Sanofi adds new liver warning to antibiotic label

By Lisa Richwine

WASHINGTON (Reuters) – Sanofi-Aventis put a stronger
warning on its antibiotic Ketek following the deaths of four
patients who took the drug and developed liver failure, U.S.
regulators said on Thursday.

Liver failure also was reported in eight other Ketek users,
including one who needed a liver transplant, the Food and Drug
Administration said. Twenty-three others developed less serious
liver damage, the FDA said.

FDA officials said the liver problems were rare and a known
complication of other antibiotics. Ketek was approved in 2004
to treat certain types of sinusitis, bronchitis and pneumonia
including cases that resist other antibiotics.

“You are looking at a playing field where all the drugs
used to treat these conditions have the potential for serious
adverse events. Given what we know today, we believe the
benefits of Ketek outweigh the potential risk” when used
according to prescribing instructions, said Dr. John Jenkins,
director of the FDA’s Office of New Drugs.

The new, bold-faced warning on Ketek’s label advises
doctors and patients to watch for signs of liver problems and
stop taking Ketek if they appear. Symptoms can include fatigue,
malaise, loss of appetite, nausea, yellow skin and dark urine.

“In certain of these cases, it appears that there are no
other likely causes of the liver injury, so it does appear they
were due to use of the drug,” Jenkins said.

FDA officials estimated the rate of reported liver problems
was about 23 per 10 million prescriptions through April 2006.

They cautioned, however, that the figure did not give a
true picture of the risk because it was likely there were more
unreported cases. Plus, it is unknown how many patients
actually took the drug they were prescribed.

“FDA will continue to evaluate Ketek-associated safety
issues and take further actions if warranted,” an agency
statement said.

Sanofi said in a statement it believed Ketek, known
generically as telithromycin, offered important benefits.

“Based on the in-depth review of the clinical trial and
post-marketing data, we continue to believe that the benefits
of Ketek outweigh the risks when the drug is used as directed”
for approved uses, said Dr. Sol Rajfer, president of science
and medical affairs at Sanofi-Aventis U.S.

The Ketek case has drawn the attention of Senate Finance
Committee Chairman Charles Grassley, a vocal FDA critic who has
questioned whether the agency dismissed problems with a major
Ketek trial in which several doctors were investigated and one
was jailed for fraud.

“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,” said
Grassley, an Iowa Republican.

Sanofi shares closed up $2.24, or 4.9 percent, at $48.17 on
the New York Stock Exchange on Thursday amid a broad market
rally.

(Additional reporting by Bill Berkrot in New York)