An antibiotic linked to a growing number of reports of liver failure, including four deaths, should bear stricter warnings about its effect on the liver, according to an internal Food and Drug Administration memo. The drug’s manufacturer, Sanofi-Aventis, said Friday it was in talks with FDA officials about those reports.
The FDA has received reports of 12 cases of acute liver failure, including the four deaths, in patients treated with Ketek, according to a copy of the memo shown to The Associated Press. FDA safety evaluators also uncovered 23 other cases where patients suffered serious liver injuries after receiving the antibiotic, which is formally called telithromycin.
The reports, when considered in proportion to the number of prescriptions filled for Ketek, exceed what’s been seen in similar antibiotics, according to the memo. The contents of the May 16 memo were first reported Friday by The Wall Street Journal.
Ronald Wassel and Dr. Allen Brinker, both of the FDA’s Division of Drug Risk Evaluation, recommended in the memo that the FDA consider restricting the use of Ketek or even withdrawing it should the liver failure rate rise to levels seen in another antibiotic, Trovan, before its use was restricted in 1999.
However, the two wrote that they cannot determine whether the drug’s risk is currently higher
However, the two wrote that they cannot determine whether the drug’s risk is currently higher than that posed by any other of the various antibiotics associated with liver problems.
“Nonetheless, the rising trend of reporting rates associated with telithromycin is of concern,” the memo reads in part. The memo was forwarded through Dr. Mark Avigan, director of the FDA’s Division of Drug Risk Evaluation, to the head of the agency’s Division of Anti-infective and Ophthalmologic Products, Dr. Janice Soreth.
FDA spokeswoman Susan Bro said it would be “premature” to discuss any steps the agency might take. The current FDA-approved label for Ketek warns of liver disfunction that can be severe but is “usually reversible.”
Sanofi-Aventis SA said it continues to believe Ketek is safe and effective when used as directed, adding that it continued to discuss the liver reports with the FDA.
“These complex evaluations require careful and rigorous analysis with leading experts before drawing any definitive conclusion,” the company said in a statement.
the Annals of Internal Medicine published a report detailing three cases of severe liver problems
In January, the Annals of Internal Medicine published a report detailing three cases of severe liver problems, including one death, in patients at a North Carolina hospital after they began taking Ketek.
That publication may have stimulated the reporting of further problems associated with Ketek, skewing perceptions of its apparent risk when compared to other drugs, according to the memo. Furthermore, reporting rates are typically higher with newer drugs. The FDA approved Ketek in April 2004.
Congress is investigating how the FDA has handled Ketek, including problems with a clinical trial that was supposed to show the drug’s safety, according to The Wall Street Journal report.
Irregularities in the execution of that trial left the FDA unable to make a “meaningful assessment” of liver safety concerns associated with the drug, according to the memo.