Severe, sometimes life-threatening allergic reaction that can cause extreme swelling (including swelling of the lips and/or throat), hives, vomiting, and other extreme adverse physical reactions and, if untreated, may interfere with heart function. Anaphylaxis can be a reaction to any allergen, but the most common triggers are food, medication, insect stings, and latex. Anaphylaxis typically occurs shortly after contact with or ingestion of the triggering allergen, but it can occur at any time.

Anaphylactic Shock:

Most severe type of anaphylaxis, in which the body’s systemic response to an allergen results in a drastic drop in blood pressure. It may result in loss of consciousness, and if not treated promptly, may lead to death.

Diclofenac:

Sold under the brand names Voltaren© and Cataflam©, Diclofenac is an NSAID used to treat the symptoms of osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis. Unlike Celebrex, Diclofenac is not a selective COX-2 Inhibitor.

Familial Adenomatous Polyposis:

A very rare, genetic condition in which the patient develops colon and rectal polyps that often lead to premature development of colorectal cancer. FAP is treated with surgery to remove existing polyps, and patients with FAP must be monitored regularly to check for regrowth of the polyps. Celebrex is currently approved for the treatment of FAP, and has been shown to reduce polyp growth when used in conjunction with standard treatments.

Osteoarthritis:

A disease of the joints, most commonly associated with old age and/or repetitive joint stress, in which the cartilage that normally cushions a joint’s movements breaks down, causing pain and inflammation in the affected joints.

Rheumatoid Arthritis:

A disease in which the immune system attacks the cartilage that cushions a joint’s movements, resulting in pain and inflammation. RA can occur in children as well as adults; it is referred to as Juvenile Rheumatoid Arthritis when it affects patients ages 2-17.

Sulfonamide:

Any of a class of drugs, typically called “sulfa” drugs, that are derived from sulfonic acid. Sulfonamides are most commonly used to treat bacterial infections, hypertension, and gout.

Celebrex comes in 100mg tablets. In clinical studies, patients’ results were measured at dosages ranging from 100mg per day or less (or in some cases, only as needed) to 800mg per day (usually administered in two 400mg doses).

Because of the drastic increase in severe complications, including fatal cardiovascular events, in patients who took the highest possible dosages of Celebrex, it is recommended that it be taken in the lowest possible effective dosage. Several factors may affect an individual patient’s prescribed dosage, including diet, body size, and severity of the condition.

Taking Celebrex as Needed

Some patients are prescribed Celebrex on an “as needed” basis, usually for treating severe pain that is chronic but not constant. Celebrex takes around 3 hours to reach maximum potency, partly dependent on food accompaniment. When taken with high-fat foods, Celebrex may take up to 2 hours longer to reach peak potency. In studies, patients who took Celebrex “as needed” experienced very few adverse reactions and side effects. However, the majority of patients for whom Celebrex is prescribed take it regularly in order to treat degenerative pain conditions (such as arthritis).

Body Size and Dosage:

Dosage is often related to body size and body mass, as these factors affect how potent a drug becomes in a patient’s system. According to Pfizer (manufacturer of Celebrex), in patients under 110 lbs., “the lowest possible dosage” should be used.

Drastic increases in absorption rates have also been discovered in patients over the age of 60 (partly due to lower average body weight) and in patients of African-American descent (for unknown reasons). These factors, along with the nature and severity of the patient’s condition, determine a doctor’s decision on dosage.

In clinical studies, dosages were not determined by individual patient factors, but rather by the condition on which the drug was tested. In some cases, that is how the drug is currently prescribed.

For example, some doctors may prescribe 200mg BID (twice daily) of Celebrex to any patient suffering from Rheumatoid Arthritis, regardless of the patient’s weight, and only adjust the dosage if the patient is under 16 or over 60.

Celebrex Dosages and Lawsuits

Clinical studies showed a much greater incidence of side effects and severe complications in patients who used high doses of Celebrex (400mg per day or more). Part of the decision of the judge in a Celebrex lawsuit is whether there is scientific evidence that a specific dosage can be linked to a litigant’s side effects or complications.

