By GARDINER HARRIS
Published: June 30, 2006
WASHINGTON, June 29 ” Federal drug regulators issued a strong warning Thursday that Ketek, a controversial antibiotic, could in rare circumstances cause serious liver injury, liver failure and even death.
“We clearly now understand that there is risk of serious liver injury with Ketek,” said Dr. John Jenkins, director of the Food and Drug Administration’s Office of New Drugs.
But Dr. Jenkins said the agency did not yet know whether the risks posed by Ketek were greater than those of other antibiotics, and he said the drug’s benefits outweighed its risks.
Ketek is manufactured by Sanofi-Aventis, the French drug giant, and it has been approved to treat bronchitis, sinusitis and mild-to-moderate pneumonia.
In a written statement, Dr. Sol Rajfer, president of science and medical affairs in the United States for Sanofi-Aventis, said, “We continue to believe that the benefits of Ketek outweigh the risks when the drug is used as directed for its approved indications.”
Thursday’s announcement was the culmination of months of internal debate in the drug agency about how to address Ketek’s risks, according to internal agency memorandums obtained by The New York Times. In addition to liver problems, Ketek can cause blurred vision and loss of consciousness. In patients with myasthenia gravis, a rare neurological disorder, it can cause death.
Fourteen adult patients in the United States have suffered liver failure after taking Ketek. At least four of them have died; 23 others suffered serious liver injury.
One F.D.A. safety reviewer in May called for a halt to Sanofi-Aventis’s tests of Ketek in children with ear infections, arguing that cutting the duration of ear pain by one day was hardly worth risking death.
Shortly after The Times reported these concerns, Sanofi-Aventis announced a “pause” in its pediatric clinical trials.
“We’re continuing to have discussions about those studies and whether they can resume,” Dr. Jenkins said.
Other antibiotics cause liver failure, but Ketek seems to do so almost four times as often, safety officials concluded in a review.
But in Thursday’s briefing, agency officials said that comparing liver-failure rates across antibiotics was fraught with problems.
“So while the number for Ketek may be higher than the others, direct comparisons are really difficult to make,” said Dr. Gerald DalPan of the division of epidemiology and surveillance at the agency.
New warnings on Ketek’s label suggest that patients who appear jaundiced or who suffer any other signs of liver injury should stop taking the drug.
Because Ketek has been reported to cause severe liver injury in patients after only a few doses, Dr. Jenkins was asked how patients could follow this advice.
“We’re providing the best possible advice to doctors to be aware of this risk and to make sure their patients are aware,” he replied.
The drug agency’s actions in regard to Ketek are being investigated by Senator Charles E. Grassley, the Iowa Republican who is chairman of the Finance Committee, and by Representatives Edward J. Markey of Massachusetts and Henry A. Waxman of California, both Democrats.
Mr. Grassley released a statement Thursday, saying, “Ketek is another example where the F.D.A. accommodated a drug maker and turned a blind eye to serious safety concerns.”
Dr. Jenkins explained that new antibiotics were desperately needed since growing resistance to antibiotics gradually rendered older drugs ineffective.
