SILVER SPRING, MD. – There do not need to be major changes to the warning labels on prescription and over-the-counter nonsteroidal anti-inflammatory medications, said a group of federal advisers on Feb. 12.
The members of the Arthritis Advisory Committee and the Drug Safety and Risk Management Advisory Committee said that the evidence that had been presented to them over the 2-day meeting about potentially new cardiovascular (CV) risks with drugs in the class was not sufficient to change labeling.
Denise Fulton/Frontline Medical News
A 16-9 FDA committee vote said there was not enough data to suggest that naproxen (photographed blue pills) presented a substantially lower risk of cardiovascular events that did either ibuprofen (photographed tan pills) or selective NSAIDS.
And, in a 16-9 vote, they said there were not enough data to suggest that naproxen presented a substantially lower risk of CV events than did either ibuprofen or selective NSAIDs, such as cyclooxygenase-2 inhibitors.
But some panelists said that even without a label change, the evidence on naproxen – which showed a trend toward a better safety profile – would probably sway them to prescribe or recommend it more often, especially in patients at risk for CV side effects. "The preponderance of evidence pushes me to the conclusion that I’m personally switching to naproxen and I’ll be pushing my patients to it," said Dr. Peter Kaboli, an internist at the Iowa City Veterans Affairs Medical Center and a member of the drug safety advisory panel.
There was a particular concern for patients with rheumatic diseases, who are considered to be at higher risk for CV events. Dr. Robert Lahita, an arthritis committee member and a professor of medicine at Rutgers Biomedical and Health Sciences, Newark, N.J., said that his rheumatoid patients "take NSAIDs like candy," and rarely follow his directions for dose or duration. "How do we address that?" he asked.
Dr. Irwin J. Russell, a fibromyalgia researcher at the Arthritis and Osteoporosis Center of South Texas, San Antonio, said that the data on NSAIDs should prompt inquiries into whether the elevated cardiovascular disease risk in rheumatic patients might be linked to their chronic use of the medications.
To get more answers on NSAID safety, the FDA advisers urged the agency to allow the PRECISION (Prospective Randomized Evaluation of Celecoxib Integrated Safety vs. Ibuprofen or Naproxen) trial to continue. That study, sponsored by Pfizer, began in the wake of a joint meeting of the same panels in 2005. It is directed by an independent academic committee and is expected to be completed by late 2015.
In June 2005, the FDA required all prescription NSAIDs to have a boxed warning on the potential for serious adverse CV events. NSAIDs also carry a warning on the potential for gastrointestinal adverse events. A Medication Guide was developed for patients to inform them of the risk of CV events and gastrointestinal bleeding with all NSAIDs.
The latest panel meeting was held because "9 years later, there are more data available and questions still remain," said Dr. John Jenkins, director of the FDA’s Center for Drug Evaluation and Research. That new data primarily came from a study authored by the Coxib and traditional NSAID Trialists’ Collaboration at Oxford (England) University (Lancet 2013:382;769-79). Most of the FDA advisers said that the data from that study were less than satisfactory, in part because they mashed together trials of different NSAIDs taken at different dosage levels.
The committee did say that it would like to see clearer warnings on over-the-counter (OTC) NSAIDs, especially emphasizing that patients should take the lowest possible dose for the shortest period of time. "Many patients are taking above what the OTC label" recommends, said Dr. Tuhina Neogi, chair of the joint committees and a rheumatologist at Boston University.
Some data presented at the meeting suggested that patients have many areas of misunderstanding when it comes to OTC NSAIDs. Dr. Byron Cryer, chairman of the Alliance for Rational Use of NSAIDs, said that a recent survey conducted by his nonprofit group found that less than half of those taking an OTC formulation said they pay attention to potential interactions or side effects. Thirty-six percent were not sure what an NSAID was, and 18% said they’d used OTC and prescription NSAIDs concomitantly.
The FDA usually follows the advice of its advisory panels.
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