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cox 2
  1. #1
    samoffat is offline New Member
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    Sep 2004

    Default cox 2

    To what extent is Bextra chemically similar to Vioxx? Enough so that we all should stop Bextra until any difference has been established to maintain safety of Bextra? I suppose better safe than sorry. Is there anything in the literature warning against Celebrex and Bextra as there was several years ago warning against Vioxx? In other words, are the mfgrs of Bextra and Celebrex any more trustworthy than Merck? Seems to me that the chemical/drug companies are as scandalous as the tobacco companies, and as dangerous. I sure will miss Bextra! Now they need to invent a way to make aspirin tummy-kind!

  2. #2
    rusty is offline Junior Member
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    Sep 2004


    I too am watching the whole Cox-2 saga with interest as I have older family members who will be affected. I notice this article has just been published by Public Citizen....

    Public Citizen: Vioxx, Other “Super Aspirins” Are Super Disasters – Other Cox-2 Alternatives Have Safety Problems Too

    Statement by Sidney M. Wolfe, MD, Director of Public Citizen’s Health Research Group, Concerning Withdrawal of Vioxx From the Market

    WASHINGTON, Sept. 30, 2004 - Today’s announcement by Merck is the latest evidence that this family of drugs, the Cox-2 inhibitors, once referred to as “super aspirins,” are turning out to be more like super disasters. As discussed below, there are safety problems with Celebrex as well as Bextra, the two other big-selling Cox-2 inhibitors that are the most-prescribed alternatives to Vioxx.

    In trying to appear “a good citizen,” Merck ignores its checkered history with Vioxx. In today’s statement announcing the withdrawal of Vioxx from the market, Peter S. Kim, Ph.D., president of Merck Research Laboratories asserted that “Merck has always believed that prospective, randomized, controlled clinical trials are the best way to evaluate the safety of medicines.” Yet after an earlier randomized trial, the VIGOR study, published almost four years ago (November 2000), that found Vioxx caused a four- to five-fold increase in heart attacks, Merck received, on Sept. 17, 2001, a warning letter from the U.S. Food and Drug Administration (FDA) because the company’s ads for the drug failed to mention this increased risk of heart attacks. In the eight-page warning letter addressed to Merck President and CEO Raymond V. Gilmartin, the FDA stated:

    You have engaged in a promotional campaign for Vioxx that minimizes the potentially serious cardiovascular findings that were observed in the Vioxx Gastrointestinal Outcomes Research (VIGOR) study, and thus, misrepresents the safety profile for Vioxx. Specifically, your promotional campaign discounts the fact that in the VIGOR study, patients on Vioxx were observed to have a four to five fold increase in myocardial infarctions (MIs) compared to patients on the comparator nonsteroidal anti-inflammatory drug (NSAID), Naprosyn (naproxen).

    In Merck’s VIGOR study, comparing rofecoxib to naproxen, there was a highly statistically significant five-fold increase in heart attacks in the overall rofecoxib group (0.5 percent) compared to the naproxen group (0.1 percent). This amounted to 20 heart attacks with rofecoxib (out of 4,047 patients) compared with four with naproxen (out of 4,029 patients). This increased number of heart attacks was also accompanied by an increase in other thrombotic (blood clotting) adverse effects such as strokes and blood clots in the legs as well as problems with hypertension in the rofecoxib group compared with the naproxen group.

    In an article published three and a half years ago in our monthly newsletter, Worst Pills, Best Pills News (now online at, we warned readers that both Vioxx and Celebrex were DO NOT USE drugs – our designation for drugs that are not safe and effective enough to use. Although Merck’s withdrawal of Vioxx “solves” the serious safety problems with this drug, the most-prescribed alternatives, Celebrex and Bextra, also have some concerns about their cardiac toxicity.

    Cardiovascular Toxicity and Cox-2 Inhibitors

    In a study published in the Aug. 29, 2000, Proceedings of the National Academy of Sciences, the ability of rabbits to withstand temporary experimental coronary artery occlusion (experimental heart attack) was significantly impaired by treatment with celecoxib (Celebrex), which completely blocked the cardioprotective effects of the COX-2 enzyme. The authors of that study concluded that COX-2 enzyme is a “cardioprotective protein.” Therefore, it is implied, drugs that block this cardioprotective enzyme, such as COX-2 inhibitors, may neutralize its protective effects.

