Yourlawyer.com (Ketek News)

Antibiotics Most Likely to Cause Drug Induced Liver Injury

Tue, 02 Dec 2008 00:00:00 -0800

Antibiotics are the drugs most responsible for the occurrence of drug induced liver injury (DILI), a new study has found. According to a press release announcing the study, DILI is the most frequent adverse drug-related event leading to abandonment of potentially promising new drug candidates during clinical trials and development.

DILI is the most common cause of death from acute liver failure and accounts for approximately 13 percent of all such cases in the U.S. It is caused by a wide variety of prescription and nonprescription medications, nutritional supplements and herbals.

"DILI is a serious health problem that impacts patients, physicians, government regulators and the pharmaceutical industry," Naga P. Chalasani, MD, lead author of the study, said in the press release. "Further efforts are needed in defining its pathogenesis and developing means for the early detection, accurate diagnosis, prevention and treatment of DILI."

The study, published in the journal Gastroenterology, consisted of an initial analysis of an ongoing prospective study of DILI. Its primary aim is to develop well-characterized cases of medication-related liver injury on which to conduct hypothesis-driven research targeted at developing means to diagnose, prevent and treat DILI, the press release said. Patients with suspected DILI were enrolled based upon predefined criteria and followed for at least six months. According to the press release, those with acetaminophen liver injury were excluded.

According to the Gastroenterology article, the study found that DILI was caused by a single prescription medication in 73 percent of the cases, by dietary supplements in 9 percent and by multiple agents in 18 percent. More than 100 different agents were associated with DILI; antibiotics (45.5 percent) and central nervous system agents (15 percent) were the most common, the press release said.

Of the dietary supplements causing DILI, compounds that claim to promote weight loss and muscle building accounted for nearly 60 percent of the cases. The study found that at least 20 percent of patients with DILI ingest more than one potentially hepatotoxic agent.

Researchers found no relationship between gender and severity of DILI, but individuals with diabetes experienced more severe DILI.

The researchers noted that DILI is a diagnosis of exclusion, meaning that detailed testing must be performed to exclude competing causes of liver disease. For that reason, the study authors recommended that in patients with suspected DILI, acute hepatitis C virus (HCV) infection should be carefully ruled out through the use of HCV RNA testing.

Ketek, Avandia Among Drugs Doctors Won't Take

Mon, 23 Jun 2008 00:00:00 -0700

When doctors were recently asked which commonly prescribed medications they would avoid, they came up with the following eight. Perhaps you might want to reconsider these medications as well. At a minimum, speak to your doctor, as there are safer options for all of these medications.

Advair: This asthma medication contains the long-acting beta-agonist (LABA) salmeterol. A 2006 study of 19 trials, which was published in the Annals of Internal Medicine, revealed that with regular use, LABAs can increase asthma attack severity. Salmeterol is more widely prescribed than other LABAs, thus the danger is greater and may contribute to as many as 5,000 asthma-related deaths in the United States annually. Another study that same year led the US Food and Drug Administration (FDA) to label Advair with a "black box,” the FDA’s strongest warning.
Avandia: In September, the Journal of the American Medical Association (JAMA) revealed in a study that those taking diabetes drug Avandia—or rosiglitazone—for at least one year suffered an increased risk of heart failure (109 percent) or a heart attack (42 percent). One possible reason is that Avandia may cause dangerous fluid retention or raise artery-clogging LDL cholesterol. The FDA asked Avandia maker, GlaxoSmithKline, to conduct a long-term study assessing users' heart risks; however, that study is not expected to commence until later this year.
Celebrex: This pain medication is linked to increased risks of stomach bleeding, kidney trouble, and liver damage. According to a 2005 New England Journal of Medicine study people taking 200 mg of Celebrex twice daily more than doubled their risk of dying of cardiovascular disease; those on 400 mg twice daily more than tripled their risk. By the way, two other drugs in this drug class—Bextra and Vioxx--were banned for similar heart damage risks, yet Celebrex remains available.
Ketek: This antibiotic, generally prescribed for respiratory-tract infections, carries a higher risk of severe liver side effects, has been linked to heart-rhythm problems and liver disease, and can interact with other medications. Although still prescribed, the FDA limited Ketek’s usage to the treatment of pneumonia early last year.
Prilosec and Nexium: The FDA has investigated a suspected link between cardiac trouble and acid-reflux drugs Prilosec and Nexium. Also, because both drugs are proton-pump inhibitors, they may be overly effective at stopping stomach acid production, raising pneumonia, bone loss risk, and fracture risk (this, by over 40 percent in patients on long-term use).
Original Visine: Because Visine shrinks ocular blood vessels in the same way Afrin does nasally, overuse of its active ingredient tetrahydrozoline can create an endless loop of vessel dilating-and-constricting that may cause more redness, increasing the need for more Visine, causing more redness, and so on.
Pseudoephedrine: Other than that this decongestant is a critical component in methamphetamine, it can raise blood pressure and heart rate, has been linked to heart attacks and strokes, and can increase symptoms of benign prostate disease and glaucoma.

Ketek Probe Raises Questions About FDA Head

Mon, 10 Mar 2008 00:00:00 -0700

A congressional Ketek probe has taken a stunning turn, as it now appears that the head of the Food & Drug Administration (FDA) may have committed perjury when he gave written testimony to a committee investigating the agency's approval of the defective drug, Ketek.

Ketek was approved by the FDA in 2004 to treat respiratory tract infections, bronchitis, sinusitis and community-acquired pneumonia. Soon after its approval however, the FDA began to receive reports that Ketek was causing liver damage in some patients. This past February, the FDA added black box warnings about liver damage to the Ketek label. In total, the FDA had reports of at least 53 cases of liver damage linked to Ketek. At least five of those cases were fatal, and one required a liver transplant. The FDA also withdrew Ketek’s approval to treat sinusitis and bronchitis.

In February, the subcommittee issued subpoenas to Health and Human Services (HHS) Secretary Michael Leavitt, asking him to produce unredacted records prepared for the FDA commissioner’s appearance at a March 2007 hearing on Ketek. Leavitt’s department oversees the FDA. The committee also approved subpoenas for two current FDA investigators, one former FDA investigator and a former employee of a company that monitored the fraudulent Ketek clinical trials. The subpoenas were necessary because the Bush Administration had refused to release the documents or allow any of the officials to testify. At first Leavitt refused to turn over the documents, but finally gave in when he was threatened with Contempt of Congress charges.

Those documents in question deal with FDA Commissioner Andrew von Eschenbach's written testimony regarding events surrounding the Ketek drug approval. According to an article on the American Chronicle website, the committee subsequently learned from an FDA insider and those familiar with the approval that the testimony was not truthful.

According to American Chronicle "Von Eschenbach is a cancer-industry insider who took the job at the FDA so he could get quick approval of new biotech drugs while using humans for cruel experiments in the name of "progress." His nomination as permanent head of the FDA took place during the 2006 lame duck session of Congress and was rubber stamped by Big Pharma friendly Senators."

During Von Eschenbach's confirmation hearings, Senator Charles Grassley, a Republican, criticized the Bush Administration on the floor of the Senate for naming Von Eshenbach to head the FDA. "People ought to be ashamed of saying Dr. Andrew von Eschenbach has done a superb job in the position he is currently occupying [acting head of the FDA].…That is an insult….In my interactions with the Department of Health and Human Services and the FDA these last 8 months, I have seen a complete and utter disrespect for congressional authority and hence the law.… This body [the Senate] should not walk hand in hand with the executive branch and sit idly by as instances of abuse and fraud continue to endanger the health and safety of American people," Grassley said.

Ketek Hearing Prompts Lawmaker to Threaten HHS Secretary with Contempt

Wed, 13 Feb 2008 00:00:00 -0800

A Ketek probe in Congress is getting ugly, with one lawmaker threatening to hold federal officials in contempt of Congress for failing to turn over documents regarding the Food & Drug Administration’s (FDA) approval of the drug. A subcommittee of the House Energy and Commerce Committee is trying to figure out how Ketek, one of the most dangerous antibiotics on the market, obtained FDA approval even though an FDA audit of Ketek clinical trials found several instances of fraud.

Ketek was approved by the FDA in 2004 to treat respiratory tract infections, bronchitis, sinusitis and community-acquired pneumonia. Soon after its approval however, the FDA began to receive reports that Ketek was causing liver damage in some patients. This past February, the FDA added black box warnings about liver damage to the Ketek label. In total, the FDA had reports of at least 53 cases of liver damage linked to Ketek. At least five of those cases were fatal, and one required a liver transplant. The FDA also withdrew Ketek’s approval to treat sinusitis and bronchitis.

Earlier this month, the subcommittee issued subpoenas to Health and Human Services (HHS) Secretary Michael Leavitt, asking him to produce unredacted records prepared for the FDA commissioner’s appearance at a March 2007 hearing on Ketek. Leavitt’s department oversees the FDA. The committee also approved subpoenas for two current FDA investigators, one former FDA investigator and a former employee of a company that monitored the fraudulent Ketek clinical trials. The subpoenas were necessary because the Bush Administration had refused to release the documents or allow any of the officials to testify.

Rep. John Dingell (D-Mich), chairman of the committee, said yesterday he would consider holding Leavitt in contempt after the HHS Secretary refused to turn over the FDA briefing documents subpoenaed by the committee. The documents were used to prepare FDA Commissioner Andrew von Eschenbach for his appearance before lawmakers last year.

The Ketek briefing documents might include information regarding a Sanofi-Aventis Ketek study that was rife with fraud. When the FDA audited Ketek study participants recruited by the drug’s maker Aventis (now Sanofi-Aventis) they found one family doctor in a small Alabama town had signed up 407 patients for the study. The doctor’s entire staff was enrolled in the trail, and it even appeared that some of the patient signatures on consent forms where forged. Eventually, that doctor was charged with fraud, and sentenced to prison. The FDA also visited several other sites with high numbers of participants, and found serious irregularities at every one.

That study prompted the FDA to issue Sanofi-Aventis a warning letter, but the fraud did not keep Ketek off the market. Last year, Von Eschenbach testified that the FDA did not use the flawed safety study to approve Ketek. Dingell and others on the committee say that statement may be untrue, and they need access to the briefing documents to make that determination.

At yesterday’s Ketek hearing, lawmakers heard from three government staffers who were also issued subpoenas. Robert West, an FDA agent who first investigated Ketek, said he tried to get permission in 2002 to look into whether Aventis was aware of fraudulent data when it submitted the study. West said his request was blocked by senior FDA officials, although he said he did not know which ones.

Ketek Faces More Scrutiny as Lawmakers OK Subpoenas

Wed, 30 Jan 2008 00:00:00 -0800

Lawmakers investigating the defective drug Ketek have been forced to subpoena current and former Food & Drug Administration (FDA) officials.   A subcommittee of the House Energy and Commerce Committee is trying to figure out how Ketek, one of the most dangerous antibiotics on the market, obtained FDA approval even though an FDA audit of Ketek clinical trials found several instances of fraud.

Ketek was approved by the FDA in 2004 to treat respiratory tract infections, bronchitis, sinusitis and community-acquired pneumonia.   Soon after its approval however, the FDA began to receive reports that Ketek was causing liver damage in some patients.   This past February, the FDA added black box warnings about liver damage to the Ketek label. In total, the FDA had reports of at least 53 cases of liver damage linked to Ketek. At least five of those cases were fatal, and one required a liver transplant. The FDA also withdrew Ketek’s approval to treat sinusitis and bronchitis.

At the same time, the FDA updated the Ketek label to include information about reports of fatal worsening of the neuromuscular condition, myasthenia gravis. At the time of the label change, the FDA knew of three reported deaths in myasthenia gravis patients taking Ketek.

Many Ketek critics say the dangerous antibiotic should never have been approved for use because of the widespread fraud committed by doctors involved in the drug’s clinical trials.   When the FDA audited Ketek study participants recruited by the drug’s maker Aventis (now Sanofi-Aventis) they found one family doctor in a small Alabama town had signed up 407 patients for the study. The doctor’s entire staff was enrolled in the trail, and it even appeared that some of the patient signatures on consent forms where forged. Eventually, that doctor was charged with fraud, and sentenced to prison. The FDA also visited several other sites with high numbers of participants, and found serious irregularities at every one.

In October, the FDA sent a Warning Letter to Sanofi-Aventis, outlining various instances of misconduct by doctors involved in the Ketek clinical trial, and criticizing the drug maker for ignoring those issues. But it appears the FDA ignored the fraud as well, because it still approved Ketek in spite of the irregularities found in the clinical trials.

The congressional subcommittee has been trying to figure out why the FDA went ahead and did so.   But the FDA hasn’t been very cooperative, so the subcommittee was forced to take the drastic action of issuing subpoenas. "Unfortunately, the FDA has been less than forthcoming with either witness or document production in connection with our drug safety investigations," said Rep. Bart Stupak, the Democratic chairman of the subcommittee on oversight and investigations.

Yesterday, the subcommittee voted 12-0 to issue a subpoena to Health and Human Services (HHS) Secretary Michael Leavitt, asking him to produce unredacted records prepared for the FDA commissioner's appearance at a March 2007 hearing on Ketek. Leavitt's department oversees the FDA.   The FDA and HHS have refused to provide those documents in the past.

