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Drugs & Supplements

COX-2 Nonsteroidal Anti-inflammatory Drugs (NSAIDs)

What are COX-2 nonsteroidal anti-inflammatory drugs (NSAIDs)?

The COX-2 inhibitors are a newer class of NSAIDs. These drugs reduce pain and inflammation just like traditional NSAIDs (drugs such as aspirin, naproxen (Naprosyn®), diclofenac (Voltaren®), and ibuprofen (Advil®, Motrin®). Both COX-2 inhibitors and traditional NSAIDs have equal ability to control pain and inflammation. However, COX-2 inhibitors have an added safety benefit; they are less likely to cause stomach problems such as ulcers, bleeding, and obstruction.

How do COX-2 NSAIDs work?

Traditional NSAIDs act by blocking the production of a family of chemicals (known as prostaglandins) that cause inflammation. Two enzymes that are important for allowing prostaglandins to cause inflammation - COX-1 and COX-2 enzymes.

Traditional NSAIDs work by blocking both COX-1 and COX-2. The COX-2 inhibitors work by blocking ONLY the COX-2 enzyme. By blocking the COX-2 enzyme, these new drugs can help block pain and inflammation and still allow the COX-1 enzyme to work. This is important because COX-1 enzymes help protect the stomach lining, which decreases the chance of having a stomach ulcer and/or bleeding.

What are the names of the newer COX-2 inhibitors?

Only one COX-2 inhibitor is available at this time - celecoxib (Celebrex®).

Both rofecoxib (Vioxx®) and valdecoxib (Bextra®) have been removed from the market because of concerns of an increased risk of heart attacks or stroke. Valdecoxib was suspended by Pfizer when the FDA found an increased rate of heart problems as well as an increased rate of rare, serious skin reactions.

How are COX-2 inhibitors safer than traditional NSAIDs?

Two large clinical trials - the CLASS study for celecoxib, and the VIGOR study for rofecoxib - collectively enrolled over 10,000 patients. Both of these studies (and other smaller studies) showed that people who took the COX-2 inhibitors had fewer gastrointestinal problems – especially ulcerations, perforations, and bleeding – compared with traditional pain relievers.

Are COX-2 inhibitors as effective as traditional NSAIDs?

Absolutely. It is important to realize, however, that celecoxib is not any more potent at relieving pain or inflammation than traditional NSAIDs. It is simply a safer alternative for those patients with an increased risk of stomach ulcers and/or bleeding.

How are COX-2 inhibitors prescribed?

Celecoxib (Celebrex) is prescribed in 100 mg or 200 mg capsules and can be taken once or twice a day, as directed by your doctor. The general dose for osteoarthritis is 100 or 200 mg a day and the dose for rheumatoid arthritis is 200 mg up to twice a day.

Do COX-2 inhibitors protect a person from a heart attack or a stroke like aspirin has been shown to do?

No. This is because these drugs do not interfere with blood clotting like aspirin does. COX-2 inhibitors may be taken with aspirin, but even this small dose places the individual at risk for aspirin-related stomach toxicity and bleeding. Check with your doctor before taking these two drugs together.

Does everyone who takes an NSAID need to be on a COX-2 inhibitor?

No. The risks from traditional NSAIDs are low for most individuals. Those who stand to benefit most from COX-2 inhibitors include those who are at increased risk for stomach complications and bleeding. Also, COX-2 inhibitors may be a safer choice for patients who are at risk for bleeding in general - those patients who are taking anticoagulants or having surgery. This is because the COX-2 inhibitors do not affect blood clotting as much as traditional NSAIDs. Patients who are taking an oral anticoagulant-such as warfarin (Coumadin®)-need to have their blood monitored more often and especially when starting a COX-2 inhibitor or traditional NSAIDs.

Do COX-2 inhibitors have similar side effects to traditional NSAIDs?

Yes, aside from the improved safety features of the COX-2 inhibitors, the other possible side effects are the same as noted for traditional NSAIDs. These include an increased chance of heart attack or stroke, rare liver and kidney problems, headaches and dizziness, allergic reactions and rashes. NSAIDs, including COX-2 inhibitors, should not be used during or immediately after a coronary artery bypass graft (CABG).

Please note: The side effects listed are the most common. All possible side effects are not included. Always contact your health care provider if you have questions about your particular medication. Patients with significant renal disease should not take NSAIDs.

How can I minimize my chances of a side effect from NSAIDs?

NSAID medicines should only be used exactly as prescribed. It is safest to use NSAIDs at the lowest possible dose and for the shortest time needed for your treatment. Do not use more than one type of NSAID at the same time. Do not add over the counter NSAIDs to any prescription dose of NSAIDs.

Please note that the chance of a person getting an ulcer or bleeding increases with the following:

  • Age > 60 years
  • Previous history of stomach ulcer disease
  • History of smoking
  • History of alcohol consumption
  • Concurrent use of prednisone or blood thinning medication
  • Poor health or multiple medical problems

Can I take a COX-2 inhibitor if I am being treated for high blood pressure?

All NSAIDs, including COX-2 inhibitors, can raise blood pressure in some people. Patients with high blood pressure who are starting any form of NSAID therapy should have their blood pressure monitored more closely. If blood pressure increases while taking both blood pressure medications and an NSAID, your doctor might consider stopping or changing your NSAID.

As with any medication, always follow the directions on the label and the instructions from your health care provider. It is not recommended to combine a COX-2 inhibitor with a traditional NSAID other than low dose aspirin, because all the safety advantages will be lost.


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This information is provided by the Cleveland Clinic and is not intended to replace the medical advice of your doctor or health care provider. Please consult your health care provider for advice about a specific medical condition. This document was last reviewed on: 5/2/2014...#13288