Though a 2007 decision by a San Francisco judge found insufficient evidence for the risks of Celebrex prescribed at 200mg per day, it is unknown whether that finding took into account the body weight, body mass, and other metabolic factors of the patients in question. It is likely that this discrepancy will become the basis of future lawsuits, even if future litigants were taking 200mg of Celebrex per day.

Except in the case of class-action suits, each lawsuit is handled individually, with respect to each patient’s personal experiences. Only a specialized legal representative can determine whether dosage will have a bearing on a specific case. Despite the 2007 decision, there is no reason to believe that Pfizer will not face future lawsuits from patients who took 200mg of Celebrex daily.

The information contained in this web site applies to the drug Celebrex, and to its generic version Celecoxib. According to the FDA, generic drugs are identical to brand-name drugs in use, dosage, effectiveness, format, risk, and active ingredient.

What is Celebrex?

Celebrex (or Celebra, as it is known outside of the US) is the brand name of the drug Celecoxib, a pain treatment medication originally developed by G.D. Searle & Co. and now manufactured by Pfizer. Celebrex is one of a class of pain treatment drugs called NSAIDs.

Chemistry of Celebrex

Chemical Formula: C₁₇H₁₄F₃N₃O₂S

Chemical Name: methylphenyl-trifluoromethyl-pyrazol-benzenesulfonamide

As is evidenced by the ending “-sulfonamide,” Celebrex is a “sulfa drug,” or a member of the drug class sulfonamides. Celebrex may cause an allergic reaction in people with a known allergy to sulfonamides.

What are NSAIDs?

NSAIDs, or Non-Steroidal Anti-Inflammatory Drugs, are used in certain patients to treat chronic pain conditions such as osteoarthritis, rheumatoid arthritis, and in some cases menstrual cramps, as well as acute pain. NSAIDs are designed to have the effectiveness of steroidal pain medications, without the side effects associated with the narcotic steroids.

How Does Celebrex Work?

Celebrex treats inflammation by preventing the body’s synthesis of a chemical called prostaglandin. Prostaglandin has a dual effect in the body: protecting the stomaching and intestinal lining with a layer of mucous (associated with the COX-1 enzyme); and causing inflammation and pain (associated with the COX-2 enzyme). Celebrex is called a Selective COX-2 Inhibitor because it is designed to target the COX-2 enzyme specifically, while sparing the protective effects of the prostaglandin formed by COX-1.

COX-2 Inhibitors have been available since the late 1990s. Learn more about the history of Celebrex.

CLASS Study: Celebrex Long-Term Arthritis Safety Study

One of the only long-term studies available on Celebrex, the CLASS study was designed to assess the long-term risks and benefits of NSAID use in patients with arthritis. The study compared the long-term effects of the NSAIDs Celebrex, Diclofenac, and Ibuprofen on 5,800 patients with Osteoarthritis and 2,200 patients with Rheumatoid Arthritis.

Although it was concluded that Celebrex did not carry a higher cardiovascular risk than the other study drugs, it was found that Celebrex combined with a low-dose aspirin regimen caused a four-fold increase in bleeding ulcers and other serious gastrointestinal complications 6 to 9 months into treatment.

Celecoxib Versus Naproxen and Diclofenac in Osteoarthritis Patients: SUCCESS-I Study

The SUCCESS-I study tested the effects of Celebrex compared to the non-selective NSAIDs in treating the pain of osteoarthritis. The study was notable because of its sample size, including over 13,000 participants from 39 countries, but it was not designed to measure cardiovascular risks. The goal of the study was to measure the comparative risk of gastrointestinal complications in patients using selective and non-selective NSAIDs. Patients were given either 200mg or 400mg of Celebrex, 100mg of Diclofenac, or 1000mg of Naproxen daily for 12 weeks.

It was concluded that Celebrex carried a lower risk of gastrointestinal complications, including bleeding ulcers, than non-selective NSAIDs, but did not provide better pain management. The study reported no significant difference in number of serious cardiovascular events during the study (10 in the Celebrex group compared to 1 in the NSAID group), however percentage notwithstanding it would seem that the Celebrex group had a ten-fold higher rate of cardiovascular complications.

