FDA Reconsiders Heart Safety of Common Pain Pills

Federal health experts are taking a second look this week at the heart safety of pain medications used by millions of Americans to treat arthritis and other everyday aches and pains.

The Food and Drug Administration on Monday began a two-day meeting 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 has a lower risk of heart problems than other NSAIDs. Panelists will also discuss whether naproxen should be relabeled based on the latest safety data. 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 ibuprofen and naproxen, 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 will have to wrestle with reams of data that are often riddled with complicating factors:

• The Oxford analysis is difficult to interpret because it combines information from hundreds of unrelated studies. While this approach is useful in getting a broad view of rare events — such as heart attacks — it is not considered the strongest form of medical evidence.
• 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.

Monday’s meeting mainly consisted of presentations dissecting the latest findings from academics, FDA scientists and drug company staffers.

The pharmaceutical companies generally staked out positions that would most benefit their respective products.

Bayer, which markets Aleve, said the drug’s labeling should reflect the new research suggesting it is a safer option.

Pfizer, maker of Advil and Celebrex, argued that there is no conclusive data that naproxen is safer than other products. The New York company said current labeling should remain in place until more conclusive evidence is available.

Pfizer is wrapping up work on a large multiyear study called PRECISION designed to definitely answer whether there is a difference in cardiovascular safety between naproxen, ibuprofen and Celebrex.

But the FDA is considering halting work on that study given that evidence already suggests lower rates of heart attack and stroke for naproxen. FDA’s panel will weigh in on the fate of the study Tuesday.

This week’s meeting is the latest chapter in an ongoing safety review of NSAIDS 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 vote Tuesday on whether over-the-counter NSAID labeling should be changed to warn patients of the short-term risks.