Source | FDA

The Food and Drug Administration is alerting health care professionals and consumers to concerns over the use of Fentora (fentanyl buccal) tablets after recent reports of deaths and other adverse events.

Fentora, a potent opioid pain medication, is used only for treatment of breakthrough pain in cancer patients receiving opioid treatment and who have become tolerant to it. Breakthrough pain is intense increases in pain that occur with rapid onset, even when opioid pain-control medication is being used.  Patients who take narcotic pain medications daily and around-the-clock develop tolerance and are more resistant to the dangerous side effects of these medications than patients who take narcotic pain medication on a less frequent basis.

The deaths reported were the result of improper selection of patients, dosing, or improper product substitution.

“FDA is monitoring this issue very closely,” said Steven Galson, M.D., M.P.H., director of FDA’s Center for Drug Evaluation and Research. “We are working with the manufacturer to ensure the safest use of this medicine. Health care professionals and patients need to be aware of the potential for fatal overdose with the improper use of Fentora.”

In its Public Health Advisory and Health Care Professional Sheet published today, FDA warned physicians and other health care professionals that it is critical to follow product labeling when administering Fentora. FDA further stated that it is dangerous to use Fentora for any short-term pain such as headaches or migraines. It is critical that Fentora not be used in patients who are not opioid tolerant.

Patients also must be under a doctor’s care and close supervision while taking Fentora and the dose should be carefully adjusted to control breakthrough pain adequately.

In addition, FDA is concerned about the improper substitution of Fentora, a quick acting pain drug, for other pain medicines.  Fentora is not the same as other fentanyl products and cannot be substituted for Actiq, another fentanyl product used to treat breakthrough cancer pain. Because Fentora delivers more fentanyl to the blood than Actiq, substituting Fentora for Actiq using the same dose can result in a fatal overdose.

On Sept.10, 2007, Cephalon Inc., the manufacturer of Fentora, sent letters to physicians and other health care providers advising them about the adverse events and deaths reported for Fentora. FDA is reviewing available information including adverse events. The agency has asked the company to strengthen warnings and improve the dosing instructions in the drug’s product labeling.  FDA also requested that the company improve their education plan for prescribers and pharmacists on the proper patient selection, dosing instructions and restrictions on substituting Fentora for other products.

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Source | FDA

Quong Hop & Co. of South San Francisco, California is expanding their recall of tofu to include the following products in the following sizes and code dates:

All varieties and sizes of SOY DELI TOFU coded DEC 17 2007
30 OZ SOY DELI ORGANIC NIGARI TOFU coded SEP 23 2007 and OCT 17 2007
12 OZ SOY DELI TOFU (water packed) coded SEP 23 and OCT 09 2007
16 OZ QUONG HOP TOFU (water packed) coded SEP 23 2007
These products are being recalled because they have the potential to be contaminated with Listeria monocytogenes, an organism which can cause serious and sometimes fatal infections in young children, frail or elderly people and others with weakened immune systems. Although healthy individuals may suffer only short term symptoms such as high fever, sever headache, stiffness, abdominal pain and diarrhea, Listeria infection in severe cases can cause miscarriages and still births among pregnant women.

The recalled “SOY DELI” and “QUONG HOP” brand products are distributed in the Midwest and West coast through supermarkets and natural food stores.

This expanded recall reflects product produced during the selected period. No additional cases of bacteria have been reported. This is a precaution being taken to help ensure product safety.

The date code can be found on the front panel of all the aforementioned products printed in blue ink.

No illnesses have been reported to date in connection with this problem.
The potential for contamination was noted after a routine test by Washington State Department of Agriculture’s Food Safety Program revealed the presence of Listeria monocytogenes in a 12 OZ vacuum pack package of “SOY DELI FIRM ORGANIC NIGARI TOFU”. The company is voluntarily recalling all products produced during the same time period as the sampled product to ensure customer safety.

Source | FDA

MCP is recalling the “Queso Cincho de Guerrero” produced by “Quesos Sabrosos Mexicanos” because it has the potential to be contaminated with Salmonella, an organism which can cause serious and serious and sometimes infections in young children, frail or elderly people and others with weakened immune systems. Healthy persons infected with Salmonella often experience fever, diarrhea (which may be bloody) nausea, vomiting and abdominal pain. In rare circumstances, infection with Salmonella can result in the organism getting into the bloodstream and producing more severe illnesses such as arterial infections (i.e., infected aneurysms), endocarditis and arthritis, and Staphylococcus aureus which can cause nausea, retching, abdominal pain, diarrhea and prostration.

