Naproxen CV safety evidence not conclusive enough to warrant label change

February 11, 2014

After examining the latest research on nonsteroidal anti-inflammatory drugs (NSAIDs)-specifically whether naproxen carries lower cardiovascular (CV) risks than ibuprofen-an FDA panel has voted down the CV safety claim for naproxen.

After examining the latest research on nonsteroidal anti-inflammatory drugs (NSAIDs)-specifically whether naproxen carries lower cardiovascular (CV) risks than ibuprofen-an FDA panel has voted down the CV safety claim for naproxen.

The panel voted 16-9 against the conclusion that naproxen (Bayer AG) has a lower risk of heart attack and stroke compared with similar NSAIDs, such as ibuprofen (Pfizer’s Advil and Johnson & Johnson’s Motrin). FDA panelists did not believe that naproxen's label should be changed.

In a two-day meeting this week, FDA reviewed the latest evidence, including a meta-analysis published in 2013 in the Lancet by Dr Neeraj Bhala of Oxford University, United Kingdom, and colleagues that suggested there may be a lower CV risk for naproxen.

A majority of the FDA panelists said the evidence was not conclusive and did not warrant changing the drug's label.

However, those panelists who voted in favor of naproxen's CV safety advantage said that the evidence was not definitive, but also cited a "duty to inform the public."

“The safety and efficacy of medications is always at the forefront of discussions for FDA. This is a classic example of its ongoing efforts to protect the general population,” said Abimbola Farinde, PharmD, MS, who serves on the faculty at Columbia Southern University, Orange Beach, Ala. She is not a member of the FDA panel.

Since 2005, labeling laws have required a CV boxed warning on NSAIDs. This was due to the withdrawal of the NSAID rofecoxib (Vioxx, Merck) from the market in 2004 because of a notable increased risk of heart attack among Vioxx users.

This led to a 2005 meeting of the Arthritis Advisory Committee (AAC) and Drug Safety and Risk Management Advisory Committee (DSARM), where FDA concluded that the three approved COX-2 selective NSAIDs, celecoxib (Celebrex, Pfizer), rofecoxib, and valdecoxib, were associated with an increased risk of serious adverse CV events compared with placebo. Valdecoxib was eventually withdrawn from the U.S. market and a boxed warning added to all NSAIDs warning of the CV risk and risk of serious gastrointestinal bleeding.

Celecoxib is still approved for the treatment of osteoarthritis and rheumatoid arthritis, but FDA is currently questioning a long-term clinical trial known as the Prospective Randomized Evaluation of Celecoxib Integrated Safety vs Ibuprofen or Naproxen (PRECISION) that was started after 2005 to evaluate the relative safety of celecoxib, ibuprofen, and naproxen. Results of PRECISION were expected last year, but full results aren't expected until 2016.