By Claudia Kalb
NEWSWEEK

It was to have been Jerry and Mary Sagen's first New Year's Eve together as a married couple. But on that morning in 1996, says Jerry Sagen, "I awoke to hear her dying." As Mary gasped her last breaths, Jerry dialed 911 and frantically blew air into her lungs, but it was too late. At first the death of the healthy 45-year-old woman was a mystery. But lst month an answer was stamped onto Mary's death certificate: accidental death due to a toxic level of the antihistamine Hismanal. (While not commenting on the case, Janssen Pharmaceutica, the maker of Hismanal, said it is difficult to confirm a drug as the ultimate cause of death and stressed that "it's been taken safely by a huge number of people.") For Jerry Sagen, 53, it was unfathomable. "You're numb," he says; "you can't believe it happened."

For millions of Americans, prescription drugs are a way of life - about 2 billion are dispensed each year. We rely on them for everything from allergies to diabetes to depression. But in a study published last week in The Journal of the American Medical Association, researchers found that adverse reactions to prescription drugs may rank somewhere between the fourth and sixth leading cause of death in the United States. Dr. Bruce Pomeranz, a professor at the University of Toronto, and his team analyzed 39 studies conducted in American hospitals over four decades (the study was funded by a scientific-research group). Of 33 million patients admitted to hospitals in 1994, more than 100,000 died from toxic reactions to medications that were administered properly, either before or after they were hospitalized. And more than 2 million suffered serious side effects.

Drugs by nature are powerful substances, and individual responses are unpredictable. While the study didn't look at specific drugs, it has been documented that antihistamines, in combination with the wrong antibiotic, can lead to abnormal heart rhythms; in rare instances the result can be fatal. (Mary Sagan was taking an antibiotic with the Hismanal, though that combination has not been linked to her death). Mixing drugs isn't the only problem. Blood thinners alone, for example, can cause fatal internal hemorrhaging. "We have to realize drugs are not magic bullets," says Pomeranz. "They don't just hit the tissue we want them to hit, they hit all the other tissues as well."

He and others say the Food and Drug Administration must work harder to address the problem. Though the FDA has been lauded for a much-needed increase in the number of new drugs it approves each year (a record 46 in 1996), critics say it hasn't done enough to monitor medications once they're on the market. The FDA requests reports on adverse drug reactions from hospitals and physicians, but few participate in this voluntary program. Information that might warn of - or perhaps even ward off - side effects is buried in doctors' offices and hospital wards. "It's the best FDA system in the world, but it's not enough," says Pomeranz. "We need more post-market surveillance."

The FDA says it hopes to soon launch a computerized system that will make it easier to report adverse drug reactions. Monitoring medications is "terribly important," says Michael Friedman, the FDA's acting commissioner. "We want to give more attention to this." But surveillance isn't the FDA's dominion alone. "I see problems at every link of the safety chain," says Thomas Moore, a senior fellow at the George Washington University Medical Center and author of "Prescription for Disaster." He says physicians need to be much more cautious about the drugs - and drug combinations - they prescribe. And patients need to become wiser consumers. While the Pomeranz study didn't deal with patients who misread or disregard warning labels - taking an incorrect dosage, for example - that is a serious cause of adverse reactions.

Some experts raised concerns about last week's study, noting that the hospitals surveyed were all teaching hospitals, where patients are sickest and receive the most drugs. And while 100,000 deaths is 100,000 too many, those represent just .32 percent of hospitalized patients. "When you realize how many drugs we use," said Dr. Lucian Leape of the Harvard School of Public Health, "maybe those numbers aren't so bad after all." Pomeranz isn't warning people to stay away from drugs. "That would be a terrible message," he says. "But we should increase our vigilance." That's a prescription everybody can live with.

SOURCE: Reprinted from the 27 April, 1998, issue of Newsweek magazine. Excerpted in the public service of the national interest of the American people.