The recall of Queso Cincho de Guerrero produced by “Quesos Sabrosos” was distributed in Indiana, Michigan, Georgia, Texas, and Illinois in retail stores.

The dry hard Mexican cheese comes in wheels of 35# to 40#, and is labeled as “Quesos Sabrosos Mexicanos”.
No illnesses have been reported to date in connection with this problem.
The potential for contamination was noted after routine testing by FDA of Salmonella and Staphylococcus aureus in the Queso Cincho.

Source | FDA

The Department of Consumer Protection has removed a product from three stores where it was sold, following a voluntary recall by the manufacturer and a U.S. Food and Drug Administration (FDA) warning consumers not to drink or serve the beverage.

The product is Baby’s Bliss Gripe Water, apple flavor, with a code of 26952V and expiration date of October 2008 (shown as “10/08″ on the label), distributed by MOM Enterprises, Inc., of San Rafael, Calif. The FDA confirmed through laboratory analysis the presence of cryptosporidium after investigating the illness of a 6-week-old infant in Minnesota who consumed the product. Cryptosporidium is a parasite that can cause intestinal infections.

“We have identified three stores in the state that have sold this beverage, and we have made sure that the product has been removed from sale,” Consumer Protection Commissioner Jerry Farrell, Jr. said. “Consumers who have this item at home should be sure it is not coded and dated as described in the FDA warning. If it is, please do not use the beverage, but discard it immediately.”

The three stores known to have carried Baby’s Bliss Gripe Water are:

Over the Moon, Avon
Bissell Pharmacy, Ridgefield
Starlight Baby, Southbury

All of the above stores have been contacted by Consumer Protection and are aware of the recall.

Symptoms of Cryptosporidium Poisoning
The most common symptom of infection is watery diarrhea. Other symptoms can include dehydration, weight loss, stomach cramps or pain, fever, nausea and vomiting. Symptoms generally begin two to ten days after becoming infected with the parasite and generally last one to two weeks. While most people with healthy immune systems will recover without treatment, the infection could be serious or life-threatening for certain individuals. Infants, children and pregnant women are susceptible to dehydration resulting from diarrhea, which can be life-threatening. Individuals with weakened immune systems are also at risk for a more serious and life-threatening form of illness.

Seek Immediate Medical Attention

Parents of children who have recently consumed apple flavored Baby’s Bliss Gripe Water and have these symptoms should seek immediate medical attention. Parents and caregivers who have given this product to their infants and children should be alert for diarrhea and other signs of Cryptosporidium infection.

The product was sold in a four-ounce plastic bottle packaged inside of a cardboard carton, labeled with the following: Baby’s Bliss. Pediatrician Recommended Gripe Water. Apple Flavor.

Source | FDA 

Johnson and Johnson and FDA informed healthcare professionals that the WARNINGS section of the prescribing information for haloperidol has been revised to include a new Cardiovascular subsection regarding cases of sudden death, QT prolongation and Torsades de Pointes(TdP) in patients treated with haloperidol, especially when given intravenously, or at doses higher than recommended. Although injectable haloperidol is only approved by the FDA for intramuscular injection, there is considerable evidence that the intravenous administration of haloperidol is a relatively common off-label clinical practice.

There are at least 28 case reports of QT prolongation and TdP, some with fatal outcome in the context of off-label intravenous haloperidol. Healthcare professionals should consider this new risk information when making individual treatment decisions for their patients.

By Michelle Massey (Texarkana Bureau)

Dallas, TX (Schmidt & Clark) September 18, 2007 –After 27 years of working as a pressman, Charles Wilson claims he developed myelodysplastic syndrome (MDS) from exposure to benzene. Wilson’s allegations will be heard by a jury on Nov. 13, just 16 months after initiating the product liability suit.

Representing Charles Wilson and his wife Laura, are attorneys Collen Clark, Michael Schmidt, and Keith Patton from the Dallas law firm of Schmidt and Clark and attorneys F. Durham III and Kirk Pittard from the Dallas law firm of Durham and Pittard.

