US regulators have recommended stronger safety warnings on the label of Sanofi-Aventis’ antibiotic Ketek, after a review linked the drug to 12 cases of liver failure and four patient deaths, according to a report in the Wall Street Journal on Friday.

At the start of the year, the US Food and Drug Administration announced that reports of liver damage in patients taking Ketek (telithromycin) had prompted an investigation to assess whether to add a warning of this possible side effect - described online in the journal Annals of Internal Medicine (January 20) - to the product’s label.

The journal article said that three patients had experienced severe liver toxicity after taking Ketek. One patient recovered, one required a transplant, and one died, and the livers of the latter two showed 'massive' tissue damage on laboratory examination. As a result, the FDA has asked doctors to monitor patients taking the antibiotic and stop treatment if symptoms of liver damage are seen.

Ketek was originally filed with the FDA in 2000, and was deemed approvable in June 2001, although the firm was asked to conduct an additional safety study after concerns over liver toxicity, abnormal heart rhythm and visual disturbances. It was finally approved in April 2004, with labelling that mentions liver toxicity as a potential side effect.

Sanofi-Aventis reported third-quarter 2005 sales of Ketek of 38 million euros ($47 million), 7.3% lower than in the third quarter of 2004, when the product was launched in the USA, but up 36% in the first nine months of the year to €159 million.

A report earlier this year by market research firm Decision Resources tipped Ketek to be a big seller, because of its efficacy in treating resistant infections affecting patients outside hospital, but a stronger liver toxicity warning on its label may well hamper the agent’s performance.