FDA Advisory Committee on the Safety of Celecoxib, Naproxen and Ibuprofen

Posted by on July 22, 2018

On April 24th – April 25th, 2018 a joint meeting of the Arthritis Advisory Committee and Drug Safety and Risk Management Committee convened to review supplemental new drug application (sNDA) 0209998/S-050 for Pfizer Pharmaceuticals’ COX-2 inhibitor Celecoxib (Celebrex). Celebrex is an oral tablet that can be used as an analgesic and for swelling and inflammation. Pfizer’s objective was to demonstrate noninferiority for cardiovascular (CV) risk of celecoxib compared to non-selective COX inhibitors – naproxen and ibuprofen,  in osteoarthritic (OA) and rheumatoid arthritis (RA) patients.

The committee also discussed drug interactions between celecoxib, ibuprofen and naproxen when each was used concomitantly with aspirin. This meeting included participation of Bayer Healthcare, Johnson & Johnson Consumer Inc., and the Consumer Healthcare Products Association (CHPA).

Data was presented from the Prospective Randomized Evaluation of Celecoxib Integrated Safety vs. Ibuprofen or Naproxen study (PRECISION) trial which compared the cardiovascular effects and outcomes of the three medications. The rates of cardiovascular death, stroke or myocardial infarction were recorded as one value for each drug. Naproxen had a rate of 2.5%, 2.7% for ibuprofen and 2.3% for celecoxib.

Each sponsor presented data outlining benefits, risks, mechanisms and possible interactions of the three NSAIDS. All parties indicated that there was low CV risk associated with these NSAIDs when used as directed. All sponsors expressed their  commitment to providing appropriate labeling as per current FDA regulations.

The meeting included 6 discussion questions and 3 voting questions. The committee voted that Celecoxib demonstrated comparable CV safety compared to naproxen and ibuprofen (15 Yes, 5 No, 1 Abstention). Many committee members emphasized that this vote was limited to the 100 mg dose used twice daily, in OA and RA patients.  Members who voted ‘No’ indicated that PRECISION was not designed to conclude safety but rather addresses non-inferiority; i.e. celecoxib was no worse than ibuprofen and naproxen. The second and third voting questions concerned changes to nonprescription labeling of naproxen and ibuprofen, respectively.

Voting on regulatory actions for naproxen, 7 members voted that no change in labeling was needed, 12 voted that a warning regarding the interaction between aspirin and naproxen should be added and 2 panelists voted that the use of aspirin and naproxen should be contraindicated. The 12 panelists who voted to add a warning, indicated that there needs to be consistency in labeling between ibuprofen and naproxen.

Voting on regulatory actions for ibuprofen, 17 members voted that no change to the current label should be made and 4 members voting that ibuprofen use with aspirin should be contraindicated. Members who voted that no change should occur, stated that no new data was presented to warrant a change. Others felt that currently, safety is not adequately addressed and therefore a contraindication for the use of ibuprofen when taken with aspirin is necessary.

The agency is not obligated to follow its panel’s recommendation, but normally does so. On June 28th  the FDA approved drug labeling supplement for celecoxib with regards to new information from the PRECISION study.

ISS has almost two decades of experience in developing regulatory strategies including support for FDA Advisory Committee meetings. We are involved in more FDA AdComms per year than even the largest pharmaceutical companies. For more information on how ISS can help you prepare for your next meeting, contact info@innovativescience.net

This post was authored by Sami Mourad and Kaela Gerald. Sami is a summer intern at ISS and a 3rd year pharmacy student at the Rutgers University Ernest Mario School of Pharmacy.


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