FDA Nod Won't Guarantee Drug Safety

Studies on Vioxx, Zocor find post-approval problems

FRIDAY, Sept. 3, 2004 (HealthDayNews) -- A 60-year-old woman with degenerative disk disease recently came into Dr. Allen Lebovits' Manhattan office with a complaint. This time, the grievance wasn't about the pain but about news reports linking Vioxx, her pain reliever, with an increased risk of heart attacks and sudden cardiac deaths.

"She didn't want to take it anymore. She's been getting good pain relief and the drug has been effective, but now she's scared," said Lebovits, co-director of the New York University Pain Management Center. "She has a history of heart disease in her family."

Lebovits expects to see more reactions just like this in the wake of new reports that heart attack rates and sudden cardiac deaths were tripled in patients taking Vioxx vs. those taking a similar drug, Celebrex. Both are in the class of medications known as cox-2 inhibitors.

But Vioxx was not the only drug to get bad press this week. A study released early from the Sept. 15 issue of the Journal of the American Medical Association reported that people who took a high dose (80 milligrams daily) of Zocor, a cholesterol-lowering statin, had an increased risk of muscle-related complications without any increased benefit.

Both Vioxx and Zocor are U.S. Food and Drug Admininstration-approved blockbuster drugs.

But while this news may be unsettling, it is not entirely unexpected: The assessment of new drugs does not stop once the FDA has approved them and the company has started to market them.

"Once we approve drugs, the monitoring of safety and efficacy does not stop there," said Kathleen K. Quinn, an FDA spokeswoman. "We continually monitor adverse events that may be called into the agency to determine if they are in accordance to the labeling or are something new. It is common to get information after approval and marketing, and we constantly review that material to determine what, if any, action may be needed."

Sometimes drugs are even taken off the market, as was the case with Baycol, another statin. The manufacturer voluntarily withdrew Baycol after reports of sometimes fatal side effects.

While the FDA has a system to track adverse events once the drug has been released, scientists are also involved in continuing research.

"A lot of drugs are approved based on their effect on an intermediate endpoint -- for example, blood pressure -- then subsequently want to do a study in which you try to determine where that lowering of blood pressure actually prevents stroke," said Dr. John C. LaRosa, president of the State University of New York Downstate Medical Center in New York City and an expert on statins. "That takes a lot more time. It's not uncommon for the biggest and most important studies about disease endpoints, and even mortality effects, to be done after a drug is approved."

LaRosa added: "The approval process is often directed toward the effectiveness of the drug to produce one of intermediate endpoint changes and a reasonable assurance that drug is safe." That leaves room for more work after approval.

Which is not to say that bad news (or good) is not going to have an effect in the "real world" of pain, patients and illness.

"I am sure people in the pain world and family doctors are now going to be much more hesitant to prescribe Vioxx to their patients," Lebovits said. The fact that there is another similar drug, Celebrex, on the market, makes that even more likely.

Is Lebovits going to follow suit? "The doctor has to use good clinical judgment and do a risk-benefit ratio. Where would the patient benefit the most, given what the risk is?" he said. "The shame is that with some patients, they lose out on good analgesic effects with some of these drugs."

More information

For more on the U.S. drug approval process, visit the Center for Drug Evaluation and Research.

SOURCES: John C. LaRosa, M.D., president, State University of New York Downstate Medical Center, New York City; Allen Lebovits, Ph.D., co-director, New York University Pain Management Center, and associate professor, anesthesiology and psychiatry, New York University School of Medicine, New York City; Kathleen K. Quinn, spokeswoman, U.S. Food and Drug Administration, Rockville, Md.
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