NationMaster - Encyclopedia: Rofecoxib

Rofecoxib (IPA: [rofəˈkɒksɪb]) is a nonsteroidal anti-inflammatory drug (NSAID) developed by Merck & Co. to treat osteoarthritis, acute pain conditions, and dysmenorrhoea. Rofecoxib was approved as safe and effective by the Food and Drug Administration (FDA) on May 20, 1999 and was subsequently marketed under the brand name Vioxx®, Ceoxx® and Ceeoxx®. In pharmacology and toxicology, a route of administration is the path by which a drug, fluid, poison or other substance is brought into contact with the body 1. ... For information on how to read IPA transcriptions of English words see here. ... Non-steroidal anti-inflammatory drugs, usually abbreviated to NSAIDs, are drugs with analgesic, antipyretic and anti-inflammatory effects - they reduce pain, fever and inflammation. ... Osteoarthritis (OA, also known as degenerative arthritis or degenerative joint disease, and sometimes referred to as arthrosis or osteoarthrosis or in more colloquial terms wear and tear), is a condition in which low-grade inflammation results in pain in the joints, caused by wearing of the cartilage that covers and... Look up Pain in Wiktionary, the free dictionary. ... Dysmenorrhea (or dysmenorrhoea), cramps or painful menstruation, involves menstrual periods that are accompanied by either sharp, intermittent pain or dull, aching pain, usually in the pelvis or lower abdomen. ...

Rofecoxib gained widespread acceptance among physicians treating patients with arthritis and other conditions causing chronic or acute pain. Worldwide, over 80 million people were prescribed rofecoxib at some time.

On September 30, 2004, Merck voluntarily withdrew rofecoxib from the market because of concerns about increased risk of heart attack and stroke associated with long-term, high-dosage use. Rofecoxib was one of the most widely used drugs ever to be withdrawn from the market. In the year before withdrawal, Merck had sales revenue of US$2.5 billion from Vioxx. ^{[citation needed]}

Rofecoxib was available on prescription as tablets and as an oral suspension. A medical prescription ) is an order (often in written form) by a qualified health care professional to a pharmacist or other therapist for a treatment to be provided to their patient. ...

The COX Enzyme

In the early 1990s, scientists discovered that the COX enzyme had two forms, now called COX-1 and COX-2. COX-1 mediated the synthesis of prostaglandins responsible for protection of the stomach lining, while COX-2 mediated the synthesis of prostaglandins responsible for pain and inflammation. By creating “selective” NSAIDS that inhibit COX-2, but not COX-1, scientists hypothesized they could offer the same pain relief as traditional NSAIDS, but with greatly reduced risk of fatal or debilitating peptic ulcers.

Rofecoxib is a selective COX-2 inhibitor or coxib (CycloOXygenase-2 InhiBitors). Others include Pfizer’s celecoxib (Celebrex) and valdecoxib (Bextra). Interestingly, at the time of its withdrawal, rofecoxib was the only coxib with clinical evidence of its superior gastrointestinal adverse effect profile over conventional NSAIDs. This was largely based on the VIGOR (Vioxx GI Outcomes Research) study, which compared the efficacy and adverse effect profiles of rofecoxib and naproxen. (Bombardier et al., 2000). Naproxen (trade names: Aleve, Anaprox, Naprogesic, Naprosyn, Naprelan) is a non-steroidal anti-inflammatory drug (NSAID) commonly used for the reduction of mild to moderate pain, fever, inflammation and stiffness caused by conditions such as osteoarthritis, rheumatoid arthritis, psoriatic arthritis, gout, ankylosing spondylitis, injury, menstrual cramps, tendinitis, bursitis, and the...

Adverse drug reactions

Main article: Non-steroidal anti-inflammatory drug Non-steroidal anti-inflammatory drugs, usually abbreviated to NSAIDs, are drugs with analgesic, antipyretic and anti-inflammatory effects - they reduce pain, fever and inflammation. ...

Aside from the reduced incidence of gastric ulceration, rofecoxib exhibits a similar adverse effect profile to other NSAIDs. Rofecoxib, however, does appear to increase the risk of adverse cardiovascular events (see below). Image File history File links Download high-resolution version (1641x2227, 1253 KB) Summary Photograph of Vioxx sample pack. ... Non-steroidal anti-inflammatory drugs, usually abbreviated to NSAIDs, are drugs with analgesic, antipyretic and anti-inflammatory effects - they reduce pain, fever and inflammation. ...

