On January 20, 2006, researchers reported three cases of severe liver toxicity following the use of Ketek. Of these cases, one patient needed a liver transplant and another died. Examination of these patients' livers showed massive tissue death. All patients had been healthy previous to the use of Ketek.
Ketek, known generically as telithromycin, is an antibiotic used for the treatment of respiratory infections including chronic bronchitis, acute bacterial sinusitis and community-acquired pneumonia. Ketek is manufactured by the French pharmaceutical giant Sanofi-Aventis.
Three cases of liver toxicity were reported to FDA MedWatch and reported in an article in the Annals of Internal Medicine. Of these cases, one patient recovered, one patient needed a liver transplant and the other died. Examination of these patients' livers showed massive tissue death. All patients had been healthy previous to the use of Ketek and were not using other prescription drugs. The two latter patients had reported some alcohol use.
Regrettably, this is not the first chapter in the Ketek saga. The initial new drug application for telithromycin was rejected by the FDA in June, 2001, citing a request for additional safety data regarding liver injuries, blurred vision, and other possible side effects. Based on these concerns, the FDA ordered Sanofi to conduct further safety tests. In October, 2001, the company started Study 3014, which proved to be an appalling disaster.
The physician who recruited the largest number of subjects (414, at $400 each according to the contract introduced in evidence at her trial) is in federal prison after pleading guilty to fraud resulting from the fabrication of data. Internal corporate documents reviewed by The Wall Street Journal indicate the company’s concern with its highest recruiter, but the concerns were not disclosed to the FDA, which uncovered the problems independently. The second-high enroller (251 patients) was found during an FDA audit to have not followed the protocol or reported adverse drug reactions; he admitted in an interview with The Wall Street Journal to never having participated in a study before. The third-highest recruiter (214 patients) was at the time of study accrual working with a probationary license under sanction of a state disciplinary board; the FDA audit found evidence of records altered with “white-out.” This same doctor was later arrested for threatening to kill his wife, after being found at his home with a loaded handgun and cocaine in his underwear.
What is perhaps most outrageous about the entire sad affair is that Study 3014 was specifically mandated to investigate liver toxicity. Now, after being on the market for two years, there is new evidence that Ketek is harmful to the liver. A recent analysis of the FDA’s post-marketing database showed that the rate of reporting of acute liver failure was 3.5 to 11 times as high for Ketek as for other antibiotics, with a reporting rate of 167 cases of acute liver failure per 1 million person-years of telithromycin use, as compared with the expected rate of 1 case per 1 million person-years.