(Chicago, December 19) — Johnson & Johnson's and the U.S. Food and Drug Administration's 1998 warnings to doctors about health risks some patients faced while taking the company's heartburn drug Propulsid went largely unheeded, placing hundreds of thousands of patients in danger, a new study shows.

Johnson & Johnson halted most sales of the drug, which generated almost $1 million in 1999, earlier this year after it was linked to erratic heart rhythms and about 8O deaths. The company and the FDA tried without success to restrict Propulsid's use among patients predisposed to irregular heartbeats and among patients taking drugs that interact with it.

The inability to ensure Propulsid was given only to patients who could safety take it is a breakdown of the health care system, from doctors to pharmacists to patients, said Dr. Walter Smalley, a lead researcher from the Vanderbilt University School of Medicine. And because all drugs are dangerous if they aren't used property, the findings could have serious ramifications for other sensitive treatments, he said in an interview.

"We might lose other drugs that are very valuable to us, that aren't intrinsically unsafe." If the problems with proper use aren't fixed, Smalley said. "We can't count on this dysfunctional system" to ensure people use drugs properly. "It's a real concern."

The study, funded by the as part of a program to monitor how drugs are used after they hit the pharmacy shelves will appear in toworrow's Journal of the American Medical Association.

Dramatic Growth

Propulsid's use grew dramatically after it was approved in 1993 for patients with nighttime heartburn. In 1998, about seven million prescriptions were written for the drug, even though reports of serious side effects were linked to its use and its label carried a prominent black box that warned against giving it in combination with other drugs, researchers said.

In the study, investigators analyzed the number of high-risk patients who were prescribed Propulsid in the 12 months before and after restrictions on its use were tightened in 1998. They reviewed databases at several health organizations, including TennCare, the Tennessee insurance program for the poor, and two managed care organizations — United Health Group and Harvard Pilgrim Health Care.

In the year before the 1998 restrictions, 26 percent to 58 percent of Propulsid users were already at risk for irregular heart beats or were taking drugs that didn't mix well with it. In the 12 months following the warnings, which included letters to 800,000 health care providers, that number fell slightly — to 24 percent to 56 percent of patients.

"In the 12 months following this regulatory action, hundreds of thousands of patients" were likely to have received Propulsid even though it was specifically not intended for them and potentially dangerous, the researchers said.

Confirmation

The study confirms that most patients who had serious side effects after taking Propulsid had health conditions or were on other medications that should have precluded its use, said Greg Panico, spokesman for Johnson & Johnson's Janssen unit.

The company agrees with the authors' conclusion that "the entire health care community should make it a priority to develop more effective methods to bring into clinical practice new information about a drug's risks and benefits," he said.

Without more emphasis on the safety of drugs, changing the labels of existing products is guaranteed to fail to alter the way doctors prescribe medications, said Dr. Raymond Woosley, chairman of Georgetown University's pharmacology department and an expert on drug safety. Several steps, including more use of computers, greater reliance on pharmacists, improved information on drug packaging and more patient involvement could improve proper drug use, he said in an editorial.

The pharmaceutical industry cannot afford to spend more than $500 million to develop a new drug only to remove it from the market because physicians prescribe it in ways (advised against) in the label," he said. "Most importantly, patients should no longer be harmed by otherwise safe medications that are used in ways known to be potentially dangerous."