Updated from 8:26 a.m. EST
There's more pain for drugmakers and new worries for drug users.
The Food and Drug Administration is now warning about heart risks related to the use of naproxen, a long-time popular pain killer sold over the counter, as well as a prescription-strength medication sold under various names.
The latest shock to the industry came Monday night when federal regulators disclosed that the National Institutes of Health last Friday halted a drug study testing whether certain anti-inflammatory drugs could reduce the risk of patients contracting Alzheimer's disease. The drugs were being tested in people 70 years of age or older who were considered to be at increased risk because of family history, but did not have symptoms of the disease.
The study compared Naproxen vs. Celebrex, which is made by
. The best-known over-the-counter version of the drug Naproxen is Aleve.
The Alzheimer's disease test was halted partly because another clinical study involving Celebrex showed that the Pfizer drug increased the risk of cardiovascular problems among patients who took high doses, a development that Pfizer disclosed last Friday and which triggered a selloff in the company's share price. The test, sponsored by the National Cancer Institute, was determining if Celebrex could prevent certain colon polyps that are a precursor to colon cancer.
But this Alzheimer's disease test, called ADAPT, was also halted because it "indicated an apparent increase in cardiovascular and cerebrovascular events" among naproxen patients vs. patients receiving a placebo, the NIH said Monday night.
The test was stopped "as a precautionary measure to ensure the safety of the study's participants," said NIH Director Dr. Elias A. Zerhouni. "The investigators made their decision based on the risk/benefit analysis specific to this trial." The ADAPT trial began in 2001 and was conducted at six U.S. sites. Approximately 2400 volunteer participants were randomly assigned to receive naproxen, Celebrex or a placebo for a time up to three years.
On Tuesday, Dr. Lester Crawford, acting director of the FDA, said his agency is keeping "all regulatory options open" and will act "as quickly as possible" after studying test data for naproxen and Celebrex.
"We are trying to process all the data that we have and make some determinations as quickly as possible," Crawford told NBC's
show. "It would be premature to say what we are going to do with either one of these drugs."
Until the agency acts, it advised patients who use over-the-counter naproxen products to "carefully follow the instructions on the label." Patients should not exceed the recommended doses for naproxen (220 milligrams twice daily) and "should not take naproxen for longer than 10 days unless a physician directs otherwise," the agency said.
Naproxen was first sold as a prescription drug under the brand name Naprosyn in 1976. The FDA approved it as an over-the-counter drug in 1994. Naproxen was developed by Syntex, which was acquired by the Swiss drug company Roche in 1994. Roche sells prescription-strength Naprosyn; Germany's
sells an over-the-counter-strength version called Aleve.
The ADAPT test found no extra cardiovascular risk among patients taking Celebrex, prompting Pfizer to remark that the results were consistent with all other Celebrex clinical trials except for the colon polyp trial announced last week.
"This is important new information that should be considered by doctors and patients as they evaluate the various treatments for arthritis and pain," said Hank McKinnell, chairman and chief executive of Pfizer.
"Millions of people simply can't get through their day without pain relief," he said. "That's why all the emerging information about arthritis medicines -- prescription and over-the-counter -- must be fully evaluated by the U.S. Food and Drug Administration and other regulatory authorities."
Because the ADAPT test and a second clinical test on Celebrex's treatment of colon polyps showed no elevated heart risk, "physicians and patients are understandably confused," McKinnell said. "That's why the full study results must be shared with the medical, scientific and regulatory experts so that we have a more complete understanding of the risks and benefits of these medicines."
Pfizer continues to sell Celebrex, pending a review by the FDA. It has suspended all direct-to-consumer advertising until the agency reviews the two colon polyp studies and the ADAPT study.
The naproxen results follow not only the stunning report about Celebrex last week but also the FDA's recent toughening of warnings on Bextra, also a Pfizer arthritis drug pain reliever, and the Sept. 30 withdrawal by
of Vioxx. Merck acted after a clinical test showed patients taking the arthritis drug and pain reliever for more than 18 months had a higher risk of heart attacks and strokes than patients receiving a placebo.
Vioxx, Bextra and Celebrex belong to a class of drugs known as COX-2 inhibitors. Naproxen is a member of the medication class known broadly as non-steroidal anti-inflammatory drugs, or NSAIDs. Older NSAIDS include aspirin as well as prescription-strength and non-prescription products such as ibuprofen.
Bayer's shares were down 21 cents, or 0.6%, to $33.40 on Tuesday. Pfizer's shares were up 68 cents, or 2.8%, to $24.97. Merck's shares were up 28 cents, or 0.9%, to $31.70.