The chief mechanism proposed to explain rofecoxib's cardiotoxicity is the suppression of prostaglandin, an anti-clotting agent in the blood (Fitzgerald, 2004). COX-2 plays a role in the production of prostaglandin. Because Vioxx inhibits the COX-2 enzyme, prostaglandin production can decrease in endothelial cells and lead to an inefficiency in declumping and vasorelaxtion. Merck, however, argues that there was no effect on prostaglandin production in blood vessels in animal testing.[1] Other researchers have speculated that the cardiotoxicity may be associated with maleic anhydride metabolites formed when rofecoxib becomes ionised under physiological conditions. (Reddy & Corey, 2005) Chemical structure of prostaglandin E1 (PGE1). ...

Vioxx has also been associated with cardiovascular disease, renal (kidney) disease, and heart arrhythmia.

Withdrawal from the market

VIGOR study

The VIGOR (Vioxx GI Outcomes Research) study, which compared the efficacy and adverse effect profiles of rofecoxib and naproxen. (Bombardier et al., 2000), had indicated a significant 4-fold increased risk of acute myocardial infarction (heart attack) in rofecoxib patients when compared with naproxen patients (0.4% vs 0.1%, RR 0.25) over the 12 month span of the study. The elevated risk began during the second month on rofecoxib. There was no significant difference in the mortality from cardiovascular events between the two groups. Nor was there any significant difference in the rate of myocardial infarction between the rofecoxib and naproxen treatment groups in patients without high cardiovascular risk. The difference in overall risk was accounted for by the patients at higher risk of heart attack: those meeting the criteria for low-dose aspirin prophylaxis of secondary cardiovascular events (previous myocardial infarction, angina, cerebrovascular accident, transient ischemic attack, or coronary artery bypass). (Bombardier et al., 2000) Acute myocardial infarction (AMI or MI), commonly known as a heart attack, is a disease state that occurs when the blood supply to a part of the heart is interrupted. ... Naproxen (trade names: Aleve, Anaprox, Naprogesic, Naprosyn, Naprelan) is a non-steroidal anti-inflammatory drug (NSAID) commonly used for the reduction of mild to moderate pain, fever, inflammation and stiffness caused by conditions such as osteoarthritis, rheumatoid arthritis, psoriatic arthritis, gout, ankylosing spondylitis, injury, menstrual cramps, tendinitis, bursitis, and the... A stroke or cerebrovascular accident (CVA) occurs when the blood supply to a part of the brain is suddenly interrupted by occlusion (an ischemic stroke- approximately 90% of strokes), by hemorrhage (a hemorrhagic stroke - less than 10% of strokes) or other causes. ... Transient ischemic attacks (TIA) are caused by temporary disturbance of blood supply to a restricted area of brain and cause recurrent and brief (less than 24 hours) neurologic dysfunctions. ... A coronary artery bypass graft (CABG) or heart bypass is a surgical procedure performed in patients with coronary artery disease (see atherosclerosis) for the relief of angina and possible improved heart muscle function. ...

Merck's scientists interpreted the finding as a protective effect of naproxen, telling the FDA that the difference in heart attacks "is primarily due to" this protective effect (Targum, 2001). Some commentators have noted that naproxen would have to be three times as effective as aspirin to account for all of the difference (Michaels 2005), and some outside scientists warned Merck that this claim was implausible before VIGOR was published [2]. No evidence has since emerged for such a large cardioprotective effect of naproxen, although a number of studies have found protective effects similar in size to those of aspirin (Karha and Topol, 2004; Solomon et al., 2002). Though Dr. Topol's 2004 paper criticized Merck's naproxen hypothesis, he himself co-authored a 2001 JAMA article stating "because of the evidence for an antiplatelet effect of naproxen, it is difficult to assess whether the difference in cardiovascular event rates in VIGOR was due to a benefit from naproxen or to a prothrombotic effect from rofecoxib." (Mukherjee, Nissen and Topol, 2001.) Merck may refer to: Merck & Co. ... Aspirin or acetylsalicylic acid (acetosal) is a drug in the family of salicylates, often used as an analgesic (against minor pains and aches), antipyretic (against fever), and anti-inflammatory. ...

