The recent voluntary recall of Vioxx (rofecoxib) by its manufacturer, Merck & Co, on September 30, 2004, was an action that has surprised healthcare providers and disappointed many patients. Vioxx, a COX-2 selective nonsteroidal antiinflammatory drug (NSAID) had been used to reduce the symptoms of arthritis, acute pain in adults, and menstrual pain (http://www.fda.gov/cder/drug/infopage/vioxx/vioxxQA.htm). The concerns regarding the safety of Vioxx were not new, however, to Merck & Co, nor to the Federal Drug Administration (FDA). The time line is interesting and raises some questions.
The search for alternatives to traditional NSAIDs began in the early 1990s in an effort to find something with comparable benefits without the high risk for gastrointestinal bleeding. Healthcare providers anxiously awaited the new generation of antiinflammatories to provide an option for those patients who were unable to take traditional NSAID medications. The "FDA originally approved Vioxx in May 1999. The original safety database included approximately 5000 patients on Vioxx and did not show an increased risk of heart attack or stroke" (http://www.fda.gov/bbs/topics/news/2004/NEW01122.html). What occurred after the initial approval is surprising.
The VIGOR (VIOXX GI Outcomes Research) was submitted to the FDA in June 2000. This study was developed to look specifically at the side effects of stomach ulcers and gastrointestinal bleeding. The results of this study showed that patients taking Vioxx did have fewer ulcers and bleeding than those taking another popular NSAID, naproxen. However, in addition to these important findings, it was also noted that there was an increased number of heart attacks in the Vioxx group than in the control group. In February 2001 after reviewing the study results, the Arthritis Advisory Committee of the FDA directed that additional safety instructions be added to the labeling of Vioxx as of April 2002.
This change in labeling procedure is concerning. When concerns about a drug arise, should something more than changing the labeling occur? Most practitioners do not routinely read package inserts on the drugs that they prescribe to see if there are any changes in the labeling. I wonder how many healthcare providers are aware that there is help available through the FDA MEDWATCH. Any person who prescribes medications can subscribe free. Notices are sent when a warning is issued, as well as monthly updates of changes. I was not aware of this until speaking with Dr Bea Turkoski, Pharmacology Columnist for Orthopaedic Nursing. This is obviously valuable information for anyone who prescribes.
Based on the concerns raised with the VIGOR study, Merck began another research study looking at heart attacks and stroke in those patients who were taking Vioxx on a long-term basis. Because the original data on short-term use of Vioxx did not show problems with heart attacks and stroke, long-term use needed to be evaluated. With any long-term study, the operative words are long-term. Research takes time.
The study that led to Merck's voluntary withdrawal was the APPROVe (Adenomatous Polyp Prevention on VIOXX) study, which began enlisting study participants in 2000. The study was halted early because as the data were being evaluated, they showed that those patients taking Vioxx 25 mg daily for more than 18 months showed an increased risk for heart attacks and stroke (http://www.merck.com/newsroom/press_releases/product/2004_0930.html). Merck voluntarily withdrew this product from the market because it believed it was in the best interest of those people taking this medication. "We are taking this action because we believe it best serves the interests of patients," said Raymond V. Gilmartin, Chairman, President, and Chief Executive Officer of Merck. "Although we believe it would have been possible to continue to market VIOXX with labeling that would incorporate these new data, given the availability of alternative therapies, and the questions raised by the data, we concluded that a voluntary withdrawal is the responsible course to take."
The FDA needs to look at the question of whether something more needs to be done to notify those who prescribe drugs that as additional research continues on many drugs that may identify additional concerns that notification needs to occur. Certainly, this would be a monumental task. In the meantime, anyone prescribing medications should consider subscribing to MEDWATCH-I just signed up.