Celebrex Has the Scientists Talking

Buffalo, NYIn what could hardly be thought of as a celebration, labeling revisions to Celebrex approved by the US Food and Drug Administration this past fall warning of adverse renal function with long-term use, has been augmented by a report coming out of the University of Buffalo (UB) that Celebrex has been shown in laboratory studies to induce irregular heartbeat.

A popular pain medication used routinely for relief from the discomfort of rheumatoid arthritis, osteo-arthritis, ankylosing spondylitis and the management of other acute pain,
The COX-2 inhibitor served to raise some eyebrows amongst researchers in Buffalo in a way they were not expecting.

While conducting basic research on potassium channels, the UB researchers found that levels of celecoxib representing the standard prescription dose (thought to be a relatively low level) nonetheless served to reduce the heart rate, and induced pronounced arrhythmia in fruit flies and the heart cells of rats.

COX-2 inhibitors have long been shown to produce cardiovascular side effects. Thus, the researchers in Buffalo tested to see if Celebrex would affect the heart in fruit flies, considered a good animal alternative for studies of the heart in other species including, oddly enough, humans.

Dr. Satpal Singh PhD, associate professor of pharmacology and toxicology in the UB School of Medicine and Biomedical Sciences, served as senior author of the study that appeared in the January 18th 2008 edition of the Journal of Biological Chemistry. He notes that the main effect of the drug in their study was induction of arrhythmia, which is "often the result of ion-channel dysfunction," he is quoted as saying.

"We examined the drug's effect on potassium channels and other ion channels in their models and were struck by the strong inhibition of the potassium channels.

"We now have shown an important new effect of Celebrex through a totally different pathway, one that is unrelated to the drug's effect as a pain reducer," Singh said. "The adverse effect arising from this unexpected mechanism definitely needs to be studied more closely, because the potassium channels inhibited by the drug are present in heart, brain and many other tissues in the human body."

Celebrex is known generically as celecoxib and is a member of a group of drugs known as nonsteroidal anti-inflammatory (NSAID). Celecoxib is a COX-2 inhibitor that works by reducing the hormones that cause inflammation and pain in the body.

Pfizer's Celebrex was given formal approval on New Years Eve 1998 and brought onto the market in 1999, the same year as Vioxx. The latter was pulled off the market in 2004 and resulted in a mammoth, multi-billion dollar settlement charge to Merck.

Celebrex, however, is still around, and still has the scientists talking. Dr. Singh:

"The adverse effects of drugs like Celebrex and Vioxx based on their selective inhibition of COX-2 currently are a topic of intense discussion in the medical community."

It should be noted that while that discussion is taking place and investigations continue, Celebrex is still on the market in spite of harboring such concerns for years.

In 2001 the American Heart Association, the National Stroke Association and the Arthritis Foundation all petitioned the manufacturer to test Celebrex for risk of heart attack and stroke. Late in 2004 Pfizer came back to reveal that one of two clinical trials showed an increased risk for cardiovascular events. However, it was reported that a discrepancy with the accompanying clinical trial prompted Pfizer to continue its study.

Meanwhile, Celebrex is still on the market. One has to wonder where all this information was at the time the drug was initially studied prior to approval, and how such a drug with such serious adverse affects not only was approved in the first place, but remains on the market.

A number of lawsuits have been launched against the manufacturer, which has been accused in the past of deceptive marketing, and the suppression of data pointing to the cardiovascular risk. Pfizer claimed, it has been reported, that Celebrex afforded superior pain relief and safety over traditional NSAIDS, and charged premium prices to support that claim: $2.53 to $6.45 per day, as compared with $0.21 to $0.31 per day for NSAID generics.

The FDA has since ordered beefed-up warnings for all NSAID class pain inhibitors, including Celebrex. Thus, Celebrex appears to be just as dangerous, and allegedly even more so, than the others.

At more than 20 times the cost.