Plavix News

Research done by the U.S. Food and Drug Administration and adverse drug reports from pharmaceutical companies has uncovered that Plavix could potentially give fatal side effects.

Plavix, an anti-clotting agent that has been given to more than 41 million patients worldwide since 1998. A group led by Dr. Charles Bennett reported in 2000 that in rare circumstances the drug can cause a catastrophic collapse of the blood system, leading the FDA to require the manufacturer to add a warning label.

One such patient was Marion Rao, a 78-year-old from Manhattan who loved to travel. Last May she had a routine stent put in to open a blocked coronary artery. She also was prescribed Plavix.

Shortly after, Rao went downhill. Bruises began appearing on her skin, a sign of internal bleeding. She consulted her doctor numerous times but they would tell her that it was nothing.

When Rao was finally admitted to the hospital, her daughter recalled, the doctor on call said: "Plavix. It's TTP." That stands for thrombotic thrombocytopenic purpura, the scientific name for the meltdown of her blood system. Other doctors disagreed. Three weeks after receiving Plavix, Rao died.

All drugs have potential risks, but some risks only become apparent when thousands, even millions of patients, have used a drug. The problem is that the FDA does not have an effective system for monitoring complications from drugs after they've been approved, according to many authorities.

Plavix's side effects, for example, were uncovered after Bennett organized 20 blood banks nationwide to be on the watch for blood disorders that might be linked to drugs. The drug has proved beneficial to many patients, but it should contain a stronger warning of possible adverse reactions, Bennett contends.

Bennett originally asked the FDA to require a black box warning on the label, the agency's strongest. The FDA, however, declined, saying that a regular cautionary note was sufficient since the life-threatening side effect was too rare to warrant a black box.

Though FDA officials have praised Bennett's efforts to discover drug problems, he apparently raised the agency's ire in a paper published in February in the journal Stroke. The study assessed how the FDA, Plavix's manufacturer and RADAR pursued adverse drug reports, documented the side effects and assessed patient outcomes over a four-year period. Basically it was a report card, and RADAR scored 92 to 100 percent; drug companies, 8 to 58 percent; and the FDA, 0 to 23 percent.

The FDA "did terrible. They flunked, and the drug companies didn't do much better," Bennett said. "The system is broken in many ways, and safety is on the bottom of their lists."

Bruce Lambert of the University of Illinois at Chicago's College of Pharmacy said restricting access to the FDA's post-marketing surveillance reports is "a bad idea."

"These reports should be wide open, especially to people like Dr. Bennett who are devoted to trying to understand adverse events," he said.

In notifying Bennett of the cutoff, the FDA's Christine M. Bechtel wrote: "While we have valued our relationship with you in the past, the thousands of requests we receive annually make it impractical and unfair to afford you and your groups special status."

Reacting to mounting criticism, the FDA on Tuesday said it will establish a new independent Drug Safety Oversight Board to monitor medicines once they're on the market and alert doctors and patients to any risks. Critics quickly pointed out that the board would be advisory and would not have the power to withdraw a drug.

Another major problem facing the FDA is the lack of a system for tracking adverse drug events for the 50 percent of medications that are used off label. Once a drug is approved, physicians can prescribe it for conditions for which it was not originally approved, but the drugs are usually not tested for safety in such off-label uses.

"Half of the drugs prescribed today are being used in situations where we don't have a good handle on whether they're either safe or effective, and that's a big problem," Bennett said.