The results of the VIGOR study were submitted to the United States Food and Drug Administration (FDA) in February 2001, which led to the introduction, in April 2002, of warnings on Vioxx labelling concerning the increased risk of cardiovascular events (heart attack and stroke). The Food and Drug Administration (FDA) is an agency of the United States Department of Health and Human Services and is responsible for regulating food (humans and animal), dietary supplements, drugs (human and animal), cosmetics, medical devices (human and animal) and radiation emitting devices (including non-medical devices), biologics, and...

NEJM controversy

Months after the preliminary version of VIGOR was published in the New England Journal of Medicine, the journal editors learned that certain data reported to the FDA was not included in the NEJM article. Several years later, when they were shown a Merck memo during the depositions for the first federal Vioxx trial, they realized that this data had been available to the authors months before publication. The editors wrote an editorial accusing the authors of deliberately withholding the data (Curfman et al, 2006a). They released the editorial to the media on December 8, 2005, before giving the authors a chance to respond. NEJM editor Gregory Curfman explained that the quick release was due to the imminent presentation of his deposition testimony, which he feared would be misinterpreted in the media. He had earlier denied any relationship between the timing of the editorial and the trial. Although his testimony was not actually used in the December trial, Curfman had testified well before the publication of the editorial.[3] The New England Journal of Medicine (NEJM) is a peer-reviewed medical journal published by the Massachusetts Medical Society with the highest impact factor for a general medical journal. ...

The editors charged that "more than four months before the article was published, at least two of its authors were aware of critical data on an array of adverse cardiovascular events that were not included in the VIGOR article." This additional data included three additional heart attacks, and raised the relative risk of Vioxx from 4.25-fold to 5-fold. All the additional heart attacks occurred in the group at low risk of heart attack (the "aspirin not indicated" group) and the editors noted that the omission "resulted in the misleading conclusion that there was a difference in the risk of myocardial infarction between the aspirin indicated and aspirin not indicated groups." The relative risk for myocardial infarctions among the aspirin not indicated patients increased from 2.25 to 3 (although it remained statitistically insignificant). The editors also noted a statistically significant (2-fold) increase in risk for serious thromboembolic events for this group, an outcome that Merck had not reported in the NEJM, though it had disclosed that information publicly in March 2000, eight months before publication. (Curfman et al., 2006b, Supplementary Material).

The authors of the study, including the non-Merck authors, responded by claiming that the three additional heart attacks had occurred after the prespecified cutoff date for data collection and thus were appropriately not included. (Utilizing the prespecified cutoff date also meant that an additional stroke in the naproxen population was not reported.) Furthermore, they said that the additional data did not qualitatively change any of the conclusions of the study, and the results of the full analyses were disclosed to the FDA and reflected on the Vioxx warning label. They further noted that all of the data in the "omitted" table was printed in the text of the article. The authors stood by the original article. (Bombardier et al., 2006).

NEJM stood by its editorial, noting that the cutoff date was never mentioned in the article, nor did the authors report that the cutoff for cardiovascular adverse events was before that for gastrointestinal adverse events. The different cutoffs increased the reported benefits of Vioxx (reduced stomach problems) relative to the risks (increased heart attacks). (Curfman et al., 2006b).

Some scientists have accused the NEJM editorial board of making unfounded accusations.[4], [5] Others have applauded the editorial. Renowned research cardiologist Eric Topol [6], a prominent Merck critic, accused Merck of "manipulation of data" and said "I think now the scientific misconduct trial is really fully backed up" [7]. Phil Fontanarosa, executive editor of the prestigious Journal of the American Medical Association, welcomed the editorial, saying "this is another in the long list of recent examples that have generated real concerns about trust and confidence in industry-sponsored studies" [8].

Alzheimer's studies

In 2000 and 2001, Merck conducted several studies of rofecoxib aimed at determining if the drug slowed the onset of Alzheimer's disease. Merck has placed great emphasis on these studies on the grounds that they are relatively large (almost 3000 patients) and compared rofecoxib to a placebo rather than to another pain reliever. These studies found an elevated death rate among rofecoxib patients, although the deaths were not generally heart-related. However, they did not find any elevated cardiovascular risk due to rofecoxib (Konstam et al., 2001). Before 2004, Merck cited these studies as providing evidence, contrary to VIGOR, of rofecoxib's safety.

