Celebrex prescribing information
by Nathan Wei, MD, FACP, FACR
Nathan Wei is a nationally known board-certified rheumatologist and author of the Second Opinion Arthritis Treatment Kit. It's available exclusively at this website... not available in stores.
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Celebrex is an anti-inflammatory drug that is categorized as a COX-2 inhibitor.
This means it blocks the cyclooxygenase pathway that leads to prostaglandin synthesis and inflammation without affecting cyclooxygenase -1 the pathway that governs normal physiologic events such as stomach protection. It exhibits anti-inflammatory, analgesic (pain), and anti-pyretic (fever) properties.
Celebrex is metabolized chiefly via cytochrome P450. Three metabolites, a primary alcohol, the corresponding carboxylic acid and its gluconide conjugate have been identified in human plasma. The metabolites are inactive as COX-1 and COX-2 inhibitors.
Clinical studies leading up to FDA approval demonstrated that the risk for gastrointestinal events such as ulcers and bleeding were less with Celebrex than with traditional non-steroidal anti-inflammatory drugs.
Celebrex comes as a 100mg or 200 mg capsule. The currently recommended dosages are 200mgs a day for osteoarthritis and 400mgs a day for rheumatoid arthritis. In practice, patients with osteoarthritis often receive the higher dose of 400 mgs.
Though it is theoretically safer for people at risk for peptic ulcer disease, it is certainly not 100% safe and should be used with caution in those at risk. Patients taking aspirin for cardiovascular prophylaxis along with Celebrex have the same rate of gastrointestinal complications as people taking other non-steroidal anti-inflammatory drugs. However, on the flip side, Celebrex does not interfere with the anti-platelet activity of aspirin like other NSAIDS do.
Potential side effects are similar to that of other non-steroidal drugs. Of note, people who are allergic to sulfa drugs should not take Celebrex because there is cross-reactivity.
More details may be found in the Physicians Desk Reference (PDR).There has been a furor raised recently over the cardiovascular safety of COX-2 drugs. Studies have shown that all NSAIDS, COX-2 or not, have the same increased risk of cardiovascular events.
Ultimately, the decision to use a COX-2 drug should be based on the same criteria as that used for any drug... do the benefits outweigh the potential risks? The lowest effective dose, as is true of any medication, should be used.
Details from clinical trials regarding some of the cardiovascular data are reported...
Celecoxib (Celebrex, Pfizer) in the Colorectal Adenoma Prevention (APC) trial the first and so far only signal of an increased CV risk for celecoxib compared with placebo. APC was stopped as a result of this finding, but a second similar trial has shown no increase in CV risk.
The APC data are particularly interesting as they show for the first time a CV signal with celecoxib. This finding led to the trial's early discontinuation. APC was a placebo-controlled trial in 2035 patients with a history of colorectal neoplasia; follow-up was between 2.8 and 3.1 years, except for those patients who died. A composite cardiovascular end point of death from cardiovascular causes, myocardial infarction, stroke, or heart failure was reached by:
• Seven of 679 patients (1%) in the placebo group; this includes 1 death from CV causes.
• Sixteen of 685 patients (2.3%) on celecoxib 400 mg (taken as 200 mg twice daily), hazard ratio 2.3 (95% CI 0.9-5.5); this includes 3 deaths from CV causes.
• Twenty-three of 671 patients (3.4%) on celecoxib 800 mg (taken as 400 mg twice daily), hazard ratio 3.4; (95% CI 1.4-7.8); this includes 6 deaths from CV causes.
This published report contains 3 events that were not included in the preliminary analysis that was released in December 2004, when the announcement about the trial being stopped was made; however, they do not change the overall conclusions reached then and repeated now, the authors comment.
The APC trialists conclude that celecoxib was associated with a dose-related increase in the composite CV end point, and these results are consistent among the individual components of the composite end point. In addition, the point estimate of the number of venous thromboembolic events was also increased (although not significantly) in patients taking the drug 4 events in the celecoxib 800-mg group and 3 on celecoxib 400 mg, in contrast with only 1 in the placebo group (hazard ratio for both doses combined 3.5 [95% CI 0.4-28.5]).
"Our results heighten concern that this class of drug may be associated with cardiovascular risk," they comment. However, they also point out that a trial very similar to APC, the Prevention of Spontaneous Adenomatous Polyps (PRESAP) trial comparing celecoxib 400 mg daily with placebo, has shown no apparent increase in cardiovascular risk in a preliminary analysis. One important difference between these 2 trials is that celecoxib was taken twice daily in APC and only once daily in PRESAP, and this supports the hypothesis that sustained inhibition of prostacyclin may contribute to the increase in CV risk, they comment.
The FDA advisory board decision was based on data indicating that while COX-2 drugs may have more cardiovascular safety issues, that they also exhibited other qualities that rendered them valuable medications in the physicians’ arsenal.
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