erious adverse effects from drugs often do not show up until after the drugs are marketed, researchers report today in an article that urges doctors to avoid prescribing new medicines if older, better-known ones are available.

The article, in The Journal of the American Medical Association, reviews 548 drugs that the Food and Drug Administration approved from 1975 to 1999. Sixteen, or 2.9 percent, were withdrawn because they turned out to be unsafe, and 45, or 8.2 percent, had to have warnings in black boxes added to their labels to alert doctors and patients to potentially dangerous reactions like heart, liver and blood disorders.

Black boxes are used to highlight special problems, particularly those that may lead to death or serious injury. In five cases, drugs with added black boxes had to be withdrawn later, because of the problems listed in the boxes.

Half the withdrawn drugs were banned within two years of approval. Over all, half the adverse reactions were detected within seven years. The F.D.A. depends on voluntary reporting, largely by doctors, to detect adverse drug reactions. The system is widely thought to pick up about 10 percent of those reactions.

In some cases, the adverse effects were known before the drugs were marketed, the authors of the report said. They suggested that some of the withdrawn drugs should not have been approved in the first place.

In other cases, the adverse effects emerged only after the drugs had gone to market and were being used by large numbers of patients. To some extent, the problem cannot be avoided, because most drugs are tested in just a few thousand patients, which may not be enough to detect every adverse effect.

The study was led by Dr. Karen E. Lasser, a primary care doctor and researcher at Cambridge Hospital in Massachusetts and a research instructor at the Harvard Medical School. Dr. Sidney Wolfe, director of the Public Citizen Research Group, a consumer group in Washington, was a co-author. They and four other Harvard researchers gathered their information from 25 editions of The Physicians' Desk Reference from 1975 to 2000. The annual book is a collection of the technical information and instructions that the Food and Drug Administration requires for all approved drugs. It includes black boxes. Most doctors consult the reference book when prescribing drugs.

The team found that seven drugs approved since 1993 and later taken off the market had been "reported as possibly contributing to 1,002 deaths."

Nearly 20 million Americans took at least one of five drugs banned from September 1997 to September 1998. Three of the five medications were new, on the market for less than two years.

Dr. Lasser said the rate of new black boxes and withdrawals did not appear to have increased because of the "fast track" approval process started in the 1990's.

New drugs are heavily promoted to doctors and patients, the article said, adding, "Their market uptake and sales volume may be explosive."

At a news conference in Washington on their findings, Drs. Lasser and Wolfe acknowledged that drugs with new properties were important innovations. But, they said, patients should be warned that new drugs might have unknown adverse effects, and that doctors should be on the lookout for heart, liver and blood problems.

Dr. Wolfe pointed out that in 2000 and 2001, after they had completed the research for their study, three more recently approved drugs were taken off the market.

When new drugs are not breakthroughs, Dr. Wolfe said, "they fall into a category that we advise should not be used."

"It's a form of Russian roulette, really, to be using such drugs," he added.

The article urges including the date of a drug's approval in the labeling, a move the F.D.A. has also proposed.

In an editorial in the medical journal, two officials of the agency, Drs. Robert J. Temple and Martin H. Himmel, agreed that doctors and patients should be aware that new drugs might have unknown adverse effects. But they said serious adverse reactions that led to changes in using drugs were not common.

"If there is a sound reason to use a recently approved drug," they wrote, "the physician need not deny the patient this treatment."

They also said new research might lead to earlier identification of drugs that can cause heart rhythm and liver problems.

The Pharmaceutical Research and Manufacturers of America, a trade group, issued a statement that called the article "misinformed and misleading." It said that adverse reactions from marketed drugs should not be described as common and that "all medicines, including aspirin, involve some risk."