NSAIDs, selective cyclo-oxygenase-2 (COX-2) inhibitors

Celecoxib (Celebrex) is included in this drug class.

How COX-2 inhibitors work: These drugs are a new type of NSAID. By inhibiting mainly the COX-2 enzyme, they decrease prostaglandins at the site of inflammation (for example in the joints), but they have less effect on prostaglandins in the GI tract. Therefore, these NSAIDs decrease, but do not eliminate, the risk of gastropathy with stomach erosions, ulcers, and bleeding. They must be obtained with a prescription but are longer-acting than most NSAIDs and have less risk of causing stomach discomfort or ulcers.

Who should not use these medications: People with allergy to aspirin or NSAIDs should not take selective COX-2 inhibitors. Those with allergy to sulfa drugs should not take celecoxib (Celebrex).

Use: COX-2 inhibitors are administered as oral tablets or capsules in various dosage regimens. Take with food to decrease stomach irritation.

Drug or food interactions: Individuals taking anticoagulants (for example, warfarin [Coumadin]) should be monitored for increased bleeding. COX-2 inhibitors may cause fluid retention, thereby decreasing the effectiveness of high blood pressure medications and diuretics (water pills).

Side effects: NSAIDs must be used with caution in patients with a history of peptic ulcer disease or conditions made worse by fluid retention, such as heart failure, high blood pressure, kidney impairment, or liver impairment. Do not use NSAIDs during the last 3 months of pregnancy. Call a doctor if any of the following occur:

• Severe stomach pain



• Bloody vomit



• Bloody or black, tarry stools



• Bloody or cloudy urine



• Unexplained bruising or bleeding



• Wheezing or breathing troubles



• Swelling in the face or around the eyes



• Severe rash or red, itchy skin

Alert: On September 30, 2004, Merck & Co, Inc, announced a voluntary withdrawal of the COX-2 inhibitor rofecoxib (Vioxx) from the US and worldwide market because of its association with an increased rate of cardiovascular events (including heart attacks and strokes) compared to that of placebo. A major Food and Drug Administration (FDA) study of rofecoxib (Vioxx) found that the risk of sudden cardiac death or heart attack apparently increased 3 times among patients who had taken higher doses of Vioxx, compared to that of patients who had not recently received any similar medication. The report showed that even patients taking the standard starting dose of 12.5 mg or 25 mg of Vioxx had a 50% greater chance of a heart attack or sudden cardiac death than the patients on any dose of celecoxib (Celebrex). One explanation for this risk is that rofecoxib does not inhibit platelets from sticking to one another and therefore blood clots may form. Celecoxib does inhibit platelets from forming clots. Blood clot formation is one of the many causes (for example high blood pressure or high cholesterol) that may result in heart attack or stroke.

Alert: On April 7, 2005, valdecoxib (Bextra, by Pfizer, Inc) was voluntarily withdrawn from the US market, pending further discussion with the FDA. The association of valdecoxib with potentially life-threatening risks, including myocardial infarction, stroke, and serious skin reactions, initiated an investigation to determine whether the benefits of the drug outweighed the risks. The serious skin reactions are most likely to occur in the first 2 weeks of treatment, but they can occur any time during therapy. Valdecoxib should be discontinued at the first sign of rash, mouth sores, and/or allergic reactions (eg, swelling, itching, shortness of breath). Other COX-2 inhibitors and traditional NSAIDs (eg, naproxen [Aleve, Naprosyn], ibuprofen [Motrin]) also have a risk for these rare, serious skin reactions, but the reported rate of the reaction appears to be greater for valdecoxib. New data regarding risks in individuals who take valdecoxib following heart bypass surgery showed an increased risk of heart attack, stroke, deep vein thrombosis (blood clots in the leg), and pulmonary embolism (blood clots in the lungs).