The panel also approved subpoenas for two current FDA investigators, one former FDA investigator and a former employee of a company that monitored the fraudulent Ketek clinical trials. The lawmakers want to question the witnesses about "their knowledge of whether Aventis was aware of substantial data integrity problems in Study 3014 at the time of submission to FDA.

The subcommittee will hold a third hearing into the Ketek debacle on February 12.

Ketek Investigation Could Yield Subpoenas

Tue, 29 Jan 2008 00:00:00 -0800

Ketek investigators at the Food & Drug Administration (FDA) could soon be subpoenaed by a congressional committee looking into the agency’s handling of the defective drug. Ketek, approved in 2004 to treat respiratory tract infections, bronchitis, sinusitis and community-acquired pneumonia, has been linked to liver failure. The FDA approved Ketek despite knowing that its clinical trials were rife with fraud.

Shortly after its approval, Ketek was linked to serious side effects, including sometimes fatal liver damage. The FDA eventually confirmed 53 cases of liver failure in patients using Ketek, including five deaths. This past February, the FDA finally added black box warnings to the Ketek label and severely restricted its use.

Congressman Bart Stupak and John Dingell, both Michigan Democrats, want to know why Ketek was able to be approved even though the FDA found instances of serious fraud in its clinical trials. Doctors participating in those clinical trials were paid $400 by Aventis (now part of Sanofi-Aventis) for every patient they convinced to participate in the Ketek study.

That huge financial incentive was too much for some doctors to resist. When the FDA audited study participants, they found one family doctor in a small Alabama town had signed up 407 patients for the study. What else they found during the audit at Dr. Ann Campbell’s was shocking. The doctor’s entire staff was enrolled in the trail. It even appeared that some of the patient signatures on consent forms where forged. So gross were Dr. Campbell’s violations that she was eventually convicted of fraud and sentenced to prison. The FDA also visited several other sites with high numbers of participants, and found serious irregularities at every one.

This afternoon, the House Energy and Commerce Committee Subcommittee on Oversight and Investigation, headed up by Dingell and Stupak, is scheduled to vote on whether or not to subpoena several FDA officials who investigated Ketek trials. The subpoenas are needed to compel the testimony of Ann Marie Cisneros, a clinical researcher who found fraudulent data in a Ketek study, two current FDA investigators, Robert West and Douglas Loveland, and one former investigator, Robert Ekey.

According to the Associated Press, the subcommittee will also consider issuing a subpoena for internal FDA documents connected with the investigators' work. Congressional aides were told the documents summarize the FDA's investigation of whether Sanofi-Aventis was aware of problems with one of its safety studies before it was submitted to an advisory committee. The document "may recommend prosecution of certain individual and/or entities for the fraudulent trials," according to a memo issued by the subcommittee.

Stupak is also seeking to subpoena the briefing book for Commissioner Andrew C. von Eschenbach to determine whether he was misled in the preparation of his testimony dealing with Ketek.

Ketek Lawsuit Filed in Illinois, Says Sanofi-Aventis Knew of Liver Failure Side Effects

Wed, 28 Nov 2007 00:00:00 -0800

Ketek users injured by the defective drug have filed suit against Sanofi-Aventis in Illinois. The 47 plaintiffs involved in the Ketek lawsuit claim that Sanofi-Aventis knew that Ketek put users at an increased risk of increased risk injuries or death from liver failure and hepatic injury.

Ketek, a powerful antibiotic, was approved by the Food & Drug Administration (FDA) in 2004 to treat sinus infections. This approval came despite serious concerns with the way clinical trails of Ketek had been conducted. Because cheaper antibiotics, like amoxicillin, were already available to treat sinus infections, the FDA required Aventis to design a study showing that Ketek would work at least as well as existing treatments before it could be approved. Aventis eventually signed up 1800 private physicians to participate in these clinical trails. These doctors were given $400 for every patient they convinced to participate in the Ketek study. That huge financial incentive was too much for some doctors to resist. When the FDA audited Ketek study participants, they found one family doctor in a small Alabama town had signed up 407 patients for the study. The doctor’s entire staff was enrolled in the trail. It even appeared that some of the patient signatures on consent forms where forged. That Ketek Clinical trial doctor was eventually convicted of fraud and sentenced to prison. The FDA also visited several other sites with high numbers of participants, and found serious irregularities at every one. In October, the FDA issued Sanofi-Aventis a warning letter for failing to respond to problems with Ketek clinical trials.

Shortly after its approval, Ketek was linked to serious side effects, including sometimes fatal liver damage. The FDA eventually confirmed 53 cases of liver failure in patients using Ketek, including five deaths. This past February, the FDA finally added black box warnings to the Ketek label and severely restricted its use.

The 47 plaintiffs involved in the Ketek lawsuit come from Illinois, North Carolina, South Carolina, Tennessee, Indiana, Arizona, Florida, New York, Pennsylvania, Kansas, Missouri, West Virginia, Utah, Maine, Delaware, Iowa, Texas, Arkansas, Virginia, Georgia, Mississippi and New Jersey. They allege that Ketek is a defective and dangerous pharmaceutical product. The complaint states that Sanofi –Aventis “engaged in deception, fraud, false pretense, false promise, misrepresentation, or the knowing, concealment, suppression, or omission of material facts regarding the risks of harm associates with the use of Ketek...," The suit claims that Sanofi-Aventis intentionally concealed from the FDA results of a study which showed serious harm associated with the use of Ketek.

The Ketek lawsuit, which was filed in St. Clair County Circuit Court on Nov. 15, seeks damages for personal and economic injuries.

Ketek Lawsuit Filed in Illinois, Says Sanofi-Aventis Knew of Liver Failure Side Effects

Wed, 28 Nov 2007 00:00:00 -0800

Ketek Warning Letter Issued By FDA Following Clinical Trial Fraud Investigation

Thu, 25 Oct 2007 00:00:00 -0700

A Ketek clinical trial was rife with irregularities including fraud, but the drug’s maker, Aventis never acted on reports about problems with the study. Now, the Food & Drug Administration (FDA) has sent a Warning Letter to Sanofi-Aventis, the successor of Aventis, outlining various instances of misconduct by doctors involved in the Ketek clinical trial, and criticizing the drug maker for ignoring those issues.

Ketek, a powerful antibiotic, was approved by the FDA in 2004 to treat sinus infections. This approval came despite serious concerns with the way clinical trails of Ketek had been conducted. However, the FDA maintains that it did not rely on the Ketek study detailed in yesterday’s Warning Letter when it approved the drug. Shortly after its approval, however, Ketek was linked to serious side effects, including sometimes fatal liver damage. The FDA eventually confirmed 53 cases of liver failure in patients using Ketek, including five deaths. This past February, the FDA finally added black box warnings to the Ketek label and severely restricted its use

Because cheaper antibiotics, like amoxicillin, were already doing a good job of treating sinus infections, the FDA required Aventis to design a study showing that Ketek would work at least as well as existing treatments before it could be approved. Aventis eventually signed up 1800 private physicians to participate in these clinical trails. These doctors were given $400 for every patient they convinced to participate in the Ketek study.

That huge financial incentive was too much for some doctors to resist. When the FDA audited study participants, they found one family doctor in a small Alabama town had signed up 407 patients for the study. What else they found during the audit at Dr. Ann Campbell’s was shocking. The doctor’s entire staff was enrolled in the trail. It even appeared that some of the patient signatures on consent forms where forged. So gross were Dr. Campbell’s violations that she was eventually convicted of fraud and sentenced to prison. The FDA also visited several other sites with high numbers of participants, and found serious irregularities at every one.

In yesterday’s Warning Letter, the FDA said that Aventis’ own records showed that there were many instances of “serious protocol violations and regulatory noncompliance by clinical investigators” involved in the Ketek clinical trial. According to the Warning Letter, the FDA found no evidence that Aventis did anything to correct the problems with the Ketek clinical trial, or remove doctors responsible for violations from the study. The FDA also criticized the drug maker for failing to make sure the Ketek clinical trail was run properly and for allowing unqualified investigators to participate.

For its part, Sanofi-Aventis claims that it acted in good faith in conducting the Ketek clinical trail. The company said it was working on a response to the FDA Warning Letter.

FDA Approving Fewer New Drugs in Wake of Vioxx, Avandia, Other Scandals

Thu, 23 Aug 2007 00:00:00 -0700

The Food & Drug Administration (FDA) is still struggling to regain credibility after its approval process came under fire as a result of scandals surrounding drugs like Vioxx, Avandia and Ketek. That could be one reason why the FDA is approving new medications at a much slower rate than in the past. Since January, the FDA has approved only 38 new drugs. During the same period in 2006, the FDA had already approved 55 new medications.

In the past several years, the FDA’s drug approval process has been criticized for allowing defective drugs to go on the market even when serious questions were raised about their safety. Ketek is a prime example of the FDA’s lax approval process. Ketek, an antibiotic used to treat sinus infections, was granted FDA approval in 2004, even though the FDA had found serious irregularities in clinical trials conducted by its manufacturer, Sanofi-Aventis. At least one doctor involved in the trial falsified data and was sent to prison for fraud. Still, Ketek was approved by the FDA in 2004. Shortly after it approved Ketek, the FDA began receiving reports that linked it to liver problems. The FDA eventually confirmed 53 cases of liver failure in patients using the antibiotic, including five deaths. This past February, the FDA finally added black box warnings to the Ketek label and severely restricted its use.

Vioxx, another FDA approved drug, has been linked to severe heart problems. In 2004, an FDA study estimated that this defective drug could have contributed to 27,785 heart attacks and sudden cardiac deaths between 1999 and 2003. After Vioxx was pulled from the market in 2004, it was revealed that the FDA had tried to silence the drug expert who headed that study. Dr. David Graham, associate director for science in the FDA Drug Center's Office of Drug Safety, told Senate investigators that he had been subjected to veiled threats and intimidation when he informed the FDA of his findings.

Avandia is another drug that has caused the FDA a great deal of embarrassment. In May, a study by the Cleveland Clinic found that the diabetes drug increased a patient’s risk of heart attack by 43-percent. In June, a congressional committee convened hearings to investigate problems with the drug. The committee heard testimony from Dr. John Buse, a diabetes expert who raised questions about Avandia’s cardiac risks in 1999. Dr. Buse told the committee that he felt pressured by the drug’s maker, SmithKlineBeecham (now part of GlaxoSmithKline) to sign a clarifying statement drafted by the company that downplayed his concerns. Testimony at that hearing also revealed that the manufacturer and the FDA had known about Avandia’s heart attack risk as far back as September 2005. However, the agency felt that more investigation was needed before conclusions could be made about Avandia’s possible safety issues.

All of these scandals have damaged the public’s confidence in the FDA’s ability to insure drug safety. The fact that the FDA has approved fewer new medications this year could be a sign that the agency is finally starting to take that seriously.

FDA Approved Ketek Despite Serious Irregularities in its Clinical Trials; Patients Often Faced Liver Failure, Even Death As a Result Of Oversight

Tue, 26 Jun 2007 00:00:00 -0700

Patients being treated with Sanofi-Aventis’ antibiotic Ketek faced serious liver damage or even death, when all that was being treated was a simple sinus infection The story of the dangerous prescription drug Ketek and how it came to be on the market is a case-study in everything that has gone wrong with the FDA drug-approval process.

Ketek was granted approval by the Food and Drug Administration (FDA) in 2004 despite serious concerns with the clinical trials conducted by its manufacture, Sanofi-Aventis. An expensive antibiotic, Ketek was created to treat sinus infectious. But because other cheaper antibiotics (most notably, the more mundane amoxicillin) were extremely effective in treating this condition, the FDA required Aventis to design a study showing that Ketek would work at least as well as existing treatments. Aventis eventually signed up 1800 private physicians to participate in these clinical trails. These doctors would be given $400 for every patient they convinced to participate in the Ketek study.

That huge financial incentive was too much for some doctors to resist. When the FDA audited study participants, they found one family doctor in a small Alabama town had signed up 407 patients for the study. What else they found during the audit at Dr. Ann Campbell’s was shocking. The doctor’s entire staff was enrolled in the trail. It even appeared that some of the patient signatures on consent forms where forged. So gross were Dr. Campbell’s violations that she was eventually convicted of fraud and sentenced to prison. The FDA also visited several other sites with high numbers of participants, and found serious irregularities at every one. Still, Ketek was approved by the FDA in 2004.

Last December, the FDA began investigating reports that Ketek was linked to liver problems. The FDA eventually confirmed 53 cases of liver failure in patients using the antibiotic, including five deaths. This past February, the FDA finally added black box warnings to the Ketek label and severely restricted its use.

Considering that there were many reliable antibiotics on the market to treat sinusitis, whey did the FDA approve Ketek despite the serious problems with its clinical trails? And Ketek has been far from the only problem drug. FDA safety recalls of medicines are double what they were a decade ago, while adding new warnings to already marketed drugs is also on the rise. What can account for this?

While there is no one factor that can explain away these problems, some FDA critics say the agency has become too cozy with the very pharmaceutical companies it is supposed to regulate. For instance, the FDA collects more than $300 million in user fees from drug companies every year. This amounts to more than half the agency’s drug review budget. As a result, many believe that the culture at the FDA has shifted to the point that the drug manufacturers are now considered the agency’s clients.

Whatever the reason, the ramifications of the problems at the FDA are all too apparent. More Americans are getting sick from the very medicines that should be keeping them well. And the FDA, the one agency that is supposed to protect patients, seems to have forgotten them.