APC Trial: Prevention of Sporadic Colorectal Adenomas with Celecoxib

The APC Trial tested the effects of daily Celebrex use in reducing colorectal polyp growth in patients who had undergone surgery to remove adenomas (non-cancerous growths in the colon and rectum). Over 2,000 patients participated in the placebo study beginning in 1999, receiving either 400mg or 800mg of Celebrex daily.

The 2004 withdrawal of Vioxx (Rofecoxib) from the market spurred great public debate over the safety of Celebrex and similar drugs, which resulted in the formation of the Cardiovascular Safety Committee (CSC) to oversee studies involving potentially risky drugs. Additionally, the APC trial was monitored by a Data Safety Monitoring Board (DSMB) which worked together with the CSC to examine the safety of the study. Study results were publicized reporting that Celebrex was associated with an increased risk of cardiovascular complications: specifically, the study found a 2.5% increased risk in patients receiving the lower dosage and a 3.4% increased risk in patients receiving the higher dosage compared to placebo. As a result, the CSC and DSMB made the decision to suspend the use of the drug in the study.

In 2008, the five-year results of the trial became available, measuring the effects of three years of Celebrex therapy after a two-year cessation of the drug. The results showed a 41% decrease in adenomas in patients who received 400mg of Celebrex daily, and a 24% decrease in patients who received 800mg daily during the course of the study. It was still concluded that the drug carried an increased risk of cardiovascular events, particularly in patients with at least two preexisting conditions putting them at greater risk of heart attack or stroke. For these patients, the risk of heart attack and stroke was 3-6% higher than in the placebo group. In patients with no preexisting risk factors, there was still a 1-3% increased incidence of cardiovascular events over placebo.

ADAPT Trial: Alzheimer’s Disease Anti-Inflammatory Prevention Trial

Beginning in 2001, the ADAPT trial, sponsored by the National Institute of Aging, tested the effectiveness of Celebrex and Naproxen (compared to placebo) at delaying the onset of Alzheimer’s Disease in just over 2600 patients with a family history of the disease. The theory was that treating the inflammation in the brain associated with Alzheimer’s might stave off the symptoms of the disease. Study participants received either 400mg of Celebrex daily or 440mg of Naproxen daily. The study was monitored by the Treatment Effects Monitoring Committee (TEMC). Two scales were used to measure the cognitive changes of the patients in the study: the Alzheimer’s Disease Assessment-Cognitive Behavior (ADAS-Cog) and the Clinician’s Interview-Based Impression of Change Plus (CIBIC-Plus).

During the study, the ban of Vioxx and interruption of the concurrent APC trial caused the ADAPT study to receive additional scrutiny. The results at that time showed a slightly higher rate of cardiovascular events in patients taking Naproxen than those taking Celebrex. Because Celebrex was determined unsafe at that time for use in the APC trial and the partial results of the ADAPT trial showed an even higher risk associated with Naproxen, the ADAPT trial, intended to run for 5-7 years, was cut short after 23 months.

A Brief History of Celebrex

1998: Celebrex is approved for the treatment of osteoarthritis and rheumatoid arthritis

When Celebrex was approved by the FDA in 1998, it was a promising new treatment for the millions of people living with the pain of osteoarthritis (approximately 27 million in the US alone) and rheumatoid arthritis (1.7 million in the US). The use of the selective COX-2 inhibitor was intended to prevent the adverse effects that were believed to be linked to the inhibiting of the COX-1 enzyme.

Celebrex was tested against other NSAIDs and against placebos in 2100 patients with rheumatoid arthritis (RA) and 4200 patients with osteoarthritis (OA). It was found to be equally as effective as other NSAIDs at relieving pain and inflammation compared to placebo. With its approval of the drug, the FDA mentioned the possibility that Celebrex carried the risk of cardiovascular complications.

