The two aspirin products, Bayer Women’s Low Dose Aspirin + Calcium and Bayer Aspirin with Heart Advantage, are misbranded, mislabelled, and confusing to consumers, according to the FDA.

According to Bayer, its Women’s Low Dose Aspirin fights heart disease and osteoporosis with a combination of 81 mg of aspirin and the equivalent of an 8-oz glass of milk in calcium for possible “lifesaving benefits.”

Bayer Heart Advantage combines the same low dose of aspirin with plant phytosterols, molecular entities found in fruits and vegetables that are valuable for their cholesterol lowering properties.

While Bayer’s web site instructs users to talk to their doctors before beginning any aspirin regimen, the message isn’t so clear on the medicine’s packaging. Both Bayer medicines are packaged to appeal directly to consumers, who might be lead to think that they can treat their heart conditions, cholesterol, and osteoporosis with these OTC medicines.

The FDA requires that medicines designed to treat heart disease and osteoporosis be reviewed by its researchers. Federal law also forbids such medications to be sold OTC.

Labeling on Bayer’s Heart Advantage claims that the drug lowers cholesterol. Labeling for Bayer Women’s says that it fights osteoporosis. Improper use of medicines containing aspirin often causes serious side effects such as gastrointestinal bleeding. Aspirin resistance can also have devastating effects on the heart.

Bayer believes that neither products violate FDA regulations, but promises to review the case and report back to the FDA within 15 business days. The FDA indicated in its letter to Bayer that the company would face legal action.

Bayer is already under fire by the FDA and general public for its marketing of Trasylol when ample studies found the drug to be highly toxic to many people.

SOURCE: Trasylol Recall › FDA warns Bayer about two OTC aspirin products

Journal editor Dr. Jeffrey M. Drazen says the litigation process and the court system is a “key defense mechanism” to insure drug safety and to obtain justice if drug manufacturers have not made the risks involved with its product clear.

The doctors say the FDA is incapable of being the sole guardian of drug safety and that without the information supplied by liability litigation, “the American public would be deprived of a vital deterrent against pharmaceutical company misconduct.”

The opinion was submitted to the Supreme Court as a friend-of-the-court brief in the matter of Wyeth v. Levine, a case expected to be heard later this year. According to the AP story, the case involves Diana Levine, a guitarist who lost her right arm below the elbow after an injection of Phenergan. She sued the drug’s manufacturer, Wyeth, alleging the company had not adequately warned consumers of the risks associated with its product. The case was tried in Vermont, and the court agreed, awarding Levine $7 million.

Wyeth is appealing the case, saying the FDA had approved the drug, and that the state court could not overrule the FDA’s judgment.

However, the editors of the New England Journal of Medicine sided with 47 state attorneys general and two former FDA commissioners in supporting Levine’s position, the AP report states.

SOURCE: Trasylol Recall › physicians favor drug safety litigation

The FDA cannot identify a patient population in which the use of Trasylol (aprotinin) outweighs the risk, Dr. John K. Jenkins, director of the FDA’s Office of New Drugs, said at an early morning news conference Monday.

However, he added, “The suspension will include a slow phase-out of Trasylol from the marketplace, to decrease the possibility of shortages of the alternative drugs.” And he added that Bayer could continue to supply the drug if physicians can identify specific patients who would benefit from it.

“Studies have found that Trasylol can increase the risk of kidney damage compared with other drugs,” Dr. Gerald Dal Pan, the FDA’s director of the Office of Surveillance and Epidemiology, said during the news conference.

In 2006, he added, the FDA limited the use of Trasylol and strengthened its warnings. Subsequently, he said, studies found that Trasylol increased the risk of in-hospital death among patients undergoing cardiac bypass surgery. In addition, Dal Pan said, two studies this year found that the drug increased the long-term mortality of patients who had undergone bypass surgery.

The suspension follows news last month that a major Canadian trial of the drug was terminated because of an increase in deaths for cardiac surgery patients using it.

The trial was designed to show that Trasylol was better than other drugs in controlling bleeding, Dal Pan said. “That study was halted because Trasylol appeared to increase the risk for death compared with two other drugs,” he said.

Based on these findings, the FDA requested last week that Bayer suspend Trasylol pending further review, Dal Pan added.

In a company statement on its Web site Monday, Bayer stressed that the suspension was temporary. “Bayer believes that the totality of the available data continue to support a favorable risk-benefit profile for Trasylol when used according to labeling,” the statement said.

