ST121, 6th Floor, 121 S. Main Street, Providence, Rhode Island, RI 02903, USA

    David D. Dore

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  1. David D. Dore
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  2. Julia R. DiBello
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  3. Kate L. Lapane
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Correspondence to David D. Dore.

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Dore, D.D., DiBello, J.R. & Lapane, K.L. Telithromycin Use and Spontaneous Reports of Hepatotoxicity. Drug-Safety 30, 697–703 (2007). https://doi.org/10.2165/00002018-200730080-00006

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