APPROVe study

In 2001, Merck commenced the APPROVe (Adenomatous Polyp PRevention On Vioxx) study, a three year trial with the primary aim of evaluating the efficacy of rofecoxib for the prophylaxis of colorectal polyps. Celecoxib had already been approved for this indication, and it was hoped to add this to the indications for rofecoxib as well. An additional aim of the study was to further evaluate the cardiovascular safety of rofecoxib. Prophylaxis refers to any medical or public health procedure whose purpose is to prevent, rather than treat or cure, disease. ... Polyp of sigmoid colon as revealed by colonoscopy. ... Celecoxib (INN) (IPA: ) is a non-steroidal anti-inflammatory drug (NSAID) used in the treatment of osteoarthritis, rheumatoid arthritis, acute pain, painful menstruation and menstrual symptoms, and to reduce numbers of colon and rectum polyps in patients with familial adenomatous polyposis. ...

The APPROVe study was terminated early when the preliminary data from the study showed an increased relative risk of adverse thrombotic cardiovascular events (including heart attack and stroke), beginning after 18 months of rofecoxib therapy. In patients taking rofecoxib, versus placebo, the relative risk of these events was 1.92 (rofecoxib 1.50 events vs placebo 0.78 events per 100 patient years). The results from the first 18 months of the APPROVe study did not show an increased relative risk of adverse cardiovascular events. Moreover, overall and cardiovascular mortality rates were similar between the rofecoxib and placebo populations. (Bresalier et al., 2005) For other uses, see Risk (disambiguation). ... A myocardial infarction occurs when an atherosclerotic plaque slowly builds up in the inner lining of a coronary artery and then suddenly ruptures, totally occluding the artery and preventing blood flow downstream. ... A stroke, also known as cerebrovascular accident (CVA),[1] is an acute neurological injury in which the blood supply to a part of the brain is interrupted. ... // A placebo is a medicine or preparation which has no inherent pertinent pharmacologic activity but which is effective only by virtue of the factor of suggestion attendant upon its administration. ...

In sum, the APPROVe study suggested that long-term use of rofecoxib resulted in nearly twice the risk of suffering a heart attack or stroke compared to patients receiving a placebo.

Other studies

Pre-approval Phase III clinical trials, like the APPROVe study, showed no increased relative risk of adverse cardiovascular events for the first eighteen months of rofecoxib usage (Merck, 2004). Others have pointed out that "study 090," a pre-approval trial, showed a 3-fold increase in cardiovascular events compared to placebo, a 7-fold increase compared to nabumetone (another [NSAID]), and an 8-fold increase in heart attacks and strokes combined compared to both control groups [9] [10]. Although this was a relatively small study and only the last result was statistically significant, critics have charged that this early finding should have prompted Merck to quickly conduct larger studies of Merck's cardiovascular safety. Merck notes that it had already begun VIGOR at the time Study 090 was completed. Although VIGOR was primarily designed to demonstrate new uses for rofecoxib, it also collected data on adverse cardiovascular outcomes. In medicine, a clinical trial (synonyms: clinical studies, research protocols, medical research) is a research study. ...

Several very large observational studies have also found elevated risk of heart attack from rofecoxib. For example, a recent retrospective study of 113,000 elderly Canadians suggested a borderline statistically significant increased relative risk of heart attacks of 1.24 from Vioxx usage, with a relative risk of 1.73 for higher-dose Vioxx usage. (Levesque, 2005). Another study, using Kaiser Permanente data, found a 1.47 relative risk for low-dose Vioxx usage and 3.58 for high-dose Vioxx usage compared to current use of celecoxib, though the smaller number was not statistically significant, and relative risk compared to other populations was not statistically significant. (Graham, 2005).

Withdrawal

Merck publicly announced its voluntary withdrawal of the drug from the market worldwide on September 30, 2004. September 30 is the 273rd day of the year (274th in leap years) in the Gregorian calendar. ...

In addition to its own studies, on September 23, 2004 Merck apparently received information about new research by the FDA that supported previous findings of increased risk of heart attack among rofecoxib users (Grassley, 2004). FDA analysts estimated that Vioxx caused between 88,000 and 139,000 heart attacks, 30 to 40 percent of which were probably fatal, in the five years the drug was on the market. September 23 is the 266th day of the year (267th in leap years). ... 2004 (MMIV) was a leap year starting on Thursday of the Gregorian calendar. ...