Sinus drug linked to liver damage, skin peeling

Mon, 07 May 2007 00:00:00 -0700

Somewhere near Quebec City lives a young mother who spent four weeks in a burn unit last year after a suspected drug reaction covered her body with burn-like red blisters and peeled off her skin from head to thigh.

The woman had been prescribed the antibiotic Ketek for a simple sinus infection.

But the 26-year-old developed toxic epidermal necrolysis, an extremely rare drug reaction where people essentially shed the outer protective layer of their skin.

The woman was found semi-conscious with swollen lips and face. Water blisters developed on her thorax, face and back and her skin was peeling all over more than 50 per cent of her body was affected, according to the most recent issue of Health Canada's adverse drug reaction newsletter.

Toxic epidermal necrolysis occurs in as few as one in a million people and Ketek is only suspected in the woman's case. She also had a history of allergic reactions to penicillin as well as to the drug class to which Ketek belongs.

But drug maker Sanofi Aventis is discussing with Health Canada whether to strengthen the existing warning about allergic reactions to include the potential for "skin events."

It would be the latest in a series of safety warnings for a drug that has been linked with severe and sometimes fatal liver damage. Some experts say it should never have been approved in the first place.

"I've run into one infectious disease physician after another who keeps saying, why do we need this drug? What exactly is the hole that it's filling," said Dr. David Ross, clinical assistant professor at George Washington University School of Medicine and Health Sciences in Washington, D.C.

Prescribed more than 390,000 times in Canada since its approval in 2003, Ketek is suspected of contributing to one death, as well as side effects such as face and joint swelling, blackouts, shortness of breath and increased pulse rate.

Health Canada has received 105 suspected adverse drug reaction reports involving Ketek, including a 55-year-old woman who died in 2004 from a heart attack and coronary artery disorder after taking 800 mg daily of Ketek for 10 days, according to the documents.

The reports are based on suspicions only, and could be due to an underlying illness. The woman had been taking antihistamines, decongestants and hormones as well.

The drug company declined to discuss the case, which it reported to Health Canada. Sanofi Aventis spokesman Sylvain Clermont said a U.S. Food and Drug Administration advisory committee recommended as recently as December that Ketek remain on the market, although the panel voted to restrict its use.

"This process was very rigorous and the conclusion was to leave the product on the market, to make sure [that] when needed, Ketek is available," Clermont said.

But a Canadian pharmaceutical expert said the drug should be shelved. "It's not needed and it can be fatal in some people," said Dr. Jim Wright, a professor in the department of anesthesiology, pharmacology and therapeutics at the University of British Columbia and director of the Therapeutics Initiative project.

Ketek has been implicated in 53 U.S. cases of toxic liver damage, four of them fatal. Recently American drug regulators issued new warnings after the advisory committee ruled that the benefits of using Ketek for sinusitis and bronchitis don't outweigh the risks.

For now, the drug remains approved in Canada for sinusitis and bronchitis, as well as for respiratory tract infections and pneumonia.

But Ketek's future is uncertain. Health Canada is reviewing the drug and is considering new information from manufacturer Sanofi Aventis. Health Canada warned last year that acute liver failure, including hepatic necrosis where the cells in the liver die leading to liver transplant or death has occurred during or immediately after treatment with Ketek.

Sanofi Issues Warning Letter About Ketek

Tue, 27 Mar 2007 00:00:00 -0700

This week, drug maker Sanofi-Aventis sent a letter to healthcare professionals outlining the various warning and prescription changes related to their antibiotic Ketek. The changes, mandated last month by the U.S. Food and Drug Administration (FDA), include a revision of approved indications for usage along with a variety of health-risk warnings.

According to the company, “The prescribing information has been revised to add a boxed warning and contraindication for myasthenia gravis patients. In addition, the indications for the treatment of acute exacerbation of chronic bronchitis (AECB) and acute bacterial sinusitis (ABS) have been removed from the labeling. These revisions follow discussions with the Food and Drug Administration (FDA) regarding its decision to follow recommendations of a December 2006 Advisory Committee that the balance of the benefits and risks no longer support continued marketing of Ketek for these two indications. It is important to note that Ketek continues to be indicated only for the treatment of community-acquired pneumonia (CAP) of mild to moderate severity.”

Sanofi adds, “Safety information regarding visual disturbances and loss of consciousness, previously in the precautions section, has been added to the warnings section. In prescribing Ketek, it is important for healthcare professionals to inform and discuss with patients the four highlighted toxicities: exacerbation of myasthenia gravis, hepatotoxicity, visual disturbances, and loss of consciousness.”

The company notes that “Ketek may cause visual disturbances particularly in slowing the ability to accommodate and the ability to release accommodation. Visual disturbances included blurred vision, difficulty focusing, and diplopia. Most events were mild to moderate; however, severe cases have been reported.” They also point to “post-marketing adverse event reports of transient loss of consciousness including some cases associated with vagal syndrome. Because of potential visual difficulties or loss of consciousness, patients should attempt to minimize activities such as driving a motor vehicle, operating heavy machinery, or engaging in other hazardous activities during treatment with Ketek.”

The company also reiterated its warnings related to hepatotoxicity (liver damage), first issued in June of last year. “Acute hepatic failure and severe liver injury, in some cases fatal, have been reported in patients treated with Ketek,” they note. “These hepatic reactions included fulminant hepatitis and hepatic necrosis leading to liver transplant, and were observed during or immediately after treatment. In some of these cases, liver injury progressed rapidly and occurred after administration of a few doses of Ketek. Physicians and patients should monitor for the appearance of signs or symptoms of hepatitis, such as fatigue, malaise, anorexia, nausea, jaundice, bilirubinuria, acholic stools, liver tenderness, or hepatomegaly.”

“In addition,” they report, “less severe hepatic dysfunction associated with increased liver enzymes, hepatitis, and in some cases jaundice was reported with the use of Ketek.”

The FDA announced the most recent changes in February. At the time, the FDA said, “The joint advisory committee, which met on December 14 and 15, 2006, advised that the available data including data acquired since the initial approval of Ketek support a conclusion that the benefits of Ketek outweigh the risks in patients with community acquired pneumonia, but not for patients with acute bacterial sinusitis or acute bacterial exacerbation of chronic bronchitis.”

Ketek was originally approved by the FDA in 2004, but the approval process for the controversial drug has come under scrutiny by both houses of Congress as the issue of prescription drug safety has gained momentum in recent months. The FDA originally rejected Ketek in 2001, citing risks including liver damage and blurred vision. In response, Sanofi-Aventis commissioned a rather dubious study of the drug that suffered from falsified data, inappropriate subjects, criminal doctors, and significant violations of the study’s guidelines.

Though that study was rejected and a subsequent clinical trial was rife with inaccuracies, an FDA advisory panel pushed for Ketek’s approval in 2003. Although the full FDA declined approval that year, they reversed their decision the following year. The controversy has ignited calls from medical professionals and congressmen for more stringent standards in the FDA’s approval of pharmaceuticals.

FDA Announces Label and Indication Changes for the Antibiotic Ketek

Thu, 15 Feb 2007 00:00:00 -0800

The Food and Drug Administration (FDA) announces revisions to the labeling for the antibiotic Ketek (telithromycin) designed to improve the safe use of Ketek by patients. The changes include the removal of two of the three previously approved indications acute bacterial sinusitis and acute bacterial exacerbations of chronic bronchitis from the drug's label. The agency has determined that the balance of benefits and risks no longer support approval of the drug for these indications. Ketek will remain on the market for the treatment of community acquired pneumonia of mild to moderate severity (acquired outside of hospitals or long-term care facilities).

In addition, the agency has worked with the company, Sanofi Aventis, to update the product labeling with a "boxed warning," FDA's strongest form of warning. The warning states that Ketek is contraindicated (should not be used) in patients with myasthenia gravis, a disease that causes muscle weakness.

FDA also worked with the manufacturer to develop a Patient Medication Guide that informs patients about the risk of the drug and how to use it safely. The Medication Guide (an FDA-approved patient information sheet) will be provided to patients with each prescription.

"Today's action is the result of comprehensive scientific analysis and thoughtful public discussion of the data available for Ketek, and includes important changes in the labeling designed to improve the safe use of Ketek by patients and give healthcare providers the most up-to-date prescribing information," said Steven Galson, MD, director of the Center for Drug Evaluation and Research.

Other labeling changes included in today's action are a strengthened warning section regarding specific drug-related adverse events including visual disturbances and loss of consciousness. Warnings for hepatic toxicity (rare but severe symptoms of liver disease) were strengthened in June 2006.

The joint advisory committee, which met on December 14 and 15, 2006, advised that the available data including data acquired since the initial approval of Ketek support a conclusion that the benefits of Ketek outweigh the risks in patients with community acquired pneumonia, but not for patients with acute bacterial sinusitis or acute bacterial exacerbation of chronic bronchitis. They also recommended a boxed warning as well as Medication Guide for the drug. The joint panel consisted of FDA's Anti-Infective Drugs and Drug Safety and Risk Management Advisory committees.

The antibiotic Ketek was originally approved in 2004 and is manufactured by Sanofi Aventis.

Ketek case keeps glare on reform

Wed, 14 Feb 2007 00:00:00 -0800

The Food and Drug Administration's missteps in approving the controversial antibiotic Ketek were cited at a congressional hearing yesterday as further evidence of the need for major drug safety reform.

FDA whistle-blowers, medical experts and members of Congress said the FDA in 2004 approved Ketek, since linked to liver failures, despite serious safety warnings from scientific reviewers and evidence of fraudulent data.

They told the House Energy and Commerce subcommittee on oversight and investigations that scientific dissent was discouraged and muzzled inside the agency regarding Ketek, and pertinent information withheld from FDA advisory committees.

"FDA approved Ketek despite knowing that it could kill people from liver damage and that tens of millions of people would be exposed to it; despite FDA knowing that the drugmaker submitted fabricated data; and despite knowing that Ketek is no better than other antibiotics, and may not even work," said David Ross, a former FDA scientist who had been one of the lead medical reviewers for Ketek.

Ross, who raised his concerns publicly last year about the Sanofi-Aventis drug and later left the agency in frustration, said the episode is emblematic of an agency culture that favors drug approvals over safety. He said "we are certain to see more Keteks" without "significant changes in our drug safety system and FDA."

On eve of the congressional hearing, the FDA withdrew its approval for two of the three main uses for Ketek, acute bacterial sinusitis and acute chronic bronchitis.

"The agency has determined that the balance of benefits and risks no longer support approval of the drug for these indications," the FDA said.

It said the drug can remain on the market for treatment of pneumonia. Last year, the FDA changed the labeling to warn of potential liver problems, and this week added a new warning that the drug should not be used in patients with myasthenia gravis, a disease that can cause life-threatening muscle weakness.

Sanofi-Aventis maintains the drug continues to be an important treatment option. The antibiotic has been prescribed nearly six million times in the United States.

The concerns about Ketek follow other highly publicized FDA problems, including the withdrawal of the painkillers Vioxx and Bextra; the slowness in providing new warnings about the dangers of widely used antidepressants and accusations the agency is too cozy with the drug industry.

An Institute of Medicine panel recently called for an overhaul of the FDA's drug safety system, saying the agency is failing to adequately protect the public.

A number of reform proposals are pending in Congress, including creating a new drug safety center inside the FDA; mandating more disclosure of clinical trial data; giving the agency authority to order rather than negotiate new labeling changes; requiring companies to carry out post-market safety studies and prohibiting ads promoting new drugs for up to two years.

Rep. Bart Stupak (D-Mich.), the subcommittee chairman, said the evidence regarding Ketek and other cases suggests that the "FDA's ability to ensure a safe drug supply has been greatly compromised" by a rush to approve new medications.

Rep. John Dingell (D-Mich.), chairman of the full Energy and Commerce Committee, added that there has been "a fundamental breakdown in policies and procedures in evaluating the safety of drugs."

The committee heard from a number of witnesses, including John Powers, a former FDA scientist, who said "Ketek was the symptom of a much larger problem" that involves a misguided review process for new antibiotics. He said this process is driven by pressure from industry, resulting in "approval of numerous antibiotics whose effectiveness is unclear."

David Graham, the FDA scientist and whistle-blower who publicly attacked the agency for its handling of Vioxx and other drugs, said "the Ketek story is about the FDA's betrayal of the public trust."

"FDA scientists were intimidated, suppressed, and ultimately compelled to leave the agency," Graham told panel. Graham added that safety issues are a second-tier concern.

"Unfortunately, Ketek is not an anomaly," said Graham. "I am here today to tell you that our nation is still at risk."

FDA restricts use of antibiotic

Mon, 12 Feb 2007 00:00:00 -0800

The government on Monday restricted use of an antibiotic linked to rare reports of severe liver problems, including several deaths, saying the drug now should be used only to treat pneumonia but not less serious bacterial infections like bronchitis and sinusitis.

The Food and Drug Administration said the antibiotic, Ketek, would remain on the market but that its label will bear a new, stern warning. The agency said it and manufacturer Sanofi-Aventis SA also created a guide for patients outlining the drug's risks and its safe use.

The changes are in line with the December recommendations of a panel of FDA expert advisers that the agency modify the label of the drug, also called telithromycin. In 17-2 votes, the outside advisers said the drug's benefits don't outweigh its risks in treating bronchitis and sinusitis, which are less serious infections than pneumonia and often spontaneously resolve on their own.

