A University of Florida rheumatologist who specializes in treating a number of chronic pain conditions is urging physicians and their patients to carefully consider all the alternatives before using drugs in a family known as COX-2 inhibitors.
“The higher the selectivity of these enzyme inhibitors, the greater the cardiovascular effects,” warned Dr. Roland Staud. Staud is an associate professor of medicine in UF’s College of Medicine. He is an expert on such chronic pain conditions as rheumatoid arthritis, fibromyalgia and lupus.
The COX-2 inhibitors are a class of drugs developed to be gentler on the stomach than older pain relievers. When Merck, the manufacturer of Vioxx, voluntarily recalled the drug in October, it was the only one in the group that showed cardiovascular risks, but several studies since then have linked Celebrex and Bextra to the same risks.
The evidence for an increased risk of heart attack or stroke was strongest for Vioxx and Bextra, intermediate for Celebrex and weak for naproxen, sold under brand names such as Aleve, Anaprox and Naprosyn. Physicians point out that every drug carries some risks, which must be balanced against the potential benefits in an individual patient.
But as Staud points out, when drugs are heavily marketed to both physicians and the public, there’s a powerful influence to prescribe the newest, latest option, even if an older and less expensive drug is equally effective.
“Physicians are pressured because their patients come in and ask for a drug because they’ve seen it on TV. The doctor may not be well informed about the specific medication and any risks associated with it,” he said.
Staud emphasized that chronic pain specialists knew that the COX-2 inhibitors came with an inherent risk, but the principal concern was with the fact that these drugs could cause gastrointestinal bleeding and ulcers.
“On the other hand, these are very effective agents and a lot of patients with inflammatory illnesses – rheumatoid arthritis, osteoarthritis or lupus, for example – may benefit strongly from these medications,” he said.
Staud said he advises his chronic pain patients to make use of all the other modalities in dealing with their illness, including exercise, sleep improvement and cognitive behavioral therapy. Massage is often very helpful, he noted.
“We also sometimes use topical products – capsaicin or nonsteroidal creams – for local application. Lidocaine patches are another option,” he said.
A problem that has been brought into the spotlight with the withdrawal of Vioxx is that the FDA does not have an effective machinery in place for monitoring side effects that turn up after a drug hits the market. When safety concerns surface, the FDA can now recall a drug, threaten to recall it, or order the maker to change the drug’s label.
Some have called for a more flexible system that would allow the FDA to temporarily suspend sales of a drug while its safety record is examined.
The New York Times has reported that 10 of the 32 members of the government panel that voted last week to let Celebrex, Bextra and Vioxx stay on the market had recently served as consultants for the makers of the drugs.
They did call for a so-called “black box” warning label on the COX-2 class of drugs citing the cardiovascular risk. Bextra already has such a warning.
Staud said any warning label would have to address two issues.
“One would be the time period over which these medications are supposed to be used, and the second would be the portion of the population at highest risk for whom these medications should not be used at all,” he said.
Even then, he noted, putting a label on a drug doesn’t assure that the user will follow it. “Despite the labels saying you should not exceed a specific dose and time, I don’t think a lot of people pay attention to them,” he said.
Looking beyond the immediate issue of whether patients should be prescribed the COX-2 non-steroidal anti-inflammatories, Staud said the Food and Drug Administration’s review system for new drugs needs to be fixed.
“I have been on an FDA advisory panel myself,” Staud said. “It is an interesting set-up, because you see all the drug company representatives sitting out in the audience. You know they are there and that they are watching carefully what you are saying.”
Staud said that in his opinion, decisions about a drug’s safety and efficacy after it is already on the market should not be made by the same group of administrators who approved the drug for use initially.
“That way, their relationships with the industry are not so tainted and they should be able to make better decisions.”