Antibiotic Label to Warn of Liver Danger

By ANDREW BRIDGES
The Associated Press
Thursday, June 29, 2006; 8:53 PM

WASHINGTON -- The label of a novel antibiotic will be updated to reflect
reports of severe liver problems, including several deaths, associated
with its use, the drug's maker and health officials said Thursday.

Sanofi-Aventis' Ketek will carry a bold-type warning about the rare
reports of liver failure and severe injury, some of them fatal, in
patients treated with the drug. The company also is providing additional
information to patients and doctors.

The Food and Drug Administration approved Ketek in 2004. The drug is
used to treat respiratory tract infections, bronchitis, sinusitis and
community-acquired pneumonia. Both the FDA and Sanofi-Aventis believe
the drug's benefits still outweigh its risks.

Through April, the FDA has received reports of 12 cases of acute liver
failure, including four deaths, among people treated with Ketek. A fifth
required a liver transplant.

"In certain of these cases, it appears there are no other likely causes
of liver injury, so it does appear they were linked to the use of the
drug," said Dr. John Jenkins, director of the Office of New Drugs in the
FDA's Center for Drug Evaluation and Research.

The FDA will continue to monitor the safety of Ketek and take further
action if necessary, said a second agency official, Dr. Gerald Dal Pan
of the Office of Epidemiology and Surveillance in the drug center.

There have been two further cases of acute liver failure reported since
April, though details were not immediately available, Dal Pan said.

The FDA also knows of 23 other cases where patients had serious liver
injuries after receiving the antibiotic, which also is called telithromycin.

The rate of reported liver problems associated with the drug is 23 per
10 million prescriptions filled, according to the FDA. In a previously
disclosed internal memo, the FDA said the rate appeared higher in
comparison with similar antibiotics.

But a study published in January that detailed several of the liver
cases associated with the drug may have stimulated the reporting of
further problems. That can skew perceptions of the risk of Ketek
compared with older but similar antibiotics.

"At this point we cannot conclude the risk is higher than with other
antibiotics used to treat these conditions," Dal Pan said.

Dr. Bruce Lavin, vice president of internal medicine for Sanofi-Aventis,
said Ketek remains an option needed by doctors when they treat people
who are infected with bacteria that have developed resistance to other
antibiotics.

The label change comes as the Senate Finance Committee investigates
allegations of fraud connected with trials of Ketek, as well as how the
FDA has handled safety issues associated with the drug.

"There are questions about whether this drug should stay on the market,
and there's great legitimacy to those questions. Ketek is another
example where the FDA accommodated a drug maker and turned a blind eye
to serious safety concerns," Sen. Charles Grassley, R-Iowa, the
committee's chairman, said in a statement.

The updated label for Ketek warns doctors and patients to watch for
signs of hepatitis such as fatigue, malaise, anorexia, jaundice and
nausea. Patients with signs or symptoms of hepatitis should stop
treatment with Ketek immediately and seek a medical evaluation,
including liver functions tests, according to the label.

The label was updated to warn of cases of death and life-threatening
acute respiratory failure seen in Ketek-treated patients with myasthenia
gravis, an autoimmune disorder marked by muscle weakness and fatigue.
The FDA knows of three such deaths. Patients with the disorder should
not be given Ketek unless other options aren't available, the company said.

This month, Sanofi-Aventis stopped enrolling children in trials of the
drug. The company said it had not identified any safety reason that
would merit the "pause," but that it wanted to confirm the trial
conformed with FDA guidelines.

U.S. sales of Ketek were an estimated $50 million in the first half of
2006, the company said.

On the Net:

Ketek information: http://www.ketek.com
© 2006 The Associated Press

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