The suit filed in July 2006 in the Marshall Court of the Eastern District of Texas, states Wilson was exposed to benzene through “blanket washes, press washes, varnish removers, plate clearness, roller washes, and other solvents and chemicals.” Defendants named in the original petition include Rycoline Products, Rogersol, Host-man Steinberg, I.C. Compound Company, Ashland, Allied Photo Offset Supply Corporation, Day International and Lastra America Corporation.

The National Cancer Institute describes myelodysplastic syndrome as “a group of diseases in which bone marrow does not make enough healthy blood cells.” The MDS foundation states “MDS is a rare disease, whose incidence is four per 100,000.”

According to court records, the plaintiff states that his illness was caused by defendants’ negligence. Wilson says the defendants knew the products were “carcinogenic, deleterious, and highly harmful” but failed to warn, provide knowledge or precautions regarding the “highly harmful substances.” He also alleges that defendants are responsible for strict liability, gross negligence and breach of warranty.

Wilson seeks punitive and exemplary damages for medical expenses, physical pain and suffering, mental anguish, physical impairment, disfigurement, loss of earnings, and loss of consortium, companionship and society.

The plaintiff has requested a jury trial. Judge Leonard Davis will preside but has referred the pre-trial proceedings to Magistrate Judge Charles Everingham.

Responding to the plaintiffs’ complaint in September 2006, Rycoline Products, Inc. denied all allegations and asserts that Wilson’s illness was caused by negligence of others. Rycoline Products develops and provides products such as printing blankets, fountain solutions, silicone and silicone replacement parts.

Continuing its defense, Rycoline said the laintiff’s injury was caused by “unintended, unexpected and/or abnormal use or misuse” of any Rycoline products. Further, Rycoline states Wilson’s employer, Frankston Packaging Company, had knowledge of the risks and hazards in Wilson’s workplace.

Although Wilson did not sue his former employer, on May 1 the defendants filed a third-party company against Frankston Packaging (FBOT), a dissolved corporation.

At a hearing on July 27, FPBOT’s attorney filed an undisclosed settlement agreement, which is pending judicial approval.

The complaints against defendants I.C. Compound, Hostman-Steinberg, Lastra America Corporation and Allied Photo Offset Supply Corporation have been dismissed with prejudice with each party paying its own costs.

As the trial date nears, defendants Ashland and Day International filed a motion for a continuance to conduct additional discovery and depose expert witnesses. Everingham denied the motion but allowed an amended scheduling order that will give the defendants more time.

The trial date remains firm for Nov. 13. Case No.: 2:06cv00286

Source | New York Times

By Gardiner Harris

Two more studies published in yet another prominent medical journal have raised questions about the safety of Avandia, a once-popular diabetes medicine.

One study found that Avandia, made by GlaxoSmithKline, doubled the risks of heart failure and raised the risks of heart attack by 42 percent. A second study found that Actos, a similar drug made by Takeda, actually lowered the risks of heart attacks, strokes and death but, like Avandia, also raised risks of heart failure.

Taken together, some of the authors said, the two studies in The Journal of the American Medical Association confirm what doctors and patients using Avandia have already done in great numbers, that is, switch to another drug. Sales of Avandia have plunged.

GlaxoSmithKline said in a written statement that the studies were flawed and “offered no new information on the safety of Avandia.” The company “continues to support Avandia as safe and effective when used appropriately,” the statement said.

In July, a federal advisory panel voted overwhelmingly that Avandia should remain on the market even though it raised the risks of heart attacks. In June, the Food and Drug Administration said it would place its strictest warnings on the labels of both Avandia and Actos because of heart failure risks.

Riven by internal disagreements, the drug agency is still pondering further regulatory actions regarding Avandia. Some in the agency say that the drug should be withdrawn, while others say that all diabetes drugs have risks and that doctors need a variety of options.

The controversy began in May when The New England Journal of Medicine published a combined analysis of more than 40 studies of Avandia that found that it significantly raised the risks of heart attacks. The study attracted wide attention, but it was also criticized by the company and some on Capitol Hill as flawed.

In the study’s aftermath, the drug agency said that it had been told in 2005 of a similar study conducted by GlaxoSmithKline that came to a similar conclusion. Critics denounced the agency’s delay in alerting patients.

Dr. Richard Hellman, president of the American Association of Clinical Endocrinologists, said that the new studies were “more evidence that we should have a very high level of caution” regarding the use of Avandia. The drug agency should further strengthen the warnings on Avandia’s label to make it clear that the drug should be used very sparingly.