"The agency has determined that the balance of benefits and risks no longer support approval of the drug for these indications," the FDA said in a statement.

The FDA announced the changes on the eve of a House subcommittee hearing on drug safety that will examine irregularities in the approval of Ketek. The FDA's handling of the antibiotic remains under investigation by the Senate as well.

A new so-called "black-box" warning on the Ketek label states the drug should not be used in patients with myasthenia gravis, a disease that causes muscle weakness, the FDA said. The label also now warns about cases of visual disturbances and loss of consciousness reported in some patients.

The label already warns of the drug's risk to the liver. An FDA review released in December cited 13 reports of liver failure in patients treated with the drug.

As of late last year, doctors had prescribed the antibiotic more than 5.6 million times in the United States since it won FDA approval in 2004.

"Ketek, when used as directed in its approved indication, continues to be an important option" for fighting infections "helps to satisfy a medical need," Sanofi-Aventis said in a statement.

FDA tightens labeling, indications for Ketek

Mon, 12 Feb 2007 00:00:00 -0800

The Food and Drug Administration on Monday announced labeling changes for the antibiotic Ketek, stripping it of two previously approved indications and adding a black-box warning, the agency's strongest. The agency removed from the label the drug's approval for use in the treatment of acute bacterial sinusitis and acute bacterial exacerbations of chronic bronchitis.

"The agency has determined that the balance of benefits and risks no longer support approval of the drug for these indications," the agency said in a news release.

With Monday's announcement, Ketek remains approved for just one indication: the treatment of mild to moderate cases of pneumonia acquired outside hospitals or long-term care facilities.

The boxed warning says the drug should not be used in patients with myasthenia gravis, which causes muscle weakness.

"Today's action is the result of comprehensive scientific analysis and thoughtful public discussion of the data available for Ketek, and includes important changes in the labeling designed to improve the safe use of Ketek by patients and give health-care providers the most up-to-date prescribing information," said Dr. Steven Galson, director of FDA's Center for Drug Evaluation and Research.

References on the label to visual disturbances and loss of consciousness associated with the drug use are also beefed up.

Warnings about toxicity to the liver were made stronger last June.

Ketek was originally approved in 2004 and is manufactured by Paris-based Sanofi Aventis.

The announcement comes a day before the House Subcommittee on Oversight and Investigations is to hold a hearing about the FDA's drug-review policies.

Witnesses are to include Sen. Chuck Grassley, R-Iowa, an agency critic, and former FDA employees who have criticized the agency's drug review policies.

Grassley has accused the FDA of withholding evidence about the drug from an advisory committee charged with reviewing it.

Critics have said the agency's reviewers have been discouraged from raising questions about the agency's review process, a charge the agency has denied.

FDA Announces Label and Indication Changes for Antibiotic Ketek

Mon, 12 Feb 2007 00:00:00 -0800

Citing various safety issues, the U.S. Food and Drug Administration (FDA) has changed the approved usages for the antibiotic Ketek (telithromycin). Two of the three currently approved indications acute bacterial sinusitis and acute bacterial exacerbations of chronic bronchitis will be removed from the product’s label.

“The agency has determined that the balance of benefits and risks no longer support approval of the drug for these indications,” the FDA explained. “Ketek will remain on the market for the treatment of community acquired pneumonia of mild to moderate severity (acquired outside of hospitals or long-term care facilities).”

Additionally, the FDA has asked drug maker Sanofi Aventis to add a “black box” warning to Ketek’s labels, stating that Ketek should not be used in patients with myasthenia gravis, a disease that causes muscle weakness. The company has also been required to strengthen the warning section regarding adverse events including visual disturbances and loss of consciousness. (In June of last year, warnings for hepatic toxicity severe symptoms of liver disease were bolstered.)

“The joint advisory committee, which met on December 14 and 15, 2006, advised that the available data including data acquired since the initial approval of Ketek support a conclusion that the benefits of Ketek outweigh the risks in patients with community acquired pneumonia, but not for patients with acute bacterial sinusitis or acute bacterial exacerbation of chronic bronchitis,” the agency noted.

Ketek was originally approved by the FDA in 2004, but the approval process for the controversial drug has come under scrutiny by both houses of Congress as the issue of prescription drug safety has gained momentum in recent months. The FDA originally rejected Ketek in 2001, citing risks including liver damage and blurred vision. In response, Sanofi Aventis commissioned a rather dubious study of the drug that suffered from falsified data, inappropriate subjects, criminal doctors, and significant violations of the study’s guidelines.

Though that study was rejected and a subsequent clinical trial was rife with inaccuracies–an FDA advisory panel pushed for Ketek’s approval in 2003. Although the full FDA declined approval that year, they reversed their decision the following year. The controversy has ignited calls from medical professionals and congressmen for more stringent standards in the FDA’s approval of pharmaceuticals.

FDA Announces Label and Indication Changes for the Antibiotic Ketek

Mon, 12 Feb 2007 00:00:00 -0800

The Food and Drug Administration (FDA) today announced revisions to the labeling for the antibiotic Ketek (telithromycin) designed to improve the safe use of Ketek by patients. The changes include the removal of two of the three previously approved indications acute bacterial sinusitis and acute bacterial exacerbations of chronic bronchitis from the drug's label. The agency has determined that the balance of benefits and risks no longer support approval of the drug for these indications. Ketek will remain on the market for the treatment of community acquired pneumonia of mild to moderate severity (acquired outside of hospitals or long-term care facilities).

In addition, the agency has worked with the company, Sanofi Aventis, to update the product labeling with a "boxed warning," FDA's strongest form of warning. The warning states that Ketek is contraindicated (should not be used) in patients with myasthenia gravis, a disease that causes muscle weakness.

FDA also worked with the manufacturer to develop a Patient Medication Guide that informs patients about the risk of the drug and how to use it safely. The Medication Guide (an FDA-approved patient information sheet) will be provided to patients with each prescription.

"Today's action is the result of comprehensive scientific analysis and thoughtful public discussion of the data available for Ketek, and includes important changes in the labeling designed to improve the safe use of Ketek by patients and give healthcare providers the most up-to-date prescribing information," said Steven Galson, M.D., Director, Center for Drug Evaluation and Research.

Other labeling changes included in today's action are a strengthened warning section regarding specific drug-related adverse events including visual disturbances and loss of consciousness. Warnings for hepatic toxicity (rare but severe symptoms of liver disease) were strengthened in June 2006.

The joint advisory committee, which met on December 14 and 15, 2006, advised that the available data including data acquired since the initial approval of Ketek support a conclusion that the benefits of Ketek outweigh the risks in patients with community acquired pneumonia, but not for patients with acute bacterial sinusitis or acute bacterial exacerbation of chronic bronchitis. They also recommended a boxed warning as well as Medication Guide for the drug. The joint panel consisted of FDA's Anti-Infective Drugs and Drug Safety and Risk Management Advisory committees.

The antibiotic Ketek was originally approved in 2004 and is manufactured by Sanofi Aventis.

Advisers Suggest Restricting Antibiotic

Sat, 16 Dec 2006 00:00:00 -0800

Benefits of an antibiotic linked to rare reports of severe liver problems, including several deaths, outweigh its risks in treating pneumonia but not less serious bacterial infections like bronchitis and sinusitis, federal health advisers said Friday.

The nonbinding recommendations raise the prospect the Food and Drug Administration could modify its approval of the Sanofi-Aventis SA drug, called Ketek, to exclude the treatment of the two lesser infections, which often clear up without drug treatment.

The FDA convened a two-day meeting of outside experts to discuss Ketek in light of concerns about its safety. An agency review found 13 reports of liver failure in patients treated with the drug through September. Reports of blurry vision also have been a concern. Doctors have prescribed the antibiotic more than 5.6 million times in the United States since the FDA approved it in 2004.

On Friday, the FDA panelists voted 16-3 to say Ketek's benefits outweigh its risks in treating pneumonia. In 17-2 votes, the outside advisers said that wasn't the case for bronchitis and sinusitis, which are less serious infections and often spontaneously resolve on their own.

Dr. John Jenkins, director of the FDA's office of new drugs, declined to say what action the agency would take. The FDA isn't bound to follow the advice of its outside experts, but usually does.

"We will be assessing the advice we received from the committee and discussing that very shortly," Jenkins said.

The panel also recommended Sanofi-Aventis develop a medication guide to be given to patients, a move backed by the company.

Dr. John Edwards, of Harbor-UCLA Medical Center in Torrance, Calif., and the panel's acting chairman, called the two-day meeting particularly challenging, since it came amid concern that companies have diminishing interest in developing new antibiotics and increased interest in safety issues linked to the drugs.

Many experts fear overuse of antibiotics is hastening the increasing resistance of many bacteria to older drugs, making the development of novel treatments critical. Some panelists suggested reserving Ketek for second-line use in treating pneumonia.

The label of the drug was changed in June to add a bold-type warning about the rare reports of liver failure and severe injury, some of them fatal. A majority of panel members said that cautionary language should be strengthened and placed in a so-called "black box" to warn doctors and patients of some of the risks associated with the drug.

The FDA's handling of Ketek remains under investigation by a Senate committee. Sen. Charles Grassley, R-Iowa, said this week the FDA intentionally withheld information from FDA advisers when they met in 2003 to consider recommending approval of the drug. FDA officials said they would comment after reviewing his allegations, contained in a 20-page letter sent to the agency.

Sanofi-Aventis said the risks associated with the drug, also known as telithromycin, appear to be comparable to those of other similar drugs and that it represents an important option in treating respiratory tract infections.

FDA Panels Urge Restricted Ketek Use

Sat, 16 Dec 2006 00:00:00 -0800

A pair of federal advisory committees has recommended against two of three existing uses for Ketek, an antibiotic from Sanofi-Aventis.

The advisors say Ketek, approved by the Food and Drug Administration in April 2004, should be discontinued as a treatment for acute bacterial sinusitis and acute bacterial exacerbation of chronic bronchitis. Committee members voted 17 to 2 late Friday afternoon against these uses, saying the risks outweigh the benefits.

However, they said Ketek should continue to be used as a treatment for community-acquired pneumonia, a common lung inflammation contracted by patients who aren't hospitalized or in extended-care facilities. The vote was 16 to 3 in favor of this use.

Many of the medical advisors also recommended that Ketek should receive a "black box" warning of some side effects. A black box warning is the most strict notice the FDA can order for a drug's label. Such a warning can depress a drug's sales because doctors are more cautious about prescribing the drug and patients are more cautious about taking it.

The FDA isn't required to follow its advisory panels' suggestions, but it usually agrees.

The panels' votes ended two days of hearings for a drug whose controversy overshadows its U.S. sales. Ketek's approval by the FDA also is the subject of a Senate Finance Committee investigation of the agency's review process. Ketek produced about $50 million in U.S. sales during the first half of 2006.

"Sanofi-Aventis will be in further discussion with the FDA regarding [the panels'] recommendations," said Dr. Doug Greene, chief medical officer for the company's U.S. operations, in a prepared statement Friday evening. "We are committed to working to ensure that healthcare professionals continue to have the information they need to address the medical needs of their patients."

The company said Ketek has been used to treat more than 6 million patients in the U.S. and more than 28 million patients worldwide. The drug is approved in more than 90 countries, but reports of side effects have depressed sales in the U.S.

Although there have been instances of liver damage, rare neuromuscular problems, blurred vision and several deaths among Ketek patients, an FDA staff report on Wednesday said the drug's benefits outweigh the risks.

However, the report also said the side effects detected after Ketek reached the market and the way clinical trials were conducted raised questions about the drug's use for sinusitis and bronchitis, which, it says, "are often self-resolving conditions."

Sanofi-Aventis strengthened the drug's label in June to further highlight the risks of side effects. The company has maintained that the benefits outweigh the risks for each of the drug's FDA-approved uses, adding that the rate of liver problems is similar to rates for several competing antibiotics.

In June, the FDA said "the benefit/risk profile for Ketek is similar to that of other approved antibiotic drugs used to treat the same types of infections." Liver problems are a "known and potential complication with some antibiotics, including Ketek," the FDA said.

FDA Asks If Antibiotic Ketek Worth Risks

Fri, 15 Dec 2006 00:00:00 -0800

Federal health officials said Thursday they would ask outside experts whether the benefits of an antibiotic linked to rare reports of severe liver problems, including several deaths, outweigh its risks .

A Food and Drug Administration review found 13 reports of liver failure in patients treated with the drug, Ketek, through September. Doctors have prescribed the antibiotic, made by France's Sanofi-Aventis SA, more than 5.6 million times in the United States since the FDA approved it in 2004 to treat respiratory tract infections, bronchitis, sinusitis and community-acquired pneumonia.

Concerns about the rare but serious health problems seen in patients treated with the drug led the FDA to convene a two-day meeting of outside experts. The panel is expected to wrap up late Friday with a recommendation to the agency.

If the outside advisers recommend keeping the drug on the market, FDA said it would then ask whether the drug's label should be further updated to ensure the safe use of the drug - or if more studies are needed.

The label of the drug already was changed in June to add a bold-type warning about the rare reports of liver failure and severe injury, some of them fatal.

The FDA's handling of Ketek remains under investigation by a Senate committee. Sen. Charles Grassley, R-Iowa, said this week the FDA intentionally withheld information from FDA advisers when they met in 2003 to consider recommending approval of the drug. FDA officials declined to comment Thursday on his allegations.

