COX-2 Inhibitors

COX-2 inhibitors are a type of NSAID. They treat the pain and inflammation of many types of arthritis and other types of short-term pain. COX-2 inhibitors are as effective as traditional NSAIDs but cause less stomach and intestinal problems. Celecoxib (Celebrex®) is the only COX-2 inhibitor available in the U.S.

What are COX-2 inhibitors?

COX-2 inhibitors are a type of nonsteroidal anti-inflammatory drug (NSAIDs). NSAIDs relieve pain and fever and reduce inflammation.

Examples of older traditional NSAIDs include ibuprofen (Advil®, Motrin®) and naproxen (Aleve®). Unlike these NSAIDs, COX-2 inhibitors work in a different way to reduce pain and inflammation.


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What conditions do COX-2 inhibitors treat?

COX-2 inhibitors are approved to treat mild-to-moderate pain and inflammation caused by:

Your provider may also choose to use a COX-2 inhibitor to treat gout, migraine headaches or other conditions.

How do COX inhibitors work?

There are two types of cyclooxygenase (COX) enzymes in your body, COX-1 and COX-2. Both enzymes make prostaglandins. Prostaglandins are hormone-like chemicals that cause inflammation, pain and fever.

The prostaglandins made by these two distinct enzymes have slightly different effects on your body.

  • COX-1 enzymes are the only enzyme that makes prostaglandins that help your blood clot and protect the lining of your stomach and intestinal tract from digestive acids. Although COX-1 inhibitors (blockers) block inflammation, they also block the helpful effects — the stomach and intestinal lining protection and blood clotting control.
  • COX-2 enzymes make prostaglandins that are mainly involved in inflammation. COX-2 inhibitors mostly block inflammation. COX-2 inhibitors don’t block COX-1 enzymes. This means that your stomach and intestinal lining protection and your body’s blood clotting ability are not severely affected.

In comparison, the more common NSAIDs (like ibuprofen and naproxen) usually affect both COX-1 and COX -2 enzymes. For this reason, these medications are called nonselective NSAIDs. Because COX-2 inhibitors more precisely target COX-2 enzymes, they’re called selective NSAIDs.


Is inflammation good or bad for your body?

Some inflammation is good. It’s part of your body’s natural healing process. However, inflammation that continues for too long can lead to chronic inflammation. Chronic inflammation damages healthy cells, tissues and organs.

What COX-2 inhibitors are available?

Celecoxib (Celebrex®) is the only COX-2 inhibitor available in the U.S.

Etoricoxib (Arcoxia®) and parecoxib (Dynastat®) are available in countries outside the U.S.

Other COX-2 inhibitors have been taken off the U.S. market because of safety concerns.

  • Rofecoxib (Vioxx®) was linked to increases in heart attacks and strokes.
  • Valdecoxib (Bextra®) was linked to an increase in heart attacks and stroke in people who had cardiac bypass surgery. It was also linked to a rare, fatal skin reaction.
  • Lumiracoxib (Prexige®) was found to cause severe liver damage in a small number of people.


How do I take a COX-2 inhibitor?

COX-2 inhibitors are available in pill form (taken by mouth) or as an oral liquid solution.

How long does a COX-2 inhibitor take to work?

Pain relief starts within 60 minutes of taking a dose. It takes a few days to reach COX-2 inhibitor’s full anti-inflammatory effects.

How long can I continue to take a COX-2 inhibitor?

For short-term (days to a couple of weeks) pain relief, you should take the lowest possible dose for the shortest possible time.

For ongoing pain relief for a condition like arthritis, your provider will review your health history and lab tests to determine if this is a safe drug choice for you to take on a more consistent basis. Your provider will review your health history and lab tests to determine if this is a safe drug choice for you.

Always follow the advice and dosing recommendations of your healthcare provider or the medication’s prescribing information. If you have any questions, call your provider.

Who should take COX-2 inhibitors?

Talk with your provider about the pros and cons of taking a COX-2 inhibitor. They are prescribed for the conditions listed in this article.

COX-2 inhibitors may be an especially useful NSAID choice if you:

  • Need to take an NSAID but have a history of gastrointestinal (stomach or intestinal) bleeding.
  • You need to continue to take a blood-thinning drug (anticoagulant) and have an upcoming surgery. You can take a COX-2 inhibitor before and after surgery to reduce pain.

What are the risks of COX-2 inhibitors?