At the same time that Pfizer was preparing to release Celebrex, Merck & Co. was preparing to release their similar drug, Vioxx, which would be marketed to the same population of patients. Celebrex beat Vioxx to the shelves narrowly, enjoying a year of virtually unrivaled sales until the release of Vioxx in 1999. Both Pfizer and Merck & Co. went to great expense to market their respective new drugs to arthritis sufferers, including an emphasis on direct-to-consumer print and television advertising.

How does Celebrex work?

Original Package Warnings for Celebrex

With its initial release, Celebrex came with a package warning about the danger of ulcers and possible interference with platelet function, as has been associated with the entire class of NSAID drugs. Because the original clinical trials were only 6 to 12 months in duration, it was undetermined whether Celebrex posed a risk of serious cardiovascular events with prolonged use.

1999: Packaging Change for Celebrex Warns of Interaction with Warfarin

In 1999, Pfizer changed the package warning on Celebrex to include the danger of interaction with the drug Warfarin, which is an anticoagulant agent. During the original clinical trials, there was no evidence of a particularly adverse reaction with Warfarin, but soon after the release of the drug, the FDA received several reports of patients who had experienced fatal cardiovascular events while taking Warfarin and Celebrex. In several reported cases of patients taking Warfarin, Celebrex reacted with the drug to enhance its anticoagulant effects to unsafe levels. This not only contributed to the possibility of cardiovascular events, but increased the risk of bleeding to death, especially if stomach or intestinal perforations are present.

1999: FDA Approves Celebrex for the Treatment of Familial Adenomatous Polyposis

In 1999, Celebrex was approved by the FDA for the treatment of Familial Adenomatous Polyposis (FAP), a rare but serious hereditary condition in which the patient develops colon polyps that tend to develop prematurely into colon and rectal cancer. During a six-month trial of 83 patients with FAP, there was a 28% reduction in colon polyps in patients who took 400mg of Celebrex daily, compared to a 5% reduction with placebo.

It was emphasized that the use of Celebrex in treating FAP should not be considered a substitute for more traditional treatments, which typically include surgical reduction of tumors and frequent endoscopic surveillance. Coupled with these aggressive techniques for managing FAP, Celebrex was believed to reduce the growth of polyps and thereby aid in the prevention of cancer development in these patients.

2004: Vioxx is Withdrawn from the Market

After studies showed that COX-2 Inhibitor Vioxx (Rofecoxib) caused a dramatic increase in fatal cardiovascular events, including heart attack and stroke, Merck & Co. withdrew the drug in September of 2004. These risks were directly proportional to the length of treatment and dosage that patients received. The Vioxx ban caused a hike in sales for competing drugs Celebrex and Bextra, the only two remaining COX-2 Inhibitors on the market.

In response to the ban of Vioxx, Pfizer agreed publicly that there was also reason for concern surrounding Celebrex, and possibly the entire class of COX-2 Inhibitors, and the risk of death by gastrointestinal perforation, heart attack, or stroke. Pfizer agreed that further studies, as well as meta-research on existing studies, were necessary to determine the absolute safety of the drug. As a concession, Pfizer agreed to suspend direct-to-consumer advertising until further notice from the FDA.

The FDA announced that there was “great concern” over Celebrex and its class of drugs (NSAIDs and COX-2 Inhibitors in particular), but at that time the FDA decided to “keep its options open” regarding the approval of Celebrex. At the same time, doctors and consumers alike were reminded to seek alternative treatments whenever possible.

2005: Bextra is Withdrawn from the Market

In 2005, Bextra (valdecoxib) was withdrawn from the market on recommendation of the FDA after, as in the case of Vioxx, it was discovered that the drug caused an increased risk of serious cardiovascular events, particularly in patients recovering from bypass or other heart surgery. Bextra, manufactured by G.D. Searle & Co. and sold by Pfizer, was also found in rare cases to cause a fatal skin reaction which, despite a related black box warning, was part of the reason for the drug’s withdrawal.

