The Food and Drug Administration has determined that the antibiotic telithromycin (Ketek) may be associated with serious liver injury and liver failure, and has been linked to four deaths and one liver transplant. The drug's maker, Sanofi-Aventis, has upgraded a caution in the drug's label on the potential for liver injury to a bolded warning that serious hepatic injury has been “observed during or immediately after treatment.” Injury has progressed rapidly after just a few doses, according to the company.
Ketek has not received a black box warning, and both the FDA and Sanofi say the drug's benefits outweigh its risks.
“We are advising both patients taking Ketek and their doctors to be on the alert for signs and symptoms of liver problems,” Dr. Steven Galson, director of the FDA's Center for Drug Evaluation and Research, said in a statement.
However, the drug maker has stopped enrollment in five pediatric trials investigating use of Ketek in acute otitis media, community-acquired pneumonia, and tonsillitis in children 6 months to 18 years old.
The new warning is based partly on an FDA analysis that found that Ketek may be associated with 12 cases of liver failure and 4 deaths since its approval in 2004. “We're engaged in ongoing discussions with the FDA regarding a detailed medical evaluation of hepatic events reported in connection with Ketek use,” said Sanofi spokeswoman Melissa Feltmann.
Ketek is currently approved for use in adults to treat community-acquired pneumonia, sinusitis, and acute exacerbation of chronic bronchitis.
Emmy Tsui, also a Sanofi spokeswoman, said therapy will continue according to protocol in children already enrolled in the five pediatric trials, but that Sanofi would not enroll any new trial participants until it was certain that its development program “remains consistent with the current thinking of the FDA regarding the structure and design of antibiotic drug development in pediatrics.”
The Senate Finance Committee has been investigating Ketek's approval, as well as a postmarketing safety study that was later found to be fraudulent.
Committee chairman CharlesGrassley (R-Iowa) said that he has been stonewalled by the FDA in his attempts to meet with the agency's special agent who investigated the fraud. In mid-June, he visited the Department of Health and Human Services headquarters to demand such a meeting.
“Based on the runaround that's gone on, I smell a cover-up,” Sen. Grassley said in a statement issued after his HHS foray.