COX-2 inhibitors may increase the risks of:

  • Heart attacks and stroke. There’s an increase in risk in all people who take COX-2 inhibitors and greater risk in those already at risk for heart disease and stroke increases. These risks may be greater at higher dosages or when used for a long time.
  • Stomach and intestinal problems. These can be life-threatening and include bleeding, ulcers, and perforation of your stomach or intestines. These reactions can occur at any time, without symptoms.

Who should not take a COX-2 inhibitor?

You and your healthcare provider will review your medical history and decide if a COX-2 inhibitor is a good medication choice for you.

You shouldn’t take a COX-2 inhibitor if you:

  • Have a history of stroke.
  • Are about to have or recently had coronary artery bypass surgery.
  • Have severe kidney problems or liver failure.
  • Have had an asthma attack or severe allergic reaction while taking another NSAID, aspirin or sulfonamide antibiotics.
  • Have an upcoming surgery (due to the increased risk of severe bleeding).

COX-2 inhibitors are not approved for use in children under the age of 2.

You should use caution if you:

Talk with your healthcare provider about taking a COX-2 inhibitor:

  • If you’re in your last three months of pregnancy.
  • If you’re considering breastfeeding your baby.
  • If you’re older or take other stomach-irritating medications. You’re more likely to experience stomach or intestinal bleeding.

What are the side effects of COX-2 inhibitors?

Side effects are more likely to happen at higher dosages and when COX-2 inhibitors are taken for a long period.

Stomach and intestinal side effects include:

Heart and blood vessel side effects include:

Kidney side effects include:

Neurological side effects include:

If you develop other side effects, contact your provider for advice.

What drugs and other substances interact with COX-2 inhibitors?

COX-2 inhibitors can interact with:

  • Aspirin and other NSAIDs, such as ibuprofen and naproxen. Taken together, these medications may increase stomach and intestinal ulcers.
  • Flunconazole (Diflucan®). Fluconazole increases the concentration of celecoxib in the body.
  • Lithium (Eskalith®). Celecoxib increases the concentration of lithium in the blood.
  • Warfarin (Coumadin®). Celecoxib increases the blood-thinning effects of warfarin.
  • Alcohol. Drinking alcohol while taking celecoxib may increase the risk of stomach ulcers.

Will I have checkups with my provider?

Your provider will want to check your blood pressure, look for symptoms of gastrointestinal bleeding and order blood work to check your kidney and liver function. Your provider will let you know how often you’ll need an office visit.

When should I call my healthcare provider?

Call your healthcare provider right away if have these symptoms:

  • Symptoms of liver problems: dark urine, feeling tired, yellow skin or eyes, light-colored stools, upset stomach or stomach pains.
  • Symptoms of bleeding problems: throwing up or coughing blood; vomit that looks like coffee grounds; blood in your urine; black, red or tarry stools; abnormal vaginal bleeding, bleeding gums or bruising or bruises that get bigger.
  • Symptoms of kidney problems: unable to pee, change in pee volume, blood in your urine or large weight gain.
  • Symptoms of an allergic reaction: rash; hives, itching; wheezing or trouble breathing; or swelling in your face, lips, tongue or throat.

Ask your healthcare provider for other important symptoms to watch for. Never hesitate to call your provider if you have concerns about a possible symptom or experience a change in how you’re feeling.

What questions should I ask my healthcare provider about COX-2 inhibitors?

Be sure to ask:

  • What are the benefits and risks of the COX-2 inhibitors?
  • What are the possible side effects?
  • What side effects should I watch for and call right away if they happen?
  • What dose will I be taking and how many times a day will I take the COX-2 inhibitor?
  • How long is it safe for me to take a COX-2 inhibitor?
  • How often will I have blood tests and other checkups?
  • How do my other health conditions, current medications and drug allergies interact with a COX-2 inhibitor?
  • How long will I need to take the COX-2 inhibitor?
  • What should I do if I want to become pregnant?

A note from Cleveland Clinic

COX-2 inhibitors are a type of NSAID. Unlike traditional NSAIDs, COX-2 inhibitors work in a different way to control inflammation and pain. COX-2 inhibitors are as effective as other NSAIDs at reducing pain and inflammation. However, they cause fewer stomach and intestinal problems, such as bleeding and ulcers. Only one COX-2 inhibitor is available in the U.S., celecoxib (Celebrex). You and your healthcare provider will discuss if a COX-2 inhibitor is the right NSAID choice for you.

Medically Reviewed

Last reviewed on 05/24/2022.

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