On November 5 the medical journal The Lancet published a meta-analysis of the available studies on the safety of rofecoxib (Jüni et al., 2004). The authors concluded that, owing to the known cardiovascular risk, rofecoxib should have been withdrawn several years earlier. The Lancet published an editorial which condemned both Merck and the FDA for the continued availability of rofecoxib from 2000 until the recall. Merck responded by issuing a rebuttal of the Jüni et al. meta-analysis that noted that Juni omitted several studies that showed no increased cardiovascular risk. (Merck & Co., 2004). The Lancet is one of the oldest and most respected peer-reviewed medical journals in the world, published weekly by Elsevier, part of Reed Elsevier. ... A meta-analysis is a statistical practice of combining the results of a number of studies. ... The circulatory system or cardiovascular system is the organ system which circulates blood around the body of most animals. ...

In 2005, advisory panels in both the U.S. and Canada encouraged the return of rofecoxib to the market, stating that rofecoxib's benefits outweighed the risks for some patients. The FDA advisory panel voted 17-15 to allow the drug to return to the market despite being found to increase heart risk. The vote in Canada was 12-1, and the Canadian panel noted that the cardiovascular risks from rofecoxib seemed to be no worse than those from ibuprofen [11] -- though the panel recommended that further study was needed for all NSAIDs to fully understand their risk profiles. Notwithstanding these recommendations, Merck has not returned rofecoxib to the market. Ibuprofen (INN) (IPA: ) is a non-steroidal anti-inflammatory drug (NSAID) widely marketed under various trademarks including Herron Blue, Act-3, Advil, Brufen, Motrin, Nuprin, Dorival and Nurofen. ...

Litigation

As of March 2006, there had been over 10,000 cases and 190 class actions filed against Merck over adverse cardiovascular events associated with rofecoxib and the adequacy of Merck's warnings. The first wrongful death trial, Rogers v. Merck, was scheduled in Alabama in the spring of 2005, but was postponed after Merck argued that the plaintiff had falsified evidence of rofecoxib use.[12] 2006 (MMVI) was a common year starting on Sunday of the Gregorian calendar. ... In law, a class action is an equitable procedural device used in litigation for determining the rights of and remedies, if any, for large numbers of people whose cases involve common questions of law and fact. ... Wrongful Death is a claim in common law jurisdictions against a person who can be held liable for a death. ... Official language(s) English Capital Montgomery Largest city Birmingham Area Ranked 30th - Total 52,419 sq mi (135,765 kmÂ²) - Width 190 miles (306 km) - Length 330 miles (531 km) - % water 3. ...

On August 19, 2005, a jury in Texas voted 10-2 to hold Merck liable for the death of Robert Ernst, a 59-year old man who allegedly died of a rofecoxib-induced heart attack. The plaintiffs' lead attorney was Mark Lanier. Merck argued that the death was due to cardiac arrhythmia, which had not been shown to be associated with rofecoxib use. The jury awarded Carol Ernst, widow of Robert Ernst, $253.4 million in damages. This award will almost certainly be capped at no more than USD$26.1 million because of punitive damages limits under Texas law.[13] As of March 2006, the plaintiff had yet to ask the court to enter a judgment on the verdict; Merck has stated that it will appeal. August 19 is the 231st day of the year (232nd in leap years) in the Gregorian Calendar. ... 2005 (MMV) was a common year starting on Saturday of the Gregorian calendar. ... Official language(s) None See: Languages of Texas Capital Austin Largest city Houston Area Ranked 2nd - Total 268,581 sq mi (695,622 kmÂ²) - Width 773 miles (1,244 km) - Length 790 miles (1,270 km) - % water 2. ... Cardiac arrhythmia is a group of conditions in which the muscle contraction of the heart is irregular or is faster or slower than normal. ...

On November 3, 2005, Merck won the second case Humeston v. Merck, a personal injury case, in Atlantic City, New Jersey. The plaintiff experienced a mild myocardial infarction and claimed that rofecoxib was responsible, after having taken it for two months. Merck argued that there was no evidence that rofecoxib was the cause of Humeston's injury and that there is no scientific evidence linking rofecoxib to cardiac events with short durations of use. The jury ruled that Merck had adequately warned doctors and patients of the drug's risk.[14] November 3 is the 307th day of the year (308th in leap years) in the Gregorian Calendar, with 58 days remaining. ... 2005 (MMV) was a common year starting on Saturday of the Gregorian calendar. ... Map of Atlantic City in Atlantic County Coordinates: Country United States State New Jersey County Atlantic Incorporated March 1854 Mayor Bob Levy Area - City 44. ... Official language(s) None, English de facto Capital Trenton Largest city Newark Area Ranked 47th - Total 8,729 sq mi (22,608 kmÂ²) - Width 70 miles (110 km) - Length 150 miles (240 km) - % water 14. ...

