News

FDA refuses companies' request to drop ulcer warning

Scott Gottlieb, New York

Two competing manufacturers of the top selling prescription "superaspirins" in the United States, vying for a marketing edge, went before a panel of the US Food and Drug Administration (FDA) last week to ask the government to relax ulcer warnings on their labels but failed to win the expanded wording that they sought.

Traditional non-steroidal anti-inflammatory drugs block both the related enzymes (cyclo-oxygenase-1 (COX 1) and cyclo-oxygenase-2 (COX 2)), which cause inflammation and pain. But COX 1 also protects the stomach lining. Researchers found that they could control pain by blocking the COX 2 pain enzyme while leaving the COX 1 enzyme alone.

The manufacturers of the two competing drugs (celecoxib (Celebrex) and rofecoxib (Vioxx)), have long maintained that COX 2 inhibitors cause fewer stomach ailments, such as ulcers, normally associated with long term use of non-steroidal anti-inflammatory drugs.

The manufacturers want the drugs to be considered in a class of their own, as they interfere only with the inflammation and pain enzyme, not the protective one.

The FDA refused, however, to put celecoxib and rofecoxib in a class by themselves. Therefore the drugs will continue to carry the same ulcer warning found on other non-steroidal anti-inflammatory drugs. The companies tested celecoxib and rofecoxib separatelyeach in trials of 8000 patientsto determine the drugs' risk of causing stomach problems.

In the study of celecoxib, the manufacturer, Pharmacia, compared the drug with the generic drugs ibuprofen and diclofenac. The FDA's panel said that the difference in the rate of ulcers was not significant enough to change the label. One important factor was that many patients in the study also took low doses of aspirin, a common prescription for prevention of heart attack, negating any benefit from celecoxib.

In a study of rofecoxib, the manufacturer, Merck, compared patients taking that drug with a group taking naproxen. Although the study showed that rofecoxib did cause fewer ulcers, the FDA's panel said that the drug's label should still retain its broad warning that rofecoxib, like celecoxib, can still cause ulcers.

Also, the panel said that patients and doctors must be warned that in the study patients taking rofecoxib had twice the risk of heart attacks or other cardiovascular side effects as naproxen users. It is believed that naproxen may work as an antiplatelet agent, much like aspirin, and thus using rofecoxib in the study instead deprived patients of the other drug's benefit.

Some critics say, however, that rofecoxib and celecoxib may themselves increase the risk of blood clots. The FDA's panel concluded that more research was needed but that meanwhile rofecoxib's label should warn of the concern.