Telithromycin use and spontaneous reports of hepatotoxicity.

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.