2004N-0559 - Joint Meeting of the Arthritis Advisory Committee and the Drug Safety and Risk Management Advisory Committee
FDA Comment Number : EC42
Submitter : Dr. Jeffrey Katz Date & Time: 02/07/2005 05:02:41
Organization : Northwestern University Medical Center
Health Professional
Category :
Issue Areas/Comments
GENERAL
GENERAL
Sirs;

It has been with great concern that my anesthesiology and pain management colleagues have observed the condemnation by the media and public of the COX-2 specific inhibitors. These drugs have tremendous use in the surgical patient due to their complete lack of platelet effect, and their time-limited use in this setting renders moot the concerns about cardiovascular safety that are already questionable at best.

Opioid (morphine-type) medications are not the magic bullet for pain medication most people believe. They have numerous side effects and there are frequently pain states that are resistant to morphine, explaining why many doctors inadvertently overdose patients trying to make them comfortable. The primary 'adjunct' to narcotics are the NSAIDs (ibuprofen type) medications, but their use around surgery or procedures is rare because they inhibit platelet function, making bleeding more likely. In fact, the only currently available injectable NSAID is Toradol, which is contraindicated before surgery.

As physicians, we are in dire need of better alternatives to narcotics only for acute pain!! Valdecoxib and parecoxib (Bextra, Dynastat) are such options. The recent CABG trial which showed valdecoxib to increase cardiac complications during/following heart bypass surgery was not compared to an NSAID because an NSAID would be consistently lethal in that setting- COX-2's are the only drugs safe enough to even ATTEMPT such a study. For general surgery they are safe as long as allergy and renal issues are attended to as they should be with NSAIDs.

The recent Alzheimer's trial demonstrating that naproxen also could increase cardiac complications demonstrates that the NSAIDs are not as benign as once thought, and that it is the lack of data on them that are being used to 'prove' their safety. It is being claimed that meloxicam is safer than a COX-2 inhibitor, for example, specifically because it has NOT BEEN STUDIED SPECIFICALLY for cardiac events!

If cardiac warnings are considered for the COX-2 class, I urge that it be considered for ALL NSAIDS unless proven otherwise. Further, I urge that the FDA allow the pharmaceutical companies to market appropriate drug safety and usage information to the public, to clarify the information and quell the hysteria being put forth by the media and excitable consumer groups.

Lastly: A warning about the data being claimed by individuals saying that the COX-2 class is 'prothrombotic' (induces blood clotting). There is NO DATA to support this. The original, and I might add only, limited paper done by Dr. Fitzgerald on this, showed that the prothrombotic data for COX-2 inhibitors WAS THE SAME AS FOR ACETAMINOPHEN. He never mentions this in any editorial, you may notice. Further, no increase in leg blood clots (DVT's) has EVER been noted with the COX-2 inhibitors, especially in hip fracture and replacement surgery studies, which are known for a very high risk for this complication.

In conclusion:
1. Please consider for any cardiovascular or thromboembolic labelling change for the COX-2's that it be applied to all NSAIDs as well

2. Please recognize we need drugs like valdecoxib (Bextra) for acute pain, as our current choices are limited and only moderately effective. Surgical and trauma acute pain are still poorly controlled in this and other countries.

3. Please allow and encourage the pharmaceutical companies to use the media to educate the public on appropriate prescription drug usage. Tobacco industries have been forced to provide anti-smoking campaigns, so perhaps it's time for Pharma to provide anti-overuse and general pharmaceutical education campaigns as well. Please do NOT muzzle them.

Thank you.

Sincerely,
Jeffrey Katz MD
Associate Professor
Dept of Anesthesiology
Section of Pain Medicine
Northwestern University Medical School and Center
Chicago, IL