U.S. Rep. Edward Markey accused the Food and Drug Administration this week of conducting a “seriously flawed” approval process for an antibiotic that may be linked to severe liver failure.
Ketek, a drug used to treat bacterial infections of the lung and sinus, is approved for use in adults and is being tested on children. A February study in the Annals of Internal Medicine said three previously healthy patients who took Ketek, also known as telithromycin, developed liver damage. One died.
The antibiotic was approved by the FDA based on “flimsy data” provided by drug maker Aventis, according to Markey, D-7th, and U.S. Rep. Henry Waxman of California, who detailed the results of an investigation conducted by their staff members.
A doctor who recruited patients for Ketek clinical trials pleaded guilty to falsifying data from the study just months after the drug was approved in April 2004, the congressmen wrote in a letter Monday to acting FDA Commissioner Andrew von Eschenbach.
“We know drug companies manipulate published studies on their drugs, hiding negative information from physicians. Here, Aventis went even further, failing to disclose to FDA grave flaws in a key safety study,” Waxman said in a news release. “FDA approved the drug on flimsy data without resolving the safety issues, and it failed to penalize Aventis.”
A local doctor said because of cheaper alternatives he has only prescribed Ketek twice, and is now reluctant to use it at all. “It’s chilling,” Dr. Victor Calcaterra said of reports linking the drug to severe liver damage. Calcaterra, an ear, nose and throat doctor at Newton-Wellesley Hospital and in Framingham, said he will probably “avoid the drug entirely until I hear more about it.”
Although Ketek is fairly new, the function it performs is replicated by many other drugs, said Dr. Thomas Treadwell, director of MetroWest Medical Center’s infectious disease clinic.
“Everybody looks at it as a sexy new drug. But it really doesn’t fill an important niche. There are many drugs that do a similar thing,” he said.
The Annals of Internal Medicine study did not conclusively link Ketek to liver damage but said “caution is advised in prescribing this drug pending additional post-marketing surveillance data.”
The FDA is “evaluating reports of serious liver damage in patients following use of Ketek,” agency spokeswoman Susan Bro said yesterday in an e-mail. Bro defended Ketek’s approval, saying the agency analyzed clinical trials and data from countries that had already approved the drug.
“All drugs have risks,” Bro wrote.
An FDA committee raised concerns about Ketek’s potential for causing liver toxicity, cardiac and visual problems before the drug was approved, Markey and Waxman wrote.
According to Markey and Waxman, a February 2004 FDA memorandum detailed several flaws in a 24,000-patient study. The alleged flaws were enrollment of patients being treated for weight loss therapy instead of conditions specified in the study protocol; documentation of patients as having completed therapy despite statements from patients that they never received the drugs; and enrollment of patients in numbers far exceeding the approved amount.
A government database recorded two deaths among 159 reports of liver damage, cardiac and vision problems in patients taking Ketek in the three months ending September 2005, Markey and Waxman wrote.
The congressman said they are concerned about the FDA’s decision to allow clinical trials in which Ketek is being given to children as young as 6 months old.
The congressmen requested a response from the FDA by June 1.