Sanofi-Aventis said the risks associated with the drug, also known as telithromycin, appear to be comparable to those of other similar drugs and that it represents an important option in treating respiratory tract infections.

FDA's credibility is questioned in antibiotic review

Fri, 15 Dec 2006 00:00:00 -0800

A Food and Drug Administration meeting to review whether a recently approved antibiotic carries an unacceptably high risk of liver failure raised questions Thursday about the credibility of the agency's internal decision-making.

The antibiotic, Ketek, was approved in 2004 to treat pneumonia and other severe respiratory infections. It appeared promising as a weapon against microbes resistant to older antibiotics. But this year a medical journal reported three cases of sudden liver failure, one fatal, in patients taking Ketek. That prompted the FDA and the manufacturer, Sanofi-Aventis, to warn doctors of rare grave risks.

Now, two of the FDA's outside scientific advisory panels are considering whether to recommend that Ketek be taken off the market. The anti-infective drugs advisory committee and the drug safety committee will vote on that question today.

But the case has also generated criticism of behind-the-scenes FDA decision-making.

A congressional investigation found that before Ketek was approved, the agency gave the anti-infective drugs committee data from a clinical trial that key FDA officials knew was tainted by scientific fraud. That study of 24,000 patients had been commissioned to resolve questions about the liver risks of Ketek. Unaware of the study's problems, which included some fictitious patients, the committee recommended approval.

FDA officials noted Thursday that they later privately informed members of the committee that the study had problems.

Before approving Ketek, FDA officials reviewed European reports to see whether its rate of liver damage was unusually high. Ketek had already been approved in Europe, where millions of patients had used it.

But the agency did not require Sanofi-Aventis to conduct another clinical trial to take the place of the compromised study. Such clinical studies, often called the "gold standard," are considered superior to analyses of reports in drug safety databases, which may contain incomplete or inaccurate information.

"This meeting is focused on a drug, but underlying that are issues about how the FDA has handled it," said Arthur A. Levin, director of the Center for Medical Consumers in New York City and a member of the FDA's drug safety advisory committee.

"My question is: Is there any precedent to support a decision where [the FDA] said, 'You need to do a study,' and then that study has problems and the agency says, 'OK, we'll rely on spontaneous reports [in databases]?' " Levin added.

Dr. David J. Graham, an FDA safety reviewer and prominent in-house critic, told the panels that the agency's decision was "an example of lowering the bar."

In "how many cases in the history of the FDA has postmarketing data from another country been used in lieu of a clinical trial?" Graham asked.

The FDA received 110 reports through April of liver problems linked to the drug. They included 12 cases of acute liver failure and 23 cases of serious liver injury. Four patients died. Doctors have written more than 5.6 million Ketek prescriptions in the U.S.

Agency experts told the advisory committees Thursday that there was definite risk of liver failure associated with Ketek, marked by a rapid onset of problems.

Sanofi-Aventis said that there was no clear evidence Ketek was riskier than other drugs, and that the liver dangers could be controlled by doctors.

Analysis: Controversial antibiotic debated

Thu, 14 Dec 2006 00:00:00 -0800

A Food and Drug Administration advisory committee will decide Friday whether to recommend that a widely used but controversial antibiotic be removed from the market.

The drug, known as Ketek, is used to treat respiratory tract infections such as bronchitis, sinusitis, and pneumonia. U.S. Doctors have written an estimated 6 million prescriptions for the drug since it was approved in April, 2004.

But FDA is revisiting that approval in two days of expert hearings Thursday and Friday because of reports suggesting the drug could carry a higher risk of liver failure and other dangerous side effects than similar antibiotics.

The hearings also come one day after a Senate committee investigation blasted agency officials for their handling of Ketek's original approval.

Ketek was never shown to be more effective than other antibiotics at curing most infections. FDA requires only that new antibiotics show evidence of "non-inferiority" to existing drugs. The rationale, experts say, is to help ensure a steady stream of available drugs to combat antibiotic resistance.

The drug was judged to be as safe as other antibiotics when it was approved in 2004, based on pre-market studies.

"Ketek is being (targeted) because of the safety concerns that have arisen," said John Jenkins, director of FDA's Office of New Drugs.

Sanofi Aventis, which manufactures Ketek, reported to FDA 212 cases of liver injury in patients who took the drug over the last two-and-a-half years. However, company and agency experts characterize the reports as initial signals of both minor and severe injuries that cannot be reliably blamed on the drug.

The company argued Thursday that the injuries occurred over 6 million uses of Ketek, and that the drug, known generically as telithromycin, carries about the same overall risk as similar antibiotics.

"Take your pick of antibiotics, they are all associated with liver injury," said James Lewis, a professor of Medicine at Georgetown University who testified on behalf of the company.

But an analysis commissioned by the agency found 35 cases of severe injuries ncluding seven resulting in a liver transplant or death that analysts say were very likely attributable to Ketek.

"What we have is a higher number of these hospitalized patients" than are seen with other drugs, said William Lee, director of the Clinical Center for Liver Diseases at the University of Texas Southwestern and one of the analysts commissioned by FDA.

The advisory committee is scheduled Friday to consider other data linking Ketek to more side effects, including temporary blindness and abnormal heart rhythms.

But the meeting is taking place against a backdrop of stark criticism from the Republican chairman of the Senate Finance Committee, which has spent the last year investigating FDA's handling of Ketek's approval.

A committee report released Wednesday concluded that FDA officials did not tell the advisory panel that recommended Ketek's approval in 2003 that unethical practices by some doctors conducting Sanofi Aventis' safety study had corrupted the trial.

Instead, FDA officials presented the study, called "3014," to the committee as usual, the report found.

"In sum, the FDA did not ensure that the public received accurate, science-based information regarding the Ketek (application)," Sen. Charles Grassley, R-Iowa, wrote in the report.

On the other hand, FDA officials have said they did not take the flawed study into account when they approved Ketek. They instead relied on European safety studies, attempting to measure Ketek's safety on the market in France, Germany, and other countries.

Jenkins, who leads the FDA division in charge of approving new drugs, said he had not yet digested the 53-page report.

"I don't want to get into the details of that today," he told reporters.

Controversy surrounding Ketek's approval is also bringing harsh criticism from inside the agency.

David Graham, a scientist in FDA's Office of Drug Safety, wrote a brief article in the New England Journal of Medicine in November condemning agency officials for resorting to overseas postmarket safety studies to approve Ketek in 2004. Such data is generally considered far less reliable than controlled studies like the discredited 3014 trial.

In addition, Ketek has shown little benefit for patients with sinusitis and bronchitis, who usually get better without any medication, he added.

In an interview, Graham called the hearings an example of "damage control" over Ketek safety issues that have come back to haunt FDA.

"They've built a house of cards with no foundation in fact or even in truth," he said.

Jenkins did not comment on the decision to present the European data to the panel in 2004.

However, he did say that the absence of additional safety issues in 4 million European patients made the officials "comfortable making the decision for approval."

FDA to assess antibiotic linked to woes

Thu, 14 Dec 2006 00:00:00 -0800

Federal health officials said Thursday they would ask outside experts whether the benefits of an antibiotic linked to rare reports of severe liver problems, including several deaths, outweigh its risks.

A Food and Drug Administration review found 13 reports of liver failure in patients treated with the drug, Ketek, through September. Doctors have prescribed the antibiotic, made by France's Sanofi-Aventis SA, more than 5.6 million times in the United States since the FDA approved it in 2004 to treat respiratory tract infections, bronchitis, sinusitis and community-acquired pneumonia.

Concerns about the rare but serious health problems seen in patients treated with the drug led the FDA to convene a two-day meeting of outside experts. The panel is expected to wrap up late Friday with a recommendation to the agency.

If the outside advisers recommend keeping the drug on the market, FDA said it would then ask whether the drug's label should be further updated to ensure the safe use of the drug or if more studies are needed.

The label of the drug already was changed in June to add a bold-type warning about the rare reports of liver failure and severe injury, some of them fatal.

The FDA's handling of Ketek remains under investigation by a Senate committee. Sen. Charles Grassley (news, bio, voting record), R-Iowa, said this week the FDA intentionally withheld information from FDA advisers when they met in 2003 to consider recommending approval of the drug. FDA officials declined to comment Thursday on his allegations.

Sanofi-Aventis said the risks associated with the drug, also known as telithromycin, appear to be comparable to those of other similar drugs and that it represents an important option in treating respiratory tract infections.

Doctor: FDA-Approved Antibiotic A 'Time Bomb'

Wed, 13 Dec 2006 00:00:00 -0800

Iraq war veteran Chuck Gregg was back home with his family last winter when he got bronchitis. His doctor prescribed Ketek, a relatively new antibiotic, CBS News chief investigative correspondent Armen Keteyian reports. Five days later, Gregg was in the hospital with liver failure.

"They run their battery of tests, and they come back and it's definitely what's called 'drug induced' or 'pharmaceutically induced hepatitis," Gregg explains.

"He survived 13 months in Iraq, you know, all over Iraq, to come home for this," adds Sherry, his wife.

The FDA has continuously updated warnings of Ketek's possible side effects, including "signs of liver problems." Gregg says because he had no previous liver problems, he had no reason to be concerned. Now he's pointing a finger at the FDA.

"Based upon the data available to me, I believe this drug is far more dangerous than other drugs that fight the same infections," says Dr. David Ross.

In an exclusive interview with CBS News, Ross, who reviewed Ketek's safety for the FDA, says he warned his superiors that the drug was, in his words, a "time bomb," and was shocked last summer when the acting head of the agency, Dr. Andrew Von Eschenbach, told employees to keep concerns about the drug in-house -- and out of the press.

"He said, 'If you don't follow the team, if you don't do what you're supposed to do, the first time you'll be spoken to, the second time you'll be benched, and the third time, you'll be traded,'" Ross says.

Instead, Ross says, he quit the FDA in disgust.

"The leaders of an agency should not be holding a meeting to suggest dissenters should be kicked off the team," says Sen. Charles Grassley. "Particularly when the life of American people are at stake."

Sen. Grassley today issued a scathing report criticizing the FDA's oversight of Ketek. CBS News has learned there is a new Congressional probe under way to determine whether Ketek should remain on the market.

The manufacturer says Ketek is safe to use. Von Eschenbach declined to speak with CBS News, citing a FDA meeting about Ketek beginning tomorrow.

Controversial antibiotic Ketek will face more FDA scrutiny

Sun, 10 Dec 2006 00:00:00 -0800

As antibiotics go, Ketek has had a pretty high profile.

Sen. Chuck Grassley, R-Iowa, tried in vain last week to block Andrew von Eschenbach's confirmation as Food and Drug Administration commissioner, partly because of what the senator views as FDA efforts to hinder his investigation of clinical trials of the drug, which has been linked to fatal liver problems.

"The way the FDA under this nominee has handled the investigation of Ketek shows the agency would like to keep its business secret," Grassley said on the Senate floor Thursday prior to von Eschenbach's confirmation. "It doesn't want these issues made public or subjected to the scrutiny."

In addition, just two months after the FDA approved Ketek in April 2004 for the treatment of pneumonia, sinusitis and bronchitis, the Public Citizen Health Research Group, a patient advocacy organization based in Washington, D.C., added the antibiotic to its list of "do not use" drugs.

Public Citizen cited reports of liver toxicity, serious vision problems and the possibility of heart rhythm disturbances.

Some of these issues will be discussed Thursday and Friday when the FDA convenes a joint meeting of its Anti-Infective Drugs and its Drug Safety and Risk Management advisory committees to discuss what it calls Ketek's "overall benefit-to-risk considerations."

Doug Greene, chief U.S medical officer for Paris-based Sanofi-Aventis, which markets Ketek, says his company is looking forward to presenting "lots of scientific information that we feel strongly reinforces the positive benefit/risk equation for Ketek for serious infections."

Worldwide, Greene says, 28 million people have taken Ketek. In the USA, Ketek sales totaled nearly $200 million in 2005, according to IMS Health, a pharmaceutical information and consulting company.

"With any new drug, there's always an ongoing process to continue to gather new information," Greene says. "We're following that process, the FDA is following that process. It's working. That's why we are here to have this discussion" at the advisory panel meeting.

But John Powers, former lead medical officer for the FDA's anti-microbial drug development and resistance initiative, calls the meeting "a kangaroo court."

Powers says he spent eight years at the FDA before leaving two months ago because of the lack of a "scientific approach, especially in the area of antibiotics."

Sanofi executives "are going to get up there and yammer on and on: 'In a test tube our drug is more potent than these older drugs,' " says Powers, who is to testify at the hearing Friday as a public citizen. "What we want to know are what are the effects in human beings?"

Health Canada Endorsed Important Safety Information on Ketek (telithromycin)

Tue, 03 Oct 2006 00:00:00 -0700

Sanofi-aventis Canada Inc. in consultation with Health Canada would like to inform health care professionals of important updated safety information regarding Ketek (telithromycin) tablets.

Based on information in published case reports and post-market adverse event reports, the Canadian Product Monograph has been revised to include information on severe and sometimes fatal hepatotoxicity in patients taking Ketek. The Product Monograph also includes updated information regarding syncope (loss of consciousness) and the use of Ketek in patients with myasthenia gravis.