    Problems with Celebrex

    Although a CLASS study involving Celebrex did not find a significantly elevated number of heart attacks in those using celecoxib compared to those using the older NSAIDs (ibuprofen or diclofenac), there was also cause for concern about heart toxicity with celecoxib. An expert from the FDA’s Division of Cardio-Renal Drug Products, Dr. Douglas Throckmorton, found that “the incidence of adverse events related to cardiac ischemia (decreased blood flow to the heart) was higher in the celecoxib [Celebrex] group ... and was most pronounced in the group of patients not taking ASA (aspirin)” as a cardiovascular protective drug. In these patients, the rate of heart attack was also highest in the celecoxib group (0.2 percent) compared with users of the other two drugs (0.1 percent). For all patients, on and off aspirin, there was a higher incidence of atrial fibrillation, a type of heart rhythm disturbance, in the celecoxib group compared to those taking ibuprofen or diclofenac. Again this was more pronounced in the group not taking aspirin. Dr. Throckmorton concluded by stating that “the data do not exclude a less apparent pro-thrombotic [blood clot-forming] effect of celecoxib, reflected in the relative rates of cardiac adverse events related to ischemia.”

    Safety Problems with the New Cox-2 inhibitor, Valdecoxib (Bextra)

    We have also warned readers of Worst Pills, Best Pills News not to use Bextra. Because the FDA and Bextra’s manufacturer, Pfizer, refused to give us unpublished data concerning the drug, we filed suit against the agency. The FDA had originally redacted all information in its reviews concerning valdecoxib and acute pain. In the course of our litigation, we received most of what we had requested in the lawsuit, including the unredacted FDA Medical Officer’s conclusions and recommendations about the use of the drug for acute pain.

    In the unredacted review the Medical Officer recommended:

    Nonapproval [for the treatment] of the acute pain, including opioid-sparing and prevention of operative pain. The only substantial multidose safety database is found in the Coronary Artery Bypass Graft (CABG) Surgery study 035. This study demonstrated an excess of serious adverse events including death in association with the use of paracoxib and valdecoxib 40 mg bid [twice daily] when added to ad lib [as needed] parenteral [injectable] narcotic analgesia. ... These finding[s] warrants further investigation before valdecoxib can be considered safe and effective for the treatment of pain, particularly multidose therapy in the perioperative setting.

    In summarizing the safety of valdecoxib the FDA Medical Officer stated:

    With two notable exceptions — edema [swelling] and hypertension — valdecoxib (Bextra) was comparable to the standard non-steroidal agents [ibuprofen, naproxen, diclofenac] used as active controls in the trials. ... The finding of a greater incidence of edema and hypertension at doses above 20 mg/day, almost uniformly in the databases and clearly when prospectively addressed in formal safety Trials 47 and 62, is of concern. ... The excess of serious cardiovascular thromboembolic [blood clots] in the valdecoxib arm of the CABG [Coronary Artery Bypass Graft] trial is of note as the entire study population received prophylactic low dose aspirin as part of the standard of care in this setting to minimize just such events. Given the emerging concern over a possible pro-thrombotic action of certain agents in the COX2 class, these data are of concern. (Emphasis added.)

    In summary, we advise patients not to use any of these “super aspirin” Cox-2 inhibitors and, instead, to rely on the older drugs in the NSAID family such as ibuprofen and naproxen.

  3. #3
    rusty is offline Junior Member
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    Sep 2004


    An update on Bextra...

    Pfizer Links Bextra, Some Heart Problems
    Fri Oct 15, 2004 03:42 PM ET

    By Toni Clarke
    NEW YORK (Reuters) - Pfizer Inc. (PFE.N: Quote, Profile, Research) on Friday said two small clinical trials showed heart bypass surgery patients taking Bextra, an anti-inflammatory in the same class as the recently withdrawn drug Vioxx, had an increased risk of stroke and heart attack.

    The company also updated its warning that Bextra can cause a rare, but sometimes fatal, skin disorder called Stevens-Johnson syndrome to note that cases of the condition are being seen more often with Bextra than with other drugs in the same class.

