This discussion focuses primarily on celecoxib (Celebrex), since it is presently the only available COX-2 specific nonsteroidal anti-inflammatory drug (NSAID) in the United States. For a discussion on reducing side effects in other, traditional types of NSAIDs, see Guidelines to Help Reduce the Side Effects of NSAIDs.
Doctors have long prescribed NSAIDs to ease the pain and inflammation of arthritis, as well as for other types of pain. These medications achieve their benefits by inhibiting certain inflammation-causing chemicals in the body called prostaglandins. Prostaglandins are among a group of substance in the body that can promote inflammation in the joints. NSAIDs block a type of enzyme in the body, called cyclooxygenase (or COX), that plays a role in the production of prostaglandin. Traditional NSAIDs inhibit two types of cyclooxygenase, known as COX-1 and COX-2. However, it has been found that COX-1 plays an important role in protecting the stomach lining. For this reason, inhibiting it can lead to the stomach irritation and ulcers that can be seen when people take most NSAIDs. It appears that for the control of arthritic and other painful symptoms, it is more important for a that a drug block COX-2, which is produced in the body when inflammation is present.
Thus, medical scientists have sought to develop newer NSAIDs that are less likely to cause such gastrointestinal (GI) problems. There have been some debates about which drugs more specifically inhibit COX-2 than others. This debate relates to different methods of testing the drugs. The most agreed-upon system of classifying the COX specificity of different NSAIDs divides the agents into three groups:
The literature on GI side effects with these medications is extensive and still somewhat controversial, but the weight of the evidence still suggests that both the COX-2 selective and COX-2 specific agents have fewer GI side effects than older NSAIDs, as well as fewer of the more serious GI side effects, such as bleeding or perforation of an ulcer.
For the rest of this discussion, the term "COX-2s" refers only to the COX-2-specific agent celecoxib (Celebrex) that is available in the United States. There is not yet sufficient medical literature to allow us to clearly separate the relative safety between these selective and specific drugs. The choice of which drug to use (in those countries where more than one choice is available) is often made based on a particular physician's impression of a drug’s relative effectiveness. In general, when COX-2 specificity is desired for treatment, celecoxib will be most doctors’ first choice due to its higher specificity.
Overall, the COX-2s appear to be equally effective in controlling inflammation compared to the older, less selective NSAIDs. Celecoxib may be considered and is used in patients who are at high risk for stomach irritation, including:
As noted below, however, GI problems can still occur with celecoxib, so precautions, such as the use of acid-blocking medications in higher-risk people, may still be needed along with the celecoxib. For other patients, the ulcer risk may simply be too high to recommend using these drugs at all, as in a patient who is actively being treated for a documented ulcer.
If any of the following guidelines are not clear, or if you think it does not apply to you, discuss the issue with your physician.
Although these drugs (again − in the United States we are referring only to celecoxib) appear to be less likely to irritate the stomach than traditional NSAIDs, such irriation can still occur. Take these general precautions:
The US Food and Drug Administration (FDA) placed the following black box warning on Celebrex, related to potential GI symptoms:
Note that if your physician has advised you to take aspirin for heart protection, this can increase your risk of ulcer and gastrointestinal bleeding. If you add celecoxib to the aspirin, ask your physician whether you should take a medication along with these to protect against ulcers, such as omeprazole (Prilosec).
Celecoxib is contraindicated (not compatible or recommended) in patients with allergy to sulfa-containing drugs (sulfonamides). Such drugs include the antibiotic trimethoprim-sulfamethoxazole (Bactrim, Septra). If you are thinking of taking celecoxib, make sure that you do not have a history of allergy to such drugs. If you aren't sure if a drug you had a bad reaction to fits in this category, ask your physician. If you are allergic to sulfa-containing drugs, do not take celecoxib.
Rofecoxib (Vioxx), a COX-2 specific agent, was removed from the market on September 30, 2004, due to questions of increased risk of heart attacks and strokes. The black box warning from the FDA about cardiovascular problems with non-specific NSAIDs also appears for Celebrex:
Therefore, the use of Celebrex should be carefully considered in a patient with a history of heart disease, hypertension or stroke. If it is decided to use Celebrex in people with such histories, attempts should be made to lower the dose and shorten the duration of use.
Celecoxib, like the non-specific NSAIDs, can adversely affect kidney function. For this reason, people with abnormal kidney function should avoid or sharply limit the use of this medication, and if it is used the kidney function should be followed. Even in people with normal kidney function, if celecoxib is used long-term, then the kidney function should be periodically checked.
Serious skin reactions have occurred in people taking COX-2 inhibitors. These are rare occurrences, but have included potentially life-threatening hypersensitivity reactions. Because many of these reactions were voluntarily reported after the drug was marketed, it is not possible to estimate their frequency or whether they are indeed related to the drug. Severe skin rashes were a major reason for the withdrawal of valdecoxib (Bextra), another COX-2 specific NSAID, from the market, according to the FDA. Therefore, if you experience any rash while you are taking Celebrex, stop taking it immediately and call your doctor.
When you are trying celecoxib for the first time, take the full dose prescribed every day, unless instructed otherwise. It may take as long as two weeks to build up to a "blood level" of the drug, and the drug may not help very much until then. However, there are situations where the pain-killing effect of celecoxib is sufficient and you don’t need to take the full dose every day. Ask your doctor what the goals are for celecoxib in your case, so that you know if you need to take it regularly to build up an “anti-inflammatory drug level.” If the goal was to reach an “anti-inflammatory level” with celecoxib, and you take the drug irregularly, you may never know whether it actually can help you. This could lead to your being switched to a second drug when the first one actually could have helped. Each new drug you take carries a risk of allergic reaction (such as skin rash). Therefore, it's important to find out if a drug can help you before switching to another.
Cease taking celecoxib if:
Call your doctor if: