April 8, 2005. Yet another painkiller in the cox-2 family has been withdrawn from the market. Health Canada asked the maker of Bextra, Pfizer Canada Inc., to discontinue sales due to safety concerns, and U.S. and European regulators have done the same.
The immediate concern is that the drug can trigger an allergic reaction that causes a life-threatening skin disease. But Health Canada is continuing a more sweeping review of painkillers, and cox-2 inhibitors such as Vioxx, Celebrex and Bextra in particular, because of mounting evidence that they increase the risk of heart disease and stroke.
"In Canada, we feel that while we complete our evaluation, it's best to withdraw the product temporarily and the company agreed," said Dr. Marc Berthiaume, the manager of marketed pharmaceuticals at Health Canada.
Bextra is prescribed principally for the treatment of osteoarthritis, rheumatoid arthritis and menstrual cramping.
Since the drug was made available for sale in Canada in December of 2002, there have been seven recorded cases of a severe allergic reaction called toxic epidermal necrolysis (also known as Stevens Johnson Syndrome). The disease is characterized by painful, blistering ulcers on the eyes, mouth, rectum, genitalia and skin, as well as a severe fever, which can be fatal. There have been no deaths in Canada, according to Health Canada.
Dr. Berthiaume also announced that there would be new "usage restrictions" on Celebrex, and the drugs should not be taken by people with risk factors for heart disease. Sales of Vioxx, a product of Merck & Co., have already been halted in Canada, meaning that cox-2 inhibitors, which are popular with arthritis sufferers, are now virtually unavailable.
Dr. Berthiaume said the safety review of cox-2 inhibitors should be completed by the end of this month. There will also be a more sweeping review of non-steroidal anti-inflammatory drugs (NSAIDS), such as naproxen, ibuprofen and diclofenac.
It is also likely that there will be public hearings so that the public and scientists can have their say on the matter, he added.
Dr. Berthiaume said patients taking cox-2 inhibitors should contact their physicians to discuss discontinuing use and finding alternative treatments.
Cox-2 inhibitors, which were touted as providing pain relief without causing the gastric problems of traditional painkillers such as ibuprofen and acetylsalicylic acid (ASA), were until recently among the biggest-selling drugs in Canada.
In 2004, there were almost 7.4 million prescriptions for this class of drugs, according to IMS Health Canada, a private company that tracks prescription drug sales.
Celebrex was the market leader with $220-million in sales, followed by Vioxx at $145-million and Bextra at $42-million. Another drug, Mobicox, is often considered a cox-2 inhibitor, but some scientists take issue with that designation. Mobicox and its generic equivalents had sales of $46-million last year, according to IMS Health.
Pfizer spokesman Don Sancton said the company disagrees with the decision by Health Canada but will comply with the request to suspend sales. The company will also "explore options" to determine when sales could resume.
Dr. Berthiaume said that is possible, but only if the company can demonstrate that the benefits of Bextra outweigh the risks.
Despite the new restrictions and more severe warnings on the label, Celebrex now has the cox-2 market almost to itself, though many scientists believe that the cardiovascular risks are similar to those of Vioxx.
Asked if Celebrex could be the next drug withdrawn from the Canadian market, Dr. Berthiaume replied: "No one has gone there."
But then he added: "It's never a final decision when it comes to pharmaco-vigilance. It's an evolving situation."