    Pfizer's shares fell 2.8 percent on concerns that sales of Bextra would be hurt and that an experimental intravenous version of the drug, called parecoxib, may never now reach the U.S. market.

    "This definitely tarnishes Bextra and diminishes the prospects for parecoxib," said Shaojing Tong, an analyst at Mehta Partners. Parecoxib is sold outside the United States under the name Dynastat.

    Bextra, which was launched in 2001, had sales last year of $687 million. It is approved to treat pain from arthritis and, like Merck & Co.'s (MRK.N: Quote, Profile, Research) Vioxx, is a COX-2 inhibitor. A recent trial showed Vioxx doubled the risk of heart attack and stroke in patients who took the drug for more than 18 months.

    The Vioxx withdrawal has cast a cloud over the entire class of COX-2 inhibitors, which also includes Pfizer's Celebrex and an experimental drug from Novartis AG (NOVN.VX: Quote, Profile, Research) called Prexige.

    Pfizer said that following the Vioxx withdrawal, it re-examined its clinical data base of 8,000 patients with rheumatoid arthritis and osteoarthritis and found no increased risk of dangerous heart events in those taking Bextra for up to a year. The company also found no increased risk in a trial of patients taking Bextra in a general surgery setting.

    Doctors said it is too early to quantify the potential risk of Bextra or Celebrex, as neither have been tested for long enough. Pfizer said it is conducting longer term trials in arthritis patients.

    The coronary bypass trials are ones that Dr. Eric Topol, of the Cleveland Clinic Foundation and an early and outspoken critic of Vioxx, said he found concerning as they show a cluster of heart attacks and strokes. He said the danger signal does not appear to be as strong as it was with Vioxx.

    "Celebrex and Bextra do appear safer than Vioxx but whether they are really safe, especially in patients with heart risk, that's an open question," Topol said.

    Pfizer has updated the label on several occasions since Bextra was approved to reflect the risk of Stevens-Johnson syndrome, a form of allergic reaction caused usually by certain types of drug. Symptoms usually begin as a blistering of the mouth and lips, spreading to the throat, tongue and other parts of the body. The blisters sometimes become so extensive as to be fatal.

    The company said the risk did not start to appear until the drug hit the market. It updated the label in April to say that deaths have occurred. The company said the number is "very small," but declined to be more specific.

    Gail Cawkwell, Pfizer's COX-2 worldwide medical team leader, said the company has reported the number of deaths to regulators, but does not believe it is "meaningful" enough to report to the general public.

    Jean Farrell, founder of the Stevens-Johnson Foundation, a non-profit organization that provides information to patients and the medical community, said that within weeks of Bextra hitting the market she had a "huge" increase in calls.

    "I had never even heard of the drug and within three weeks we already had six cases of SJS reported to us."

    Shares of Pfizer fell 80 cents to $28.28 in afternoon trading on the New York Stock Exchange. (Additional reporting by Ransdell Pierson in New York and Julie Steenhuysen in Chicago)

  4. #4
    rusty is offline Junior Member
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    Sep 2004


    And Celebrex...

    Pfizer to Test Heart Safety of Celebrex
    Mon Oct 18, 2004 04:18 PM ET

    By Toni Clarke and Ransdell Pierson
    NEW YORK (Reuters) - Pfizer Inc. on Monday said a major new trial will test whether its popular Celebrex arthritis drug increases the risk of heart attacks, as seen with Merck and Co.'s recalled Vioxx pill.

    Celebrex is in the same family of medicines as Vioxx, which was taken off the market last month after a trial showed it doubled the risk of heart attack and stroke in patients taking it to determine if it can prevent recurrence of colon polyps.

    Pfizer's new global study will enroll more than 4,000 patients who have had a recent heart attack and who also have a history of osteoarthritis -- the most common form of arthritis in which the joints are harmed by wear and tear.

    If the trial is successful, it could help ensure the continued success of Celebrex, which had 2003 sales of $1.9 billion. If it fails, it could jeopardize not only Celebrex but Pfizer's newer drug Bextra. Like Vioxx, they both selectively block the inflammation-causing COX-2 enzyme.