The FDA also said Monday that it plans to do a detailed review of the preliminary results from the Canadian trial before deciding whether to allow Trasylol back on the U.S. market.

Trasylol was first approved by the FDA in 1993, and has had a checkered history since then.

In the Canadian trial, called BART, an elevated 30-day and overall death risk caused the study’s Data Safety Monitoring Board (DSMB) to recommend stopping patient enrollment. The trial had been set to recruit about 3,000 adults who were candidates for a variety of cardiac surgeries and were at high risk of bleeding.

On Sept. 12, a U.S. Food and Drug Administration advisory panel recommended that Trasylol remain on the market, despite mounting evidence that it might have serious side effects.

In February, a study published in the Journal of the American Medical Association found patients on the drug were at greater risk of dying over the next five years than those given two other medications. The same researchers had linked the drug to an increased risk of kidney failure, heart failure and stroke in a study published in 2006.

“Our present findings deal with death,” one of the JAMA study’s authors, Dr. Dennis T. Mangano, said at the time. Mangano, director of the Ischemia Research and Education Foundation, a California-based nonprofit group, said that “the death rate for aprotinin patients far outstrips that for the other two drugs.”

His team’s study tracked the long-term survival of nearly 3,900 heart patients who underwent coronary artery bypass surgery at 62 medical centers worldwide. The researchers tabulated survival at six weeks, six months, and then annually for five years.

The five-year death rate for patients given Trasylol was 20.8 percent, compared to 15.8 percent for those given another drug, aminocaproic acid, and 14.7 percent for those given tranexamic acid. Both alternative drugs are available in generic versions.

After the 2006 report from Mangano’s group, the FDA advised doctors to carefully monitor Trasylol patients for kidney, heart and brain damage — an action taken after Bayer disclosed study data showing that it increased the risk of death, kidney damage, congestive heart failure and stroke.

The drug does have its defenders.

Dr. T. Bruce Ferguson Jr., associate director of cardiothoracic and vascular surgery at East Carolina University, wrote an accompanying editorial to the JAMA study. He said he believed the study “was inadequate to address the question they were asking because of the way the database was designed.”

“The most important factor they were unable to control was why patients got aprotinin,” Ferguson said. “There were no data to address that issue, and therefore it cannot account for physician-related bias.”

For example, the higher rate of death and other complications linked to the drug might be due to aprotinin being prescribed for “higher-risk patients who could be expected to have a worse outcome and higher mortality,” Ferguson said. Other studies have shown that “in carefully selected patients, aprotinin is a good drug,” he said.

The information used in the study was thorough and complete, Mangano countered. “In terms of the database, we had between 7,000 and 10,000 pieces of data per patient from 59 centers in 16 countries, including 23 of the 25 top cardiac centers in the United States,” he said.

“The findings speak for themselves,” Mangano added. “I think they are as accurate as you can get.”

He believes that the drug’s use should be restricted to about 5 percent of patients in whom other drugs could not be used.

SOURCE: Trasylol Recall › Trasylol Pulled From Worldwide Market

Known as BART, the study randomly administered one of three drugs to the patients: Trasylol, Cyklokapron (tranexamic acid) and Amicar (aminocaproic acid).

BART sought to answer questions about Trasylol’s safety and efficacy, despite the fact that the drug has been in use for over twenty years. Was Trasylol more effective than alternative drugs in controlling bleeding during cardiac surgery? And, how did rates of death, organ failure, and other serious complications measure in Trasylol compared to the alternative drugs?

Experts conducting the study found that Trasylol’s safety risks were so high, they ended the trial before its scheduled completion. Death rates among Trasylol patients were alarmingly higher than in patients who were given the alternative therapies. Dr. Paul C. Herbert, a critical care physician at Ottawa Hospital and one of the lead investigators, told BusinessWeek magazine that Trasylol represented a 53% increase in risk in dying compared to the other drugs. That “translates into for every 50 patients treated with aprotinin, one patient would die,” he explained.

Strangely, earlier Trasylol tests were small and not designed to study death. Information about the drug’s toxicity in some patients, therefore, remained hidden.

Dr. Eric J. Topol, director of the Scripps Translational Science Institute and dean of the Scripps School of Medicine, reacted to the results of BART with the same frustration as many North American consumers. In remarks made to BusinessWeek magazine, he wondered “why it takes so long for the truth to come out.”

“How many patients were lost because of this misadventure in therapeutics?” he asked.

SOURCE: Trasylol Recall › One in fifty Trasylol patients dies