Bad news on drugs is often delayed

Dangerous side effects come to light years after products reach market

October 01, 2004|By Erika Niedowski | Erika Niedowski,SUN STAFF

Dr. Karen E. Lasser has never prescribed Vioxx or Celebrex or any of the new arthritis drugs because, well, they're too new.

The internist at Cambridge Hospital and Harvard Medical School has found that, even after the Food and Drug Administration has deemed a medication safe and effective, serious side effects crop up over time.

"Basically the chance of a new drug having a serious problem is one in five," said Lasser. "In general, I really try to avoid the new drugs for this reason."

Merck & Co.'s Vioxx is only the latest product to be pulled from pharmacy shelves. Bayer Pharmaceutical Division withdrew Baycol, a cholesterol-lowering drug, in 2001 because of reports of a sometimes-fatal muscle reaction. Glaxo-Wellcome withdrew Lotronex, a treatment for irritable bowel syndrome, after reports of serious intestinal problems. Warner-Lambert Co. pulled its diabetes drug Rezulin after it was blamed for about 60 deaths tied to liver problems.

Before they win approval from the FDA, all drugs must go through clinical trials to ensure they are both safe and effective. But such trials often involve only a few thousand people over a fairly short period of time.

What's more, those who are enrolled sometimes aren't representative of the patients who end up taking the drug.

"Most of the people in those studies don't have underlying diseases of other types. You exclude those people who have any other problems," said Dr. Bruce Smith, a rheumatologist at Thomas Jefferson University Hospital in Philadelphia. "You only find out about the side effects when you start seeing them in the real world in people with three other diagnoses and 10 or 12 other meds."

The mass use of a drug after it has hit the market, in essence, is a giant clinical trial that sometimes reveals the unexpected.

In the case of Vioxx, there were signs several years ago that the drug might have serious side effects. It was approved by the FDA in 1999 for the reduction of pain and inflammation caused by osteoarthritis. The next year, Merck submitted to the federal regulatory agency a safety study that found an increased risk of cardiovascular problems, including heart attacks and strokes, in patients taking Vioxx compared with those taking naproxen - another nonsteroidal anti-inflammatory. That ultimately led to a change in product labeling information.

In a 2002 study in the Journal of the American Medical Association, Lasser found that serious adverse reactions are common after drugs are approved and that a medication's safety can't be known with certainty until it has been on the market for years.

Ten percent of the 548 medications approved by the FDA in 1975 through 1999 were either given a new "black box" warning label - the agency's most severe alert about side effects - or were withdrawn from the market, the study found.

What's more, nearly 20 million people in the United States took at least one of the five drugs withdrawn from the market between September 1997 and September 1998. Three of the drugs had been on the market less than two years.

But, even over a longer period of time, only a portion of the adverse events showed up.

"Half of all problems only come out within seven years," said Lasser.

Tom Schaible, vice president of medical affairs at Centocor, a Pennsylvania-based pharmaceutical company that won approval yesterday for another arthritis medication, said that no drug is absolutely safe - not even aspirin.

So the FDA often requires companies to submit post-marketing research studies and insists they report adverse drug reactions within 15 days. It posts safety alerts, recalls, withdrawals and label changes on its MedWatch Web site.

Sun staff writers Julie Bell and Ivan Penn contributed to this article.

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