In the first study, researchers from Wake Forest University did yet another combined analysis of Avandia studies, this time limiting themselves to four long-term studies. The authors’ hope was that, by focusing on such a select set, their analysis would avoid some of the limitations of the May analysis.

The redo came to a conclusion almost identical to that of the study published in May. Dr. Sonal Singh, an assistant professor of internal medicine at the Wake Forest School of Medicine and a co-author of the study, said the drug agency should consider withdrawing Avandia from the market.

In addition to its deleterious effects on the heart, Avandia can cause blindness, and it doubles the risks of bone fractures in women, Dr. Singh said in an interview.

“If you use Avandia to treat patients with Type 2 diabetes,” he said, “their chance of getting heart failure due to Avandia is one in 30 and their risk of getting a heart attack is one in 220. All due to the drug.”

Dr. Singh added, “There are older and cheaper drugs that are far better to treat diabetes.”

In the second study, researchers at the Cleveland Clinic combined data from 19 trials of Actos and found that the drug seemed to lower the risks of heart attack, stroke and death by about 20 percent. The study confirmed that Actos increased the risks of heart failure, but this problem is mostly reversible.

“I think this shows that these drugs aren’t the same,” said Dr. A. Michael Lincoff, vice chairman for research in the department of cardiovascular medicine at the Cleveland Clinic.

Dr. Lincoff said that Actos not only appeared to be safer than Avandia, but also offered some protection to the heart. Most diabetics die of heart disease.

In an accompanying editorial, two doctors from Brigham and Women’s Hospital in Boston wrote that Avandia would probably not have been approved in 1999 had its heart risks been known.

In an interview, Dr. Daniel H. Solomon, a co-author of the editorial, called Avandia “a drug of last resort.”

Dr. Solomon wrote that the Avandia situation should be used to improve the nation’s drug-safety system. Among his proposals is that when several drugs are available to treat a condition, new drugs must prove that they improve or extend people’s lives before they are approved. Now, many drugs are approved only after they improve laboratory results, like blood sugar or cholesterol levels.

Source | New York Times

By Stephanie Saul

Back in the ’60s, when University of Michigan students were holding protests over civil rights and the Vietnam War, an undergraduate named Steven E. Nissen was at the center of the political dissent.

Four decades later, that former campus activist is now Dr. Nissen, who is shaking up the nation’s pharmaceutical industry.

His questioning of the safety of the Avandia diabetes medication in late May, for example, prompted a federal safety alert and led to a sales decline of about 30 percent for the drug, which brought in $3.2 billion for GlaxoSmithKline last year. Now, with a federal panel soon to decide whether it can remain on the market, Avandia’s future is uncertain.

The drug is the latest example of why Dr. Nissen, 58, whose day job is chairman of cardiovascular medicine at the Cleveland Clinic, has emerged as a Naderesque figure and the nation’s unofficial arbiter of drug safety.

Admirers laud him not only for raising safety questions about Avandia, but also for sounding early warnings about the painkiller Vioxx, as well as other drugs. By digging deeply into companies’ own clinical trial data — information that used to be available only to federal drug regulators who did not always mine it as aggressively — Dr. Nissen is among a new cadre of activist scientists demanding greater vigilance on drug safety.

But Dr. Nissen also has critics, who say he seeks the spotlight as much as the safety of medicine. Others see a conflict of interest in his self-appointed role as the drug industry watchdog while he also presides over industry-financed research worth millions of dollars. “I’m an insider and an outsider at the same time,” Dr. Nissen says in an official Cleveland Clinic biography.

His crusading for drug safety, and his recent informal advisory role to members of Congress on legislation to strengthen drug safety enforcement, have fostered speculation that Dr. Nissen, a Democrat who has worked with members from both parties, covets an official public platform. Some see him angling to be the commissioner of the Food and Drug Administration, an agency whose decision-making he has frequently questioned.

Although Dr. Nissen denies that he is campaigning for the job, or even that he is really interested in it, he refuses to rule it out. “I want to fix the F.D.A.,” Dr. Nissen said in a recent interview.

He also wants to influence health policy more generally. In one of his final acts this year as the president of the American College of Cardiology, a doctors’ group, Dr. Nissen gave a speech calling for universal health insurance.

People listen to Dr. Nissen partly because of his unabashed self-confidence and outgoing personality. Friends from college remember his mischievous air, a demeanor that has endured alongside his willingness to raise tough questions.

