The abrupt withdrawal last week of the best-selling painkiller Vioxx is an event rich in ironies and lessons that may ultimately lead to a rethinking of the way drug safety is evaluated in the United States.
Drugs whose stated advantage is that they are safer than their competitors -- which was Vioxx's claim -- are likely to get much closer scrutiny. The Food and Drug Administration in the future may force companies to run new, definitive clinical studies specifically to address safety issues even after a drug is on the market and in widespread use.
Release Announcing Vioxx Withdrawal (PDF)
Vioxx's Removal May Not Affect Care Much (The Washington Post, Oct 1, 2004)
Merck Withdraws Arthritis Medication (The Washington Post, Oct 1, 2004)
Merck Withdraws Arthritis Drug Vioxx (The Washington Post, Sep 30, 2004)
A Weekly Shot of News and Notes (The Washington Post, Sep 28, 2004)
Wasabi as Decongestant? Just Say Nose (The Washington Post, Sep 28, 2004)
More Heart News
Vioxx, taken by 1.3 million Americans, was removed from sale worldwide on Thursday because it raised the risk of cardiovascular disease, the nation's leading cause of death. Proof of that hazard did not come until five years after the drug was licensed and three years after the first hints of a problem.
"We will want more data on [the safety of] long-term use for both drugs in the pipeline and those already approved," Steven K. Galson, acting director of the FDA's Center for Drug Evaluation and Research, said last week, two days after the agency learned that Merck & Co. planned to withdraw its blockbuster drug.
Vioxx's downfall is likely to spur other changes as well, experts said.
It may lead doctors and patients to take a fresh look at the consequences of direct-to-consumer advertising, the root of much of Vioxx's enormous popularity in a field full of competing pain relievers. It may also dampen some of the enthusiasm for expensive, targeted, "smart" drugs, which sometimes turn out to be no better -- or in Vioxx's case, actually worse -- than their cheaper, blunter, dumber ancestors.
"I think there are important issues here that we would be foolish not to reflect upon," said David Wofsy, a physician at the University of California at San Francisco and president of the American College of Rheumatology.
Vioxx, whose generic name is rofecoxib, is a "selective COX-2 inhibitor." When it and others in the same family were in development, their main appeal was that they were expected to cause fewer stomach ulcers than many existing painkillers.
COX-2 inhibitors block the action of an enzyme used throughout the body to make a large and diverse family of compounds called prostanoids that are involved in regulating myriad physiological actions, including inflammation, blood clotting and protection of the stomach lining from the destructive effects of digestive acids.
The fact that Vioxx acts only on COX-2 distinguishes it from aspirin and the large family of nonsteroidal anti-inflammatory drugs (NSAIDs) that includes Motrin (ibuprofen) and Aleve (naproxen), which block not only COX-2 but also a related enzyme called COX-1. Blocking COX-1 is responsible for the stomach-irritating effects those drugs can cause.