The U.S. Food and Drug Administration is advising doctors to consider alternatives to pain reliever Celebrex in the wake of a study that showed it increased the risk of heart attack and strokes at high doses.
Pfizer Inc. said Friday it will leave Celebrex on the market, although the same problems led Merck & Co. to withdraw its painkiller Vioxx from the market in September.
“We’re leaving open all regulatory decisions as we move forward. But we do not have a decision on the fate of the product,” Acting FDA Commissioner Lester Crawford said Friday. “We do have great concern about this product (Celebrex) and the class of products.”
Crawford said doctors should think about other types of drugs to help patients relieve pain. Doctors said they were already inundated with calls from nervous patients and were pledging to curtail their use of the drug.
Both Celebrex and Vioxx are a type of drug called cox-2 inhibitors. Vioxx was pulled from the market in September because it doubled patients’ risk of heart attack and stroke.
“I think the trial concludes the controversy about whether there is a class effect of these drugs. Now there is clear evidence of it,” said Dr. Garret A. FitzGerald, a cardiologist at the University of Pennsylvania. “You would need to believe the earth is flat if you thought this was just a coincidence.”
National Institutes of Health director Dr. Elias Zerhouni said that he ordered a full review of the more than 40 agency-supported studies involving cox-2 inhibitors.
Risk at high doses found
News of the increased heart risk for Celebrex patients came in one of two long-term cancer prevention trials.
The National Cancer Institute, which was conducting the study for Pfizer, said patients in the clinical trial taking 800 milligrams of Celebrex had a 3.4 times greater risk of cardiovascular events compared to a placebo. For patients in the trial taking 400 milligrams of Celebrex the risk was 2.5 times greater. The average duration of treatment in the trial was 33 months.
In the 2,000 patient study, 15 individuals taking 400 mgs, 20 patients taking 800 mgs and 6 patients on placebo suffered either a cardiac-related death, heart attack or stroke.
The study was intended to show whether Celebrex could prevent precancerous growths called polyps in patients that had already had at least one such growth.
A separate cancer study done by Pfizer found no increased heart risk with patients taking 400mg of Celebrex per day.
What next for Pfizer?
Pfizer chairman and chief executive Hank McKinnell, who takes Celebrex, told CNN’s Paula Zahn that he plans to continue using the drug. Dr. Joseph Feczko, president of worldwide development for Pfizer, said the results in the trial finding increased risk of heart attacks were inconsistent with the other cancer prevention trial and a “large body of data” that the company had collected.
FitzGerald, who has been critical of cox-2 inhibitors, said he doesn’t believe Pfizer should take Celebrex off market but must find the appropriate patient population for the drug. Cox-2s were developed to be gentler on the stomach than older pain relievers called nonsteroidal anti-inflammatory drugs, such as naproxen, that are associated with gastrointestinal problems. But unlike Vioxx, Celebrex was never statistically proven to decrease the risk of ulcers. It also doesn’t reduce pain better than older drugs.
For the first nine months of the year, worldwide sales of Celebrex more than doubled from a year earlier to $2.3 billion, accounting for 6 percent of Pfizer’s total sales of $37.6 billion during that period. Last year, Pfizer spent $87.6 million to advertise Celebrex, according to TNS Media Intelligence/CMR. It recently launched a new campaign for the drug and placed full-page ads in newspapers touting Celebrex’s safety in the wake of the Vioxx recall.
Those claims prompted U.S. Rep. Joe Barton, R-Texas, and U.S. Rep. John Dingell, D-Mich., to ask Pfizer on Friday for documents regarding Celebrex and Bextra, the company’s other Cox-2 inhibitor. They want to know what information Pfizer had about the NCI study when it made the safety statements.