Dr. Nissen also has a statistician’s zeal for drilling deep into clinical data, seeking signs that some widely used drugs pose undisclosed risks to patients. In discussing his work, he describes sleepless nights poring over numbers.

Dr. Nissen’s article in The New England Journal of Medicine, published in May, was based on his review of 42 clinical studies of Avandia involving nearly 28,000 patients. His conclusion, that the drug seems to raise the risk of heart attacks, was widely covered in the news media, including this newspaper.

After the Nissen article appeared on the journal’s Web site on May 21, the F.D.A., which said it had been evaluating the drug’s risks, issued a safety alert advising Avandia patients to consult their doctors.

The agency also scheduled a hearing on July 30, at which a panel of expert advisers could recommend restrictions, or even a ban, on Avandia’s use. The F.D.A. has asked Dr. Nissen to attend to answer questions.

GlaxoSmithKline has challenged the significance of Dr. Nissen’s findings and has defended the drug’s safety. Avandia, which has been used by about seven million people, is merely the latest drug to become a target of Dr. Nissen, who describes himself as an advocate of patients.

In 2005, for example, Dr. Nissen attacked the experimental diabetes drug Pargluva, from Bristol-Myers Squibb, saying it posed serious heart risks. Although an F.D.A. advisory panel had overwhelmingly recommended its approval, Pargluva never made it to market.

Dr. Nissen, who had warned of the dangers of the painkiller Vioxx, from Merck, before it was withdrawn in 2004, challenged Merck’s follow-on product, Arcoxia, which failed to win approval this year. He called Arcoxia the “son of Vioxx,” telling a reporter, “This is a genie I don’t want to see let out of the bottle.”

In his article on Avandia, Dr. Nissen was careful to note the limitations of his analysis. In some media interviews, though, he was less guarded. On the ABC television program “Nightline,” Dr. Nissen predicted that the deaths caused by Avandia could “dwarf” the carnage of Sept. 11, 2001.

Dr. Michael A. Weber, a professor of medicine at SUNY Downstate Medical Center in Brooklyn, is among the doctors who worry that Dr. Nissen’s Avandia rhetoric has been inflammatory. Dr. Weber cited Dr. Nissen’s reference to the World Trade Center attack as “something that doesn’t need to be part of a good clinical scientific discussion.”

GlaxoSmithKline complained about the same thing. “In some of his comments to the media, Dr. Nissen has gone beyond discussing the scientific findings of his study to language that frightens patients,” a company spokeswoman, Mary Anne Rhyne, said in an e-mail message.

Even Dr. Delos M. Cosgrove, Dr. Nissen’s supervisor at the Cleveland Clinic, where his department of 90 cardiologists handled 234,000 patient visits last year, says he advised Dr. Nissen simply to talk about the science.

Among his contributions to the clinic is his pioneering work in using ultrasound images to measure fatty plaque inside the walls of coronary arteries, a procedure known as intravascular ultrasound.

While some other drug safety critics avoid all industry ties, Dr. Nissen actively seeks industry-financed research. To avoid undue influence, he says, he insists that charities be given any industry consulting and speaking fees that he would have personally received.

Beneficiaries of the money, hundreds of thousands of dollars over the years, have included the American College of Cardiology. Another recipient has been the Cleveland Museum of Art, one of the major museums and galleries that has shown the work of his wife, Linda Butler, an award-winning photographer.

Dr. Sidney M. Wolfe, the head of the consumer organization Public Citizen’s Health Research Group, is generally supportive of Dr. Nissen’s efforts on behalf of drug safety. “He’s very smart and he’s done a lot of good,” Dr. Wolfe said.

But he says that Dr. Nissen’s diverting drug company money to charity is not an adequate buffer from industry influence. “It’s still a conflict of interest,” Dr. Wolfe said.

Dr. Nissen’s industry ties have enabled critics to question his analysis of Avandia, for example, because he has served as a consultant for Takeda and Eli Lilly, the companies that together market Avandia’s main competitor, Actos.

Pointing out that he does not personally receive money from any company, Dr. Nissen said his work for Takeda, Eli Lilly or any other drug maker does not affect his scientific detachment.

“My involvement with any company does not bias my scientific perspective and I scrupulously avoid even the appearance of a conflict of interest,” he said.

And Dr. Nissen says he believes his alarms about drug safety have sometimes caused the Cleveland Clinic to miss out when companies award contracts for clinical research trials.

