Cox-2 Inhibitors
WHY COX-2 INHIBITORS WERE PULLED OFF THE MARKET
COX-2 Inhibitor drugs Vioxx (manufacturer Merck) and Bextra (manufacturer
Pfizer) were pulled off the market five years after being approved. The drugs showed evidence of increased risk of heart attack with use. Have you ever wondered why drugs like this were put on the market in the first place? Why the FDA didn’t catch the signs beforehand? This is alarming, due to the fact that an estimated 20 million individuals used the drugs during the 5 year course on the market. The New England Journal estimates a shocking 80 million population usage of Vioxx.
Vioxx: Reasons for getting pulled off the Market
COX-2 Inhibitor Vioxx showed little evidence in clinical trials to cause a great risk of heart attack. The drugs were approved and given to aid symptoms of osteoarthritis, acute pain, and menstrual pain. However, in 2004, five years after the initial trial, the VIGOR (Vioxx Gastrointestinal Outcomes Research) discovered evidence of cardiac toxicity. Merck voluntarily removed the drug from the market.[1] This conclusion was supported by three large, randomized trials: VIGOR, Merck, and The National Cancer Institute.[2]
The VIGOR trail “compared rofecoxib (50mg daily) with naproxen (500 mg twice daily) in 8076 patients with rheumatoid arthritis.” Subjects with recent cardiovascular events and those who were taking aspirin were excluded. The evidence of myocardial infarction showed to be five times as prevalent in the rofecoxib group as in the naproxen group.2 Similarly, the Adenomatous Polyp Prevention on Vioxx (APPROVe) trail, which ultimately led to the drug’s withdrawal, enrolled a relatively young group and excluded patients with recent ischemic cardiovascular disease.” Therefore, evidence of a high increased risk of myocardial infarction (heart attack) is confirmed with the clinical trail of young, healthy adults.[3] The Merck and National Cancer Institution presented similar data.
Bextra: Reasons for being pulled off the Market
Pfizer, Inc., manufacturer of Bextra (valdecoxib) was asked by the FDA to withdraw the drug in 2005. According to the Food and Drug Administration (FDA), Bextra showed an association “with an increased risk of serious adverse cardiovascular events in two short-term trails in patients immediately post-operative from coronary artery bypass graft surgery.”[4] The FDA based the withdraw request based on the following information:
- Lack of adequate data on cardiovascular safety of long-term use of Bextra, along with the increased risk of unfavorable cardiovascular events in short-term coronary artery bypass surgery (CABG) trials that FDA believes may be relevant to chronic use.
- Reports of serious and potentially life-threatening skin reactions, including deaths, in patients using Bextra. The reactions occurred in patients with and without prior history of sulfa allergy, and after both short and long-term use.
- Lack of demonstrated advantages for Bextra compared with other NSAIDs.[5]
Additionally, the FDA requested manufacturers of all markets prescription NSAIDs and COX-2 selective NSAID to review the package insert for their products, and include a boxed warning and a Medication guide. The boxed warning includes increased risk for cardiovascular disease and life-threatening GI bleeding. Even over the counter NSAIDs must include the revised labeling.
[2] www.nejm.org / A Lesson in Unexpected Problems
[4] www.fda.gov/medwatch/report / Alert for Healthcare Professionals: Valdecoxib (marketed as Bextra)
[5] www.fda.gov/medwatch//report / FDA Public Health Advisory