The Bextra ban, though a blow to the pharmaceutical company, was a blessing for the sales of Celebrex, which enjoyed an all-time high after the Bextra ban. At that time, Celebrex became the only COX-2 Inhibitor on the market, and for many chronic pain sufferers, steroidal pain killers are not desirable as an alternative to NSAIDs because of their side effects. Thus, the FDA determined that the benefits of Celebrex outweighed the risks, and the drug was allowed to stay on the market, but with additional safety information enclosed. It was also suggested to the medical community that all patients be advised of the risks and alternatives to NSAIDs, and that they be prescribed in the lowest effective doses. Additionally, it was reiterated that Celebrex is not recommended for patients at otherwise higher risk of cardiovascular complications, patients who are pregnant or breast feeding, or patients with liver problems.

2005: FDA Approves Celebrex for the Treatment of Ankylosing Spondylitis

In 2005, the FDA added Ankylosing Spondylitis to its list of approved uses for Celebrex. Ankylosing Spondylitis, also called spinal arthritis, is a chronic inflammatory disease which can cause rigidity and loss of movement in the neck and spine. During the two pre-approval clinical trials of 6-12 weeks in duration, patients took between 100mg and 400mg of Celebrex daily. The study measured patients’ pain intensity and range of motion, and around half of subjects showed significant improvement compared to placebo. Patients taking the highest dose (400mg daily) showed the most improvement on average. Long-term results of the study are not available.

2006: FDA Approves Celebrex for the Treatment of Juvenile Rheumatoid Arthritis

In 2006, The FDA approved the use of Celebrex for the Treatment of Juvenile Rheumatoid Arthritis (JRA). This disease affects an estimated 300,000 patients aged 2-17 in the US alone. After a six-month clinical study showing only mild to moderate side effects and no other complications, the drug received approval. Celebrex has never been tested on patients under 2 years of age. The study results did not rule out cardiovascular complications with continued and prolonged use, as was seen in the case of Vioxx, but based on the patients’ reports of pain relief the benefits were seen to outweigh the risks.

There is debate about whether longer-term testing should be necessary before a drug can be deemed safe for new usages, especially since drug companies are anxious to release new drugs in order to make sales. It is still unknown whether the treatment of JRA with Celebrex may carry a greater risk of serious complications with prolonged use. Official reports on the long-term effects of Celebrex on JRA sufferers are not yet available, but the drug is still currently being prescribed to JRA sufferers.

Learn more about Celebrex Dosages.

Short-term Effects of Celebrex

In short-term studies, patients suffering from chronic pain, such as is associated with arthritis, experienced the same level of pain relief with COX-2 Inhibitors as with other NSAIDs, but with fewer immediate gastrointestinal side effects.

Long-term Effects of Celebrex

Celebrex was designed specifically for use with chronic conditions requiring long-term pain management. Over the course of long-term pain management therapy using Celebrex, patients on average found Celebrex to be effective, particularly at higher dosages. However, side effects including stomach ulceration occurred at a higher rate in patients who were on high dosages of the medication (400mg or more per day). Additionally, in long-term studies, COX-2 Inhibitors, especially administered in high dosages, caused a higher incidence of fatal cardiovascular events than placebo.

While Celebrex may ease the painful symptoms of osteoarthritis and rheumatoid arthritis, it does not slow down or halt the progression of these diseases.

Though Celebrex remains on the market while many COX-2 Inhibitors have been banned, it is recommended that the minimum dose be used, and it is not recommended at all for patients with a higher-than-average risk of cardiovascular complications, including stroke and heart attack.

Absorption Variations

Celebrex is processed at different rates by different people. On average, the measure of drug absorbency versus time, called the area under the curve (AUC), varies within test sub-groups. A higher AUC means that a lower dosage of the medication is required for maximum potency, compared to the average. In studies, the following variations in AUC were found:

• Elderly patients (aged 65 and up) had a 50% higher AUC.
• Blacks showed a 40% higher AUC than caucasions, for unknown reasons.
• Patients with Hepatitis A showed a 40% higher AUC, and patients with Hepatitis B showed a 180% higher AUC.
• Patients with renal insufficiency showed a 40% lower AUC than average.

