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Celebrex Trial Halted Due to Adverse Cardiovascular Events

Celebrex Trial Halted Due to Adverse Cardiovascular Events
27/06/2012 Mike

Yael Waknine
Medscape 2004. © 2004 WebMD Inc.
Dec. 20, 2004

The U.S. Food and Drug Administration (FDA) has warned healthcare professionals and patients via a statement that use of celecoxib (Celebrex, made by Pfizer Inc.) may be associated with an increased risk of adverse cardiovascular (CV) events, including cardiovascular death, acute myocardial infarction (MI), and stroke. Celecoxib is indicated in the treatment of osteoarthritis, rheumatoid arthritis, pain, and colon polyps.

The alert was based on emerging information that included interim reports from one of three long-term National Institutes of Health (NIH) prevention studies involving celecoxib use. The NIH evaluated the progress of these studies because of recent information linking adverse CV events to use of other cyclooxygenase 2 (COX-2) selective inhibitors.

Based on these interim results, the National Cancer Institute (NCI) stopped drug administration at 33 months in a three-year trial evaluating the use of celecoxib for the prevention of colon polyps in approximately 2,000 patients.

According to the NCI’s report to the FDA, patients in the study receiving 400 mg of celecoxib twice daily were 3.4 times more likely to experience adverse CV events compared with placebo. In patients receiving 200 mg of celecoxib twice daily, the risk was 2.5 times greater. Currently approved dosing regimens for celecoxib range from 100 to 400 mg twice daily.

These results are similar to those of a recent study showing an increased risk of adverse CV events in users of rofecoxib (Vioxx, made by Merck), leading to its withdrawal from the global market. Use of valdecoxib (Bextra, made by Pfizer Inc.) has also been linked to an increased risk of adverse CV events, most notably when used for pain management immediately after coronary artery bypass graft (CABG) surgery. Valdecoxib and celecoxib are the only COX-2 inhibitors currently available in the U.S.

The FDA notes that the two other celecoxib trials evaluated by the NIH (one involving a once-daily 400-mg dose) have not yielded an increased rate of adverse CV events over a similar period of time and have been allowed to continue.

Prior to this alert, the only available information concerning long-term use of celecoxib use was obtained from a one-year study of 400 mg of celecoxib given twice daily compared with ibuprofen and diclofenac in the treatment of osteoarthritis and rheumatoid arthritis. The study did not reveal a difference in CV event risk between the COX-2 inhibitors and the other nonsteroidal anti-inflammatory drugs.

The FDA is not aware of any long-term studies assessing the possible risk of adverse CV events in patients using nonselective COX inhibitors.

Emerging clinical data regarding adverse CV events and other risks of celecoxib will continue to be evaluated by the FDA in order to determine whether further regulatory action is required. Physicians are advised to consider the evolving data when prescribing for patients and informing them of risks associated with therapy. The FDA recommends using the lowest effective dose of celecoxib if alternative therapy is not appropriate.

In accordance with FDA recommendations, Pfizer has agreed to alter the promotional materials for physicians to encourage the use of alternative therapies and to stop direct-to-consumer advertising. Adverse events related to use of celecoxib should be reported to the FDA’s MedWatch program by phone at 1-800-FDA-1088, by fax at 1-800-FDA-0178, online at www.fda.gov/medwatch, or by mail to 5600 Fishers Lane, Rockville, MD 20852-9787.

Reviewed by Gary D. Vogin, MD