Evidence continues to grow that the popular pain reliever Vioxx may cause high blood pressure, swelling, and other health problems. And with the latest study, there’s a new concern: High rates of misuse of the popular arthritis remedy, with many patients taking daily doses at twice the usual recommended level.
And it’s not that they are necessarily “doubling up” their prescribed doses for better pain relief. Researchers at Vanderbilt University Medical Center say that patients are often being prescribed the highest 50 milligram dose by their doctors for daily pain relief.
“That’s a cause for concern, because no one should be taking 50 milligram doses for more than five days, but we’re finding that many people are taking it for [everyday] problems,” says study researcher Marie R. Griffin, MD, MPH, professor of medicine and preventive medicine.
“There is no proof that the higher dose is more effective than the 25 milligram dose recommended for chronic pain, and there is pretty good evidence that the higher dose can be more harmful,” she tells WebMD. “Just about all the nonsteroidal medications can cause increases in blood pressure, so this is something that needs to be watched, considering about 10% of the U.S. population takes some type of NSAID. However, there have now been a number of studies showing that especially at 50 milligrams, Vioxx seems to do this more than the others.”
Higher Doses, Higher Risks
Vioxx is a Cox-2 inhibitor, a group of anti-inflammatory medications used to treat arthritis and other painful conditions. These drugs, which also include Bextra and Celebrex, were developed as alternatives to traditional anti-inflammatory drugs like ibuprofen. In general, Cox-2 inhibitors cause less stomach irritation and ulcers. Anti-inflammatory drugs, both old and new, are together known as NSAIDs (non-steroidal anti-inflammatory drugs).
In Griffin’s study, tracking prescription records of 40,000 people taking any type of NSAID, her team found that about one in six patients getting Vioxx were prescribed a monthly course at a dose higher than the recommended 25 mg. About 15% of Vioxx users were taking at least 50 mg a day. However, this 50 mg dose is recommended only for short-term use of sudden, severe pain; daily doses should be prescribed at either 25 mg or 12.5 mg doses, Griffin says.
Her study appears in the June issue of Pharmacoepidemiology and Drug Safety.
Pre-licensing Vioxx studies compared the effects of various doses of Vioxx to other NSAIDs - 2,400 mg of ibuprofen and 150 mg of Voltaren. About twice as many patients taking 50 mg doses of Vioxx - 10% - developed high blood pressure during the first six months of use compared with lower doses of Vioxx or other NSAIDs. They were also about 1 1/2 times more likely to develop leg swelling caused by fluid retention.
In the last six weeks, several studies have suggested possible health problems with Vioxx, even when taken at the recommended lower doses.
In late May, Canadian researchers reported in The Lancet an increased risk for heart failure among elderly people using Vioxx that wasn’t noted in those taking its rival, Celebrex. Compared to Celebrex users, those taking Vioxx were 80% more likely to be admitted to the hospital with heart failure.
And in the June issue of the Journal of Rheumatology, researchers at the Arthritis Research Center Foundation in Wichita, Kan., noted that in examining data on 8,500 patients, patients taking Vioxx were 21% more likely to develop high blood pressure and 23% more likely to develop leg swelling than those taking Celebrex.
Lead researcher Frederick Wolfe, MD, tells WebMD that most of the patients he studied were on the lower 25 mg dose of Vioxx. Only 9% of those in the study took the 50 mg dose, he says.
Beware, or Be Aware?
“My overall impression is that a 50 mg dose is worse, and usually unnecessary,” he tells WebMD. Yet he says he’s not surprised that so many patients in Griffin’s study were taking the higher dose or that it has been linked to a much greater rate of high blood pressure and swelling.
“The problem with observational studies like this is by the time they are published, doctors usually already know about the suspected problems,” says Wolfe, director of the Wichita-based Arthritis Research Center Foundation. “So doctors may have been more likely to detect high blood pressure because they are asking their patients about it.”
Mary Elizabeth Blake, a spokeswoman for Vioxx manufacturer Merck, says Griffin’s report contains no new information on the safety of Vioxx, and like Griffin, she notes that all NSAIDs are associated with high blood pressure and swelling.
“This is well understood and is reflected in the labeling for all prescription NSAIDs, including the Cox-2 inhibitors,” Blake tells WebMD. “Those state that the lowest dose should be sought for each patient.”
Griffin words it differently: “There is absolutely no reason why anyone should take the 50 mg dose for chronic pain,” she tells WebMD. “At this higher dose, you’re not getting any benefit for the risk you’re incurring.”
She also says it’s especially important for anyone taking Vioxx, or any other NSAID, to keep close tabs on their blood pressure.
“If you notice any changes in your blood pressure or with swelling or heart problems, consider that Vioxx may be the cause,” says Griffin. “Your doctor may not connect an increase in high blood pressure to Vioxx, but you should be aware of that possibility. Although it can cause new hypertension, the problem is usually more common in people who already have high blood pressure. We’re not just talking about different readings; people wind up in the emergency room from this.”
Revision date: June 20, 2011
Last revised: by Janet A. Staessen, MD, PhD