Chicago ? One in five new drugs has serious side effects that do not show up until well after the medicine has received government approval, according to a study that exposes what one researcher calls an alarming game of medical Russian roulette.

The researchers went so far as to suggest that doctors should prescribe older drugs when possible, unless the new one is truly superior.

“It’s like playing Russian roulette when a doctor prescribes a newly approved drug that doesn’t have a big breakthrough,” said Dr. Sidney Wolfe of Public Citizen Health Research Group, one of the researchers who worked on the study.

Pressure from pharmaceutical companies and doctors’ failure to closely read warning labels are partly to blame, the researchers said. They said the findings should prompt the Food and Drug Administration to consider raising its threshold for approving new drugs when safe and effective alternatives exist.

The findings are based on an analysis of 548 drugs approved from 1975 through 1999. Of these, 56, or more than 10 percent, were later given a serious-side-effect warning or taken off the market for safety reasons. The number climbed to approximately 20 percent when researchers took into account drugs that were approved toward the end of the period studied.

The study, led by Dr. Karen Lasser of Cambridge Hospital and Harvard Medical School, appears in today’s Journal of the American Medical Assn.

The study analyzed what are known as “black-box” warnings published in the Physicians Desk Reference, a compendium of drugs and labeling information published annually. Black-box warnings highlight the most serious side effects.

Sixteen drugs studied were withdrawn from the market, nearly half of them more than two years after they had won approval.

They include the diabetes drug Rezulin, which was approved in 1997 but has been linked to dozens of cases of fatal liver damage. Lasser said doctors continued to prescribe it an unsafe manner even after it was given a black-box warning, and it was ultimately withdrawn from the market in 2000.

Two allergy drugs, Seldane and Hismanal, were linked with potentially fatal heart problems in certain patients but were not removed from the market until several years after receiving black-box warnings.

Most troublesome new drugs do not represent any advance in treatment and are at best no better than older, safer drugs already on the market, Wolfe said.

Unless a new drug is a breakthrough, it should be avoided until its safety record is better known, the researchers said.