The Food and Drug Administration holds a two-day meeting beginning Monday to examine the latest research on anti-inflammatory medicines called NSAIDS, which serve as the backbone of U.S. pain treatment.
The key question is whether naproxen the key ingredient in Bayer's Aleve and many other generic pain pills carries a lower risk of heart attack and stroke than rival medications like ibuprofen, sold as Advil by Pfizer and Motrin by Johnson & Johnson, among others.
Debate about whether one drug is safer than others in the class has waged for more than a decade without a clear answer, underscoring the lingering questions that hang over even the most established medicines.
The FDA is asking its panel of medical experts to review a massive analysis published last year suggesting that naproxen does not increase the risk of heart problems as much as its peers. The finding came from Oxford University researchers who reviewed results from more than 700 NSAID studies involving roughly 350,000 patients.
On Tuesday panelists will vote on whether naproxen should be relabeled to reflect its apparent safety advantage. The FDA is not required to follow the group's advice, though it often does.
If implemented, the labeling change could reshape the multibillion-dollar market for drugs used to treat muscle pain, arthritis and headaches. Last year U.S. consumers bought more than 275 million boxes of over-the-counter NSAIDs, representing $1.7 billion in sales, according to retail tracker IRI. Prescription NSAIDs brought in billions more, led by the Pfizer's blockbuster Celebrex, with sales of $2.9 billion.
But before any changes can be made, FDA advisers must weigh reams of data that are often riddled with complicating factors:
The Oxford analysis is difficult to interpret because it pools information from hundreds of unrelated studies. While this approach is useful in getting a broad view of rare events such as heart attacks it's not considered the most reliable form of medical research.
Almost all of the data under discussion come from studies of prescription NSAID pain relievers, which are taken at higher doses and for longer periods than over-the-counter NSAIDs. But panelists will be asked to make recommendations on the use of non-prescription drugs as well.
Panelists will also be asked to make recommendations for narrow subgroups of patients, including those with a history of heart problems.
This week's FDA meeting is the latest chapter in an ongoing safety review that stretches back to 2004, when Merck & Co Inc. pulled its blockbuster pain reliever Vioxx off the market due to links to heart attack and stroke.
Vioxx had been heavily advertised as a new kind of NSAID that was supposed to be easier on the stomach. But its withdrawal shook the medical establishment and ushered in a new era of drug safety at the FDA.
In 2005, the agency added boxed warnings about the risk of heart attack and stroke to all prescription NSAIDS, including Celebrex and high-dose versions of ibuprofen and naproxen. Celebrex is the only drug from the same class as Vioxx that remains on the market.
The agency also beefed up labeling on lower-dose, over-the-counter NSAIDs like Aleve, Motrin and Advil. Those drugs currently warn patients to take the lowest dose possible for only a few days at a time to avoid the same risks as prescription NSAIDs.
But that advice is also getting a second look this week. A recent analysis by Danish researchers suggests heart problems can emerge with all NSAIDS after less than a week of treatment.
The FDA panel will also vote Tuesday on whether over-the-counter NSAID labeling should be changed to warn patients of the short-term risks.