The first federal trial on rofecoxib, Plunkett v. Merck, began on November 29, 2005 in Houston, Texas. The trial ended in a hung jury and a mistrial was declared on December 12, 2005. According to the Wall Street Journal, the jury hung by an eight to one majority, favoring the defense. Upon retrial in February 2006 in New Orleans, Louisiana, where the Vioxx multi-district litigation (MDL) is based, a jury found Merck not liable, even though the plaintiffs had the NEJM editor testify as to his objections to the VIGOR study. Nickname: Space City Location in the state of Texas Coordinates: Counties Harris County Fort Bend County Montgomery County Mayor Bill White Area - City 1,558 kmÂ² (601. ... Official language(s) None See: Languages of Texas Capital Austin Largest city Houston Area Ranked 2nd - Total 268,581 sq mi (695,622 kmÂ²) - Width 773 miles (1,244 km) - Length 790 miles (1,270 km) - % water 2. ... New Orleans is the largest city in the state of Louisiana, United States of America. ... Official language(s) de jure: none de facto: English & French Capital Baton Rouge Largest city New Orleans [1] Area Ranked 31st - Total 51,885 sq mi (134,382 kmÂ²) - Width 130 miles (210 km) - Length 379 miles (610 km) - % water 16 - Latitude 29Â°N to 33Â°N - Longitude 89Â°W...

On January 30, 2006, a New Jersey state court dismissed a case brought by Edgar Lee Boyd, who blamed Vioxx for gastiointestinal bleeding that he experienced after taking the drug. The judge said that Boyd failed to prove the drug caused his stomach pain and internal bleeding.

In January 2006, Garza v. Merck began trial in Rio Grande City, Texas. The plaintiff, a 71-year-old smoker with heart disease, had a fatal heart attack three weeks after finishing a one-week sample of rofecoxib. On April 21, 2006 the jury awarded the plaintiff $7 million compensatory and $25 million punitive. The punitive amount will be reduced to under $1 Million.

On April 5, 2006, the jury held Merck liable for the heart attack of 77-year-old John McDarby, and awarded Mr McDarby $4.5 million in compensatory damages based on Merck's failure to properly warn of Vioxx safety risks. After a hearing on April 11, 2006, the jury also awarded Mr McDarby an additional $9 million in punitive damages. The same jury found Merck not liable for the heart attack of 60-year-old Thomas Cona, a second plaintiff in the trial.

Merck has reserved $970 million to pay for its Vioxx-related legal expenses through 2007. 2007 (MMVII) is the current year, a common year starting on Monday of the Gregorian calendar and the AD (or CE) era. ...

Merck sales representatives are now being subpoenaed to court over selling Vioxx to doctors- patients are claiming the reps knew of the side effects and are partially responsible for the wrongful deaths.

Political impact of Vioxx litigation in America

The recall and litigation over rofecoxib has provoked debate over drug safety in the United States. Some argue that the U.S. Food and Drug Administration does not do enough to monitor product safety and that the rofecoxib withdrawal is an argument against tort reform. It has also been argued that litigation is an imperfect means of regulation that would overdeter companies for complying with FDA requirements, and that large awards like that in Ernst would inhibit research and development. The United States Food and Drug Administration is the government agency responsible for regulating food, dietary supplements, drugs, cosmetics, medical devices, biologics and blood products in the United States. ... Tort reform is the phrase used by its advocates who claim it is a change in the legal system to reduce litigations alleged adverse effects on the economy. ...

Other COX-2 inhibitors

It is currently unknown whether the increased risk of adverse cardiovascular events is common to all COX-2 inhibitors. Recent studies have demonstrated the increased risk of cardiovascular events associated with the use of celecoxib (Celebrex), valdecoxib (Bextra) and parecoxib (Dynastat). (Solomon et al., 2005; Nussmeier et al., 2005) Celecoxib (INN) (IPA: ) is a non-steroidal anti-inflammatory drug (NSAID) used in the treatment of osteoarthritis, rheumatoid arthritis, acute pain, painful menstruation and menstrual symptoms, and to reduce numbers of colon and rectum polyps in patients with familial adenomatous polyposis. ... Valdecoxib is a prescription drug used in the treatment of osteoarthritis, rheumatoid arthritis, and painful menstruation and menstrual symptoms. ... Injectible prodrug of valdecoxib. ...