Osteoarthritis is a degenerative disease in which the cartilage cushioning the joints becomes damaged and worn. With Rheumatoid Arthritis, an autoimmune malfunction causes the immune system to attack the joints themselves. In both cases, the body responds with pain and inflammation. Doctors have long sought to treat pain by addressing inflammation. Celebrex is a type of COX-2 Inhibitor, a class of drugs commonly prescribed to treat the symptoms of chronic pain conditions such as arthritis.

COX-2 Inhibitors like Celebrex target pain by prohibiting the absorption of the enzyme cyclooxygenase. COX-2 Inhibitors were intended to be an improvement on traditional NSAIDs, which equally target COX-1 and COX-2 enzymes, thereby causing a much higher incidence of gastrointestinal damage.

Understanding COX-2 Inhibitors

Many pain medications work by affecting the interaction of two enzymes found in blood vessels, the stomach, and the kidneys. These enzymes, COX-1 and COX-2, are responsible for the body’s production of a chemical called prostaglandin. Prostaglandin has multiple functions in the body, some of which are harmful, and some of which are protective.

So-called “good prostaglandin,” formed by the COX-1 enzyme, functions to protect the stomach lining and gastrointestinal tract by preventing stomach acid from penetrating tissues. COX-2, on the other hand, is responsible for the production of so-called “bad prostaglandin,” which causes a chemical reaction resulting in inflammation and pain.

COX-2 inhibitors were created with the goal of targeting COX-2 enzymes specifically, while sparing the COX-1 enzymes that protect the gastrointestinal tract from injury. Traditional pain killers such as ibuprofen target COX-1 and COX-2 enzymes almost equally, resulting in their association with stomach pain and ulcers as a side effect of pain relief. Specialized drugs like Celebrex specifically target the COX-2 enzyme with 7 to 300 times more preference than the COX-1 enzyme, theoretically providing a much greater proportion of pain relief compared to the possible gastrointestinal damage.

The “super-aspirins” Celebrex, Vioxx, and Bextra offer a potent form of COX-2 inhibitor which, although it does not directly damage the gastrointestinal lining as in the case of aspirin, still causes side effects similar to those of traditional pain killers.

When a new drug hits the market, it is protected by patent laws for a certain period of time and cannot be produced by any other manufacturer until its original patent expires. The patent lasts for 20 years, and begins long before clinical trials. The idea behind this patent period is that the manufacturer who makes the original investment in developing the drug can recoup those costs by enjoying exclusive production rights for a limited time. By the time a drug is released and approved for use, the patent normally covers it for another 7-12 years, after which generic versions can be produced.

Facts about Generic Drugs

Generic drugs are required to contain the same active ingredients as their brand-name counterparts. Inactive ingredients, such as colorings and flavorings, can vary. Generic versions of drugs must also be identical to the originals in dosages, routes of administration (e.g. tablets vs. ointment), strength, safety, quality, purity, and intended use.

Companies wishing to produce generic drugs must first apply to the FDA, and they usually do so before the patent has expired to allow time for production. Generic drugs normally cost 30-80% less than exclusive brand-name drugs. The price of brand-name drugs usually drops when generic versions become available, both to stay competitive and because, in theory, the original manufacturer of the drug has by that time recouped its original research expenses. In many cases, a drug’s original manufacturer will later produce a generic version of its own drug and sell it without the brand name. According to the FDA, about 50% of generic drugs are produced by brand-name drug manufacturers.

Generic drug manufacturers are subject to the production standards of the FDA, ensuring consumers that generic drugs are produced in clean, safe environments. The FDA conducts 3500 inspections of generic drug manufacturing plants per year.

Celebrex Vs. Celecoxib

Celecoxib is the active ingredient of the drug Celebrex. A generic drug is referred to by the name of its active ingredient, so if you buy generic Celebrex it will be called Celecoxib. Patent law prohibits a generic drugs from taking the exact appearance of the brand-name alternative, but in all other ways generic drugs are considered equal to brand-name drugs.

Your rights and guarantees as a consumer are the same, as are the associated risks and side effects, regardless of whether you take brand-name or generic drugs. Generic Celecoxib carries the same black box warning as brand-name Celebrex, concerning the risk of severe cardiovascular complications including heart attack and stroke.