FDA Issues Public Health Advisory About Liver Toxicity with the Antibiotic Telithromycin (KETEK)

On Jan. 20, 2006, the Food and Drug Administration (FDA) issued a Public Health Advisory warning of life-threatening liver toxicity with the use of the widely-prescribed antibiotic telithromycin (KETEK). The FDA advisory followed a report in the Annals of Internal Medicine that described three cases of severe liver toxicity, including one death, in patients taking telithromycin. This report is available on the Internet at www.acponline.org/journals/annals/hepatotoxicity.htm.

One of the three patients recovered when telithromycin was stopped. Of the two remaining patients, one required a liver transplant and one died. When the livers of the latter two patients were examined in the laboratory, they showed massive tissue death. These two patients had reported some alcohol use but all three patients had previously been healthy and were not using other prescription drugs.  

Telithromycin was approved by the FDA in April 2004 for the treatment of mild to moderate community-acquired pneumonia, acute worsening of chronic bacterial bronchitis, and acute inflammation of the sinuses caused by bacteria. The drug belongs to a new family of antibiotics called ketolides. Ketolides are similar to the macrolide family of antibiotics, which includes erythromycin (E-MYCIN), clarithromycin (BIAXIN), and azithromycin (ZITHROMAX, ZMAX). In 2005, more than three million prescriptions were filled in the U.S. for telithromycin.

Almost two years ago, we listed telithromycin as a DO NOT USE drug in the June 2004 Worst Pills, Best Pills News because numerous other, safer antibiotics are approved to treat the same infections as this drug, including other forms of erythromycin. This recommendation was made after our examination of the FDA’s reviews of data submitted by telithromycin’s manufacturer, Aventis Pharmaceuticals of Kansas City, MO, to the FDA. These documents are available on the FDA’s Web site at www.fda.gov/ cder/foi/nda/2004/21-144_Ketek.htm.

The original new drug application for telithromycin was filed with the FDA in March 2000. Of the small fraction of drugs that are reviewed by any FDA advisory committee, most are reviewed by only one advisory committee, but this drug was reviewed by two separate advisory panels before it was ultimately cleared for marketing in April 2004.  

Panelists at the Jan. 8, 2003 advisory committee meeting reviewed data from a large U.S. safety study that indicated a risk for heart, liver, and eye toxicity with telithromycin use. It was also revealed at this meeting — three years ago — that the FDA already had received 54 reports of liver-related adverse drug reactions from countries in which the drug had already been previously marketed. Nineteen of these 54 reports were categorized as serious.

Telithromycin can also cause an electrical disturbance in the heart known as QT prolongation. QT prolongation can develop into a life-threatening heart rhythm disturbance known as torsades de pointes. Two cases of torsades de pointes were reported at the advisory committee meeting, and the events were suspected to be telithromycin-related. QT prolongation is an adverse effect also associated  with some macrolides, fluoroquinolones, and cephalosporin antibiotics.

Some patients taking telithromycin in clinical trials also reported blurred vision that significantly impaired their ability to perform daily activities. The visual disturbances mainly occurred in women and the young. Visual adverse effects occurred from one to three hours after a dose. The effect lasted for up to 20 hours. The FDA has received 167 reports of visual adverse events from countries in which the drug was first marketed. Of these, 42 were categorized as serious. Telithromycin appears to cause more visual disturbances compared to macrolides already on the market.

If you or a family member develop any of the symptoms of potential liver toxicity while taking telithromycin, you should notify the prescribing physician immediately. These symptoms are:

• Pruritus (itchy skin)
• Jaundice (yellowing of the skin or whites of the eyes)
• Dark urine
• Upper right-sided abdominal tenderness (location of the liver)
• Unexplained “flu-like” symptoms

Telithromycin can be added to the growing list of mistakes that the FDA should not have approved since the passage of the Prescription Drug User Fee Act (PDUFA) in 1992. The passage of this law allowed the FDA to collect money from drug companies to speed new drug reviews, in effect making the drug companies the FDA’s primary clients, not the American public. This is clearly evident from the fact that an unprecedented 17 new drug safety withdrawals have occurred since the passage of PDUFA.

Because of PDUFA, the FDA is under tremendous pressure to approve new drugs very quickly. Telithromycin, however, is not a case of the FDA rushing to approve a new drug. This drug was under review at the agency for four years. Despite the fact that the only unique feature of telithromycin is its toxicity, the drug was approved. It appears that another adverse effect of PDUFA is that there is also pressure to approve new drugs no matter the risks are to patients.    

We continue to agree with the editors of the highly respected French drug journal Prescrire International, who in 2003 called telithromycin “a needless addition to the other macrolides.”

What You Can Do

There is no reason to take telithromycin. There are safer and equally effective antibiotics available that are approved to treat the same illnesses.

If you or a family member experience the symptoms of potential liver toxicity listed above, contact the prescriber immediately. Do not stop taking this antibiotic without an urgent call to your physician so you can be placed on a different, safer antibiotic.