FDA panel suggests warning labels for Vioxx

Vioxx and a host of other popular painkillers, including Celebrex and Bextra, have all been linked to an increased risk of heart trouble. However, the Food and Drug Administration recently stated that the drugs should be made available to those who need them.

The makers of these drugs, including Merck and Pfizer, developed these medications, known as COX-2 inhibitors, since they cause fewer stomach problems in comparison to other painkillers. Although Merck withdrew its popular Vioxx from the market last fall, the drug may be made available with a black box warning for patients that require it. The drug was withdrawn after disturbing results were reported in a large trial involving Vioxx. The study was halted two months early because some patients had developed serious heart problems.

It was not long before people questioned whether two drugs in the same family, Pfizer's Celebrex and Bextra, could also cause heart attacks and strokes. Those concerns were answered last week when FDA advisory panels announced that results of several studies show that the Vioxx, as well as Celebrex and Bextra, also can lead to heart problems. Although the panels did not state that these drugs should be pulled from shops, they did recommend stronger warnings to accompany these COX-2 inhibitors.

COX-2 inhibitors work by inhibiting various forms of an enzyme called cyclooxygenase-2 (COX-2). COX-2 controls the production of prostaglandins, hormone-like substances that are involved in many biological functions including the transmission of pain signals, inflammation, and the protection of the linings of the stomach and intestine. When an anti-inflammatory drug suppresses COX-2, it cuts off a chain of events in which prostaglandins are produced and pain is transmitted to the patient's brain.

Research findings suggest that when COX-2 is inhibited, the activity of prostacycin may be suppressed as well. This poses a risk for heart trouble, since platelets would then be free to form clumps and blood vessels would be able to constrict.

"The cardiovascular problems appear to be a class effect," said Dr. Eric Topol, director of cardiovascular medicine at the Cleveland Clinic, in an article in TIME magazine. "But the magnitude of risk does seem to differ from drug to drug." The risk from Celebrex varied in different studies. The panel was informed that no cardiovascular problems were seen at the normal dose of 200 mgs. Heart problems appear in a colon polyp study by patients who were taking 400 mg. Celebrex. Meanwhile, Dr. Peter S. Kim, president of Merck Research Laboratories, has told the FDA committees, "There are unique benefits to Vioxx. The science has progressed and we need to take that science into consideration."

U.S. FDA panelists voted to allow sales of Vioxx, Celebrex, and Bextra while at the same time acknowledging the COX-2 drugs pose risks for heart problems. After weighing the issue of benefits versus risks, the panel concluded that the benefits outweigh possible risks to consumers and the COX-2 drugs should remain available to people who need them.

Panelists voted overwhelmingly to keep Celebrex on the market, but the vote was closer for Vioxx and Bextra. New and larger studies may be conducted to confirm the side effect of this class of drugs. Other suggestions from the panel included: possible restrictions on the drugs such as a black box warning, more patient information with the drugs, possible restrictions for who could get the drugs, and a possible ban on direct-to-consumer advertising.

Although the FDA is not required to follow the recommendations of advisory panelists, it often does.