But his adversarial reputation can also work the other way. Because of Dr. Nissen’s reputation, companies may seek him out for research projects.

After the withdrawal of Merck’s Vioxx, for example, Pfizer chose Dr. Nissen to lead a 20,000-patient study of whether its similar drug, Celebrex, carries heart risks.

“In the view of Pfizer, who is co-sponsoring the trial, they know that whatever we report will be believable,” Dr. Nissen said. The study, which will cost millions of dollars, is expected to be completed in 2010.

A Pfizer spokesman, Raymond F. Kerins Jr., said the company picked Dr. Nissen because it seeks advice from leading experts. “These experts ask excellent — and often tough — questions,” Mr. Kerins said.

Although he is the son of a doctor, Dr. Nissen initially rebelled against following that path.

In college in the late 1960s and early ’70s, while working as an editor at his campus newspaper, The Michigan Daily, he became active in the antiwar movement, the civil rights movement, the women’s movement and the Human Rights Party, a largely student-run group that elected two members to the Ann Arbor City Council.

One of those council members, Jerry DeGrieck, remembers the young Steve Nissen’s work in leading a voter registration drive.

Those extracurricular activities left little time for classes, which is why Dr. Nissen likes to recall that he was on the “eight-year plan” at Michigan, and says he was lucky to have been accepted to the University of Michigan medical school after finally getting his bachelor’s degree, in 1974.

Mr. DeGrieck, now a government public health policy adviser in Seattle, says he never imagined that his college friend would become one of the nation’s most influential doctors. But he says he is not surprised at all by Dr. Nissen’s activism.

“He’s always questioned authority,” Mr. DeGrieck said.

Source | New York Times

By Gardiner Harris

In 1962, the Food and Drug Administration reviewer who uncovered the dangers of thalidomide got a presidential medal. Yesterday, the F.D.A. safety supervisor who accurately warned about the heart dangers of the diabetes drug Avandia left the agency under a cloud.

Times have changed at the F.D.A.

In recent years, F.D.A. reviewers who uncovered drug dangers have been investigated criminally, rebuked publicly and threatened with retaliation.

This week, the F.D.A. disclosed in a Congressional hearing that it had asked GlaxoSmithKline, maker of Avandia, and Takeda Pharmaceuticals and Eli Lilly & Company, makers of a competing medicine, to carry the so-called black box warning of heart risks because ‘’despite existing warnings, these drugs were being prescribed to patients with significant heart failure.'’

The drug makers say such a warning takes weeks or months to put in place. The F.D.A., meanwhile, is working to make the black-box warnings more prominent on packaging.

Source | New York Times

By Stephanie Saul and Gardiner Harris

A medical study intended to demonstrate the heart safety of a well-known diabetes treatment seems, instead, to have added to the controversy over the drug.

Its manufacturer, GlaxoSmithKline, says preliminary results of the clinical trial provide reassurance that the drug, Avandia, an oral medication for Type 2 diabetes that has been used by an estimated seven million people worldwide, does not raise the risk of a heart attack or death from cardiovascular disease.

Influential doctors said that the data published online yesterday in a major medical journal did nothing to ease their concerns about the heart risks. The doctors raised their concerns in three editorials accompanying the Avandia study in The New England Journal of Medicine.

Questions about the safety of Avandia and how regulators have dealt with its risks are to be the subject of a Congressional hearing today. The data could intensify criticism, expected at the hearing, that the Food and Drug Administration should have warned about the potential heart risks years ago.

A supervisor in the drug safety office at the agency said in an interview yesterday that she was rebuked last year after calling for a stronger warning label on Avandia and a competing drug, Actos.

The supervisor, Dr. Rosemary Johann-Liang, said that in March 2006 she approved a recommendation from a safety reviewer at the agency that the drugs be required to carry the strongest warning, a so-called black box warning, because they posed a risk of unusual swelling that could lead to heart failure.

But after officials at the agency who dealt more closely with Glaxo complained, Dr. Johann-Liang said she was ordered to retract her approval of the warning, lost her power to approve such assessments and no longer supervised reviews of the safety of Avandia and Actos.

“This was a very careful review that came to an inescapable conclusion,” Dr. Johann-Liang said in the interview. “They decided to act like the review never happened and punish me for approving it.”

