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Severe Hepatotoxicity with Telithromycin

Three cases of hepatitis, two resulting in liver failure, are reported in association with brief courses of telithromycin.

Derived from macrolides, ketolides feature side-chain modifications that add acid stability and reduce the development of resistance. Telithromycin was the first ketolide approved for use in the U.S. More than 30% of this agent is metabolized in the liver.

Now, three cases of severe hepatotoxicity associated with telithromycin have been reported. Two of the cases were treated at the same North Carolina medical center. The first patient developed symptoms of hepatitis while taking telithromycin for an ear and sinus infection. The drug was stopped on the third day of therapy, and the man recovered uneventfully. The second patient developed hepatic failure during or soon after a 5-day course of telithromycin. She subsequently underwent liver transplantation. Her removed liver was found to be shrunken, with extensive necrosis. The third patient developed hepatic failure within 1 week of completing a 5-day course of telithromycin. He died within days, and his liver showed massive necrosis with lymphocytic infiltration.

Comment: This report describes three cases of telithromycin-associated hepatitis. In these cases, no other etiology or cofactor was discerned, although the two patients with severe disease drank alcohol. That telithromycin might be associated with liver necrosis is not unexpected. A paper by Peters (Toxicol Pathol 2005; 33:146) anticipated this effect, noting that telithromycin has the potential for hepatotoxic metabolites and that both elevated aminotransferases and hepatic necrosis were seen in animal and clinical trials. The current report bolsters the importance of continued postapproval data collection, a process recently highlighted in two editorials in the New England Journal of Medicine.

— Neil M. Ampel, MD

Published in Journal Watch Infectious Diseases February 7, 2006

Citation(s):

Clay KD et al. Severe hepatotoxicity of telithromycin: Three case reports and literature review. Ann Intern Med 2006 Mar 21 . (http://www.acponline.org/journals/annals/hepatotoxicity.htm)

Hunter D. First, gather the data. N Engl J Med 2006 Jan 26; 354:329-31.

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Vlahakes GJ. The value of phase 4 clinical testing. N Engl J Med 2006 Jan 26; 354:413-5.

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