Acute liver failure including fulminant hepatitis and hepatic necrosis leading to liver transplant or death have been observed during or immediately after the completion of Ketek treatment.

Exacerbations of myasthenia gravis have led to death or life-threatening acute respiratory failure with a rapid onset in patients taking Ketek.

Syncope, usually associated with vagal syndrome, has been reported in patients taking Ketek.

Alterations in hepatic enzymes have been commonly observed in clinical studies with telithromycin. Hepatitis and hepatocellular injury were observed infrequently.

Most post-marketing cases of hepatic dysfunction were reversible after discontinuation of Ketek, however cases of severe hepatotoxicity, including necrosis, hepatic failure and death have occurred. In some of these cases liver injury occurred after administration of only a few doses of Ketek and progressed rapidly. The mechanism underlying severe hepatocellular injury is unknown. Severe reactions, in some but not all cases, have been associated with serious underlying diseases or concomitant medications.

In light of this safety information, the Product Monograph has been revised to include the following recommendations:

Ketek is contraindicated in patients with a previous history of hepatitis and/or jaundice associated with the use of this drug.
Ketek is contraindicated in patients who are hypersensitive to telithromycin or to any macrolide antibiotic.
Physicians and patients should monitor for symptoms of hepatitis, such as fatigue, malaise, anorexia, nausea, jaundice, bilirubinuria, acholic stools, liver tenderness, hepatomegaly, or pruritus.
Patients with symptoms of hepatitis must be advised to discontinue Ketek and immediately seek medical evaluation, which should include liver function tests. If clinical hepatitis or transaminase elevations combined with other systemic symptoms of hepatocellular injury occur, Ketek should be permanently discontinued.

The Product Monograph has also been updated regarding the exacerbations of myasthenia gravis and regarding syncope, usually associated with vagal syndrome. These side effects and the following recommendations should be taken into consideration when prescribing Ketek:

Ketek is not recommended for patients with myasthenia gravis, however if no other therapeutic alternatives are available then such patients must be closely monitored and advised to discontinue Ketek treatment and immediately seek medical attention if they experience any exacerbation of their symptoms.
Patients should be cautioned about the potential effects of syncope on activities such as driving a vehicle, operating machinery or engaging in other potentially hazardous activities.

FDA Completes Safety Assessment of Ketek New Safety Information to be Added to Product Labeling

Fri, 30 Jun 2006 00:00:00 -0700

The Food and Drug Administration (FDA) today completed its safety assessment of Ketek (telithromycin) and is advising health practitioners and patients to be aware of rare but potentially serious health risks. Ketek is the first FDA-approved antibiotic of the ketolide class. It is indicated for the treatment of acute exacerbation of chronic bronchitis; acute bacterial sinusitis; and community acquired pneumonia of mild to moderate severity, including pneumonia caused by resistant strep infections. The drug has been associated with rare cases of serious liver injury and liver failure with four reported deaths and one liver transplant after the administration of the drug. The manufacturer is revising the drug labeling to address this safety concern.

Although it is difficult to determine the exact frequency of Ketek-associated adverse events on the basis of FDA’s mandatory and voluntary reporting systems, the agency has concluded that the drugs’ benefit to patients for the approved indications outweighs its risk, including the rare risk of liver failure, and supports its continued availability.

“We are advising both patients taking Ketek and their doctors to be on the alert for signs and symptoms of liver problems," said Dr. Steven Galson, Director for FDA’s Center for Drug Evaluation and Research. "Patients experiencing such signs or symptoms should discontinue Ketek and seek medical evaluation, which may include tests for liver function." The signs and symptoms of liver failure include fatigue, malaise, loss of appetite, nausea, yellow skin and dark-colored urine.

The warning, which Ketek’s manufacturer is adding to the drug’s labeling, results from FDA’s vigilant monitoring of all drugs after their introduction to the market. When the agency approved the drug in 2004, based on data in the marketing application, the risk of liver injury with Ketek was similar to that of other marketed antibiotics. A safety evaluation conducted one year after approval was consistent with this. However, as the product entered into wider use, FDA’s adverse event monitoring system received some reports of serious liver problems in patients taking Ketek, including some cases of acute liver failure leading to death or requiring liver transplantation.

Following receipt of these reports, FDA conducted a rigorous and thorough assessment of existing data, and continued to engage in U.S. and ex-U.S. monitoring of additional post market events. This work involved efforts by experts in the agency’s Office of Surveillance and Epidemiology and the Office of New Drugs, as well as by recognized external liver disease experts. FDA tracked reports of adverse events associated with Ketek via MedWatch and also had the benefit of three case reports described in the February ’06 issue of Annals of Internal Medicine. FDA has now completed its evaluation of this information and determined that additional warnings are required.

FDA will continue to evaluate Ketek-associated safety issues and take further actions if warranted. It is important to note that negative effects on liver function are a known and potential complication with some antibiotics, including Ketek, and as drug usage becomes more widespread, it is expected that rare adverse events may be detected or reported in greater numbers.

Ketek is manufactured by Sanofi Aventis.

New bold warning added to Ketek

Thu, 29 Jun 2006 00:00:00 -0700

Sanofi-aventis said Thursday it has added a new bolded warning to the labeling of its antibiotic Ketek (telithromycin).

The company said that, after conferring with the Food and Drug Administration, the drug's prescribing information has been changed to warn of a risk of liver damage and also advises physicians against using Ketek in patients with a condition known as myasthenia gravis.

"This update is based on a rigorous analysis of the available data, including consultation with leading experts to ensure that we had the most informed understanding possible with respect to hepatic and myasthenia gravis adverse events," said Sol Rajfer, president of U.S. science and medical affairs at sanofi-aventis.

He added, "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 its approved indications."

Ketek is approved to treat acute bacterial exacerbation of chronic bronchitis (AECB), acute bacterial sinusitis (ABS), and mild to moderate community-acquired pneumonia (CAP) caused by susceptible pathogens.

The antibiotic is used to treat mild to moderate CAP caused by multi-drug resistant S. pneumoniae (MDRSP), Sanofi-aventis said.

The company noted it suspended enrollment in a Ketek pediatric trial earlier this month to confirm the trial design is consistent with FDA expectations, adding the enrollment was not halted for safety reasons.

Available in the United States since 2004, sales of Ketek in the first half of 2006 were about $50 million, the firm said.

Deaths renew concerns over drug safety program

Sat, 17 Jun 2006 00:00:00 -0700

Four deaths from liver failure linked to a new antibiotic have renewed concerns about the nation's drug safety program, leading some experts to question the effectiveness of internal fixes made at the Food and Drug Administration since the withdrawal of the discredited painkiller Vioxx.

"This is another example that we should see as a signal that the current system needs reform," said Arthur Levin, director of the Center for Medical Consumers, a New York-based advocacy group, and a member of the FDA's drug safety advisory committee.

"It's not about the FDA not doing it's job it's that the process we have in place, and the authority the FDA has at present, simply aren't up to the task," he said.

Marketed as Ketek, the antibiotic linked to the liver deaths was approved in 2004 as a treatment for serious respiratory infections that have become increasingly resistant to older drugs.

At the time, government regulators recognized the potential for liver damage but concluded that the risk was about the same as for other antibacterial drugs.

After Vioxx was linked to higher rates of heart attacks and strokes and removed from sale in 2004, the FDA set up an in-house drug safety board and pledged to improve communication about emerging problems.

Critics say the agency needs a stronger, more independent safety office, additional funding, better databases and new legal powers to compel manufacturers to track adverse drug reactions.

Doctors in North Carolina were the first to raise concerns about Ketek. They submitted an article to the Annals of Internal Medicine, reporting three cases of acute liver failure in previously healthy patients who had taken the drug.

In January, the journal put an "early release" version of their findings on its Web site and followed up with a fuller article in the print edition two months later.

Drug reactions account for more than half of all cases of liver failure, a medical catastrophe that is otherwise extremely rare and in these cases, the doctors discovered, Ketek was the common denominator.

A May 16 internal memo by FDA safety investigators suggested that the problems with Ketek may be more serious than those identified in the journal article.

In the memo, a copy of which was reviewed by the Los Angeles Times, investigators described a total of 12 cases of liver failure among Ketek patients.

Four patients died, and one required a liver transplant. One patient had taken only a single dose of the drug before becoming ill.

The FDA investigators also compared data on three similar drugs and found that liver failure in patients taking Ketek although rare occurred at much higher rates than in patients taking the other medications.

The investigators recommended that the agency issue its strongest possible warning for Ketek an action that would likely lead to severely restricted use of the drug, which is manufactured by Sanofi-Aventis.

More than 5 million prescriptions for Ketek have been written since it received FDA approval.

The company defends the drug and said it was cooperating fully with the FDA to address any new advice to doctors.

An FDA spokeswoman said the agency has reached no decision. "There is an ongoing investigation looking into the safety of this drug, and we have made clear that, if the data warrant changes we will make them," said Susan Bro.

The FDA issued a public health advisory when the medical journal article was published, urging doctors to closely monitor patients for signs of liver problems.

The case is already prompting calls for more demanding standards in the approval of new antibiotics. The standard now is that drug-makers must demonstrate that a new antibiotic is not inferior to an older one.

Further complicating the controversy is a separate FDA investigation into scientific fraud in a large safety study of Ketek.

Criminal investigators from the agency discovered "serious data integrity problems" including a fictitious patient, tests performed too late to be of use, and "suspiciously similar" results for multiple patients, according to a 2004 FDA memo reviewed by the Times.

Grassley is refused interview on controversial antibiotic

Thu, 15 Jun 2006 00:00:00 -0700

After months of trying to get firsthand information from a government official familiar with a controversial new antibiotic, Sen. Charles Grassley, R-Iowa, marched into the Department of Health and Human Services headquarters Wednesday asserting his congressional right to receive the data.

After a brief meeting with senior HHS and Food and Drug Administration officials, Grassley departed empty-handed and angry.

“This is extraordinary for me,” the senior Republican said outside the headquarters. “I haven’t had to go to an agency like this since 1983 to get information I requested.

“I smell a coverup,” he said.

FDA officials denied any impropriety, saying they were cooperating with Grassley’s staff and had sent 400 boxes of documents related to the approval and safety of the drug, Ketek. Some information had to be withheld, the agency said, because of continuing investigations.

The senator, a persistent critic of the FDA, said he went to HHS out of frustration over the agency’s refusal to make available one employee involved with an investigation into the antibiotic.

A powerful drug approved in 2004 for the treatment of chronic lung and sinus infections, it has been at the center of the newest controversy over the agency’s actions in reviewing new drugs and monitoring their safety.

Liver failure and disease associated with the drug have been reported, but the overriding issue involves the integrity of the clinical trials done to establish its safety and efficacy.

The agency acknowledges that there were major improprieties in a 25,000-patient clinical trial done for the drug’s developer, Aventis.

One person has gone to prison for fraud in connection with that trial, data from several other trial sites have been discarded because basic standards were not met, and the agency told the company it could not say anything about the trial results on its product label.

Nonetheless, the FDA allowed Aventis to use much of the data to support the company’s contention that the drug is safe. It also allowed Aventis to present the data to an FDA advisory panel without telling its members of the widespread fraud allegations clouding the trial.

Documents show that some FDA employees argued that the trial should have been discarded because of the company’s inadequate oversight.

Grassley has pressed to speak with an agent in the FDA’s Division of Scientific Investigations who, he said, “is key to understanding what the FDA did when it became clear that the safety study required by the FDA in order to approve the drug was fraudulent and faulty. Did FDA managers turn a blind eye and let the drug maker off too easy, or did the FDA do the right thing?”

In reply, FDA spokeswoman Susan Bro said: “We would like to do whatever we can to help (Grassley) fulfill his constitutional duty as well as ours to the American people. However, we will not compromise an ongoing investigation.”

FDA officials also said that having a senator interview a government investigator in the midst of an inquiry raised the possibility of politicizing criminal proceedings.

Ketek is one of the few antibiotics developed and approved in recent years. The agency has made a priority of encouraging companies to work in the field of antibiotics, which inevitably become less useful as bacteria become resistant.

Enrollment of children in drug study suspended

Fri, 09 Jun 2006 00:00:00 -0700

French pharmaceutical company Sanofi-Aventis SA said Thursday it has suspended enrollment in studies of its antibiotic Ketek in children, amid reports the drug can cause liver failure in adults. The company denied the studies were halted because of safety concerns and said it was only trying to ensure the trials’ design complied with FDA requirements.

The Paris-based company said the Food and Drug Administration did not request the action. It also said the suspension was not linked to a published report which said an FDA official last month requested the trials be halted because Ketek could be deadly.

According to a government Web site, Sanofi-Aventis is conducting four different studies of Ketek in 3,920 youngsters. The first started last June.

The drug is approved only for adults to treat respiratory tract infections, bronchitis, sinusitis and community-acquired pneumonia.

Sanofi spokeswoman Lisa Kennedy couldn’t immediately say how many children had been enrolled or when enrollment might resume.

Safety issues arose about Ketek in January after researchers reported three cases of severe liver problems, including one death. Ketek’s market share and prescriptions have plummeted since then.

In the 22 weeks ended June 2, Ketek’s share of the antibiotic market fell by more than half to 0.6 percent while the number of prescriptions plunged 69 percent to 24,476. Prescriptions vary on a weekly basis but the data provided by pharmaceutical tracking firm Verispan LLC show the drug’s use has been declining steadily.