Newer and more specific COX-2 inhibitors, including etoricoxib (Arcoxia) and lumiracoxib (Prexige), are currently (circa 2005) undergoing Phase III/IV clinical trials. It is likely that these trials will be extended in order to supply additional evidence of cardiovascular safety. Etoricoxib (brand name Arcoxia®) is a new COX-2 selective inhibitor from Merck & Co. ... Lumiracoxib (rINN) is a COX-2 selective inhibitor non-steroidal anti-inflammatory drug, manufactured by Novartis and sold in 21 countries, including the United Kingdom, Australia, Argentina and Brazil, under the trade name PrexigeÂ®. The Therapeutic Arthritis Research and Gastrointestinal Event Trial was conducted to test its efficacy against Naproxen... In medicine, a clinical trial (synonyms: clinical studies, research protocols, medical research) is a type of research study. ...

Regulatory authorities worldwide now require warnings about cardiovascular risk of COX-2 inhibitors still on the market. For example, in 2005, EU regulators required the following changes to the product information and/or packaging of all COX-2 inhibitors (EMEA 2005):

Miscellaneous

Different types of Acne Vulgaris: A: Cystic acne on the face, B: Subsiding tropical acne of trunk, C: Extensive acne on chest and shoulders. ...

References

External links

[edit]Non-steroidal anti-inflammatory drugs (primarily M01A and M02A, also N02BA)

Salicylates: Aspirin (Acetylsalicylic Acid), Diflunisal, Ethenzamide -- Arylalkanoic acids: Diclofenac, Indometacin, Sulindac Non-steroidal anti-inflammatory drugs, usually abbreviated to NSAIDs, are drugs with analgesic, antipyretic and anti-inflammatory effects - they reduce pain, fever and inflammation. ... A section of the Anatomical Therapeutic Chemical Classification System. ... A section of the Anatomical Therapeutic Chemical Classification System. ... A section of the Anatomical Therapeutic Chemical Classification System. ... Aspirin or acetylsalicylic acid (acetosal) is a drug in the family of salicylates, often used as an analgesic (against minor pains and aches), antipyretic (against fever), and anti-inflammatory. ... Diflunisal is a generic NSAID (Non Steroidal Anti Inflammatory Drug). ... Ethenzamide is a common analgesic and antiinflammatory drug that is used for the relief of fever, headaches, and other minor aches and pains. ... Diclofenac (marketed as VoltarenÂ®, VoltarolÂ®, DiclonÂ®, DicloflexÂ® Difen and CataflamÂ®) is a non-steroidal anti-inflammatory drug (NSAID) taken to reduce inflammation and an analgesic reducing pain in conditions such as in arthritis or acute injury. ... Indomethacin is an indole derived non-steroidal anti-inflammatory drug. ... Sulindac is a non-steroidal anti-inflammatory drug of the arylalkanoic acid class that is marketed in the U.S. as Clinoril. ...

2-Arylpropionic acids (profens): Carprofen, Flurbiprofen, Ibuprofen, Ketoprofen, Ketorolac, Loxoprofen, Naproxen, Tiaprofenic acid, Carprofen is a non-steroidal anti-inflammatory drug that is used by veterinarians as a supportive treatment for the relief of arthritic symptoms in geriatric dogs. ... Flurbiprofen is an NSAID (non-steroidal anti-inflammatory drug) used to treat the inflammation and pain of arthritis. ... Ibuprofen (INN) (IPA: ) is a non-steroidal anti-inflammatory drug (NSAID) widely marketed under various trademarks including Herron Blue, Act-3, Advil, Brufen, Motrin, Nuprin, Dorival and Nurofen. ... Ketoprofen, (RS)2-(3-benzoylphenyl)-propionic acid (chemical formula C16H14O3) is one of the propionic acid class of non-steroidal anti-inflammatory drug (NSAID) with analgesic and antipyretic effects. ... Ketorolac or ketorolac tromethamine (marketed as ToradolÂ® - generics have been approved) is a non-steroidal anti-inflammatory drug (NSAID) in the family of propionic acids, often used as an analgesic, antipyretic (fever reducer), and anti-inflammatory. ... Loxoprofen (INN) is a non-steroidal anti-inflammatory drug in the propionic acid derivatives group. ... Naproxen (trade names: Aleve, Anaprox, Naprogesic, Naprosyn, Naprelan) is a non-steroidal anti-inflammatory drug (NSAID) commonly used for the reduction of mild to moderate pain, fever, inflammation and stiffness caused by conditions such as osteoarthritis, rheumatoid arthritis, psoriatic arthritis, gout, ankylosing spondylitis, injury, menstrual cramps, tendinitis, bursitis, and the... Tiaprofenic acid is pharmaceutical, belonging to the class called NSAIDs (Non-Steroidal Anti-Inflammatory Drugs) used to treat pain, especially arthritic pain. ...

