Bad reactions to prescription and over-the-counter medicines kill more than 100,000 Americans and seriously injure an additional 2.1 million every year - far more than most people realize, researchers in Toronto say.

Such reactions, which do not include prescribing errors or drug abuse, rank at least sixth among U.S. causes of death - behind heart disease, cancer, lung disease, strokes and accidents, says a report based on an analysis of existing studies.But while Utah doctors agree that patients need to be aware of the potential danger of drug reactions and interactions, they characterize the study, released in the Journal of the American Medical Association, as "fatally flawed."

"We're not saying, `Don't take drugs.' They have wonderful benefits," said Dr. Bruce H. Pomeranz, principal investigator and a neuroscience professor at the University of Toronto, who authored the study.

"But what we're arguing is that there should be increased awareness also of side effects, which until now have not been too well understood."

Dangerous reactions range from allergies to medications to potentially deadly combinations like those that occur when Pepto-Bismol or aspirin are used by someone who takes a prescription blood thinner.

"Adverse drug reactions are a serious problem, yes," said Dr. David Classen, lead author of LDS Hospital's 1996 study of drug reactions and interactions and an infectious disease specialist. "How often does it lead to death of a patient? Rarely. But it can mean longer time in the hospital, complications, getting back to work later. And patients suffer some kind of pain or discomfort as an outcome of it."

The newest study, which analyzed 39 other studies of hospital patients from 1966 to 1996, is "very weak," Classen said, because "studies conducted with different variables and perspectives cannot be combined together in any rigorous scientific fashion.

"The study is fatally flawed - not valid by serious scientific standards."

In the study, Pomeranz and two colleagues at his school, Jason La-za-rou and Paul Corey, said that serious drug reactions affected 6.7 percent of patients overall and fatal drug reactions 0.32 percent.

Pomeranz and his colleagues did not explore which medications or illnesses were involved.

The most surprising result was the large number of deaths, the authors said. They found adverse drug reactions ranked between fourth and sixth among leading causes of death, depending on whether they used their most conservative or a more liberal estimate.

In 1994, between 76,000 and 137,000 U.S. hospital patients died, and the "ballpark estimate" is 106,000, Pomeranz said. An additional 1.6 million to 2.6 million patients were seriously injured, with the ballpark estimate 2.1 million, he said. More than two-thirds of the cases involved reactions outside hospitals rather than in hospitals, the authors reported.

The study's estimates drew both praise and criticism.

Barbara Crouch, director of the Intermountain Poison Control Center, said that calls regarding adverse reactions to medications "are a fairly small percentage" of the calls they receive. But she added that "we do get plenty of calls, and it's an issue and a concern."

"Even if we do everything right, drug reactions are going to occur," said Linda Tyler of the Drug Information Service at University of Utah Hospital, which tracks adverse reactions. "What everyone is really highly committed to is prevention. Part of the problem is these numbers are very hard to track."

LDS Hospital found last year that half of its adverse reactions were potentially preventable, said spokesman Jess Gomez, including 42 percent that happened because patients were given too much medicine for their weight and kidney function.

The hospital now automatically calculates patients' kidney function daily. It has reduced adverse antibiotic reactions 75 percent, and the hospital suggested that other facilities could easily do the same.

Classen has other "must-do" suggestions to prevent adverse reactions and interactions.

He tells patients to write down every allergy they have and tell the doctor every time he writes a prescription. Patients also need to list every medication being taken, including over-the-counter remedies.

Finally, patients need to ask the doctor to adjust the dose for age, weight and kidney function.