Approved in 2004, Ketek captured only a small part of the antibiotics market because physicians often shy away from new products until they establish a track record, especially when there are other drugs available, doctors said.

Dr. Jilan Shah, associate program director of infectious diseases at Cabrini Medical Center in Brooklyn, N.Y., said he had expected Ketek’s sales to increase in the future as patients become increasingly resistant to other antibiotics. But he said he has changed his mind because of the level of liver toxicity associated with the drug.

Four deaths

On Thursday, The New York Times cited internal FDA memos which said that some safety officials wrote the agency should consider forcing Sanofi-Aventis to remove Ketek from the market, severely restrict its use, or add a prominent waning label about its potentially fatal side effects.

The report also said that by April, the FDA had reports of 110 cases of liver problems associated with Ketek, and that the rate of acute liver failure connected to the drug was about four times the rate of such events seen in other antibiotics.

Before Sanofi-Aventis’ announcement, Sen. Chuck Grassley, R-Iowa, asked the FDA to explain what it was doing to inform parents about the safety concerns surrounding pediatric trials of Ketek. Grassley has been investigating the FDA actions regarding the approval and post-market surveillance of Ketek.

Last month, there were reports of an internal FDA memo that said the drug should bear stricter warnings about its effect on the liver. The memo said the FDA had received reports of 12 cases of acute liver failure, including four deaths, in patients treated with Ketek.

FDA spokeswoman Susan Bro said the agency was not considering removing Ketek from the market but that it was conducting a review of the drug’s safety. She said the review would be completed shortly.

Doctors are not waiting for any FDA decision. Dr. Len Horovitz, an attending physician in the pulmonary division of Lenox Hill Hospital, has stopped prescribing Ketek even though his patients haven’t suffered any adverse reactions.

“There are other drugs you can use so why use it?” Horovitz asked. “It looks like something is up with the drug.”

Sanofi-Aventis antibiotic linked to liver failure

Tue, 23 May 2006 00:00:00 -0700

According to an internal FDA communication first reported in the Wall Street Journal, the FDA has received reports of 12 cases of liver failure, including four deaths, in patients taking the drug. The memo is also reported to express the FDA's concern that these adverse events appear to be more frequent in patients taking Ketek than in those taking similar antibiotics.

Sanofi-Aventis has indicated that it still believes Ketek to be safe when used according to its label. "These complex evaluations require careful and rigorous analysis with leading experts before drawing any definitive conclusion," the company said in a statement quoted by the Associated Press.

Ketek, known generically as telithromycin, is used to treat mild to moderate respiratory infections. The drug was approved in Europe in 2001 but was not approved in the US until April 2004 after the FDA asked for more safety information in 2001 and 2003.

Antibiotic linked to liver failure

Fri, 19 May 2006 00:00:00 -0700

The U.S. Food and Drug Administration wants to add a warning label on packaging for an antibiotic that has been linked to liver failure.

An internal FDA memo written by the Division of Drug Risk Evaluation described "profound" liver injury in some patients occurring within the first few days of taking the medication. The memo said that 12 of the cases had few other possible causes, The Wall Street Journal reported.

The liver-failure rate was "clinically remarkable" and "consistent with an association" between the medication and liver failure, the FDA document stated.

The estimated rate of reported liver failures linked to Ketek was 23 per 10 million prescriptions as compared with a reported rate on competing products of of 6.6 per 10 million prescriptions for Avelox, six for Tequin and 2.1 for Levaquin.

A large clinical trial that was intended to prove the drug's safety was hampered by fraud and other problems, yet the FDA approved the medication anyway. In 2005, 3.35 million prescriptions were written for Keteck.

Despite concerns about safety, the FDA approved Ketek for sinusitis, bronchitis and pneumonia.

The FDA's drug memo recommends a warning on the label in either bold type or a black box, mentioning "reports of liver necrosis and liver failure."

Antibiotic Linked to Liver Problems

Fri, 19 May 2006 00:00:00 -0700

An antibiotic linked to a growing number of reports of liver failure, including four deaths, should bear stricter warnings about its effect on the liver, according to an internal Food and Drug Administration memo. The drug's manufacturer, Sanofi-Aventis, said Friday it was in talks with FDA officials about those reports.

The FDA has received reports of 12 cases of acute liver failure, including the four deaths, in patients treated with Ketek, according to a copy of the memo shown to The Associated Press. FDA safety evaluators also uncovered 23 other cases where patients suffered serious liver injuries after receiving the antibiotic, which is formally called telithromycin.

The reports, when considered in proportion to the number of prescriptions filled for Ketek, exceed what's been seen in similar antibiotics, according to the memo. The contents of the May 16 memo were first reported Friday by The Wall Street Journal.

Ronald Wassel and Dr. Allen Brinker, both of the FDA's Division of Drug Risk Evaluation, recommended in the memo that the FDA consider restricting the use of Ketek or even withdrawing it should the liver failure rate rise to levels seen in another antibiotic, Trovan, before its use was restricted in 1999.

However, the two wrote that they cannot determine whether the drug's risk is currently higher than that posed by any other of the various antibiotics associated with liver problems.

"Nonetheless, the rising trend of reporting rates associated with telithromycin is of concern," the memo reads in part. The memo was forwarded through Dr. Mark Avigan, director of the FDA's Division of Drug Risk Evaluation, to the head of the agency's Division of Anti-infective and Ophthalmologic Products, Dr. Janice Soreth.

FDA spokeswoman Susan Bro said it would be "premature" to discuss any steps the agency might take. The current FDA-approved label for Ketek warns of liver disfunction that can be severe but is "usually reversible."

Sanofi-Aventis SA said it continues to believe Ketek is safe and effective when used as directed, adding that it continued to discuss the liver reports with the FDA.

"These complex evaluations require careful and rigorous analysis with leading experts before drawing any definitive conclusion," the company said in a statement.

In January, the Annals of Internal Medicine published a report detailing three cases of severe liver problems, including one death, in patients at a North Carolina hospital after they began taking Ketek.

That publication may have stimulated the reporting of further problems associated with Ketek, skewing perceptions of its apparent risk when compared to other drugs, according to the memo. Furthermore, reporting rates are typically higher with newer drugs. The FDA approved Ketek in April 2004.

Congress is investigating how the FDA has handled Ketek, including problems with a clinical trial that was supposed to show the drug's safety, according to The Wall Street Journal report.

Irregularities in the execution of that trial left the FDA unable to make a "meaningful assessment" of liver safety concerns associated with the drug, according to the memo.

Parker & Waichman, LLP Retained by Patients Diagnosed with Liver Damage after Using Ketek

Fri, 19 May 2006 00:00:00 -0700

Parker & Waichman, LLP (www.yourlawyer.com) announces that it has been retained by individuals who suffered liver damage and liver failure after using the antibiotic Ketek. Ketek is manufactured by Sanofi-Aventis (NYSE: SNY) and is commonly prescribed to treat bacterial infections in the lungs and sinuses. It has been reported that the FDA and Sanofi-Aventis are in discussions about revising Ketek’s safety label after FDA reviewers recommended a strong warning about cases of liver failure. The Wall Street Journal reported that an internal FDA report linked Ketek to 12 cases of liver failure, including four deaths. For more information on Ketek please visit:
http://www.yourlawyer.com/topics/overview/Ketek and http://www.ketek-liver-failure.com.

Ketek was approved by the FDA in 2004 for the treatment of respiratory infections. The FDA rejected the drug in 2001 and 2003, asking for more safety information. On January 20, 2006 the Annals of Internal Medicine released an article detailing liver toxicity in three Ketek patients. This article detailed patients at Carolinas Medical Center, in Charlotte, North Carolina, who developed various liver problems after using the drug. One patient took Ketek for just five days and died from liver failure, another patient required a liver transplant after using the drug, and the third person developed hepatitis after using the medication but later recovered. While the authors of this article stated that these cases don’t conclusively prove that Ketek caused the liver problems, the FDA issued a public health advisory on January 20, 2006 that warned of a possible link. The FDA advisory is available at http://www.fda.gov/medwatch/safety/2006/safety06.htm#Ketek.

Parker & Waichman, LLP is encouraging all patients who have been diagnosed with liver damage or liver failure during or after the use of Ketek to request a free case evaluation by visiting http://www.yourlawyer.com/topics/overview/Ketek or by calling 1-800-LAW-INFO (1-800-529-4636).

About Parker & Waichman, LLP

Parker & Waichman, LLP is a leading products liability and personal injury law firm that represents plaintiffs nationwide. The firm has offices in New York and New Jersey. Parker & Waichman, LLP has assisted thousands of clients in receiving fair compensation for injuries resulting from defective medications and medical devices. The firm is currently representing individuals injured by Ortho Evra, Vioxx, Bextra, Zyprexa, Tequin, ReNu with MoistureLoc, Guidant defibrillators and many other defective drugs and medical products. For more information on Parker & Waichman, LLP please visit: (http://www.yourlawyer.com) or call (800) LAW-INFO ((800) 529-4636).

Contact:

Parker & Waichman, LLP

Jason Mark, Esq.

Melanie H. Muhlstock, Esq.

1 (800) LAW-INFO

1 (800) 529-4636, Toll-free

info@yourlawyer.com

www.yourlawyer.com

www.yourlawyer.com/topics/overview/Ketek

www.ketek-liver-failure.com

Markey criticizes FDA

Wed, 03 May 2006 00:00:00 -0700

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.

Health Canada Advisory: Antibiotic Ketek and Possible Association With Liver Failure

Wed, 08 Feb 2006 00:00:00 -0800

Health Canada is advising Canadians about a possible link between use of the antibiotic Ketek and potentially serious liver problems.

There have been international reports of patients using Ketek who experienced liver failure requiring transplant or resulting in death, although no such cases have been reported in Canada. Ketek (the brand name for telithromycin), which has been marketed in Canada since May 2003, is indicated for the treatment of pneumonia, throat and sinus infections and chronic bronchitis, as well as serious or multi-drug resistant infections.

An article in the Annals of Internal Medicine recently reported three cases of liver failure associated with Ketek. All three patients had jaundice (yellowing of the skin) and abnormal liver function. One patient recovered, one required a transplant, and one died. Health Canada is currently reviewing Canadian cases of less serious liver problems and other safety information for Ketek.

Meanwhile, Health Canada is providing the following interim recommendations to healthcare professionals and patients:

1) Ketek should not be used for patients who have pre-existing liver problems.
Patients taking Ketek should contact their health care provider immediately if they notice yellowing of their eyes or skin, or experience any other symptoms of liver problems, such as blurry vision, loss of appetite, dark urine, pale stools, itching or abdominal pain.

2) Patients who have been prescribed Ketek and are not suffering side effects such as those described should continue taking their medicine, unless otherwise directed by their health care provider.

3) Canadian healthcare professionals and patients will be advised if further precautionary measures are necessary.

Managing adverse reactions of marketed health products depends on the active participation of both healthcare professionals and consumers in reporting them. Spontaneously reported post- marketing adverse reactions are generally presumed to underestimate the risks associated with health product treatments.

Antibiotic Ketek and possible association with liver failure

Tue, 07 Feb 2006 00:00:00 -0800

Health Canada is advising Canadians about a possible link between use of the antibiotic Ketek and potentially serious liver problems.

There have been international reports of patients using Ketek who experienced liver failure requiring transplant or resulting in death, although no such cases have been reported in Canada. Ketek (the brand name for telithromycin), which has been marketed in Canada since May 2003, is indicated for the treatment of pneumonia, throat and sinus infections and chronic bronchitis, as well as serious or multi-drug resistant infections.

An article in the Annals of Internal Medicine recently reported three cases of liver failure associated with Ketek. All three patients had jaundice (yellowing of the skin) and abnormal liver function. One patient recovered, one required a transplant, and one died. Health Canada is currently reviewing Canadian cases of less serious liver problems and other safety information for Ketek.

Meanwhile, Health Canada is providing the following interim recommendations to healthcare professionals and patients:
•    Ketek should not be used for patients who have pre-existing liver problems.
•    Patients taking Ketek should contact their health care provider immediately if they notice yellowing of their eyes or skin, or experience any other symptoms of liver problems, such as blurry vision, loss of appetite, dark urine, pale stools, itching or abdominal pain.
•    Patients who have been prescribed Ketek and are not suffering side effects such as those described should continue taking their medicine, unless otherwise directed by their health care provider.
Canadian healthcare professionals and patients will be advised if further precautionary measures are necessary.

Managing adverse reactions of marketed health products depends on the active participation of both healthcare professionals and consumers in reporting them. Spontaneously reported post- marketing adverse reactions are generally presumed to underestimate the risks associated with health product treatments.

FDA Issues Public Health Advisory Concerning Reports of Serious Liver Toxicity and Death Following Use of the Antibiotic Ketek (Telithromycin)

Sat, 21 Jan 2006 00:00:00 -0800

The FDA has issued a serious public health advisory warning of an article published on Friday in Annals of Internal Medicine reporting that three patients experienced serious liver toxicity after taking Ketek (telithromycin). These cases have also been reported to FDA MedWatch.

Telithromycin is an antibiotic of the ketolide class. It was the first ketolide antibiotic to be approved by the FDA in April, 2004 for the treatment of respiratory infections in adults. It is marketed and is widely used in several countries including Japan and countries in Europe.