N-Arylanthranilic acids (fenamic acids): Mefenamic acid -- Pyrazolidine derivatives: Phenylbutazone This article needs to be cleaned up to conform to a higher standard of quality. ... Phenylbutazone, often known as bute, is a crystalline substance having the structure shown at right. ...

Oxicams: Meloxicam, Piroxicam -- Coxibs: Celecoxib, Etoricoxib, Parecoxib, Rofecoxib, Valdecoxib -- Sulphonanilides: Nimesulide Meloxicam is a nonsteroidal anti-inflammatory drug used to relieve the symptoms of arthritis, primary dysmenorrhoea, pyrexia; and as an analgesic, especially where there is an inflammatory component. ... Piroxicam (US trade name Feldene) is a nonsteroidal anti-inflammatory drug used to relieve the symptoms of arthritis, primary dysmenorrhoea, pyrexia; and as an analgesic, especially where there is an inflammatory component. ... Celecoxib (INN) (IPA: ) is a non-steroidal anti-inflammatory drug (NSAID) used in the treatment of osteoarthritis, rheumatoid arthritis, acute pain, painful menstruation and menstrual symptoms, and to reduce numbers of colon and rectum polyps in patients with familial adenomatous polyposis. ... Etoricoxib (brand name Arcoxia®) is a new COX-2 selective inhibitor from Merck & Co. ... Injectible prodrug of valdecoxib. ... Valdecoxib is a prescription drug used in the treatment of osteoarthritis, rheumatoid arthritis, and painful menstruation and menstrual symptoms. ... Nimesulide structure formula Nimesulide is a prescription non-steroidal anti-inflammatory drug (NSAID) with analgesic and antipyretic properties. ...

Topically used products: Diclofenac, Flurbiprofen, Ibuprofen, Indometacin, Ketoprofen, Naproxen, Piroxicam Diclofenac (marketed as VoltarenÂ®, VoltarolÂ®, DiclonÂ®, DicloflexÂ® Difen and CataflamÂ®) is a non-steroidal anti-inflammatory drug (NSAID) taken to reduce inflammation and an analgesic reducing pain in conditions such as in arthritis or acute injury. ... Flurbiprofen is an NSAID (non-steroidal anti-inflammatory drug) used to treat the inflammation and pain of arthritis. ... Ibuprofen (INN) (IPA: ) is a non-steroidal anti-inflammatory drug (NSAID) widely marketed under various trademarks including Herron Blue, Act-3, Advil, Brufen, Motrin, Nuprin, Dorival and Nurofen. ... Indomethacin is an indole derived non-steroidal anti-inflammatory drug. ... Ketoprofen, (RS)2-(3-benzoylphenyl)-propionic acid (chemical formula C16H14O3) is one of the propionic acid class of non-steroidal anti-inflammatory drug (NSAID) with analgesic and antipyretic effects. ... Naproxen (trade names: Aleve, Anaprox, Naprogesic, Naprosyn, Naprelan) is a non-steroidal anti-inflammatory drug (NSAID) commonly used for the reduction of mild to moderate pain, fever, inflammation and stiffness caused by conditions such as osteoarthritis, rheumatoid arthritis, psoriatic arthritis, gout, ankylosing spondylitis, injury, menstrual cramps, tendinitis, bursitis, and the... Piroxicam (US trade name Feldene) is a nonsteroidal anti-inflammatory drug used to relieve the symptoms of arthritis, primary dysmenorrhoea, pyrexia; and as an analgesic, especially where there is an inflammatory component. ...

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