Caution Urged On Alternative PainkillersMar 8, 2005 | THE BALTIMORE SUN
As patients have turned to other painkillers to avoid the cardiovascular risks associated with Vioxx, Bextra and Celebrex, scientists are casting suspicion on several of the substitutes, especially Mobic.
Prescriptions for Mobic have tripled since September, when the maker of Vioxx voluntarily withdrew the COX-2-inhibiting painkiller because of findings of heart problems. Immediately, the maker of Mobic began courting former Vioxx users, through ads and company representatives' visits to doctors.
The marketing push paid off, making Mobic the fastest growing prescription drug for arthritis. Its share of new prescriptions soared from 5 percent to 19 percent, as of last month.
Weighing benefits, risks
But is Mobic safer than Vioxx, Bextra or Celebrex, which are all COX-2 inhibitors? Some researchers and doctors have expressed doubts. They say Mobic (meloxicam) and several other painkillers may actually work in similar ways and pose similar risks.
"I think they need to be looked at more closely," says University of Texas Southwestern gastroenterologist Byron Cryer, an expert on painkiller risks. "These drugs are getting a get-out-of-jail-free card."
Last month, a Food and Drug Administration advisory panel decided Vioxx, Bextra and Celebrex have significant cardiovascular risks, recommending the agency limit their use, but not recommending removal from the market. FDA action is expected within weeks. Agency officials say that as part of a review of all non-steroidal anti-inflammatories (NSAIDS), they are examining Mobic and similar drugs.
Researchers and public health advocates generally mention five drugs as potentially in the COX-2 inhibitor class: Mobic, diclofenac, etodolac, nabumetone and nimesulide.
Elsewhere, officials have gone further. Australia's drug regulatory agency, the Therapeutic Goods Administration, has placed Mobic in the COX-2 family.
"Meloxicam should not be prescribed for patients with increased risks of cardiovascular events such as heart attacks, and treatment should be limited to the shortest time needed," said University of Sydney Professor Dr. Martin Tattersall.
Vioxx, Bextra and Celebrex are classified as COX-2 inhibitors because they block the cyclooxygenase-2 enzyme. (All anti-inflammatory drugs block this substance, but the so-called COX-2 inhibitors do so more selectively.) When the COX-2 inhibitors first appeared in the late 1990s, pharmaceutical companies aggressively marketed them, emphasizing that the medicines seemed to have fewer gastro-intestinal side effects than older painkillers. The new products became top sellers.
New drugs are COX-2 blockers
Last fall, however, being a COX-2 inhibitor became a liability. Several studies found that the drugs raised the risk of heart attack and stroke. It turns out that the COX-2 enzyme has a dual role: It triggers pain and inflammation, but it also seems to protect the heart, perhaps by keeping blood thin or lowering blood pressure. So blocking it can decrease pain, though perhaps with a price.
Vioxx, Bextra and Celebrex aren't the only drugs that selectively inhibit the COX-2 enzyme. Researchers say that Mobic and some other painkillers, such as diclofenac, are also strong COX-2 blockers, even though they haven't been marketed as such.
Referring to Mobic and diclofenac, University of Pennsylvania pharmacologist Garrett FitzGerald said they would likely turn out to be "Celebrex in sheep's clothing." FitzGerald, also a cardiologist, is an expert on COX-2 inhibitors and heart disease.
The drugs' makers say their products are safe. "We are confident in Mobic. We have observed no trends that indicate an increased risk," said John Yonsky, a spokesman for Boehringer Ingelheim Pharmaceuticals, the German company that makes the drug and, along with Abbott, markets it in the United States.
Wyeth Pharmaceuticals spokesman Lowell Weiner defended etodolac, which is sold by the company under the name Lodine.
"Lodine is a non-steroidal anti-inflammatory drug. It is not a COX-2 inhibitor," he said. "Wyeth stands by the safety of Lodine." Most of the attention has so far focused on Mobic and diclofenac, which is sold as Voltaren. At the FDA's COX-2 hearing, FDA safety officer Dr. David Graham singled out Mobic.
Mobic as risky as Vioxx?
In a study that has yet to be published, he and a collaborator examined heart attack risks among 650,000 Californians taking pain relievers. They found that Mobic appeared to be as risky as Vioxx, which is generally seen as the COX-2 inhibitor that is the most dangerous to the heart.
Graham emphasizes that one study is not enough to prove that a drug is dangerous, yet says the results should encourage cautious use and more research: "If you've got lots of people using it, you want to find out if it's safe."