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On June 29, the Food and Drug Administration (FDA) announced that new warnings about liver toxicity, including the possibility of death, have been added to the package insert for the antibiotic telithromycin (KETEK). The FDA advisory was issued in response to a report in the Annals of Internal Medicine that described three cases of severe liver toxicity, including one death, in patients taking telithromycin (see Worst Pills, Best Pills News March 2006). Telithromycin is produced by...
On June 29, the Food and Drug Administration (FDA) announced that new warnings about liver toxicity, including the possibility of death, have been added to the package insert for the antibiotic telithromycin (KETEK). The FDA advisory was issued in response to a report in the Annals of Internal Medicine that described three cases of severe liver toxicity, including one death, in patients taking telithromycin (see Worst Pills, Best Pills News March 2006). Telithromycin is produced by Sanofi-Aventis, which has its U.S. headquarters in Bridgewater, NJ.
The FDA approved telithromycin in April 2004 as the first member of a new family of antibiotics called ketolides. The drug was listed as a Do Not Use drug two months later in the June 2004 Worst Pills, Best Pills News because of liver toxicity, the possibility of heart rhythm disturbances, and debilitating vision disturbances. There are numerous other antibiotics approved for the same infections that are safer than telithromycin.
Now, Congress is becoming concerned about the drug. In fact, the Senate Finance Committee is investigating allegations that the FDA approved telithromycin in 2004 despite unresolved questions about its efficacy and safety. Allegedly, the FDA did this with the knowledge of concerns over the validity of some of the clinical safety data, said Sen. Charles Grassley (R-Iowa), chairman of the committee.
Grassley is “committed to getting to the bottom of the matter,” he said in The Wall Street Journal June 13.
The new liver toxicity warning that now appears in telithromycin’s professional product labeling:
Hepatotoxicity [liver toxicity] Acute hepatic failure and severe liver injury, in some cases fatal, have been reported in patients taking KETEK. These hepatic reactions included fulminate hepatitis [inflammation of the liver] and hepatic necrosis [liver cell death] leading to liver transplant, and were observed during or immediately after treatment. In some of these cases, liver injury progressed rapidly and occurred after administration of a few doses of KETEK. Physicians and patients should monitor for the appearance of signs or symptoms of hepatitis, such as fatigue, malaise, anorexia [loss of appetite], nausea, jaundice [yellowing of skin or eyes], bilirubinuria [dark colored urine], acholic stools [pale or clay colored], liver tenderness, or hepatomegaly [enlarged liver]. Patients with signs or symptoms of hepatitis must be advised to discontinue KETEK and immediately seek medical evaluation, which should include liver function tests. If clinical or transaminase elevations [liver function tests] combined with other system symptoms occur, KETEK should be permanently discontinued. |
Physicians and patients should monitor for the appearance of signs or symptoms of hepatitis, such as fatigue, malaise, anorexia [loss of appetite], nausea, jaundice [yellowing of skin or eyes], bilirubinuria [dark colored urine], acholic stools [pale or clay colored], liver tenderness, or hepatomegaly [enlarged liver]. Patients with signs or symptoms of hepatitis must be advised to discontinue KETEK and immediately seek medical evaluation, which should include liver function tests. If clinical or transaminase elevations [liver function tests] combined with other system symptoms occur, KETEK should be permanently discontinued.
Approving the drug was a mistake
The FDA should have never approved telithromycin for use in the United States. The original New Drug Application (NDA) was filed in March of 2000, and the drug subsequently went through two reviews by a committee of outside advisers. This is very unusual for any drug.
Since 2001, telithromycin has also been marketed in a number of countries, including Canada and the United Kingdom.
After the first FDA advisory committee meeting, Sanofi-Aventis committed to undertake a large safety study to assess the risks of liver toxicity, heart rhythm disturbances and debilitating vision disturbances associated with telithromycin.
The FDA reviewed this study and made the results available to the public. Agency reviewers found that the way the study was managed and conducted was so flawed that the results could not be interpreted. In other words, the safety study’s results were meaningless. Strangely enough, Sanofi-Aventis cited the results of the study as evidence of telithromycin’s safety, including its safety for the liver.
The FDA asked for reports of adverse drug reactions from about two dozen countries in which telithromycin was already on the market. The FDA said it found that the reporting rates for liver toxicity, heart rhythm disturbances, and vision disturbance were similar among telithromycin and other antibiotics. However, spontaneous adverse drug reaction reports are notoriously difficult to interpret because so few adverse reactions are actually reported.
Incomprehensibly, the FDA deemed telithromycin “safe” according to a very low standard — certainly one that does not prevent the American public from suffering needless adverse drug reactions.
What You Can Do
There is no medical reason that you should be taking telithromycin because there are numerous safer, FDA-approved antibiotics available for the treatment of the same infections as telithromycin.
Telithromycin is not approved to treat serious life-threatening infections. If you experience the previously listed signs or symptoms of potential liver toxicity, follow the directions in the new warnings to stop taking the drug and seek medical evaluation immediately.