Senator Charles E. Grassley, Republican of Iowa, has investigated Dr. Johann-Liang’s accusations. Mr. Grassley sent a letter on Monday to the Food and Drug Commissioner Andrew C. von Eschenbach demanding that he investigate the case.

“I hope you recognized what is wrong with this picture,” Mr. Grassley wrote. “I also sincerely hope that this is not standard practice within the F.D.A.”

A spokeswoman for the agency, Susan Cruzan, said it was investigating the accusations.

Avandia has been awash in controversy since an article in The New England Journal of Medicine on May 21 and an accompanying editorial cited evidence from clinical trials indicating that Avandia, in addition to the risk of heart failure, could raise a patient’s risk of heart attacks.

Since then, Glaxo and the drug agency have cautioned doctors and patients to await the results of a long-term patient trial, the Record, created to test the heart safety.

It was the interim results of that study that Glaxo rushed to submit for publication by yesterday in advance of the hearing today by the House Oversight and Government Reform Committee. The company had intended the study in the prestigious peer-reviewed New England Journal to be part of a news media blitz to counter negative publicity about the drug, which generates annual revenues exceeding $3.2 billion.

Concerns about the drug were raised in the May 21 article, when Dr. Steven E. Nissen and colleagues from the Cleveland Clinic wrote an analysis suggesting that the popular medication increased the risk of heart attacks by 43 percent. Dr. Nissen’s paper was based on a review of more than 40 studies of the drug. It was also published by The New England Journal of Medicine.

Dr. Nissen, chief of cardiovascular medicine at the prominent clinic, is among witnesses scheduled to testify today along with Dr. von Eschenbach.

In a conference call yesterday with reporters, a vice president for clinical development at Glaxo, Dr. Murray Stewart, an endocrinologist, said data did not support Dr. Nissen’s conclusions. “Nissen suggested that there were more cardiovascular deaths,” Dr. Stewart said. “This does not support that. This shows less cardiovascular deaths.”

Since the study, involving 4,447 people, began nearly four years ago, 29 patients in the Avandia group have died from cardiovascular causes. A greater number, 35, have died of cardiovascular problems in the group taking other drugs.

Several doctors who wrote the accompanying editorials published yesterday, including the Journal editors, saw the results less positively than Glaxo did. The editorials questioned the structure of the study and pointed out that although fewer Avandia patients have died, more had heart attacks than in the group taking other drugs, 43 to 37.

Although those heart attacks represented a relatively tiny number in the overall study, one editorial, by the Journal’s editors, struck an anxious tone. “In short, there is continued uncertainty about the cardiovascular safety of rosiglitazone,” they wrote, referring to the generic name of the medicine.

Of the patients in the Record study, which is to continue through late next year, about half take Avandia in combination with other medications and half take two diabetes medications, metformin with sulfonylurea.

The editorials raised questions about the structure of the Record study. In his editorial, Dr. David M. Nathan, a diabetes expert who teaches at Harvard, questioned the high number of patients who dropped out of the study without explanation and further monitoring, as well as the decision by the creators of the study to use a combination of metformin and sulfonylurea as the comparison group. That combination was associated with a 96 percent increase in diabetes-related mortality in another study, Dr. Nathan wrote.

Glaxo said the metformin-sulfonylurea combination was chosen because it is the most common Type 2 diabetes treatment worldwide.

“The interim results of the Record trial do not provide any assurance of the safety of treatment with rosiglitazone,” Dr. Nathan said, suggesting in his editorial that doctors should use medications other than Avandia.

An editorial by Dr. Bruce M. Psaty of the University of Washington and Dr. Curt D. Furberg of Wake Forest University recalculated Dr. Nissen’s analysis using interim results of the Record study in addition to the studies that Dr. Nissen used. They found that Avandia increased a patient’s risk of having a heart attack 33 percent.

“In my mind, it’s not small,” Dr. Furberg said, calculating that such a risk, extrapolated to the millions of patients who have taken Avandia, would translate to thousands of extra heart attacks.

The company’s decision to release interim results of the Record trial were highly unusual and reflected Glaxo’s concern about the controversy and the concerns of patients in the trial. As a result of the negative publicity about the drug, two patients have dropped out, the Glaxo medical director, Dr. Ronald L. Krall, said yesterday.

Dr. Stewart said the telephones of doctors involved in the Record trial throughout Europe, Australia and New Zealand had been ringing with calls from concerned patients, raising questions about whether the trial can continue.