A 44 y/o AD male patient comes to the clinic after playing softball the previous night. He’s complaining of a sore knee after running hard during the game. On physical exam, he has no evidence of broken bones or joint/ligament injuries. He has no significant medical history, no allergies, and is on no other medications. He doesn’t smoke and is only an occasional user of ethanol. His labs are WNL from a recent 5-year AF physical.

The PA seeing sick call wants to give him a COX2 because he’s AD but needs your countersignature because it’s a non-formulary medication at your hospital.

Do you concur and sign off or not? Why or why not?

SELECT  here for discussion

No. Please NO.

Based on the risk factors (or lack thereof) for GI toxicity from NSAIDs, this patient is at VERY low risk. The assessment of this patient shows he is NOT a candidate for a COX2 inhibitor.

The question with all of the new, expensive prescription drugs should be, “Is the incremental benefit worth the incremental cost?” Is the additional money for a COX2 worth the potential benefit in a specific patient?” Is it cost-effective to prescribe for everyone (i.e. the benefit is just that great) or just a select few with the greatest chance for benefit (i.e the cost makes it prohibitive to prescribe for everyone)? Since the number needed to treat for COX2s is relatively large and the price difference between generic NSAIDs and the COX2s is significant, we need to reserve the COX2 inhibitors for those at greatest risk and those most likely to benefit. (FYI – a thirty day supply of generic ibuprofen 800mg is ~ $2.00 versus a thirty day supply of either celecoxib or valdecoxib @ almost $42.00 – a TWENTY fold increase!)

So how can a provider quantify a patient’s risk to better target COX2 therapy to the most appropriate patients (i.e. those at highest risk for GI toxicities)? The ARAMIS (Arthritis, Rheumatism, and Aging Medical Information System) database was started and has been maintained by Dr Singh at Stanford University. The S.C.O.R.E. (Standardized Calculator Of Risk for Events) tool uses this database to assign weighted risk for different patient characteristics to determine a patient’s risk for GI toxicity. This tool is attached for your use. Answer the 5 or 6 questions in there, determine the # of points based on the individual patient, and compare the patient’s total points/total score to the risk level at the bottom. This will help give you some basis for targeting these medications to the patients most likely to benefit from them.

Several other issues regarding COX2 prescribing we should ALL be looking at include:

1)    COX2 inhibitors and aspirin (even low-dose aspirin) – even low doses of aspirin (as low as 50-75mg) are enough to negate the potential GI benefit of a COX2 inhibitor. If the patient needs low dose aspirin, the addition of a COX2 represents additional cost without the potential benefit.

2)    COX2 inhibitor and proton pump inhibitors (PPIs) – PPIs have been effective in preventing ulcers in patients on NSAIDs. If you have a patient on a PPI, the addition of a COX2 vice a non-selective NSAIDs, is probably not worth the additional cost. A non-selective NSAID (i.e. generic ibuprofen or naproxen) plus a formulary PPI, is far less expensive than a COX2 inhibitor alone…. and probably at least as effective.

3)    Antacids and H2 receptor antagonists do NOT prevent NSAID-induced ulcers. They may help with the dyspepsia some patients experience with NSAIDs but they do NOT prevent NSAID-induced ulcers.

Some other therapeutic ideas may include:

1)    Consider non-acetylated salicylates – salsalate or magnesium salicylate appear to cause less GI bleeding and erosions.

2)    Consider acetaminophen – the drug of choice for osteoarthritis. Useful for minor arthritis pain without the GI toxicity of aspirin or NSAIDs.

3)    Consider misoprostol with non-selective NSAIDs – this agent has been show to prevent NSAID-induced ulcers. Doses vary between 100 mcg po four times a day to 200 mcg po four times a day. The incidence of diarrhea is often unacceptable and the compliance with a four times a day regimen is marginal at best. Lower doses (100 mcg po four times a day) appear to be as effective with less diarrhea. This prostaglandin agonist is pregnancy category “X” (contraindicated).

Some future hopes? These may include the nitric oxide releasing NSAIDs (NO-NSAIDs) and the phospholipid NSAIDs. The NO-NSAIDs maintain and/or increase the gastric mucosal blood flow, thus minimizing gastric injury from NSAIDs. The phospholipids NSAIDs help maintain the mucus gel layer of the gastric mucosa, maintaining the structural barrier protecting the mucosa and reducing erosions and bleeds. Neither of these are FDA approved yet nor commercially available.

This Pearl is meant for academic and educational purposes only. This Pearl is meant to raise important points regarding the safe and cost-effective pharmacotherapy of patients. It is not meant to be the definitive reference for the treatment or prophylaxis of various diseases. Although every effort is taken to ensure this Pearl is correct and factual, errors may occur. The Pharmacoeconomic Center assumes no liability for incorrect information or harm that may occur from the use of the information included in this Pearl.