As Of May 1, 2006 There Are 23 Reports Of Serious Liver Injury, Including 12 Cases Of Liver Failure, In U.S.
After finding the antibiotic Ketek (telithromycin) has been associated with 12 cases of liver failure, including four deaths, staff members at the FDA's drug safety office have recommended adding a "black-box" warning to the label, or package insert, for Ketek stating that "severe, life-threatening, and in some cases fatal" liver toxicity has been reported in patients taking Ketek.
This black-box warning recommendation was first reported in a May 19, 2006 Wall Street Journal (WSJ) article by Anna Wilde Mathews, which references "a confidential May 16 memorandum by the FDA's Division of Drug Risk Evaluation reviewed by The Wall Street Journal" as the source of this information. According to this May 19 WSJ article, "The document concludes that the Ketek rates are 'consistent with an association' between the drug and liver failure."
In more detail, Ms. Wilde reports:
The internal FDA memo analyzes incidents reported through the end of April in people in the U.S. who were prescribed Ketek after the drug won FDA approval. The reviewers found 23 reported cases of serious liver injury, as well as the 12 liver failures, that were "associated" with Ketek. The FDA also got reports of 44 liver-related events that weren't serious. . . .
Calling some of the liver-failure cases "clinically remarkable," the memo describes "profound" liver injury that set in as soon as a few days after some patients took Ketek and had a "signature of rapid onset and tempo." The document says that many of the 12 cases appeared to have few other possible causes and occurred in people who were "generally healthy." Besides the four deaths, one patient had a liver transplant and three others were considered for transplants but recovered.
Ms. Wilde's article also covers the official FDA response to the black-box warning recommendation as well as the reaction from Sanofi-Aventis SA, the drug company that makes Ketek. Starting with the FDA:
In a statement, an FDA spokeswoman said that the memo reflects the drug-safety office's "interpretation of adverse-event data" and recommends "labeling revisions be considered but not product withdrawal." . . .
The FDA spokeswoman said that the safety reviewers found "the numerical risk appears higher in the Ketek database" but "they are not able to conclude greater risk for liver injury in patients receiving Ketek than other drugs in the category." The finding will be "carefully considered along with all other sources of expert review" in the FDA's final assessment of Ketek, she said.
As for Aventis-Sanofi, the drug company which makes Ketek:
In a statement, Sanofi-Aventis said it "continues to believe that Ketek is safe and effective when used as directed." It said that it is engaged in "ongoing discussions with the FDA regarding a detailed medical evaluation of hepatic events" reported in connection with Ketek use and that it is evaluating the data with leading experts. The company said a detailed response to the findings in the memo would be inappropriate while it is in discussions with the agency.
Regarding the black-box warning, according to Ms. Wilde's article the confidential FDA memo reviewed by The Wall Street Journal:
. . .recommended that the Ketek label carry a warning about liver risk set apart by bold type or a black box, which is reserved for the most serious safety concerns. Among other things, the proposed warning would mention reports of liver necrosis and liver failure, and say that in some cases liver injury "progressed rapidly and occurred after administration of a few doses of Ketek." The suggested labeling would also warn doctors to watch patients for signs of hepatitis.
Ketek's current label includes only some cautionary language that liver dysfunction "has been reported with the use of Ketek" and that "these events were generally reversible."
Last year, Ketek was prescribed 3.35 million times in the U.S. and had sales of $193 million, according to a company that tracks prescription drug sales, IMS Health.
On another aspect, Senator Charles Grassley of Iowa as well as Congressmen Edward Markey of Massachusetts and Henry Waxman of California recently told the FDA that they want to know more about allegations of fraud and irregularities concerning a large clinical trial that was designed to demonstrate the Ketek's safety. That drug-safety study was being conducted after the FDA initially refused to approve Ketek because of the agency's concerns about liver damage and other serious side effects. Later, seemingly because of those allegations of improper conduct and procedures, the study was discontinued -- but the FDA approved Ketek in April 2004. Now, Sen. Grassley, Rep. Markey, and Rep. Waxman want to know more about the discontinued study and the FDA approval of Ketek.
(Posted by: Tom Lamb)