Ketek: A Timeline of Lies

Washington, DCDespite information indicating that using Ketek (telithromycin) carried a serious risk of liver disease and other problems, the US Food and Drug Administration (FDA) approved the antibiotic for sale in April, 2004.

This occurred even though evidence that the drug was effective was unreliable at best and fraudulent at worst. Use of Ketek has caused serious liver damage in a number of patients and has also resulted in at least four deaths, leading many people to wonder how, with all the evidence against it, Ketek was ever approved for use in the United States.

Back in February 2000, Sanofi-Aventis, makers of Ketek, applied to the FDA for approval of its drug. The FDA denied the request because there was evidence of serious side-effects including liver damage, loss of consciousness and blurred vision. At that time the FDA requested Sanofi-Aventis gather further information on Ketek before resubmitting their application.

In response, Sanofi-Aventis began a study (known as 3014) to further support its application for approval. The study was conducted by Pharmaceutical Product Development, involved over 24,000 subjects and was full of errors, omissions, and fabrications. It was so bad that the FDA rejected the study as completely unreliable.

Some of the problems with the study include the following:

• One doctor falsified data, used friends, relatives, and people who did not have respiratory infections, and used subjects who did not ever receive medication. Internal reports published in the Wall Street Journal (May, 2006) confirm that Sanofi-Aventis was worried about this doctor, but did not inform the FDA of its concerns.
  
  
• Another doctor was found to have committed over 20 violations of the study's guidelines.
  
  
• Yet another doctor did not report adverse drug reactions.

An advisory panel recommended approval of Ketek in 2003, although that panel was unaware of the unreliable nature of study 3014. The FDA declined Ketek at that point, but then approved it later in 2004 for adult treatment of acute bacterial infections due to chronic bronchitis, acute bacterial sinusitis and pneumonia.

Approval of Ketek was based on the prior data that the FDA had previously used to reject the Ketek application, and on information that Ketek had been marketed in other countries with only minor problems. What is troubling about the data from other countries is that the FDA admits that most adverse reactions to medicines are underreported, meaning that data taken from adverse reaction reports in other countries is most likely unreliable.

In January, 2006, the European Medicines Agency asked Sanofi-Aventis to add stronger warnings about the risk of liver failure to the Ketek label.

After reports in the United States about serious reactions to Ketek, including death from liver failure, an article appeared in the New England Journal of Medicine defending the drug and claiming Ketek was as safe as other antibiotics. However, all six of the article's authors had financial connections to Sanofi-Aventis: Five were paid consulting fees and one was an employee of Sanofi-Aventis.

In May 2006, the FDA requested a black box warning be added to the Ketek label warning about "severe, life-threatening, and in some cases fatal" liver toxicity that had been reported as a possible side-effect for patients.

Then, on June 30, 2006, the FDA issued a warning that only a few doses of Ketek could cause liver failure.

Although Ketek had only been on the market for two years, the FDA received reports of 110 cases of liver problems associated with the antibiotic. Of these, 12 cases involved acute liver failure and 23 cases involved serious liver injury. Of the cases of acute liver failure, four people died and one required a liver transplant. One of the patients who died was a 49 year-old woman who took only two does of Ketek before she was hospitalized. The FDA reports that most of these adverse reactions occurred in otherwise healthy people.

A safety review of the antibiotic found that Ketek causes liver failure in 23 people for every ten million prescriptions, almost four times as often as other antibiotics. Problems with blurred vision and loss of consciousness are unique to Ketek and not usually found in antibiotics. Additionally, Ketek can lead to death for people who have a rare neurological disorder known as myasthenia gravis.

Ketek was scheduled for testing on infants and children, however that testing was postponed in June after repeated calls for Sanofi-Aventis to pull the study. The company denied that the postponement of the study had anything to do with recent concerns about the risks associated with Ketek.

Given the large amount of information indicating that Ketek is a dangerous drug, how could the FDA still approve it for sale? Patients have been injured and lives have been lost because people were not properly informed of the risks associated with taking Ketek.