“While it is difficult to determine the actual frequency of adverse events from voluntary reporting systems such as the MedWatch program, the FDA is continuing to evaluate the issue of liver problems in association with use of telithromycin in order to determine if labeling changes or other actions are warranted.”

The FDA is continuing efforts to ascertain the frequency of liver-related adverse events reported for approved antibiotics, including telithromycin.

The FDA is providing the following recommendations to healthcare providers and patients while the investigation is taking place:

Healthcare providers should monitor patients taking telithromycin for signs or symptoms of liver problems. Telithromycin should be stopped in patients who develop signs of liver problems.
Patients who have been prescribed telithromycin and are not experiencing side effects such as jaundice should continue taking their medicine as prescribed unless otherwise directed by their healthcare provider.
Patients who notice any yellowing of their eyes or skin or other problems like blurry vision should contact their healthcare provider immediately.
As with all antibiotics, telithromycin should only be used for infections caused by a susceptible microorganism. Telithromycin is not effective in treating viral infections, so a patient with a viral infection should not receive telithromycin since they would be exposed to the risk of side effects without any benefit.

The article in Annals of Internal Medicine reports three separate, serious adverse events after taking telithromycin. As stated in the public health advisory: “All three patients developed jaundice and abnormal liver function. One patient recovered, one required a transplant, and one died.”

When the livers of the transplant and deceased patients “were examined in the laboratory, they showed massive tissue death. These two patients had reported some alcohol use. All three patients had previously been healthy and were not using other prescription drugs.”
The three patients were all treated by physicians in the same geographic area. The significance of this, if any, “is not clear at the present time.”

According to the advisory: “In pre-marketing clinical studies, including a large safety trial and data from other countries, the occurrence of liver problems was infrequent and usually reversible. Based on the pre-marketing clinical data, it appeared that the risk of liver injury with telithromycin was similar to that of other marketed antibiotics. Nonetheless, the product label advises doctors about the potential for liver-related adverse events associated with the use of telithromycin.”

FDA probing death linked to new antibiotic

Fri, 20 Jan 2006 00:00:00 -0800

Researchers reported Friday three cases of severe liver problems, including one death, in patients at a North Carolina hospital after they began taking a novel antibiotic.

Federal regulators said they were reviewing an unknown number of U.S. cases involving the drug, telithromycin, and were consulting with their counterparts overseas.

One patient at Carolinas Medical Center in Charlotte, N.C., died after taking telithromycin, which is marketed as Ketek, researchers at the hospital said. Another required and received a liver transplant, while the third recovered from drug-induced hepatitis after treatment with Ketek was stopped.

The severity of the cases warranted the researchers’ alerting doctors to what they called a “possible link with telithromycin,” said Dr. John Hanson, who works in the liver transplant center at Carolinas Medical Center.

The reports do not prove the drug caused the problems, researchers said. Nor is there enough information to support major changes in how the drug is prescribed, Hanson said. Two of the three patients reported some use of alcohol, although there was no prior evidence of liver damage.

The cases are discussed in a paper to be published March 21 in the journal Annals of Internal Medicine. The journal released an electronic version on Friday.

The drug is made by Sanofi-Aventis. A company spokeswoman did not immediately return a message seeking comment left midday Friday.

The Food and Drug Administration approved the drug, marketed as Ketek, in 2004 for treatment of acute bacterial infections from chronic bronchitis, acute bacterial sinusitis and community-acquired pneumonia. On Friday, FDA spokeswoman Susan Bro said the agency would comb through its databases for other reports of liver problems in patients treated with the drug.

“Because these liver problems are significant and somewhat idiosyncratic or unpredictable, the FDA is evaluating the use of this medicine in both the U.S. and abroad where it is used and marketed to determine whether additional warning guidance is merited,” Bro said.

Bro cautioned that patients on the drug who experience any sort of liver distress, including jaundice, should talk to their doctors immediately.

FDA Public Health Advisory Ketek (telithromycin) Tablets

Fri, 20 Jan 2006 00:00:00 -0800

Today, January 20, 2006, Annals of Internal Medicine published an article reporting three patients who experienced serious liver toxicity following administration of Ketek (telithromycin). These cases have also been reported to FDA MedWatch. Telithromycin is marketed and used extensively in many other countries, including countries in Europe and Japan.

While it is difficult to determine the actual frequency of adverse events from voluntary reporting systems such as the MedWatch program, the FDA is continuing to evaluate the issue of liver problems in association with use of telithromycin in order to determine if labeling changes or other actions are warranted. As a part of this, FDA is continuing to work to understand better the frequency of liver-related adverse events reported for approved antibiotics, including telithromycin.

While FDA is continuing its investigation of this issue, we are providing the following recommendations to healthcare providers and patients:

Healthcare providers should monitor patients taking telithromycin for signs or symptoms of liver problems. Telithromycin should be stopped in patients who develop signs or symptoms of liver problems.
Patients who have been prescribed telithromycin and are not experiencing side effects such as jaundice should continue taking their medicine as prescribed unless otherwise directed by their healthcare provider.
Patients who notice any yellowing of their eyes or skin or other problems like blurry vision should contact their healthcare provider immediately.
As with all antibiotics, telithromycin should only be used for infections caused by a susceptible microorganism. Telithromycin is not effective in treating viral infections, so a patient with a viral infection should not receive telithromycin since they would be exposed to the risk of side effects without any benefit.

The case review in today’s online publication by Annals of Internal Medicine reports three serious adverse events following administration of telithromycin. All three patients developed jaundice and abnormal liver function. One patient recovered, one required a transplant, and one died. When the livers of the latter two patients were examined in the laboratory, they showed massive tissue death. These two patients had reported some alcohol use. All three patients had previously been healthy and were not using other prescription drugs. The FDA is also aware that these patients were all treated by physicians in the same geographic area. The significance of this observation is not clear at the present time.

In pre-marketing clinical studies, including a large safety trial and data from other countries, the occurrence of liver problems was infrequent and usually reversible. Based on the pre-marketing clinical data, it appeared that the risk of liver injury with telithromycin was similar to that of other marketed antibiotics. Nonetheless, the product label advises doctors about the potential for liver-related adverse events associated with the use of telithromycin.

Telithromycin is an antibiotic of the ketolide class. It was the first antibiotic of this class to be approved by the FDA in April, 2004 for the treatment of respiratory infections in adults caused by several types of susceptible microorganisms including Streptococcus pneumoniae and Haemophilus influenzae.

Replidyne halts faropenem test using Ketek

Sun, 01 Jan 2006 00:00:00 -0800

U.S. firm Replidyne said Tuesday it has temporarily halted its study comparing faropenem to Ketek, due to the latter drug's safety issue.

The company said it has been conducting a phase 3 clinical trial comparing faropenem medoxomil to placebo and to the antibiotic Ketek in patients being treated for acute exacerbation of chronic bronchitis (AECB).

Replidyne said it has put that study on hold while it considers whether to exclude from the trial the Ketek treatment arm, in light of recent data linking the antibiotic to liver damage.

The company said it made the decision based on the recommendations of an FDA advisory panel issued in mid-December that the risks of Ketek outweigh the benefits of using the drug for the treatment of patients with AECB.

"We believe that stopping enrollment in this trial to consider the inclusion of Ketek in the study is the appropriate and responsible action at this time to consider the new scientific evidence presented at the recent FDA Advisory Committee meeting," said Kenneth Collins, president and CEO of Replidyne.

Collins noted that, while the temporary suspension of the trial would cause some delay, he added, "we do not expect that it will impact the total time to complete the clinical program."

Collins also said the decision would not impact the company's development of its pediatric clinical program for faropenem.

Ketek Lawyer Liver Lawsuit Damage Attorney Side Effects

Sun, 01 Jan 2006 00:00:00 -0800

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Ketek Injury Lawyers and Attorneys

Our Ketek injury lawyers and attorneys are currently representing hundreds of people who suffered liver damage as a result of this defective antibiotic Ketek. Ketek has been the subject of numerous Food & Drug Administration (FDA) safety reviews, and in 2007, the FDA ordered Sanofi-Aventis to place a black box warning on the Ketek label regarding serious side effects, including liver failure. In addition to its numerous safety issues, the clinical trials for Ketek were riddled with fraud, a situation that has resulted in a long-running congressional investigation. The Ketek injury lawyers and attorneys at our firm are working to insure that Sanofi-Aventis is held accountable for the injuries caused by this defective drug and to help the victims of Ketek.

Our Dedicated Experienced Lawyers and Attorneys Have Years of Experience Handling Defective Drug Lawsuits Such as Ketek.

Critics of Ketek, including the defective drug lawyers at our firm, have long questioned the wisdom of the FDA decision to approve Ketek. When Aventis (now Sanofi-Aventis) submitted Ketek to the agency for approval in 2001 and 2003, the FDA refused on the basis that the drug maker had not provided sufficient evidence that Ketek was as safe and effective as antibiotics already on the market. However, in 2004 the FDA relented and approved Ketek for the treatment of respiratory tract infections, bronchitis, sinusitis and community-acquired pneumonia. The Ketek injury lawyers at our firm believe the FDA committed a serious error in approving Ketek, especially considering the fact that so many safer, less expensive antibiotics were already available to treat the conditions that Ketek was intended to treat.

Within months of its introduction to the market, some patients being treated with Ketek experienced liver problems. In January 2006, the FDA issued a Public Health Advisory warning about serious liver problems associated with the use of Ketek. The FDA warning followed the early release via the internet of a March 2006 article published in the Annals of Internal Medicine. In that article, researchers detailed three cases of severe liver problems, including one death, that occurred in patients at a North Carolina hospital after they began taking Ketek. One patient at Carolinas Medical Center in Charlotte, N.C., died after taking Ketek. Another patient received a liver transplant, and the third contracted drug-induced hepatitis but recovered after treatment with Ketek was stopped.

Our Ketek injury attorneys are aware of evidence that suggests the FDA and Sanofi-Aventis knew of liver problems associated with Ketek long before the Public Health Advisory was issued. According to a statement by the consumer advocacy group Public Citizen following that advisory, "Panelists at the Jan. 8, 2003 advisory committee meeting reviewed data from a large U.S. safety study that indicated a risk for heart, liver, and eye toxicity with [Ketek] use. It was also revealed at this meeting-three years ago--- that the FDA already had received 54 reports of liver-related adverse drug reactions from countries in which the drug had already been previously marketed. Nineteen of these 54 reports were categorized as serious."

Ketek Labeling Changes

On May 19, 2006 the FDA said it was able to connect 12 cases of liver failure, which included four deaths, to Ketek. Based upon these finding, the FDA urged Sanofi-Aventis to add a warning label to the drug. The FDA eventually confirmed 53 cases of liver failure in patients using Ketek, including five deaths. In February 2007, Sanofi-Aventis finally added a black box warning concerning liver failure to the Ketek label and the FDA severely restricted its use. In addition, Sanofi-Aventis also added a boxed warning and contraindication for myasthenia gravis patients. Information regarding visual disturbances and loss of consciousness, previously in the precautions section, was moved to the more prominent warnings section of the Ketek label. Our Ketek injury lawyers do not feel the actions taken by the FDA and Sanofi-Aventis go far enough, and believe that this defective drug should never have been allowed on the market at all.

The FDA approved Ketek despite documented evidence of fraud in some of the clinical trials Aventis submitted to the agency during the approval process. This fraud included instances where doctors enrolled phony subjects in the Ketek trials and falsified consent forms by forging subject signatures. One doctor actually was charged criminally and was sent to jail because of Ketek fraud. in October 2007, the FDA sent Sanofi-Aventis a warning letter regarding the conduct of Ketek clinical trials. The FDA said that Aventis’ own records showed that there were many instances of “serious protocol violations and regulatory noncompliance by clinical investigators” involved in the Ketek clinical trial. According to the warning letter, the FDA found no evidence that Aventis did anything to correct the problems with the Ketek clinical trial, or remove doctors responsible for violations from the study. The FDA also criticized the drug maker for failing to make sure the Ketek clinical trail was run properly and for allowing unqualified investigators to participate.

Ketek Investigation

In February 2008, a congressional committee looking into Ketek fraud subpoenaed Health and Human Services (HHS) Secretary Michael Leavitt, asking him to produce unredacted records prepared for the FDA commissioner’s appearance at a March 2007 hearing on Ketek. Leavitt’s department oversees the FDA, and both FDA and HHS had refused to provide those documents in the past. At the same time, the panel also approved subpoenas for two current FDA investigators, one former FDA investigator and a former employee of a company commissioned by Aventis to monitor the fraudulent Ketek clinical trials.

At a hearing in Congress on February 12, testimony from one subpoenaed witness revealed that in 2002, the FDA had denied the request of one of its own agents to investigate whether or not Aventis knew about the Ketek fraud as it happened. For his part, Secretary Leavitt refused to turn over subpoenaed documents to the committee, causing some lawmakers to threaten him with contempt charges. Because of the obstruction on the part of Leavitt, the FDA and Sanofi-Aventis, governmental investigations have failed to get to the bottom of the Ketek debacle. It is becoming increasingly clear that many of the questions arising from the Ketek debacle might only answered in the course of Ketek lawsuits filed on behalf of those injured by this defective drug.

Legal Help

If you or a loved one have been injured as a result of Ketek, you have valuable legal rights. Please fill out our online form or call 1-800-LAW-INFO (1-800-529-4636) for a free consultation with an experienced Ketek injury lawyer / attorney at our firm.