    Pfizer said that it is confident Celebrex does not pose a heart risk based on its experience in multiple studies over several years and said some small trials suggest the anti-inflammatory nature of Celebrex may protect against certain heart problems.

    The study is scheduled to begin in early 2005 and will compare Celebrex to a placebo, although all patients will also be allowed to take certain pain-killers, such as ibuprofen, to curb excessive pain.

    "We don't expect the placebo group to have no treatment," said Mitch Gandelman, a senior Pfizer research executive. "The likelihood will be that they will take Tylenol or another non-steroidal anti-inflammatory drug."

    The trial will last at least two years, Pfizer said. Vioxx was withdrawn after increased risk of so-called heart events showed up after 18 months. The heightened risk was not seen in patients that had been taking the Merck drug for less than 18 months.

    The Vioxx dangers raised questions about the whole class of COX-2 inhibitors.

    Asked if Pfizer might extend its new trial of Celebrex beyond two years given the negative three-year trend seen with Vioxx, a Pfizer spokesman said, "I don't think we want to speculate beyond two years."

    Although Celebrex has been on the market since 1999 and its sister drug Bextra was introduced in 2001, Pfizer has never completed long-term trials comparing their safety to placebos.

    The Pfizer pills were approved by U.S. regulators, in part, based on placebo-controlled trials that lasted only a few months, Pfizer said.

    "Bextra and Celebrex both included three months of placebo data, as per FDA requirements," Pfizer spokeswoman Mariann Caprino said in an interview earlier this month.

    Caprino said placebo trials of Bextra submitted to European regulators, however, lasted six months.

    In approving the two Pfizer drugs, the U.S. Food and Drug Administration relied mainly on large trials that compared them to ibuprofen and diclofenac, another standard treatment.

    Vioxx was also approved primarily on trials that tested it against standard treatments, although Merck did provide the FDA data from a four-month trial that compared the now-recalled drug to placebo.

    Pfizer, whose shares closed up 50 cents, or 1.75 percent, to $29 on the New York Stock Exchange, said it will discuss the study design with the FDA and other regulatory agencies before completing the study design. (Additional reporting by Ransdell Pierson and Julie Steenhuysen in Chicago.)

  5. #5
    MONHEIT_LAW_PC is offline New Member
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    Dec 2004


    Erythema multiforme, a mild blistering skin eruption, is a milder version of Stevens Johnson Syndrome (SJS). EM can progress into Stevens Johnson Syndrome (SJS) or TEN (Toxic Epidermal Necrolysis). The most severe skin rash reactions to drug therapy are Stevens Johnson Syndrome (SJS) and TEN, which are skin diseases that result in eruptions resembling burns and are characterized by epidermal loss. Bextra causes Stevens Johnson Syndrome (SJS) and TEN.

    For more information on this, see:

    Stevens-Johnson rash syndrome and toxic epidermal necrolysis usually begin with fever, headache, cough, and body aches, which may last from 1 to 14 days. Later the rest of the body develops a rash and blisters in an irregular pattern.
    The Stevens Johnson rash caused by Bextra includes enlarged and spread out rashes, that often forming blisters in their center.

    Stevens-Johnson rash (Syndrome), also known as (SJS) is a potentially deadly skin disease that usually results from a drug reaction. Stevens Johnson rash is related to a similar disease called Toxic Epidermal Necrolysis. Stevens Johnson rash results from a sulfa drug-related allergic reaction. The skin of the blisters is very loose and easy to rub off. In toxic epidermal necrolysis, large areas of skin peel off, often with just a gentle touch or pull. In many people, 30% or more of the body surface peels away. The affected areas of skin are painful, and the person feels very ill with chills and fever. In some people, the hair and nails fall out.

    Both Stevens Johnson Rash and TEN (Necrolysis) can be deadly. Even when not fatal, SJS and TEN are extremely painful. Drugs that have been linked to Stevens-Johnson Syndrome, including:

    • Bextra
    • Carbamazepine
    • Allopurinol
    • Phenytoin
    • Sulfa antibiotics

    Stevens Johnson rash can cause severe pain, not to mention the visual stress and anxiety.
    Michael Monheit, Esquire
    Monheit Law, PC

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